PROCESS FOR MAKING QUINOLONYL LACTAM ANTIMICROBIALS AND NOVEL INTERMEDIATE COMPOUNDS

Abstract: The present invention provides processes for making compounds of the structure (Q-L<1>)-L-(L<2>-B), wherein (I) Q is a quinolone moiety; (II) B is a lactam moiety; and (III) L, L<1>, and L<2> together comprise a linking moiety; comprising the steps of: (1) coupling a compound of formula (III) with a lactam-containing compound to form an intermediate compound; and (2) cyclizing the intermediate by reaction with an organosilicon compound to give a compound of the formula (Q-L<1>)-L-(L<2>-B). Preferably, the process additionally comprises a step prior to the coupling step, wherein protected forms of the compound of formula (III) and the lactam compound are formed; and deprotection steps after the cyclization step, wherein the protecting groups are removed. Preferred antimicrobial compounds made by these processes are those where the beta-lactam moiety is a penem, a carbapenem, a cephem, or a carbacephem. Also preferred are those compounds where L<1>, L, and L<2> form a carbamate moiety, or a secondary or tertiary amine moiety. The present invention also provides novel intermediate compounds of the formula (M-L<1>)-L-(L<2>-B), where (I) M has a structure according to formula (IV), (II) B is a lactam moiety, and (III) L, L<1>, and L<2> together comprise a linking moiety.

Description: PROCESS FOR MAKING QUINOLONYL LACTAM ANTIMICROBIALS AND NOVEL INTERMEDIATE COMPOUNDS BACKGROUND OF THE INVENTION This invention relates to processes for making antimicrobial compounds. The compounds made by this invention contain, as integral substituents, a quinolone moiety and a lactam-containing moiety. The invention further relates to novel intermediate compounds that are useful in making the antimicrobial compounds. The chemical and medical literature describes a myriad of compounds that are said to be antimicrobial, i.e., capable of destroying or suppressing the growth or reproduction of microorganisms, such as bacteria. In particular, antibacterials include a large variety of naturally-occurring (antibiotic), synthetic, or semi- synthetic compounds. They may be classified (for example) as the aminoglycosides, ansamacrolides, beta-lactams (including penicillins and cephalosporins), lincosaminides, macrolides, nitrofurans, nucleosides, oligosaccharides, peptides and polypeptides, phenazines, polyenes, polyethers, quinolones, tetracyclines, and sulfonamides. Such antibacterials and other antimicrobials are described in Antibiotics. Chemotherapeutics. and Antibacterial Agents for Disease Control (M. Grayson, editor, 1982), and E. Gale et al., The Molecular Basis of Antibiotic Action 2d edition (1981), both incorporated by reference herein. Recently, a new class of highly potent, broad spectrum antimicrobials was discovered, combining beta-lactam moieties with quinolone moieties. These compounds have been referred to as "Quinolonyl Lactam Antimicrobials" (herein referred to as "QLAs)." Such compounds are described in European Patent Publication 366,189, White and Demuth, published May 2, 1990; European Patent Publication 366,193, Demuth and White, published May 2, 1990; European Patent Publication 366,640, Demuth and White, published May 2, 1990; and European Patent Publication 366,641, White and Demuth, published May 2, 1990. Other such compounds are described in Australian Patent Publication 87/75009, Albrecht et al., published January 7, 1988; Australian Patent Publication 88/27554, published June 6, 1989; European Patent Publication 335, 297, Albrecht et al., published October 4, 1989; and Albrecht et al., "Dual-Action Cephalosporins: Cephalosporin 3'-Quinolone Carbamates", 34 J. Medicinal Chemistry 2857 (1991). Manufacture of QLAs generally involves synthesis of suitably protected substituent beta-lactam and quinolone moieties, a linking process, and appropriate <» tr --< •• • de-protection steps. The specific linking process depends, of course, on the specific lactam and quinolone substituent moieties used, as well as the type of linkage desired. Several such linking processes have been described in the literature. However, the overall yields of these processes are sometimes low, due in part to degradation caused by the use of harsh reagents and polar solvents (e.g., water), and to poor solubility of the components in organic solvents, particularly the quinolone or related heterocyclic component. Additionally, the linking processes known in the art offer limited synthetic flexibility. It has now been discovered that Unking processes which employ a quinolone precursor and, optionally, utilize organosilicon compounds in the linking step are useful in making QLAs. Such processes surprisingly allow efficient synthesis of QLA precursors under reaction conditions that provide good solubility of the quinolone precursor or related heterocyclic component, and do not use the harsh reagents and polar solvents taught by the prior art. Sensitive functional groups in the reaction substrate and product tolerate these mild reaction conditions. Additionally, these processes are particularly useful when used in conjunction with the ring closure methodology for quinolones and related heterocyclic moieties, specifically described and claimed in co-pending application Serial No. , filed August 2, by Randall et al. The mild reaction conditions of these processes may allow for improved QLA yields and purities, and provide the synthetic flexibility to make QLAs that, if prepared utilizing the prior art, might be accessable only in low to moderate yields. SUMMARY OF THE INVENTION The present invention provides methods of making a compound of the formula (Q - Ll) - L - (L2 - B) the method comprising the steps of: (1) coupling a compound having a structure according to Formula (III) (HI) wherein (A) (1) A 1 is N or C(R 7 ); where (a) R? is hydrogen, hydroxy, alkoxy, nitro, cyano, halogen, alkyl, or -N R 8 )^ 9 ), and (b) R 8 and R^ are, independently, hydrogen, alkyl, alkenyl, a carbocyclic ring, or a heterocyclic ring; or R 8 and R^ together comprise a heterocyclic ring including the nitrogen to which they are bonded; (2) A- is N or C(R 2 ); where R 2 is hydrogen or halogen; (3) A^ is N or C(R^); where R^ is hydrogen; (4) R! is hydrogen, alkyl, a carbocyclic ring, a heterocyclic ring, alkoxy, hydroxy, alkenyl, arylalkyl, or -N(R8)(R9); (5) R3 is hydrogen, halogen, alkyl, a carbocyclic ring, or a heterocyclic ring; (6) R 4 is hydroxy; (7) R*> is hydrogen, halogen, nitro, hydrazino or -N(R 8 )(R9); and (8) X is a leaving group (B) and (1) when A- is C(R 2 ), R- and R^ may together comprise -O-(CH2) n -O-, where n is from 1 to 4; (2) when A^ is C(R^), R^ and R^ may together comprise a heterocyclic ring; and (3) when A^ is C(~ ), R 7 and R^ may together comprise a heterocyclic ring including A* and the carbon atom to which R3 is bonded; or a protected form, salt, ester, or solvate thereof; with a lactam-containing compound having a structure according to Formula (II), to form an intermediate compound; and (2) cyclizing the intermediate compound by reaction with an organosilicon compound to give a compound of the formula (Q - L 1 ) - L - (L 2 - B); wherein (I) Q has a structure according to Formula (I) wherein (A) (1) A 1 is N or C(R 7 ); where (a) R 7 is hydrogen, hydroxy, alkoxy, nitro, cyano, halogen, alkyl, or -N(R 8 )(R 9 ), and (b) R 8 and R 9 are, independently, R 8a where R 8a is hydrogen, alkyl, alkenyl, a carbocyclic ring, or a heterocyclic ring; or R 8 and R 9 together comprise a heterocyclic ring including the nitrogen to which they are bonded; (2) A- is N or C(R 2 ); where R 2 is hydrogen or halogen; (3) A- is N or C(R^); where R 5 is hydrogen; (4) R\ is hydrogen, alkyl, a carbocyclic ring, a heterocyclic ring, alkoxy, hydroxy, alkenyl, arylalkyl, or -N(R 8 )(R 9 ); (5) R~ is hydrogen, halogen, alkyl, a carbocyclic ring, or a heterocyclic ring; (6) R4 is hydroxy; and (7) R*> is hydrogen, halogen, nitro, hydrazino or -N(R 8 )(R 9 ); (B) and (1) when A 2 is C(R 2 ), R 2 and R 3 may together comprise -O-(CH2) n -O-, where n is from 1 to 4; (2) when A 3 is C(R^), R^ and R^ may together comprise a heterocyclic ring; and (3) when A* is C(R 7 ), R 7 and R 3 may together comprise a heterocyclic ring including A* and the carbon atom to which R3 is bonded; (C) and provided that one of R 1 , R 3 , or R 6 is a covalent bond to ιΛ (π) B has a structure according to Formula (II): wherein (A) R 10 is hydrogen, halogen, alkyl, alkenyl, heteroalkyl, a carbocyclic ring, a heterocyclic ring, R 8 -O-, R CH=N-, (R 8 )(R 9 )N-, R 17 -C(=CHR 0 )-C(=O)NH-, R 17 -C(=NO- R 19 )-C(=O)NH-, or R 18 -(CH 2 ) m -C(=O)NH-; where (1) m is an integer from 0 to 9; (2) R 17 is hydrogen, alkyl, alkenyl, heteroalkyl, heteroalkenyl, a carbocyclic ring, or a heterocyclic ring; (3) R 18 is R 17 , -Y 1 , or -CH(Y 2 )(Rl 7 ); (4) R 19 is R 17 , arylalkyl, heteroarylalkyl,-C(R 2 2)(R23 _ COOH, -C(=O)O-R 17 , or -C(=O)NH-R 17 , where R 22 and R 23 are, independently, R^ 7 or together comprise a carbocyclic ring or a heterocyclic ring including the carbon atom to which R 22 and R23 are bonded; (5) R 20 is R 19 halogen, -Y 1 , or -CH(Y 2 )(R 17 ); (6) Y 1 is -C(=O)OR 21 , -C(=O)R 21 , -N(R 4 )R21, -S(O) p R 29 , or -OR 29 ; and Y 2 is Y 1 or -OH, -SH, or -SO 3 H; (a) p is an integer from 0 to 2; (b) R 24 is hydrogen; alkyl; alkenyl; heteroalkyl; heteroalkenyl; a carbocyclic ring; a heterocyclic ring; -SO3H; -C(=O)R 25 ; or, when R 18 is -CH(N(R 24 )R 21 )(R 17 ), R 24 may comprise a moiety bonded to R to form a heterocyclic ring; and (c) R 25 is R 17 , NH(Rl 7 ), N(R 17 )(R 2 6), O(R 26 ), or S(R 26 ); where R 26 is alkyl, alkenyl, a carbocyclic ring, a heterocyclic ring, or when R 25 is -N(R 1 )(R 26 ), R 26 may be a moiety bonded to R* 7 to form a heterocyclic ring; and (7) R 21 is R 29 or hydrogen; where R 29 is alkyl; alkenyl; arylalkyl; heteroalkyl; heteroalkenyl; heteroarylalkyl; 5 a carbocyclic ring; a heterocyclic ring; or, when Y is - N(R 24 )R 21 and R 21 is R 29 , R 21 and R 24 may together comprise a heterocyclic ring including the nitrogen atom to which R 24 is bonded; (B) R 1 - is hydrogen, halogen, alkoxy, or R 27 C(=O)NH-, where 10 R 27 is hydrogen or alkyl; (C) bond "a" is a single bond or is nil; and bond "b" is a single bond, a double bond, or is nil; except bond "a" and bond "b" are not both nil; (D) R 12 is -C(R 8 )-, or -CH 2 -R 28 -; where R 28 is -C(R 8 ), -O-, or 15 -N-, and R 28 is directly bonded to N" in Formula (II) to form a 5-membered ring; except, if bond "a" is nil, then R* 2 is (1) -C(R 8 )(XΪ)-, where (a) X ■ is -R 2 1 ; -OR 30 ; -S(O) r R 30 , where r is an 20 integer from 0 to 2; -OC(=O)R 30 ; or -N(R 30 )R 3 1 ; and (b) R 30 and R 3 ^ are, independently, alkyl, alkenyl, a carbocyclic ring or a heterocyclic ring; or R 0 and R 3 together comprise a 25 heterocyclic ring including the nitrogen atom to which R 30 and R 3 • are bonded; or (2) -CH 2 -R 32 -; where R 32 is -C(R 8 )(R 2 1), -O-, or -NR 8 , and R 32 is directly bonded to N" in Formula (II) to form a 5-membered ring; 30 (E) (1) if bond "b" is a single bond, R 13 is -CH(R 33 ); or, -C(O)NHSO 2 -, if bond "a" is nil; or -C*(R 33 )- if R 4 contains a R > moiety; where R 33 is hydrogen or COOR 46 where R 46 is hydrogen, alkyl or alkenyl, and C* is linked to R 36 to form a 3- 35 membered ring; (2) if bond "b" is a double bond, R 13 is -C(R 33 )=; or (3) if bond "b" is nil, R 13 is hydrogen, -SO3H, -PO(OR 34 )OH, -C(O)NHSO 2 N(R 3 )(R 3 5), -OSO3H, -CH(R 35 )COOH, or -OCH(R 34 )-COOH; where R 34 is hydrogen, alkyl, alkenyl, a carbocyclic ring, or a heterocyclic ring; and R 3 ^ is hydrogen, alkyl, alkenyl, or -NHR 8 ; or, if R 13 is -C(O)NH- SO N-(R 34 )(R 3 5), R 34 and R 35 may together comprise a heterocyclic ring including the nitrogen to which R 34 and R 3 ^ are bonded; and (F) (1) if bond "a" or bond V is nil, then R 14 is a covalent bond; (2) if bond "a" and "b" are single bonds, R 14 is -W- C"'=C(R 8a )-R 37 -, or -W-C"'(R 36 )-R 37 -; or (3) if bond "a" is a single bond and bond "b" is a double bond, R 14 is -C(R 8 )(R 38 )-W-C"'-R 37 -; -W-C(R 8 )- (R38). C '".R37. ; or .W-C"-R 37 -; (4) where (a) W is O; S(O) s , where s is an integer from 0 to 2; or C(R 38 ), where R 38 is hydrogen, alkyl or alkoxy; (b) R 36 is hydrogen; alkyl; alkenyl; -COOH; or, if RI 3 is -C*(R 33 ), R 36 may be linked to C* to form a 3-membered carbocyclic ring; (c) R 37 is covalent bond, alkyl, alkenyl, a carbocyclic ring, or a heterocyclic ring; and (d) C" is directly bonded to R 13 to form a 5- or 6-membered ring; and (III) (A) L is -C(=Z)-; -S(O) v -; -N(R 44 )-; -N+(R 4 )(R 4 5)- ; -N(R 44 )-N(R 44 )-; -O-; =N-; or a covalent bond; and L is bonded to L 3 and L 4 ; where (1) Z is O. S. or +NfH ; (2) v is 0, 1 or 2; (3) R 44 is hydrogen, substituted or unsubstituted lower alkyl, aryl, acyl, hydroxy, alkoxy, aryloxy, or acyloxy; and (4) R 4 ^ is hydrogen, unsubstituted or substituted lower alkyl, or substituted or unsubstituted aryl; (B) L 1 is L 3 or R 15 L 3 ; where (1) when L is -C(=Z)-, L 3 is a covalent bond, oxygen, sulfur, or nitrogen; and when L is other than -C(=Z)-, L 3 is a covalent bond; (2) R\- is alkyl, alkenyl, heteroalkyl, a heterocyclic ring, a carbocyclic ring, or \- together with L 3 is a heteroalkyl or a heterocyclic ring; and (3) Li is bonded to Q at the point of attachment of R*, R 3 or R*\ whichever is a covalent bond; (C) L 2 is L 4 , -X 2 t -R 39 -L 4 , or -X 3 t -R 39 -L 4 ; where (1) when L is -C(=Z)-, L 4 is a covalent bond, oxygen, sulfur, or nitrogen; and when L is other than -C(=Z)-, L 4 is a covalent bond; (2) X 2 is oxygen, or S(O) v , where v is 0, 1, or 2; (3) X 3 is nitrogen; -N(R 40 )-; -N+(R 1)(R 42 )-; or R 43 - N(R 4 *); and is linked to R 14 by a single or double bond; or, if R 4 is covalent bond, X 3 is linked to B by a single or double bond; where (a) R 40 is R 8 ; -OR 8 ; or -C(=O)R 8 ; (b) R 41 and R 42 are, independently, hydrogen; alkyl; alkenyl; carbocyclic rings; heterocyclic rings; or, if R 6 is R 16 X, then R 4 * and R 42 together with "Q" may comprise a heterocyclic ring as R^; (c) R 43 is N(R 41 ), oxygen or sulfur; (4) t is O or l; (5) R 39 is alkyl, alkenyl, heteroalkyl, heteroalkenyl, a carbocyclic ring, or a heterocyclic ring; and (6) (a) if bond "a" or bond M b" is nil, then L 2 is bonded directly to R* 2 or R 3 ; or (b) if bond "a" and bond "b" are not nil, then L 2 is bonded to R^ 4 ; (D) provided that if L 1 , L 2 and R 37 are each a covalent bond, then L cannot be a covalent bond; or a protected form, salt, pharmaceutically-acceptable salt, biohydrolyzable ester, or solvate thereof. The present invention further relates to a process for making an intermediate compound having a structure according the formula (M - ) - L - L- - B) the method comprising the coupling of a compound having a structure according to Formula (HI) wherein (A) (1) A 1 is N or C(R 7 ); where (a) R 7 is hydrogen, hydroxy, alkoxy, nitro, cyano, halogen, alkyl, or -N(R 8 )(R 9 ), and (b) R 8 and R 9 are, independently, hydrogen, alkyl, alkenyl, a carbocyclic ring, or a heterocyclic ring; or R 8 and R 9 together comprise a heterocyclic ring including the nitrogen to which they are bonded; (2) A 2 is N or C(R 2 ); where R 2 is hydrogen or halogen; (3) A 3 is N or C(R^); where R^ is hydrogen; (4) R! is hydrogen, alkyl, a carbocyclic ring, a heterocyclic ring, alkoxy, hydroxy, alkenyl, arylalkyl, or -N(R 8 )(R 9 ); (5) R 3 is hydrogen, halogen, alkyl, a carbocyclic ring, or a heterocyclic ring; (6) R 4 is hydroxy; (7) R 6 is hydrogen, halogen, nitro, hydrazino or -N(R 8 )(R 9 ); and (8) X is a leaving group (B) and (1) when A 2 is C(R 2 ), R 2 and R 3 may together comprise -O-(CH 2 )n"0 _ > where n is from 1 to 4; (2) when A 3 is C(R 5 ), R 4 and R- may together comprise a heterocyclic ring; and (3) when A 1 is C(R 7 ), R 7 and R 3 may together comprise a heterocyclic ring including A^ and the carbon atom to which R 3 is bonded; or a protected form, salt, ester, or solvate thereof; with a lactam-containing compound having a structure according to Formula (II) wherein (I) M has a structure according to Formula (IV) wherein (A) (1) A 1 is N or C(R 7 ); where (a) R 7 is hydrogen, hydroxy, alkoxy, nitro, cyano, halogen, alkyl, or -N(R 8 )(R 9 ), and (b) R 8 and R 9 are, independently, R 8a where R 8a is hydrogen, alkyl, alkenyl, a carbocyclic ring, or a heterocyclic ring; or R 8 and R 9 together comprise a heterocyclic ring including the nitrogen to which they are bonded; (2) A 2 is N or C(R 2 ); where R 2 is hydrogen or halogen; (3) A 3 is N or C(R 5 ); where R 5 is hydrogen; (4) R! is hydrogen, alkyl, a carbocyclic ring, a heterocyclic ring, alkoxy, hydroxy, alkenyl, arylalkyl, or -N(R 8 )(R 9 ); (5) R 3 is hydrogen, halogen, alkyl, a carbocyclic ring, or a heterocyclic ring; (6) R 4 is hydroxy; (7) R6 is hydrogen, halogen, nitro, hydrazino, or -N(R 8 )(R 9 ); and (8) X is a leaving group; (B) and (1) when A 2 is C(R 2 ), R 2 and R 3 may together comprise -O-(CH 2 ) n -O-, where n is from 1 to 4; (2) when A 3 is C(R^), R 4 and R 5 may together comprise a heterocyclic ring; and (3) when A 1 is C(R 7 ), R 7 and R 3 may together comprise a heterocyclic ring including A 1 and the carbon atom to which R 3 is bonded; (C) and provided that one of R^, R 3 , or R*> is a covalent bond to i; (II) B has a structure according to Formula (II): wherein (A) RlO is hydrogen, halogen, alkyl, alkenyl, heteroalkyl, a carbocyclic ring, a heterocyclic ring, R -O-, R 8 CH=N-, (R 8 )(R 9 )N-, R 17 -C(=CHR 20 )-C(=O)NH-, R 17 -C(=NO- R 19 )-C(=O)NH-, or R 18 -(CH 2 ) m -C(=O)NH-; where (1) m is an integer from 0 to 9; (2) R 17 is hydrogen, alkyl, alkenyl, heteroalkyl, heteroalkenyl, a carbocyclic ring, or a heterocyclic ring; (3) R^ is R^. -Y^ or -CH Y 2 )^ 17 ); (4) R 19 is R 17 , arylalkyl, heteroarylalkyl, -C(R 22 (R 23 )-COOH, -C(=O)O-R 17 , or -C(=O)NH-RΪ 7 , where R 22 and R 23 are, independently, R 17 or together comprise a carbocyclic ring or a heterocyclic ring including the carbon atom to which R 22 and R 23 are bonded; (5) R 20 is R 1 halogen, -Y 1 , or -CH(Y )(R 17 ); (6) Y 1 is -C(=O)OR 21 , -C(=O)R 21 , -N(R 2 )R 1, -S(O) p R 29 , or -OR 29 ; and Y 2 is Y 1 or -OH, -SH, or -SO 3 H; (a) p is an integer from 0 to 2; (b) R 24 is hydrogen; alkyl; alkenyl; heteroalkyl; heteroalkenyl; a carbocyclic ring; a heterocyclic ring; -SO3H; -C(=O)R 25 ; or, when R 18 is -CH(N(R 2 )R 1 )(R 17 ), R 24 may comprise a moiety bonded to R 2 to form a heterocyclic ring; and (c) R25 is RI 7 , -NH(Rl 7 ), -N(Rl 7 )(R26) t O(R26), or S(R26); where R 26 is alkyl. 5 alkenyl, a carbocyclic ring, a heterocyclic ring, or when R 25 is -N(R 17 )(R 26 ), R 26 may be a moiety bonded to R* 7 to form a heterocyclic ring; and (7) R21 is R 29 or hydrogen; where R 29 is alkyl; alkenyl; 10 arylalkyl; heteroalkyl; heteroalkenyl; heteroarylalkyl; a carbocyclic ring; a heterocyclic ring; or, when Y is N(R 24 )R 1 and R 21 is R 29 , R 2 1 and R 24 may together comprise a heterocyclic ring including the nitrogen atom to which R 4 is bonded; 15 (B) R 1 - is hydrogen, halogen, alkoxy, or R 27 C(=O)NH-, where R 7 is hydrogen or alkyl; (C) bond "a" is a single bond or is nil; and bond "b" is a single bond, a double bond, or is nil; except bond "a" and bond "b" are not both nil; 20 (D) R 12 is -C(R 8 )-, or -CH 2 -R 28 -; where R 28 is -C(R 8 )-, -O-, or -N-, and R 28 is directly bonded to N" in Formula (II) to form a 5-membered ring; except, if bond "a" is nil, then R^ 2 is (1) -Cfl^XX 1 )-, where 25 (a) X 1 is -R 21 ; -OR 30 ; -S(O) r R 30 , where r is an integer from 0 to 2; -OC(=O)R 30 ; or N(R 30 )R 3 1 ; and (b) R 30 and R 3 1 are, independently, alkyl, alkenyl, a carbocyclic ring or a heterocyclic 30 ring; or R 30 and R 3 * together comprise a heterocyclic ring including the nitrogen atom to which R 30 and R 3 1 are bonded; or (2) -CH 2 -R 32 -; where R 32 is -C(R 8 )(R 21 ), -O-, or -NR 8 , and R 32 is directly bonded to N" in Formula 35 (II) to form a 5-membered ring; (E) (1) if bond "b" is a single bond, R 13 is -CH(R 33 ); or, -C(O)NHSO 2 -, if bond "a" is nil; or -C*(R 33 )- if R* 4 contains a R 3 ^ moiety; where R 33 is hydrogen or COOR 46 , where R 46 is hydrogen, alkyl or alkenyl, and C* is linked to R 36 to form a 3- membered ring; (2) if bond "b" is a double bond, R^ 3 is -C(R 33 )=; or (3) if bond "b" is nil, R 13 is hydrogen, -SO3H, -PO(OR 34 )OH, -C(O)NHSO 2 N(R 34 )(R 3 5), -OSO3H, -CH(R 35 )COOH, or -OCH(R 34 )-COOH; where R 34 is hydrogen, alkyl, alkenyl, a carbocyclic ring, or a heterocyclic ring; and R 3 ^ is hydrogen, alkyl, alkenyl, or -NHR 8 ; or, if R 13 is - C(O)NHSO 2 N-(R 34 )(R 35 ), R 34 and R 35 may together comprise a heterocyclic ring including the nitrogen to which R 34 and R ^ are bonded; and (F) (1) if bond "a" or bond "b" is nil, then R 14 is covalent bond; (2) if bond "a" and "b" are single bonds, R 14 is -W- C"'=C(R 8 )-R 37 -, or -W-C (R 36 )- R 37 -; or (3) if bond "a" is a single bond and bond "b" is a double bond, R 14 is -C(R 8 )(R 38 )-W-C"'-R 37 -; -W-C(R 8 )- (R 8 )-C'"-R 37 -; or -W-C"'-R 37 -; (4) where (a) W is O; S(O) s , where s is an integer from 0 to 2; or C(R 38 ), where R 38 is hydrogen, alkyl or alkoxy; (b) R 36 is hydrogen; alkyl; alkenyl; -COOH; or, if R 13 is -C*(R 33 ), R 36 may be linked to C* to form a 3-membered carbocyclic ring; (c) R 37 is covalent bond, alkyl, alkenyl, a carbocyclic ring, or a heterocyclic ring; and (d) C" is directly bonded to R 13 to form a 5- or 6-membered ring; and (III) (A) L is -C(=Z)-; -S(OV; -N(R 44 )-; -N+(R )(R 45 ); -N 44 )- N(R 44 )-; -O-; =N-; or a covalent bond; and L is bonded to L 3 and L 4 ; where (1) Z is O, S, or +N(H) 2 ; (2) v is 0, 1 or 2; (3) R 44 is hydrogen, substituted or unsubstituted lower alkyl, aryl, acyl, hydroxy, alkoxy, aryloxy, or acyloxy; and (4) R 4 ^ is hydrogen, unsubstituted or substituted lower alkyl, or substituted or unsubstituted aryl; (B) L 1 is L 3 or R 15 L 3 ; where 5 (1) when L is -C(=Z)-, L 3 is a covalent bond, oxygen, sulfur, or nitrogen; and when L is other than -C(=Z)-, L 3 is a covalent bond; (2) R 15 is alkyl, alkenyl, heteroalkyl, a heterocyclic ring, a carbocyclic ring, or R^ together with L 3 is a 10 heteroalkyl or a heterocyclic ring; and (3) L* is bonded to Q at the point of attachment of R^, R 3 or R6, whichever is a covalent bond; (C) L 2 is L 4 , -X 2 t -R 39 -L 4 , or -X 3 t -R 39 -L 4 ; where (1) when L is -C(=Z)-, L 4 is a covalent bond, oxygen, 15 sulfur, or nitrogen; and when L is other than -C(=Z)-, L 4 is a covalent bond; (2) X 2 is oxygen, or S(O) v , where v is 0, 1, or 2; (3) X 3 is nitrogen; N(R 40 ); N+(R 1 )(R 42 ); or R 43 - N(R 4 1); and is linked to R* 4 by a single or double 20 bond; or, if R^ 4 is covalent bond, X 3 is linked to B by a single or double bond; where (a) R 40 is R 8 ; -OR 8 ; or -C(=O)R 8 ; (b) R 4 1 and R 42 are, independently, hydrogen; alkyl; alkenyl; carbocyclic rings; heterocyclic 25 rings; or, if R 6 is R 16 X, then R 4 and R 42 together with Q" may comprise a heterocyclic (c) R 43 is N(R 4 *), oxygen or sulfur; (4) t is O or l; 30 (5) R 39 is alkyl, alkenyl, heteroalkyl, heteroalkenyl, a carbocyclic ring, or a heterocyclic ring; and (6) (a) if bond "a" or bond "b" is nil, then L 2 is bonded directly to R* 2 or R^ 3 ; or (b) if bond "a" and bond "b" are not nil, then L 2 35 is bonded to R 14 ; (D) provided that if L*, L 2 and R 37 is each a covalent bond, then L is not a covalent bond; or a protected form, salt, ester, or solvate thereof. The present invention further relates to the intermediate lactam compounds of the formula (M - L 1 ) - L - (L 2 - B), wherein M, L 1 , L, L 2 and B are as described hereinbefore. These intermediates are preferably prepared according to the processes of the present invention. DESCRIPTION OF THE INVENTION The present invention encompasses methods for making QLAs. The invention further encompasses novel compounds which are useful as intermediates for making QLAs. The QLAs made by the methods of the present invention are useful for treating infectious disorders in humans or other animal subjects. Thus, these QLAs must be pharmaceutically acceptable. As used herein, such a "pharmaceutically-acccptable" component is one that is suitable for use with humans and/or animals without undue adverse side effects (such as toxicity, irritation, and allergic response) commensurate with a reasonable benefit/risk ratio. QLAs The antimicrobial compounds ("QLAs") made by the methods of this invention encompass any of a variety of lactam moieties linked, by a linking moiety, to a quinolone moiety at the 1-, 5-, or 7-position of the quinolone. These compounds include those having a structure according to the general formula (Q - Ll) - L - (L 2 - B) wherein (I) Q has a structure according to Formula (I) wherein (A) (1) A 1 is N or C(R 7 ); where (a) R 7 is hydrogen, hydroxy, alkoxy, nitro, cyano, halogen, alkyl, or -N(R 8 )(R 9 ) (preferably hydrogen or halogen), and (b) R 8 and R 9 are, independently, R 8a where R 8a is hydrogen, alkyl, alkenyl, a carbocyclic ring, or a heterocyclic ring; or R 8 and R 9 together comprise a heterocyclic ring including the nitrogen to which they are bonded; (2) A 2 is N or (preferably) C(R 2 ); where R 2 is hydrogen or halogen; (3) A 3 is N or (preferably) C(R 5 ); where R 5 is hydrogen; (4) is hydrogen, alkyl, a carbocyclic ring, a heterocyclic ring, alkoxy, hydroxy, alkenyl, arylalkyl, or -N(R 8 )(R 9 ) (preferably alkyl or a carbocyclic (5) R 3 is hydrogen, halogen, alkyl, a carbocyclic ring, or a heterocyclic ring (preferably a heterocyclic ring); (6) R 4 is hydroxy; and (7) R*> is hydrogen, halogen, nitro, hydrazino or -N(R 8 )(R 9 ); (B) and (1) when A 2 is C(R 2 ), R 2 and R 3 may together comprise -O-(CH 2 ) n -O-, where n is from 1 to 4; (2) when A 3 is C(R^), R 4 and R^ may together comprise a heterocyclic ring; and (3) when A^ is C(R 7 ), R 7 and R 3 may together comprise a heterocyclic ring including A^ and the carbon atom to which R 3 is bonded; (C) and provided that one of R*, R 3 , or R > is a covalent bond to (H B has a structure according to Formula (II): wherein (A) R 10 is hydrogen, halogen, alkyl, alkenyl, heteroalkyl, a carbocyclic ring, a heterocyclic ring, R 8 -O-, R 8 CH=N-, (R 8 )(R 9 )N-, Rl 7 C(=CH-R 20 )-C(=O)NH-, Rl 7 -C(=NO- (preferably alkyl); where (1) m is an integer from 0 to 9 (preferably from 0 to 3); (2) R 17 is hydrogen, alkyl, alkenyl, heteroalkyl, heteroalkenyl, a carbocyclic ring, or a heterocyclic ring (preferably alkyl, a carbocyclic ring, or a 5 heterocyclic ring); (3) R 18 is R 17 -Y 1 , or -CH(Y 2 )(Rl 7 ); (4) R 19 is R 17 , arylalkyl, heteroarylalkyl, -C(R 22 (R 23 )COOH, -C(=O)O-R 17 , or -C(=O)NH-R 17 , where R 22 and R 23 are, independently, R* 7 or 10 together comprise a carbocyclic ring or a heterocyclic ring including the carbon atom to which R 22 and R 23 are bonded (preferably R 17 -C(R 22 ) (R 23 )-COOH) or; (5) R 20 is R 19 halogen, -γl, or -CH(Y 2 )(Rl 7 ) 15 (preferably R •■ 9 or halogen); (6) Y 1 is -C(=O)OR 21 , -C(=O)R 21 , -N(R 24 )R 2 1, -S(O) p R 29 , or -OR 29 ; and Y 2 is Y 1 or -OH, -SH, or -SO 3 H; (a) p is an integer from 0 to 2 (preferably 0); 20 (b) R 24 is hydrogen; alkyl; alkenyl; heteroalkyl; heteroalkenyl; a carbo-cyclic ring; a heterocyclic ring; -SO3H; -C(=O)R 25 ; or, when R 18 is -CH(N(R 24 )R 21 )(Rl 7 ), R 24 may comprise a moiety bonded to R 2 ^ to 25 form a heterocyclic ring; and (c) R 25 is R 17 , -NH(R 17 ), -N(R 17 )(R 26 ), -O(R 26 ), or -S(R 26 ); where R 26 is alkyl. alkenyl, a carbocyclic ring, a heterocyclic ring, or (preferably) when R 2 ^ is 30 -N(R 17 )(R 26 ), R 26 may be a moiety bonded to R 7 to form a heterocyclic ring; and (7) R is R 29 or hydrogen; where R 29 is alkyl; alkenyl; arylalkyl; heteroalkyl; hetero-alkenyl; heteroarylalkyl; a carbocyclic ring; a heterocyclic ring; or, when Y is 35 -N(R 2 )R 21 and R 21 is R 29 , R 21 and R 24 may together comprise a heterocyclic ring including the nitrogen atom to which R 24 is bonded (preferably hydrogen, alkyl, a carbocyclic ring, or a heterocyclic ring); (B) R 1 1 is hydrogen, halogen, alkoxy, or R 7 C(=O)NH- (preferably hydrogen or alkoxy), where R 27 is hydrogen or alkyl (preferably hydrogen); 5 (C) bond "a" is a single bond or is nil; and bond "b" is a single bond, a double bond, or is nil; except bond "a" and bond "b" are not both nil; (D) R 12 is -C(R 8 )-, or -CH 2 -R 28 - (preferably -C(R 8 )-); where R 28 is -C(R 8 ), -O-, or -N-, and R 28 is directly bonded to N" 10 in Formula (II) to form a 5-membered ring; except, if bond "a" is nil, then R^ 2 is ( 1 ) (preferably) -C(R 8 )(X 1 )-, where (a) X 1 is -R 2 1 ; -OR 30 ; -S(O) r R 30 where r is an integer from 0 to 2 (preferably 0); 15 -OC(=O)R 30 ; or -N(R 3 )R 3 - ; and (b) R 30 and R 3 * are, independently, alkyl, alkenyl, a carbocyclic ring or a heterocyclic ring; or R 30 and R 3 ^ together comprise a heterocyclic ring including the nitrogen atom 20 to which R 30 and R 3 - are bonded; or (2) -CH 2 -R 32 -; where R 32 is -C(R 8 )(R 21 ), -O-, or -NR 8 , and R 32 is directly bonded to N" in Formula (II) to form a 5-membered ring; (E) (1) if bond "b" is a single bond, R 13 is 25 (preferably) -CH(R 33 )-; or, -C(O)NHSO -, if bond "a" is nil; or -C*(R 33 )- if R 14 contains a R 36 moiety; where R 33 is hydrogen or (preferably) -COOR 4 ^, where R 4 ^ is hydrogen, alkyl, or alkenyl, and C* is linked to R 3 > to form a 3-membered ring; 30 (2) if bond "b" is a double bond, R 13 is -C(R 33 )=; or (3) if bond "b" is nil, R 3 is hydrogen, -SO3H, -PO(OR 3 )OH, -C(O)NHSO 2 N(R 3 )(R 3 5), -OSO3H, -CH(R 35 )COOH, or -OCH(R 34 )-COOH (preferably -SO3H or -C(O)NH-SO 2 N(R 34 )(R 3 5)) ; 35 where R 34 is hydrogen, alkyl, alkenyl, a carbocyclic ring, or a heterocyclic ring; and R 3 ^ is hydrogen, alkyl, alkenyl, or -NHR 8 ; or (preferably), if R 13 is -C(O)NH-SO 2 N(R 34 )(R 35 ), R 34 and R 35 may together comprise a heterocyclic ring including the nitrogen to which R 34 and R 35 are bonded; and (F) (1) if bond "a" or bond "b" is nil, then R 14 is covalent bond; (2) if bond "a" and "b" are single bonds, R 14 is -W- C"'=C(R 8 )-R 37 -, or -W-C'"(R 36 )- R 37 -; or (3) (preferably) if bond "a" is a single bond and bond "b M is a double bond, R 14 is -C(R 8 )(R 38 )-W-C"'-R 37 -; (preferably) -W-C(R 8 )-(R 38 )-C"'-R 37 -; or -W-C"'- R 37 -; (4) where (a) W is O; S(O) s , where s is an integer from 0 to 2 (preferably 0); or C(R 38 ), where R 38 is hydrogen, alkyl or alkoxy; (b) R 36 is hydrogen; alkyl; alkenyl; -COOH; or, if R 13 is -C*(R 33 ), R 36 may be linked to C* to form a 3-membered carbocyclic ring; (c) R 37 is covalent bond, alkyl, alkenyl, a carbocyclic ring, or a heterocyclic ring; and (d) C" is directly bonded to R 13 to form a 5- or 6-membered ring; and (III) (A) L is -C(=Z)-; -S(O) v -; -N(R 44 )-; -N+fR 44 )^ 4 *)-; -N(R 4 )-N(R 44 )-; -O-; =N-; or a covalent bond (preferably -C(=Z)-; -N(R 44 )); and L is bonded to L 3 and L 4 ; where ( 1 ) Z is O, S, or +N(H) 2 (preferably O or S); (2) v is 0, 1 or 2; (3) R 44 is, independently, hydrogen, substituted or unsubstituted lower alkyl, aryl, acyl, hydroxy, alkoxy, aryloxy, or acyloxy (preferably hydrogen or substituted or unsubstituted lower alkyl); and (4) R 4 ^ is hydrogen, (preferably) unsubstituted or substituted lower alkyl, or substituted or unsubstituted aryl; (B) L 1 is L 3 or R 15 L 3 ; where (1) when L is -C(=Z)-, L 3 is a covalent bond, oxygen, sulfur, or (preferably) nitrogen; and when L is other than -C(=Z)-, L 3 is a covalent bond; (2) R! 5 is alkyl, alkenyl, heteroalkyl, a heterocyclic ring, a carbocyclic ring, or R^ together with L 3 is a heteroalkyl or a heterocyclic ring; and (3) L 1 is bonded to Q at the point of attachment of R , R 3 or R >, whichever is a covalent bond; (C) L 2 .s L 4 , -X 2 t -R 39 -L 4 , or -X 3 t -R 39 -L 4 ; where (1) (preferably) when L is -C(=Z)-, L 4 is a covalent bond, oxygen, sulfur, or nitrogen (preferably oxygen or sulfur); and when L is other than -C(=Z)-, L 4 is a covalent bond; (2) X 2 is oxygen, or S(O) v , where v is 0, 1, or 2; (3) X 3 is nitrogen; N(R 40 ); N+(R 41 )(R 42 ); or R 43 - N(R 41 ); and is linked to R 14 by a single or double bond; or, if R* 4 is covalent bond, X 3 is linked to B by a single or double bond (preferably nitrogen; N(R 40 ); N+(R 4 - ) (R 42 )); where (a) R 40 is R 8 ; -OR 8 ; or -C(=O)R 8 (preferably R 8 ); (b) R 41 and R 42 are, independently, hydrogen; alkyl; alkenyl; carbocyclic rings, heterocyclic rings; or, if R 6 is R 16 X, then R 41 and R 42 together with Q" may comprise a heterocyclic (c) R 43 is N(R 4 1), oxygen or sulfur; (4) t is O or l; (5) R 39 is alkyl, alkenyl, heteroalkyl, heteroalkenyl, a carbocyclic ring, or a heterocyclic ring; and (6) (a) if bond "a" or bond "b" is nil, then L 2 is bonded directly to R 12 or R 3 ; or (b) if bond "a" and bond "b" are not nil, then L 2 is bonded to R 14 ; (D) provided that if L^, L 2 and R 37 is each a covalent bond, then L is not a covalent; or a protected form, salt, pharmaceutically-acceptable salt, biohydrolyzable ester, or solvate thereof. Preferred antimicrobial QLAs made by the processes of this invention include those where R 3 is a covalent bond to L 1 , and those where R*> is a covalent bond to L V Where the QLAs synthesized using the present methods are used as intermediates, they may contain various functional groups (e.g., alcohols, amines, carboxylic acids, etc.) that may be present in a protected form, utilizing protecting groups (e.g., esters, carbonates, ethers, silyl ethers, amides, carbamates, etc.) introduced by methods well known in the art. The art is also replete with methodology to remove these protecting groups. Where the compounds synthesized are used as antimicrobials, they may be in acid form, or as a pharmaceutically-acceptable salt, biohydrolyzable ester or solvate thereof. Intermediates The novel intermediates of the present invention have a structure according the formula (M - L 1 ) - L - (L 2 - B), where M has a structure according to Formula (TV) and B has a structure according to Formula (II). The Formula (HI) compound are prepared by coupling a compound of Formula (III) with a lactam compound of Formula (II). Preferred substituents for the "M" component (Formula (IV)) are the same as those listed for the Formula (I) component (quinolone) of the QLAs. Similarly, preferred substituents for L 1 , L, L 2 and B are the same as those listed for the QLAs. These intermediates may be coupled to the lactam moiety under reaction conditions that are less harsh than those described in the literature, and may therefore allow for improved QLA yields and purities. Examples of the intermediate compounds of the present invention are described hereinbelow. Definitions and Usage of Terms: The following is a list of definitions for terms used herein. "AcyP or "carbonyP is a radical formed by removal of the hydroxy from an carboxylic acid (i.e., R-C(=O)-). Preferred alkylacyl groups include (for example) acetyl, formyl, and propionyl. "Acyloxy" is an oxygen radical having an acyl substituent (i.e., -O-acyl); for example, -O-C(=O)-aIkyl. "Acylamino" is an amino radical having an acyl substituent (i.e., -N-acyl); for example, -NH-C(=O)-alkyl. "Alkyl" is an unsubstituted or substituted saturated hydrocarbon chain radical having from 1 to 8 carbon atoms, preferably from 1 to 4 carbon atoms. Preferred alkyl groups include (for example) methyl, ethyl, propyl, isopropyl, and butyl. "Alkenyl" is an unsubstituted or substituted hydrocarbon chain radical having from 2 to 8 carbon atoms, preferably from 2 to 4 carbon atoms, and having at least one olefinic double bond. "Alkoxy" is an oxygen radical having a hydrocarbon chain substituent, where the hydrocarbon chain is an alkyl or alkenyl (i.e., -O-alkyl or -O-alkenyl). Preferred alkoxy groups include (for example) methoxy, ethoxy, propoxy and allyloxy. "Alkylamino" is an amino radical having one or two alkyl substituents (i.e., -N-alkyl). "Aryl" is an aromatic carbocyclic ring radical. Preferred aryl groups include (for example) phenyl, tolyl, xylyl, cumenyl and naphthyl. "Arylalkyl" is an alkyl radical substituted with an aryl group. Preferred arylalkyl groups include benzyl and phenylethyl. "Arylamino" is an amine radical substituted with an aryl group (i.e., -NH- aryl). "Aryloxy" is an oxygen radical having a aryl substituent (i.e., -O-aryl). "Carbocyclic ring" is an unsubstituted or substituted, saturated, unsaturated or aromatic, hydrocarbon ring radical. Carbocyclic rings are monocyclic or are fused, bridged or spiro polycyclic ring systems. Monocyclic rings contain from 3 to 9 atoms, preferably 3 to 6 atoms. Polycyclic rings contain from 7 to 17 atoms, preferably from 7 to 13 atoms. "Cycloalkyl" is a saturated carbocyclic ring radical. Preferred cycloalkyl groups include (for example) cyclopropyl, cyclobutyl and cyclohexyl. "Halo", "halogen", or "halide" is a chloro, bromo, fluoro or iodo atom radical. Chloro and fluoro are preferred halides. "Heteroatom" is a nitrogen, sulfur or oxygen atom. Groups containing one or more heteroatoms may contain different heteroatoms. "Heteroalkyl" is an unsubstituted or substituted saturated chain radical having from 3 to 8 members comprising carbon atoms and one or two heteroatoms. "Heteroalkenyl" is an unsubstituted or substituted chain radical having from 2 to 8 carbon atoms, preferably from 2 to 6 carbon atoms, having at least one olefinic double bond, and having one or two heteroatoms. "Heterocyclic ring" is an unsubstituted or substituted, saturated, unsaturated or aromatic ring radical comprised of carbon atoms and one or more heteroatoms in the ring. Heterocyclic rings are monocyclic or are fused, bridged or spiro polycyclic ring systems. Monocyclic rings contain from 3 to 9 atoms, preferably 4 to 8 atoms, more preferably from 5 to 8 atoms, most preferably from 4 to 6 atoms. Polycyclic rings contain from 7 to 17 atoms, preferably from 7 to 13 atoms. "Heterocycloalkyl" is a saturated heterocyclic ring radical. Preferred heterocycloalkyl groups include (for example) piperazine, pyrrolidine, piperadine, and morpholine. "Heteroaryl" is an aromatic heterocyclic ring radical. Preferred heteroaryl groups include (for example) thienyl, furyl, pyrrolyl, pyridinyl, pyrazinyl, thiazolyl, quinolinyl, pyrimidinyl and tetrazolyl. "Heteroarylalkyl" is an alkyl radical substituted with an heteroaryl group. Also, as referred to herein, a "lower" hydrocarbon moiety (e.g., "lower" alkyl) is a hydrocarbon chain comprised of from 1 to 6, preferably from 1 to 4, carbon atoms. "Organosilicon compounds", as referred to herein, are those silicon- containing compounds that are commonly utilized in silylation reactions, that is, reactions which substitute a hydrogen atom bound to a heteroatom (e.g., -OH, =NH, -SH, etc.) with a silyl group, usually a trialkylsilyl group, including reactions of a tautomer of a heteroatom system to form a silyl derivative (e.g., silyl enol ethers), forming a silicon - heteroatom bond. Many such reagents are well known in the art, as described in the following articles, all incorporated by reference herein: E. Plueddemann, "Silylating Agents", in: Kirk-Othmer, 3d ed., Vol. 20, "Encyclopedia of Chemical Technology" (1982); I. Fleming, "Organic Silicon Chemistry", in: Vol. 3, "Comprehensive Organic Chemistry" (D. Jones, editor, 1979); B. Cooper, "Silylation in Organic Synthesis", Proc. Bioche . 9 (1980); W. Weber, "Silicon Reagents for Organic Synthesis (1983); B. Cooper, "Silylation as a Protective Method in Organic Synthesis, Chem. Ind. 794 (1978); J. Rasmussen, "O-Silylated Enolates - Versatile Intermediates for Organic Synthesis" 91 Synthesis (1977). Such organosilicon compounds include chlorotrimethylsilane, N,O-bis(trimethylsilyl)acetamide, N,O-bis(trimethylsilyl)- trifluoroacetamide, bis(trimethylsilyl)urea, hexamethyldisilazane, N-methyl-N- trimethylsilyl-trifluoroacetamide. 1-trimethylsilylimidazole, trimethylsilyl trifluoro- methanesulfonate, tert-butyldimethylchlorosilane, 1 -(tert-butyldimethylsilyl)- imidazole, N-tert-butyldimethyl-N-methyltrifluoroacetamide, tert-butyldimethylsilyl trifluoromethanesulfonate, tert-butyldiphenylchlorosilane, tert-butyl-methoxy- phenylbromosilane, dimethylphenylchlorosilane, tnethylchlorosilane, triethylsilyl trifluoromethanesulfonate, and triphenylchlorosilane. A "protected form", as referred to herein, is a derivative of the described compound wherein certain functional groups contained in the structures (such as carboxyl, hydroxyl, and amino groups) are blocked in order to prevent undesired competing side reactions and, occasionally, to improve the solubility of the compound. Suitable protecting groups for carboxyl substituents include, for example, esters. Protecting groups for hydroxyl substituents include, for example, ethers, esters, and carbonates; and protecting groups for amino substituents include, for example, carbamates and amides. If various protecting groups are employed, then appropriate methods for introducing and removing the protecting groups, that will not decompose the quinolone or related heterocyclic compound, may be required to efficiently obtain antibacterially active products or intermediates thereof. Appropriate protecting groups for these processes are well known in the art. For hydroxyl groups, suitable derivatives include, for example, alkyl ethers [such as allyl, tert-butyl, and 2-(trimethylsilyl)ethoxymethyl], silyl ethers (such as trimethylsilyl, tert-butyldimethylsilyl, tert-butyldiphenylsilyl), esters (such as acetate and trifluoroacetate) and carbonates (such as allyl and vinyl). For amines, suitable carbamates include, for example, tert-butyl and 2-trimethylsilyl, and suitable amides include, for example, trifluoroacetamide. For carboxylic acids, suitable esters include, for example, allyl, p-methoxybenzyl, p-nitrobenzyl, diphenylmethyl, 2,2,2- trichloroethyl, 2-trimethylsilylethyl, 2-methylthioethyl, trimethylsilyl, t- butyldiphenylsilyl, t-butyl, and tributylstannyl esters. Such protecting groups and methods for their introduction and removal are described in T. W. Greene et al., Protective Groups in Organic Synthesis. 2d edition, J. Wiley and Sons (1991), incorporated by reference herein. A "biohydrolyzable ester" is an ester of a QLA that does not essentially interfere with the antimicrobial activity of the compounds, or that are readily metabolized by a human or lower animal subject to yield an antimicrobially-active quinolonyl lactam. Such esters include those that do not interfere with the biological activity of quinolone antimicrobials or beta-lactam antimicrobials (cephems, for example). Many such esters are known in the art, as described in World Patent Publication 87/05297, Johnston et al., published September 11, 1987, (incorporated by reference herein). Such esters include lower alkyl esters, lower acyloxy-alkyl esters (such as acetoxymethyl, acetoxyethyl, aminocarbonyloxymethyl, pivaloyloxymethyl and pivaloyloxyethyl esters), lactonyl esters (such as phthalidyl and thiophthalidyl esters), lower alkoxyacyloxyalkyl esters (such as methoxycarbonyloxymethyl, ethoxycarbonyloxyethyl and isopropoxy- carbonyloxyethyl esters), alkoxyalkyl esters, choline esters and alkyl acylamino alkyl esters (such as acetamidomethyl esters). As defined above and as used herein, substituent groups may themselves be substituted. Such substitution may be with one or more substituents. Such substituents include (for example) those listed in C. Hansch and A. Leo, Substituent Constants for Correlation Analysis in Chemistry and Biology (1979), incorporated by reference herein. Preferred substituents include (for example) alkyl, alkenyl, alkoxy, hydroxy, oxo, nitro, amino, aminoalkyl (e.g., aminomethyl, etc.), cyano, halo, carboxy, alkoxyaceyl (e.g., carboethoxy, etc.), thiol, aryl, cycloalkyl, heteroaryl, heterocycloalkyl (e.g., piperidinyl, morpholinyl, pyrrolidinyl, etc.), imino, thioxo, hydroxyalkyl, aryloxy, arylalkyl, and combinations thereof. Also, as used in defining the structure of the compounds of this invention, a particular radical may be defined for use as a substituent in multiple locations. For example, the R 8 substituent is defined as a potential substituent of R 7 , but is also incorporated into the definition of other substituents (such as R 1 , R >, and R 10 ). As used herein, such a radical is independently selected each time it is used (e.g., R 8 need not be alkyl in all occurrences in defining a given compound of this invention). Lactam-containing moiety: Groups R 12 , R 13 , and R 14 , together with bonds "a" and "b" of formula (II), form any of a variety of lactam-containing moieties known in the art to have antimicrobial activity. Such moieties wherein either bond "a" or bond "b" are nil (i.e., do not exist) are monocyclic; if both bonds exist, the structures are bicyclic. Preferably, bond "a" is a single bond and bond "b" is a double bond. Preferred lactam moieties include the cephems, oxacephems and carbacephems of the representative formula: wherein, referring to formula (II), bond "a" is a single bond; bond "b" is a double bond; R 12 is -C(R 8 )-, where R 8 is hydrogen; R 13 is -C(R 33 )=, where R 33 is COOH; and R 14 is -W-C(R 8 )(R 38 )-C"-R 37 , where R 8 and R 38 are hydrogen, R 37 is methylene, and W is S (for cephems), O (for oxacephems) or C(R 38 ) (for carbacephems). Other preferred lactam moieties include the isocephems and iso-oxacephems of the representative formula: wherein, referring to formula II, bond "a" is a single bond; bond "b" is a double bond; R 12 is -C(R 8 ) where R 8 is hydrogen; R 13 is -C(R 33 )=, where R 33 is COOH; and R 14 is -C(R 8 )(R 38 )-W-C"'-R 37 where R 8 and R 38 are each hydrogen, R 37 is methylene, and W is S (for isocephems) or O (for iso-oxacephems). Other preferred lactam-containing moieties include the penems, carbapenems and clavems, of the representative formula: wherein, referring to formula (II), bond "a" is a single bond; bond "b" is a double bond; R 12 is -C(R 8 ), where R 8 is hydrogen; R 13 is -C(R 33 )=, where R 33 is COOH; and R 14 is -W-C'"-R 37 , where R 37 is methylene, and W is S (for penems), C(R 38 ) (for carbapenems), or O (for clavems). Such lactam moieties are described in the following articles, all incorporated by reference herein: R. Wise, "In Vitro and Pharmacokinetic Properties of the Carbapenems", 30 Antimicrobial Agents and Chemotherapy 343 (1986); and S. McCombie et al., "Synthesis and In Vitro Activity of the Penem Antibiotics", 8 Medicinal Research Reviews 393 (1988). Other preferred lactam-containing moieties of this invention include the penicillins of the representative formula: wherein, referring to formula II, bond "a" is a single bond, bond "b" is a single bond; R 12 is -C(R 8 )-, where R 8 is hydrogen; R 13 is -CH(R 33 )- where R 33 is COOH; and R 14 is -W-C"'(R 36 )-R 37 - where R 36 is methyl, R 37 is methylene, and W is S. Other preferred lactam-containing moieties include the monocyclic beta- lactams, of the representative formula. wherein, referring to formula (II), bond "a" is a single bond; bond "b" is nil; R 12 is - C(R 8 )-, where R 8 is hydrogen; R 14 is covalent bond; and R 13 is -SO3H (for a monobactam), -PO(OR 34 )OH (for a monophospham); -C(O)NHSO 2 N(R 3 )(R 35 ) (for a monocarbam), -OSO3H (for a monosulfactam), -CH(R 35 )COOH (for nocardicins), or -OCH(R 34 )COOH. Such lactam moieties are described in C. Cimarusti et al., "Monocyclic 8-lactam Antibiotics", 4 Medicinal Research Reviews 1 (1984), incorporated by reference herein. Other preferred lactam moieties include the monocyclic beta-lactams of the representative formula: wherein referring to formula II, bond "a" is nil, bond "b" is a single bond; R^ 2 is -C(R 8 )(R 29 )- where both R 8 and R 29 are hydrogen; and R 14 is covalent bond. Other preferred lactam moieties include the clavams of the representative formula: wherein, referring to formula (II), bond "a" is a single bond; bond "b" is a single bond; R 12 is -C(R 8 )-, where R 8 is hydrogen; R 13 is -CH(R 33 )-, where R 33 is COOH; and R 14 is W-C"'=C-(R 8 )-R 37 , where R 8 is hydrogen and R 37 is methylene, and W is O. Other preferred lactam moieties include the 2,3-methyleno-penams and carbapenams of the representative formula: wherein, referring to formula (II), bond "a" is a single bond; bond "b" is a single bond; R 12 is -C(R 8 )-, where R 8 is hydrogen; R 13 is -C*(R 33 ), where R 33 is COOH; and R 14 is W-C"'(R 36 )-R 37 > where R 37 is covalent bond, R 36 is linked to C* to form a 3-membered carbocyclic ring, and W is C(R 38 ) or sulfur. Lactam moieties of this invention also include the lactivicin analogs of the representative formula: wherein, referring to formula (II), bond "a" is nil; bond "b" is a single bond; R^ is -CH 2 -R 32 , where R 32 is O; R 13 is -CH(R 33 )-, where R 33 is COOH; and R 14 is covalent bond. Other lactam moieties include the pyrazolidinones of the representative formula: wherein, referring to formula (I), bond "a" is a single bond; bond "b" is a double bond; R 12 is -CH 2 -R 28 -, where R 28 is -N-; R* 3 is -C(R 33 )-, where R 33 is COOH; and R 14 is W-C"'-R 37 -, where R 37 is methylene, and W is C(R 38 ). Other lactam moieties include the gamma-lactams of the representative formula: wherein, referring to formula (II), bond "a" is a single bond; bond "b" is nil; R 12 is -CH 2 -R 28 -, where R 28 is -C(R 8 ) and R 8 is hydrogen; R 13 is -SO3H, -PO(OR 34 )OH, -C(O)NHSO 2 N(R 3 )(R 35 ), -OSO3H, -CH(R 35 )COOH, or -OCH(R 34 )COOH; and R 14 is covalent bond. Preferred lactam-containing moieties include cephems, isocephems, iso- oxacephems, oxacephems, carbacephems, penicillins, penems, carbapenems, and monocyclic beta-lactams. Particularly preferred lactam-containing moieties for compounds made by this invention are penems, carbapenems, cephems, and carbacephems. R 10 , in formula (II), is any radical that may be substituted at the active stereoisomeric position of the carbon adjacent to the lactam carbonyl of an antimicrobially-active lactam. (As used herein, the term "antimicrobially-active lactam" refers to a lactam-containing compound, without a quinolonyl substituent moiety, which has antimicrobial activity.) This "active" position is beta (i.e., 7-beta) for oxacephems and carbacephems (for example). The active position is alpha for penems, carbapenems, clavems and clavams. Appropriate R*° groups will be apparent to one of ordinary skill in the art. Many such R ° groups are known in the art, as described in the following documents (all of which are incorporated by reference herein): Cephalosporins and Penicillins: Chemistry and Biology (E. Flynn, editor, 1972); Chemistry and Biology of β-Lactam Antibiotics (R. Morin et al., editors, 1987); "The Cephalosporin Antibiotics: Seminar-in-Print", 34 Drugs (Supp. 2) 1 (J. Williams, editor, 1987); New Beta-Lactam Antibiotics: A Review from Chemistry of Clinical Efficacy of the New Cephalosporins (H. Neu, editor, 1982); M. Sassiver et al., in Structure Activity Relationships among the Semi-svnthetic Antibiotics (D. Perlman, editor, 1977); W. Durckheimer et al., "Recent Developments in the Field of Beta-Lactam Antibiotics", 24 Angew. Chem. Int. Ed. Engl. 180 (1985); G. Rolinson, "Beta- Lactam Antibiotics", 17 J. Antimicrobial Chemotherapy 5 (1986); European Patent Publication 187,456, Jung, published July 16, 1986; and World Patent Publication 87/05297, Johnston et al., published September 11, 1987. For penems, carbapenems, clavems and clavams, R*° is preferably lower alkyl, or hydroxy-substituted lower alkyl. Particularly preferred R*° groups include hydrogen, hydroxymethyl, ethyl, [l(R)-hydroxyethyl], [l(R)-[(hydroxysul- fonyl)oxyethyl]], and [1 -methyl- 1-hydroxyethyl]. Except for penems, carbapenems, clavems and clavams, preferred R*° groups are amides, such as: acetylamino, preferably substituted with aryl, heteroaryl, aryloxy, heteroarylthio and lower alkylthio substituents; arylglycylamino, preferably N-substituted with heteroarylcarbonyl and cycloheteroalkylcarbonyl substituents; arylcarbonylamino; heteroarylcarbonylamino; and lower alkoxyiminoacetylamino, preferably substituted with aryl and heteroaryl substituents. Particularly preferred R 10 groups include amides of the general formula R 18 -(CH 2 ) m -C(=O)NH- and R 18 is R 17 . Examples of such preferred R 10 groups include: [(2-amino-5-halo-4-thiazolyl)acetyl]amino; [(4-aminopyridin-2-yl)acetyl]amino; [[(3,5-dichloro-4-oxo-l(4H)-pyridinyl)acetyl]amino3; [[[2-(aminomethyl)phenyl]acetyl]amino]; [(lH-tetrazol-l-ylacetyl)amino]; [(cyanoacetyl)amino] ; [(2-thienylacetyl)amino] ; [[(2-amino-4-thiazoyl)acetyl]amino]; and sydnone, 3-[-2-amino]-2-oxoethyl. When Rl° is R 18 -(CH 2 ) m -C(C=O)NH-, and R 18 is -γl, preferred R 10 groups include the following: [suIfamoylphenylacetyl]amino; [[(4-pyridinylthio)acetyl]amino]; [[[(cyanomethyl)thio]acetyl]amino]; (S)-[[[(2-amino-2-carboxyethyl)thio]acetyl]amino]; [[[(trifluoromethyl)thio]acetyl]amino]; and (E)-[[[(2-aminocarbonyl-2-fluoroethenyl)thio]acetyl]amino]. When R 10 is R 18 -(CH 2 ) m -C(=O)NH-, and R 18 is -CH(Y 2 )(R 17 ), preferred R 10 groups include the following: [carboxyphenylacetyljamino; [(phenoxycarbonyl)phenylacetyl]amino; [4-methyl-2,3-dioxo- 1 -piperazinecarbonyl-D-phenylglycyl]amino; [[[3-(2-furylmethyleneamino)-2-oxo- 1 - imidazoIidinyl]carbonyl]amino]phenyl]-acetyl]amino; (R)- [(aminophenylacetyl)amino] ; (R)-[[amino(4-hydroxyphenyl)acetyl]amino]; (R)-[(amino- 1 ,4-cyclohexadien- 1 -ylacetyl)amino]; [(hydroxyphenylacetyl)amino]; (R)-[[[[(4-ethyl-2,3-dioxo-l-piperazinyl)carbonyl]amino](4-hydroxy- phenyl)acetyl]amino] ; (R)-[[[[(5-carboxy-lH-imidazol-4-yl)carbonyI]amino]phenylacetyl]amino]; (R)-[[[[(4-hydroxy-6-methyl-3-pyridinyl)carbonyl]amino](4- hydroxyphenyl)acetyl]amino] ; (R)-[(phenylsulfoacetyl)amino] ; (2R,3S)-[[2-[[(4-ethyl-2,3-dioxo-l-piperazinyl)carbonyl]amino]-3-hydroxy- l-oxobutyl]amino]; [[carboxy(4-hydroxyphenyI)acetyl]amino]; (R)-[[amino[3-[(ethylsulfonyl)amino]phenyl]acetyl]amino]; (R)-[[amino(benzo[b]thien-3-yl)acetyl]amino]; (R)-[[amino(2-naphthyl)acetyl]amino]; (R)-[[amino(2-amino-4-thiazolyl)acetyl]amino]; [[[[(6,7-dihydroxy-4-oxo-4H- 1 -benzopyran-3-yl)carbonyI]amino](4- hydroxyphenyl)acetyl]amino]; (R,R)-[[2-[4-[2-amino-2-carboxyethyloxycarbonyl]aminophenyl]-2- hydroxyacetyl] amino]; and (S)-[[(5-hydroxy-4-oxo- 1 (4H)-pyridin-2-yl)carbonylamino(2-amino-4- thiazolyl)acetyl]amino] . Another prefe ed R 10 group is R 17 -C(=CHR 20 )-C( ))NH-. Another class of preferred R 10 groups (for lactam-containing moieties other than penems, carbapenems, clavems and clavams) include those of the formula: R 1 7 -C(=NO-R 1 9 )-C(=O)NH-. Examples of this preferred class of R*° groups include: 2-phenyl-2-hydroxyiminoacetyl; 2-thienyl-2-methoxyiminoacetyl; and 2-[4-(gamma-D-glutamyloxy)phenyl]-2-hydroxyiminoacetyl. (Z)[[(2-amino-4-thiazolyl)(methoxyimino)acetyl]amino]; [[(2-furanyl(methoxyimino)acetyl]amino]; (Z)-[[(2-amino-4-thiazolyl)[( 1 -carboxy- 1 - methyl)ethoxyimino]acetyl]amino]; (Z)-[[(2-amino-4-thiazolyl)( 1 -carboxymethoxyimino)acetyI]amino]; [[(2-amino-4-thiazolyl)[(lH-imidazol-4-ylmethoxy)imino]acetyl]amino]; (Z)-[[(2-amino-4-thiazolyl-3-oxide)(methoxyimino)acetyl]amino]; and (S,Z)-[[(2-amino-4-thiazolyl)[carboxy(3,4-dihydroxyphenyl)- methoxyimino]acetyl]amino]. Suitable R 1 1 groups are among those well-known in the art, including those defined in the following documents (all incorporated by reference herein). W. Durckheimer et al., "Recent Developments in the Field of Beta-Lactam Antibiotics", 24 An ew. Chem. Int. Ed. Engl. 180 (1985); G. Rolinson, "Beta- Lactam Antibiotics", 17 J. Antimicrobial Chemotherapy 5 (1986); and European Patent Publication 187,456, Jung, published July 16, 1986. Preferred R 1 1 groups include hydrogen, methoxy, ethoxy, propoxy, thiomethyl, halogen, cyano, formyl and formylamino. Particularly preferred R* * groups include hydrogen, methoxy, halogen, and formylamino. Quinolone Moieties: Groups A*, A 2 , A 3 , R-, R 3 , and R 4 of Formula I form a moiety (herein, "quinolone moiety") present in any of a variety of quinolone, naphthyridine or related heterocyclic compounds known in the art to have antimicrobial activity. Such heterocyclic moieties are well known in the art, as described in the following articles, all incorporated by reference herein: J. Wolfson et al., "The Fluoroquinolones: Structures, Mechanisms of Action and Resistance, and Spectra of Activity In Vitro", 28 Antimicrobial Agents and Chemotherapy 581 (1985); and T. Rosen et al., 31 J. Med Chem. 1586 (1988); T. Rosen et al., 31 J. Med. Chem. 1598 (1988); G. Klop an et al., 31 Antimicrob. Agents Chemother. 1831 (1987); 31:1831-1840; J. P. Sanchez et al., 31 J. Med. Chem. 983 (1988); J. M. Domagala et al., 31 J. Med. Chem. 991 (1988); M. P. Wentland et al., in 20 Ann. Rep. Med. Chem. 145 (D. M. Baily, editor, 1986); J. B. Cornett et al., in 21 Ann. Rep. Med. Chem. 139 (D. M. Bailey, editor, 1986); P. B. Fernandes et al., in 22 Ann. Rep. Med. Chem. 117 (D. M. Bailey, editor, 1987); R Albrecht, 21 Prog. Drug Research 9 (1977); and P. B. Fernandes et al., in 23 Ann. Rep. Med. Chem. (R. C. Allen, editor, 1987). Preferred quinolone moieties include those where A 1 is C(R 2 ), A 2 is C(R 2 ), and A 3 is C(R 5 ) (i.e., quinolones); A 1 is nitrogen, A 2 is C(R 2 ), and A 3 is C(R 5 ) (i.e., naphthyridines); A 1 is C(R 7 ), A 2 is C(R 2 ), and A 3 is nitrogen (i.e., cinnoline acid derivatives); and where A^ is nitrogen, A 2 is nitrogen, and A 3 is C(R^) (i.e., pyridopyrimidine derivatives). More preferred quinolone moieties are those where A 1 is C(R 7 ), A 2 is C(R 2 ), and A 3 is C(R 5 ) (i.e., quinolones); and where A 1 is nitrogen, A 2 is C(R 2 ), and A 3 is C(R^) (i.e., naphthyridines). Particularly preferred quinolone moieties are where A 1 is C(R 7 ), A 2 is C(R 2 ), and A 3 is C(R^) (i.e., quinolones). R! is preferably alkyl, aryl, cycloalkyl and alkylamino. More preferably, R* is ethyl, 2-fluoroethyl, 2-hydroxyethyl, t-butyl, 4-fluorophenyl, 2,4-difluorophenyl, methylamino and cyclopropyl. Cyclopropyl is a particularly preferred R 1 group. Preferred quinolone moieties also include those where A^ is C(R 7 ) and R^ and R 7 together comprise a 6-membered heterocyclic ring containing an oxygen or sulfur atom. These compounds are prepared by an additional reaction step subsequent to the cyclization step (2) described herein. Specifically, after the QLA (wherein "Q" has two fused rings) is formed using the processes of the present invention, the third fused ring (i.e., between N' and A 1 ) is formed by methods known in the art. (See, for example, Bouzard et al., "Utilisation du Fluorure de Tetrabutylammonium comme Agent de Cyclisation dans la Synthese D'Antibacteriens Derives D'Acide Pyridone-4-Carboxylique-3", 29 Tet. Lett. 1931- 1934 (1988)). R 2 is preferably hydrogen or halo. More preferably R 2 is chlorine or fluorine. Fluorine is a particularly preferred R 2 group. Preferred R 3 groups include nitrogen-containing heterocyclic rings. Particularly preferred are nitrogen-containing heterocyclic rings having from 5 to 8 members. The heterocyclic ring may contain additional heteroatoms, such as oxygen, sulfiir, or nitrogen, preferably nitrogen. Such heterocyclic groups are described in U.S. Patent 4,599,334, Petersen et al., issued July 8, 1986; and U.S. Patent 4,670,444, Grohe et al., issued June 2, 1987 (both incorporated by reference herein). Preferred R 3 groups include unsubstituted or substituted pyridine, piperidine, morpholine, diazabicyclo-[3.1.1]heptane, diazabicyclo[2.2.1]heptane, diazabicyclo[3.2.1]octane, diazabicyclo-[2.2.2] octane, thiazolidine, imidazolidine, pyrrole and thiamorpholine, as well as the following particularly preferred R 3 groups include piperazine, 3-methylpiperazine, 3-aminopyrrolidine, 3- aminomethylpyrrolidine, 3-(l-aminoethyl)pyrrolidine, N,N-dimethylaminomethyl- pyrrolidine, N-methylaminomethylpyrrolidine, N-ethylaminomethylpyrrolidine, pyridine, N-methylpiperazine, and 3,5-dimethylpiperazine. QLAs made by the processes of the present invention preferably have a quinolone moiety (Formula (I)) that is member of one of the following classes of compounds. 1. A 1 is -C(R 7 )-; A 2 is -CF-; and A 3 is -CH-; 2. Al is -CH-, -CF-, -CC1-; A 2 is -CF-; A 3 is -CH-; R 4 is OH and pharmaceutically-acceptable salts; R^ is H; and R 1 is cyclopropyl, ethyl, 2,4-difluorophenyl, 4-fluorophenyl, or t-butyl; 3. A 1 is -N-; A 2 is -CF-; and A 3 is -CH-; 4. A 1 is -N-; A 2 is -CF-; A 3 is -CH-; R 4 is OH and pharmaceutically- acceptable salts; R*> is H; and R 1 is cyclopropyl, ethyl, 2,4-difluorophenyl, 4-fluorophenyl, or t-butyl; and 5. Rl, R 3 , or R*> is a lactam-containing moiety. Linking Moieties: A variety of linking moieties may be employed for attaching the quinolone and lactam moieties. Such linking moieties include, for example, carbamates, secondary amines, tertiary amines, quaternary amines (i.e., ammonium), heteroarylium, thioethers, ethers, dithiocarbamates, ureas, thioureas, imines, guanidiniums, carbonates, trithiocarbonates, reverse carbamates, xanthate, reverse dithiocarbamate. These and other useful linking moieties are described in European Patent Publication 366,189, White and Demuth, published May 2, 1990. Preferred linking moieties are carbamates, secondary amines, tertiary amines, quaternary amines, and dithiocarbamates. Particularly preferred are carbamates, secondary amines and tertiary amines. The specific physical, chemical, and pharmacological properties of the quinolonyl lactams of this invention may depend upon the particular combination of the integral lactam-containing moiety, quinolone moiety and linking moiety comprising the compound. For example, selection of particular integral moieties may affect the relative susceptibility of the quinolonyl lactam to bacterial resistance mechanisms (e.g., beta-lactamase activity). Preferred lactam moieties, quinolone moieties, linking moieties, and QLAs are described in the following documents, all of which are incorporated by reference herein: European Patent Publication 366,189, White and Demuth, published May 2, 1990; European Patent Publication 335, 297, Albrecht et al., published October 4, 1989; and U.S. Patent Application Serial No. 07/511,483, Demuth and White, filed April 18, 1990. Methods of Manufacture The processes of this invention, when making a QLA, comprise the steps of: (1) coupling a compound having a structure according to Formula (III) with a lactam compound of the Formula (II) to form an intermediate compound; and (2) cyclizing the intermediate by reaction with an organosilicon compound to give Q-L-B. The intermediate compounds (M-L -L-L 2 -B) of the present invention are prepared by the coupling step (1). The identity of the compound of Formula (III) and the lactam compound used in coupling Step (1) will be dictated, in part, by the linking group (i.e., -L*-L- L 2 -) of the desired intermediate or QLA end product. Using the present disclosure, those skilled in the art will recognize which materials will be utilized to prepare the desired intermediate or QLA according to the present invention. That is, the starting materials and resulting intermediates must be appropriately substituted to allow synthesis of the desired linking moiety. The following general reaction schemes exemplify means for obtaining the various linking moieties described above. For each linking moiety, an exemplary reaction scheme is provided for making an intermediate of the formula (M - L^) - L - (L 2 - B) (coupling step) and a QLA (the cyclization step). For example, intermediates and QLAs having a carbamate linking moiety may be made according to the processes of the present invention as follows: Step (1): (m)-NH + X-C(O)-O-CH 2 -Lact > (IV)-N-C(O)-O-CH 2 -Lact Step (2): Cyclize to yield Quin-N-C(O)-O-CH 2 -Lact where "(HI)" represents a compound of Formula (III), which is described above; "(IN)" represents a moiety of Formula (IV), which is described above; X is a reactive leaving group (such as alkoxy, halo, or N-heteroalkyl); "Lact" generically represents an appropriately protected lactam-containing structure (such as carbapenem, penem, cephem, monocyclic beta-lactam, oxacephem, or carbacephem); and "Quin" represents an appropriately protected quinolone. The sequence can be envisioned as formation of the intermediate lactam carbonate derivative, followed by acylation of an amino functionality of a compound of Formula (HI) to form a carbamate coupled lactam intermediate, followed by cyclization to form a carbamate-linked QLA. When making carbamate-linked interemediates and QLAs, an optional step of reacting the compound of Formula (HI) with an organosilicon compound may be performed prior to the coupling step (1). This step is illustrated in Examples 1 through 5 hereinbelow. Alternatively, "reversed" carbamate linking-moieties can be prepared by the following sequence: Step (l): + H 2 N-CH 2 -Lact → Lact-CH 2 -NHC(=O)O-CH 2 -(IV) Step (2): Cyclize to yield Lact-CH 2 -NHC(=O)O-CH 2 -Quin where "(III)" represents a compound of Formula (III), which is described above; "(TV)" represents a moiety of Formula (IV), which is described above; X is a reactive leaving group (such as alkoxy, halo, or N-heteroaryl); "Lact" generically represents an appropriately protected lactam-containing structure (such as a penem, carbapenem, cephem, or carbacephem); and "Quin" represents an appropriately protected quinolone. The sequence can be envisioned as formation of a carbonate derivative of a compound of Formula (III), followed by acylation of a lactam amino functionality to form a carbamate coupled conjugate of the lactam intermediate (step(l)), followed by cyclization to form a reversed carbamate linked QLA. Lactam-Quinolones having a dithiocarbamate linking moiety may be made by the following general reaction sequence: Lact-CH 2 -SC(=S)N-(IV) Step (2): Cyclize to yield Lact-CH 2 -SC(=S)N-Quin where "(III)" represents a compound of Formula (III), which is described above; "(rV) H represents a moiety of Formula (IV), which is described above; X is a reactive leaving group (such as halo, a sulfonate ester, acetate, thiobenzoate or other activated hydroxyl functionality); "Lact" generically represents an appropriately protected lactam-containing structure (such as a penem, carbapenem, cephem, monocyclic beta-lactam, oxacephem, or carbacephem); and "Quin" represents an appropriately protected quinolone. The sequence can be envisioned as formation of a dithiocarbamate salt of a compound of Formula (III), followed by nucleophilic displacement of the lactam X substituent to form a dithiocarbamate coupled conjugate of the lactam intermediate (intermediate), followed by cyclization to yield a dithiocarbamate linked QLA. Alternatively, "reversed" dithiocarbamate conjugates can be prepared by the following sequence. Lact-CH -NH 2 + CS 2 → Lact-CH 2 -NHC(=S)S-M + Step (1): Lact-CH 2 -NHC(=S)S-M '1 - + X-CH 2 -(III) → Lact-CH 2 -NH C(=S)S-CH 2 -(IV) Step (2): Cyclize to give Lact-CH 2 -NHC(=S)S-CH 2 -Quin where "(III)" represents a compound of Formula (III), which is described above; "(IV)" represents a moiety of Formula (IV), which is described above; X is a reactive leaving group (such as halo, a sulfonate ester or other activated hydroxyl functionality); "Lact" generically represents an appropriately protected lactam- containing structure (such as a penem, carbapenem, cephem, oxacephem, or carbacephem); and "Quin" represents an appropriately protected quinolone. The sequence can be envisioned as formation of the lactam dithiocarbonate salt, followed by nucleophilic displacement of the suitable compound (III) X substituent to form a "reversed" dithiocarbamate coupled conjugate of the lactam intermediate (step (1)), followed by cyclization to form a reverse dithiocarbamate-linked QLA. Lactam-quinolones having a thiourea or urea linking moiety may be made by the following general reaction sequence: Lact-CH 2 -X + M+-YCN → Lact-CH 2 -N=C=Y Step (1) Lact-CH 2 -N=C=Y + HN-(III) → Lact-CH 2 -NHC(=Y)N-(IV) Step (2) Cyclize to yield Lact-CH-,NH(C=Y)N-Quin (thiourea: Y=S; urea: Y=O) where "(III)" represents a compound of Formula (III), which is described above; "(IV)" represents a moiety of Formula (IV), which is described above; X is a reactive leaving group (such as halo, a sulfonate ester, dichloroacetate, thiobenzoate or other activated hydroxyl functionality); and Y is either O or S. "Lact" generically represents an appropriately protected lactam-containing structure (such as a penem, carbapenem, cephem, monocyclic beta-lactam, oxacephem, or carbacephem), and "Quin" represents an appropriately protected quinolone. The sequence can be envisioned as formation of the intermediate lactam isothiocyanate (Y = S) or isocyanate (Y = O); followed by reaction with the amino substituent of a compound of Formula (III) to form a thiourea (Y = S) or urea (Y = O) coupled conjugate of the lactam and Formula III compound (intermediate) (step (1)), followed by cyclization to form a thiourea- (Y = S)- or urea- (Y = O) linked QLA. Lactam-quinolones having an imine, amine or ammonium linking moiety may be made by the following general reaction sequence: Step (1): Lact-CH 2 HO + HN-(III) → Lact-CH=N-(IV) (an imine) → Lact-CH 2 -N(R )-(IV) (an amine) → Lact-CH 2 -N + (R )(R 5)-(IV) (an ammonium) Step (2): cyclization of the amine or ammonium intermediate to yield Lact- CH=N-Quin, Lact-CH 2 -N(R )-Quin or Lact-CH 2 -N + (R 4 )(R 5 )-Quin, respectively where "(III)" represents a compound of Formula (III), which is described above; "(IV)" represents a moiety of Formula (IV), which is described above; R 44 and R 4 ^ are described above; "Lact" generically represents an appropriately protected lactam-containing structure (such as a penem, carbapenem, cephem, oxacephem, or carbacephem; and "Quin" represents an appropriately protected quinolone. The sequence can be envisioned as the condensation of the amine of a compound of Formula (III) with the lactam aldehyde to form the imine coupled lactam intermediate conjugate. Reduction of the imine yields the corresponding amine coupled lactam intermediate conjugate. Alkylation yields the corresponding quaternary ammonium-coupled lactam intermediate conjugate. Cyclization of the desired intermediate will yield an imine-, amine-, or ammonium-linked QLA. Lactam-quinolones having an amine linking moiety may alternatively be made by the following general reaction sequence: Step (l): Lact-CH 2 X + HN-(III) → Lact-CH 2 -N(R 4 )-(IV) (an amine) → Step (2): cyclization of the amine to yield Lact-CH -N(R 44 )-Quin where "(III)" represents a compound of Formula (III), which is described above; "(IV)" represents a moiety of Formula (IV), which is described above; R 44 and R 4 ^ are described above; "Lact" generically represents an appropriately protected lactam-containing structure (such as a penem, carbapenem, cephem, oxacephem, or carbacephem; X is a leaving group described above and "Quin" represents an appropriately protected quinolone. Alternatively, the quaternary ammonium conjugate can be prepared by the following general sequence. Step (1): Lact-CH 2 -X + (R 4 )(R 5 )N-(III) → Lact-CH 2 -N + (R 4 )(R 45 )-(IV) Step (2): Cyclize to yield Lact-CH 2 -N+(R 4 )(R 5 )-Quin where "(III)" represents a compound of Formula (III), which is described above; "(IV)" represents an intermediate compound of Formula (IV), which is described above; R 44 and R 4 ^ are described above, X is a reactive leaving group (such as halo, a sulfonate ester, or other activated hydroxyl functionality, etc.). This sequence can be envisioned as a quaternization of a tertiary amino group of a compound of Formula (III) with the lactam material to obtain the quaternary ammonium coupled conjugate between the lactam and compound of Formula (HI) (step (1)), followed by cyclization to form the ammonium-linked QLA. Lactam-quinolones having an amide linking moiety may be made by the following general sequence: Step ( 1 ): Lact-CH 2 -NH 2 + X-C(=O)-(III) → Lact-CH 2 -NHC(=O)-(IV) Step (2): Cyclize to yield Lact-CH 2 -NHC(=O)-Quin where "(III)" represents a compound of Formula (III), which is described above; "(IV)" represents an intermediate compound of Formula (IV), which is described above; X is a reactive leaving group (such as halo, an HOBt ester, mixed anhydride or other activated carboxyl functionality); "Lact" generically represents an appropriately protected lactam-containing structure (such as a penem, carbapenem, cephem, oxacephem, or carbacephem); and "Quin" represents an appropriately protected quinolone. The reaction can be envisioned as an acylation of the lactam amino substituent with the activated carboxyl group of a compound of Formula (III), to form an amide coupled conjugate of the lactam and Formula (HI) compound (intermediate), followed by cyclization to form the amide-linked QLA. Lactam-quinolones having a guanidinium linking moiety may be made by the following general reaction sequence: H 2 NC(=S)N-(III) → RSC(=NH 2 + X)N-(III) Step (1): RSC(=NH 2 + X-)N-(III) + Lact-CH 2 -NH 2 → Lact-CH 2 -NHC(=NH 2 + X-)N-(IV) Step (2): Cyclize to yield Lact-CH 2 -NHC(=NH 2 + X-)N-Quin where "(III)" represents a compound of Formula (III), which is described above; "(IV)" represents an intermediate compound of Formula (IV), which is described above; "Lact" generically represents an appropriately protected lactam-containing structure (such as penem, carbapenem, cephem, oxacephem, or carbacephem): and "Quin" represents an appropriately protected quinolone. The sequence can be envisioned as formation of the isothiouronium salt of a compound of Formula (III), followed by reaction with the lactam amino substituent to form a guanidinium coupled conjugate of the lactam and compound of Formula (III) (intermediate), followed by cyclization to form a guanidinium-linked QLA. Lactam-quinolones having a heteroarylium linking moiety may be made by the following general reaction sequence: Step (l): Lact-CH 2 -X + N Het -(III) → Lact-CH 2 -N + H et-(IV) Step (2): Cyclize to yield Lact-CH 2 N + HefQ um where "(III)" represents a compound of Formula (III), which is described above; "(TV)" represents an intermediate compound of Formula (IV), which is described above; X is a reactive leaving group (such as halo, a sulfonate ester, acetate, thiobenzoate or other activated hydroxyl functionality); "N^g." is an heteroaryl moiety, N"1Het is a heteroaryl having a ring quaternary nitrogen atom, "Lact" generically represents an appropriately protected lactam-containing structure (such as a penem, carbapenem, cephem, monocyclic beta-lactam, oxacephem, or carbacephem); and "Quin" represents an appropriately protected quinolone that contains a heteroaromatic nitrogen-containing substituent (for example, pyridine). The sequence can be envisioned as an alkylation of the heteroaromatic nitrogen- containing substituent of a compound of Formula (III) by the lactam to form the pyridinium-type conjugate (intermediate), followed by cyclization to form the pyridinium-linked QLA. Lactam-quinolones having a xanthate linking moiety may be made by the following general reaction sequence: Step (1): M + -SC(=S)O-(III) + Lact-CH 2 -X → Lact-CH 2 -SC(=S)O-(IV) Step (2): Cyclize to form Lact-CH 2 -SC(=S)O-Quin where "(HI)" represents a compound of Formula (III), which is described above; "(IV)" represents an intermediate compound of Formula (IV), which is described above; X is a reactive leaving group (such as halo, a sulfonate ester, acetate, thiobenzoate or other activated hydroxyl functionality); "Lact" generically represents an appropriately protected lactam-containing structure (such as a penem, carbapenem, cephem, monocyclic beta-lactam, oxacephem, or carbacephem); and "Quin" represents an appropriately protected quinolone. The sequence can be envisioned as formation of the xanthate salt of a compound of Formula (III), followed by nucleophilic displacement of the lactam X substituent to form a xanthate coupled conjugate of the lactam and Formula (III) compound (intermediate), followed by cyclization to yield the xanthate-linked QLA. Lactam-quinolones having a thioether, sulfoxide or sulfone linking moiety may be made by the following general reaction sequence: Step (1): Lact-CH 2 -X + HS-(III) → Lact-CH 2 -S-(IV) (a thioether) → Lact-CH 2 -SO-(IV) (a sulfoxide) → Lact-CH SO 2 -(IV) (a sulfone) Step (2): Cyclization of the thioether, sulfoxide or sulfone to form Lact-CH 2 -S-Quin, Lact-CH 2 -SO-Quin, or Lact-CH 2 -SO 2 -Quin, respectively where "(III)" represents a compound of Formula (III), which is described above; "(IN)" represents an intermediate compound of Formula (IV), which is described above; X is a reactive leaving group (such as halo, a sulfonate ester, acetate, thiobenzoate or other activated hydroxyl functionality, etc.); "Lact" generically represents an appropriately protected lactam-containing structure (such as a penem, carbapenem, cephem, monocyclic beta-lactam, oxacephem, or carbacephem); and "Quin" represents an appropriately protected quinolone. The sequence can be envisioned as nucleophilic displacement of the lactam X group with a thio- containing compound of Formula (III) to form the thioether coupled conjugate (intermediate). Oxidation of the thioether yields the corresponding sulfoxide conjugate. Further oxidation produces the sulfone lactam intermediate conjugate. Cyclization of the thioether, sulfoxide, or sulfone intermediate will form a thioether- linked, a sulfoxide-linked, or sulfone-linked QLA, respectively. Lactam-quinolones having an isothiouronium linking group may be made by the following general reaction sequence: RC(=O)N=C=S + HN-(III) → H 2 NC(=S)N-(III) Step (1): H 2 NC(=S)N-(III) + Lact-CH 2 -X → Lact-CH 2 -SC(=NH 2 + X-)N-(IV) Step (2): Cyclize to give Lact-CH 2 -SC(CNH 2 + X-)N-Quin where "(III)" represents a compound of Formula (III), which is described above; "(IV)" represents an intermediate compound of Formula (IV), which is described above; X is a reactive leaving group (such as halo, a sulfonate ester, acetate, thiobenzoate or other activated hydroxyl functionality); "Lact" generically represents an appropriately protected lactam-containing structure (such as a penem, carbapenem, cephem, monocyclic beta-lactam, oxacephem, or carbacephem; and "Quin" represents an appropriately protected quinolone. The sequence can be envisioned as formation of the thiourea-containing compound of Formula (HI), followed by nucleophilic displacement of the lactam X substituent to form a isothiouronium coupled conjugate (intermediate), followed by cyclization to QLA. In the reaction sequences described herein, certain functional groups contained in the Lact, (III) and (IV) structures, (such as carboxyl, hydroxyl, and amino groups) may need to be in a protected form. If various protecting groups are employed, then appropriate deprotecting chemistry, that will not decompose the coupled conjugate, may be required to obtain antibacterially active products. Depending on the R 10 group desired, the lactam starting material may be available from any of a variety of commercial sources. Synthetic methods for producing such lactams are well-known in the chemical literature. See, for example, Antibiotics. Chemotherapeutics. and Antibacterial Agents for Disease Control, pages 107-125 (M. Grayson, editor, 1982), incorporated by reference herein. Preferably, the processes of the present invention additionally comprise steps for protecting the lactam and compound of Formula (III) prior to the coupling step. In particular, the carboxylate groups at R 4 and R^ 3 are in a protected form, using, for example, an ester group. Alternatively, the compound may be further reacted to form another QLA moiety that is known to have antimicrobial activity. For example, the QLA may be further reacted to yield a compound where A* is -C(R 7 )- and R 7 and R* together comprise a heterocylic 6-membered, oxygen- (pyridobenzoxazine) or sulfur- (pyridobenzthiazine) contaning ring including N* and A 1 . A preferred process of this invention additionally comprises: (a) a step, prior to said coupling step, wherein a compound of Formula (II), a compound of Formula (III), or both are protected; and (b) deprotection steps, after said cyclization step, wherein the protecting groups are removed. The coupling step is carried out in solution, using any of a variety of suitable solvents. Such solvents include, for example: halocarbon solvents, such as methylene chloride, chloroform, and dichloroethane; ethers, such as diethyl ether and tetrahydrofuran (THF); aromatic solvents, such as benzene and toluene; dialkylamides, such as N,N-dimethylformamide; or mixtures thereof. In particular, in the formation of carbamate linkages, halocarbon solvents are preferred. Most preferred is methylene chloride and dichloromethane. In particular, in the formation of amine linkages, halocarbon and dialkylamides and mixtures thereof are preferred. More preferred is dichloroethane or dichloromethane, and N,N-dimethylformamide, or mixtures thereof. Most preferred is a mixture of dichloroethane or dichloromethane, and N,N- dimethylformamide. In coupling reactions wherein an organosilicon compound is employed, the coupling step is preferably conducted at temperatures less than about 0°C. Preferably the temperatures are from about -78°C to about -15°C, more preferably from about -20°C to about -15°C. Preferably, reagents are mixed in the coupling step so as to allow control of the temperature within these ranges. In coupling reactions wherein an organosilicon compound is not employed, the coupling step is preferably conducted at temperatures from about -78°C to about 50°C. More preferably the temperatures are from about -50°C to about 25°C; even more preferably from about -20°C to about 0°C. Preferably, reagents are mixed in the coupling step so as to allow control of the temperature within these ranges. Methods for the cyclization of quinolone precursors, including the intermediates of the present invention, to yield QLAs (and quinolones generally) is specifically described and claimed in co-pending application Serial No. , filed August 2, 1994, by Randall, et al. The cyclization step is carried out in a mixture of the substrate and one or more of a variety of known solvents. Such solvents include, but are not limited to: halocarbon solvents, such as methylene chloride, chloroform, and dichloroethane; ethers, such as diethyl ether and tetrahydrofuran (THF); aromatic solvents, such as benzene and toluene; alkyl nitriles, such as acetonitrile; and mixtures thereof. Halocarbon, ether, and alkyl nitrile solvents are preferred. More preferred solvents include methylene chloride, THF, acetonitrile, or mixtures thereof. The cyclization reaction (step (2)) is carried out at a temperature sufficient to effect cyclization of the intermediate compound formed in the coupling step). The cyclization reaction is preferably carried out at temperatures greater than -15°C. More preferred is where the reaction is conducted at temperatures from about 0°C to about 110°C. Most preferred reaction temperatures are from about 25°C to about 50°C. Preferably, reagents are mixed in the reaction step so as to allow control of the temperature within these ranges. Preferably, from about 1 to about 14 mole equivalents of the silyl-containing compound will be added for each mole of the intermediate compound (i.e., a mole ratio of organosilicon compound to intermediate of from about 1:1 to about 14:1 ). More preferred is a mole ratio of from about 2:1 to about 12: 1. Most preferred is a mole ratio of about 2:1 to about 6:1. Procedures for making a variety of lactam and Formula (III) starting materials are well known in the art. For example, procedures for preparing lactam- containing moieties are described in the following references, all incorporated by reference herein (including articles cited within these references): Cephalosporins and Penicillins: Chemistry and Biology (E. H. Flynn, ed, 1972) Chapters 2, 3, 4, 5, 6, 7, 15 and Appendix I; Recent Advances in the Chemistry of b-Lactam Antibiotics (A.G. Brown and S. M. Roberts, ed., 1985); Topics in Antibiotic Chemistry. Vol. 3, (Part B) and Vol. 4, (P. Sommes, ed., 1980); Recent Advances in the Chemistry of b-lactam Antibiotics (J. Elks, ed., 1976); Structure-Activity Relationships Among the Semisvnthetic Antibiotics (D. Perlman, ed, 1977); Chapts. 1, 2, 3, 4; Antibiotics. Chemotherapeutics and Antibacterial Agents for Disease Control (M. Grayson, ed, 1982); Chemistry and Biology of b-Lactam Antibiotics, Vols 1-3 (K. B. Morin and M. Gorman, eds, 1982); 4 Medicinal Research Reviews 1-24 (1984); 8 Medicinal Research Review 393-440 (1988); 24 Angew. Chem. Int. Ed. Engl. 180-202 (1985); 40 J. Antibiotics 182-189 (1987); European Patent Publication 266,060; 42 J. Antibiotics 993 (1989); U.S. Patent 4,742,053; 35 Chem. Pharm. Bull. 1903-1909 (1987); 32 J. Med. Chem.. 601-604 (1989); U.S. Patent 4,791,106; Japanese Patent Publication 62 158291; 31 J. Med. Chem. 1987-1993 (1988); 30 J. Med. Chem.. 514-522 (1987); 28 Tet. Let. 285-288 (1987); 28 T Let. 289-292 (1987); 52 J. Org. Chem.. 4007-4013 (1987); 40 J. Antibiotics. 370- 384 (1987); 40 J. Antibiotics. 1636-1639 (1987); 37 J. Antibiotics. 685-688 (1984); 23 Heterocvcles. 2255-2270; 27 Heterocvcles. 49-55; 33 Chem. Pharm. Bull. 4371-4381 (1985); 28 Tet. Let. 5103-5106 (1987); 53 J. Org. Chem.. 4154-4156 (1988); 39 J. Antibiotics. 1351-1355 (1986); 59 Pure and Appl. Chem.. 467-474 (1987); 1987 J.C.S. Chem. Comm.: 44 Tetrahedron. 3231-3240 (1988); 28 T_sL Let.. 2883-2886, (1987); 40 J. Antibiotics. 1563-1571 (1987); 33 Chem. Pharm. Bull.. 4382-4394 (1985); 37 J. Antibiotics. 57-62 (1984); U.S. Patent 4,631,150; 34 Chem. Pharm. Bull.. 999-1014 (1986); 52 J. Org. Chem.. 4401-4403 (1987); 39 Tetrahedron. 2505-2513 (1983); 38 J. Antibiotics. 1382-1400 (1985); European Patent Application 053,815; 40 J. Antibiotics. 1563-1571 (1987); 40 J. Antibiotics. 1716-1732 (2987); 47 J. Org. Chem.. 5160-5167 (1981); U.S. Patent 4,777,252; U.S. Patent 4,762,922; European Patent Publication 287,734; U.S. Patent 4,762,827; European Patent Publication 282,895; European Patent Publication 282,365; and U.S. Patent 4,777,673. General procedures for preparing compounds of Formula (III) follow the reaction scheme for preparing the related quinolone, with the exception that the final cyclization step known in the art (affected by a strong base) is not performed. Such methods are described in the following references, all incorporated by reference herein (including articles listed within these references): U.S. Patent No. 5, 140,033, issued August 18, 1992 to Schriewer et al.; U.S. Patent No. 4,886,810, issued December 12, 1989 to Matsumoto et al.; U.S. Patent No. 4,885,386, issued December 5, 1989 to Wemple et al.; U.S. Patent No. 4,684,648, issued August 4, 1987 to Tone et al.; European Patent Publication 522,277, Cecchetti et al., published January 13, 1993; European Patent Publication 470,578, Yokomoto et al., published February 12, 1992; Europeant Patent Publication 319,906, Matsumoto et al., published June 14, 1989; Europeant Patent Publication 287,951, Ueda et al., published October 26, 1988; Europeant Patent Publication 195,316, Irikura et al., published March 6, 1986; German Patent Publication DE-3702393, Schwiewer et al., published August 11, 1988; German Patent Publication DE-3641312, Preiss, published June 9, 1988; German Patent Publication DE-3601567, Petersen et al., published July 23, 1987; German Patent Publication DE-3600891, Schriewer et al., published July 16, 1987; German Patent Publication DE-3504643, Petersen et al., August 14, 1986; German Patent Publication DE-3420743, Petersen et al., published December 5, 1985; Japanese Patent Publication JP/02215749, Furumiya et al., published August 28, 1990; Japanese Patent Publication JP/60172981, Hayakawa, published September 6, 1985; World Patent Publication 92/03136, Chu et al., published March 5, 1992; World Patent Publication 89/06649, Domagalia et al., published July 27, 1989; Chu et al., "An Alternative Synthesis of Temafloxacin, a Potent Antibacterial Agent", 70(5) Can. J. Chem. 1323-27 (1992); Remuzon, "Fluoronaphthyridines and Quinolones as Antibactertial Agents", 34(1) J. Med. Chem. 29-37 (1991); Cecchetti et al., "One-pot Synthesis of Rufloxacin", 21(22) Svnth. Commun. 2301-08 (1991); Chu et al., "Synthesis of 4-oxo-4H quino[2,3,4-ij][l,4]benoxazine-5-carboxylic Acid Derivatives", 24(2) J. Hetercvcl. Chem. 453-456 (1987); Egawa et al., "A New Synthesis of 7H-Pyrido[l,2 > 3,-de][l,4]benzoxazine Derivatives Including an Antibacterial Agent, Ofloxacin", 34(10) Chem. Pharm. Bull. 4098-4102 (1986). Additional references describing methods for preparing the compounds of Formula (II) are described in the following references, all incorporated by reference herein (including articles listed within these references): 31 J. Med. Chem.. 503- 506 (1988); 32 J. Med. Chem.. 1313-1318 (1989); 1987 Liebigs Ann. Chem.. 871- 879 (1987); 14 Drugs Exptl. Clin. Res.. 379-383 (1988); 31 J. Med. Chem.. 983- 991 (1988); 32 J. Med. Chem.. 537-542 (1989); 78 J. Pharm. Sci.. 585-588 (1989); 26 J. Het. Chem.. (1989); 24 J. Het. Chem.. 181-185 (1987); U.S. Patent 4,599,334; 35 Chem. Pharm. Bull.. 2281-2285 (1987); 29 J. Med. Chem.. 2363- 2369 (1986); 31 J. Med. Chem.. 991-1001 (1988); 25 J. Het. Chem.. 479-485 (1988); European Patent Publication 266,576; European Patent Publication 251,308, 36 Chem. Pharm. Bull.. 1223-1228 (1988); European Patent Publication 227,088; European Patent Publication 227,039; European Patent Publication 228,661; 31 J. Med. Chem.. 1586-1590 (1988); 31 J. Med. Chem.. 1598-1611 (1988); 23 J Med. Chem.. 1358-1363 (1980); 21 Progress in Drug Research. 9-104 (1977). The following non-limiting examples illustrate the processes of the present invention. EXAMPLE 1 Synthesis of [5R-[5α,6α(R*)]]-3-[[[4-(3-Carboxy-l-cycloρropyl-6-fluoro- 1 ,4-dihydro-4-oxo-7-quinolinyl)- 1 -piperazinyl]carbonyloxy]methyl]-6-(l -hydroxy- ethyI)-7-oxo-4-thia-l -azabicyclo[3 2.0]hept-2-ene-2-carboxylic acid. To a solution of 2,4,5-trifluoroacetophenone (15.0 g) (Compound 1) in THF (300 mL) is added piperazine (29.6 g). The mixture is refluxed under N 2 for 1 hour and the THF is removed under reduced pressure. The residue is slurried in EtOAc (150 mL), and the excess piperazine is filtered off and rinsed with EtOAc. The EtOAc filtrate is washed with water (2 x 150 mL) and the combined aqueous layers are extracted with EtOAc (75 mL). The combined EtOAc layers are dried (MgSO_j) and treated with activated charcoal. The solvents are evaporated in vacuo and the residue is crystallized from isopropyl ether to give Compound 2. To a solution of Compound 2 (9.4 g) in CHCI3 (141 mL) is added a solution of di-t-butylcarbonate (9.39 g) in CHCI3 (50 mL). The reaction is stirred for 5 minutes under N 2 at ambient temperature and evaporated in vacuo. Hexanes are added to give Compound 3. To a cooled solution of Compound 3 (10.0 g) in THF (100 mL) under N 2 at 0-5°C is added a 60% oil immersion of NaH (2.5 g), portionwise. The reaction mixture is stirred for 15 minutes and diethylcarbonate (14.2 mL) is added. The reaction is stirred for 18 hours under N 2 at ambient temperature and quenched with a 28: 1 mixture of water and HOAc (100 mL). The organic portion is evaporated in vacuo and the residue is subjected to column chromatography (silica, 10:89:1% EtOAc/Hexane/HOAc). The residue is crystallized from hexanes to give Compound 4. To a solution of Compound 4 (11.95 g) in toluene (47.8 mL) is added dimethylformamide dimethylacetal (5.95 mL). The reaction is heated to reflux for 20 hours under N 2 and concentrated in vacuo to obtain Compound 5. Compound 5 is carried directly to the next step by dissolving in EtOH (47.8 mL) and adding cyclopropyl amine (3.2 mL). The mixture is stirred for 2 hours at ambient temperature under N 2 . The volatiles are removed in vacuo and the residue is crystallized from 20% EtOAc/hexanes to give Compound 6. To a cooled solution of Compound 6 (12.06 g) in anisole (97.7 mL) at 5- 10°C is added trifluoroacetic acid (TFA) (97.7 mL). After stirring for 5 minutes under N , the ice bath is removed and the reaction is warmed to ambient temperature. After 2 hours, most of the TFA and some of the anisole is removed in vacuo. The residue is slurried in Et 2 O (300 mL) and filtered. The solid is dissolved in a mixture of CH 2 C1 2 (100 mL) and saturated NaHCO3 (100 mL) and stirred for 10 min. The CH 2 C1 2 portion is separated, dried (MgSO_j), treated with activated charcoal, and evaporated in vacuo. The residue is crystallized with hexane to give the mono-hydrate of Compound 7. A solution of Compound 7 (2.1 g) in CH C1 (50 mL) is dried (Na SO 4 ) and the dried solution is transferred to a second vessel, under N 2 . The solution is cooled (-15°C) and N,O-bis(trimethylsilyl)acetamide (2.7 mL) is added. The mixture is allowed to stir for 15 minutes under N to yield a silylated form of Compound 7, which is used without further characterization. In a third vessel, a solution of Compound 8 (2.06 g) in CH C1 2 (50 mL) prepared according to U.S. Patent 4,631,150, Battistini et al., issued December 23, 1986 (incorporated by reference herein), is dried (Na 2 SO_j) and the dried solution is transferred to a fourth vessel, under N 2 . N,N-diisopropylethylamine (1.05 mL) is added and the solution is stirred for 15 minutes at ambient temperature, under N 2 , and cooled to -78°C. In a fifth vessel, to cooled (-78°C) CH 2 C1 (40 mL) is added 20% phosgene in toluene (3.45 mL) under N 2 . The forementioned solution of Compound 8 is added dropwise while maintaining the solution temperature at less than -60°C. The reaction is stirred for 15 minutes and warmed to -15°C to provide Compound 9, which is then reacted in situ by dropwise addition of the forementioned solution of Compound 7, while maintaining the temperature below - 15°C. The reaction is stirred at -15°C under N 2 until complete. The reaction mixture is quenched with water (160 mL), warmed to 0°C and stirred 10 minutes. The organic portion is separated and dried with (Na 2 SO_ι). The volatiles are evaporated in vacuo and the residue is subjected to column chromatography (silica) to give Compound 10. To a solution of Compound 10 (1.2 g) in CH3CN (21 mL) is added BTMSA (1.09 mL). The reaction mixture is stirred under N 2 at ambient temperature until complete. The reaction is quenched with water (21 mL), and the resulting slurry is filtered and washed with a mixture of water and CH3CN (5:1) to provide Compound 11. To a solution of Compound 11 (1.1 g) in benzene (25 mL) is added bis(tributyltin) oxide (1.43 mL), under N 2 . The mixture is heated to reflux until completion, whereupon the volatiles are removed in vacuo and the residue obtained is subjected to column chromatography (silica) to provide Compound 12. To a solution of Compound 12 (0.9 g) in THF (8 mL) and acetic acid (0.62 mL) is added tetra-n-butyl ammonium fluoride (3.21 mL of a IM solution in THF), under N 2 . The mixture is stirred at ambient temperature overnight and, upon completion, is diluted with ether (15 mL). The solution is stirred for a half-hour, allowing the product to crystallize. The slurry is filtered through troyfelt and the solid residue is washed with ether to obtain Compound 13. To a solution of Compound 13 (0.75 g) in CH 2 C1 2 (45 mL) is added tetrakis(triphenylphosphine)palladium (0) (135 mg), under N 2 . The mixture is cooled (-10 to -5°C) and a cooled solution (<-10°C) of sodium ethylhexanoate (389 mg) in THF (22 mL) is added dropwise. The mixture is stirred for approximately 30 minutes, whereupon the resulting slurry is filtered and washed successively with CH 2 C1 2 and acetone, to obtain Compound 14. To a solution of Compound 14 (0.55 g) in absolute ethanol (77 mL) is added highly acidic ion-exchange resin (1.1 g, Amberlite IR-120 - plus), under N 2 . The mixture is stirred at ambient temperature for approximately 5 hours, whereupon it is filtered through a sintered glass filtration funnel to remove the resin. The filtrate is reduced in vacuo to approximately one third of its volume, whereupon water (27 mL) is added. The mixture is strirred for a few minutes and then filtered. The solid obtained is washed with water and dried in vacuo overnight to obtain [5R-[5α,6α(R*)]]-3-[[[4-(3-Carboxy-l-cyclopropyl-6-fluoro-l,4-dihydro- 4-oxo-7-quinolinyl)- 1 -piperazinyl]carbonyloxy]methyl]-6-( 1 -hydroxyethyI)-7-oxo- 4-thia-l-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid (Compound 15). EXAMPLE 2 Synthesis of [5R-[5α,6α(R*)]]-3-[[[4-(3-Carboxy-l-cycloproρyl-6-fluoro- 1 ,4-dihydro-4-oxo-7-quinolinyl)- 1 -piperazinyl]carbonyloxy]-methyl]-6-( 1 - hydroxyethyl)-7-oxo-4-thia-l-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid. To a cooled solution of Compound 1 (10.0 g) (prepared in the same manner as Compound 3 in Example 1) in THF (100 mL) under N at 0-5°C is added a 60% oil immersion of NaH (2.5 g), portionwise. The reaction mixture is stirred for 15 minutes and diallylcarbonate (16.9 mL) is added. The reaction is stirred for 18 hours under N 2 at ambient temperature and quenched with a 28:1 mixture of water and HO Ac (100 mL). The organic portion is evaporated in vacuo and the residue is subjected to column chromatography (silica). The residue is crystallized from hexanes to give Compound 2. To a solution of Compound 2 (10.5 g) in toluene (42 mL) is added dimethylformamide dimethylacetal (5.1 mL). The reaction is heated to reflux for 20 hours under N 2 and concentrated in vacuo to obtain Compound 3. Compound 3 is carried directly to the next step by dissolving in EtOH (42 mL) and adding cyclopropylamine (2.73 mL). The mixture is stirred for 2 hours at ambient temperature under N . The volatiles are removed in vacuo and the residue is crystallized from 20% EtOAc hexanes to give Compound 4. To a cooled solution of Compound 4 (9.75 g) in anisole (79 mL) at 5-10°C is added TFA (79 mL). After stirring for 5 minutes under N 2 , the ice bath is removed and the reaction is warmed to ambient temperature. After 2 hours, most of the TFA and some of the anisole is removed in vacuo. The residue is slurried in Et 2 O (250 mL) and filtered. The solid is dissolved in a mixture of CH 2 C1 2 (80 mL) and saturated NaHCO3 (80 mL) and stirred for 10 min. The CH 2 C1 2 portion is separated, dried (MgSO4), treated with activated charcoal, and evaporated in vacuo. The residue is crystallized from hexanes to give Compound 5. To a solution of Compound 5 (2.2 g) in CH 2 C1 2 (55 mL) is added activated molecular sieves (400 mg). The solution is transferred to a second vessel, under N 2 , and cooled (-15°C). N,O-Bis(trimethylsilyl)acetamide (2.75 mL) is added and the mixture is allowed to stir for 15 minutes. Concurrent with this procedure, Compound 6 (2.09 g), prepared according to U. S. Patent 4,631,150, Battistini et al., issued December 23, 1986 (incorporated by reference herein), is dissolved in CH 2 C1 (55 mL) in a third vessel and activated 4 A molecular sieves (500 mg) are added, under N 2 . After stirring for 30 minutes, the solution is transferred via canula to a fourth vessel and N,N-diisopropylethylamine (1.08 mL) is added under N 2 . The solution is stirred for 15 minutes at ambient temperature and cooled to -78°C. In a fifth vessel, to cooled (- 78°C) CH 2 C1 2 (45 mL) is added 20% phosgene in toluene (3.5 mL) under N 2 . The forementioned solution of Compound 6 is added dropwise while maintaining the solution temperature at less than -60°C. The reaction is stirred for 15 minutes and warmed to -15°C to provide Compound 7 which is then reacted in situ by dropwise addition of the forementioned solution of Compound 5, while maintaining the temperature below -15°C. The reaction is stirred at -15°C under N until complete. The reaction mixture is quenched with water (30 mL), warmed to 0°C and stirred 10 minutes. The organic portion is separated and dried with (Na 2 SO4). The volatiles are evaporated in vacuo and the residue is subjected to column chromatography (silica) to give Compound 8. To a solution of Compound 8 (2.1 g) in CH3CN (30 mL) is added BTMSA (1.89 mL). The reaction mixture is stirred under N 2 at ambient temperature until complete. The reaction is quenched with water (30 mL), and the resulting slurry is filtered and washed with a mixture of water and CH3CN (5:1) giving Compound 9. To a solution of Compound 9 (1.8 g) in THF (16 mL) and acetic acid (1.25 mL) is added tetra-n-butyl ammonium fluoride (6.1 mL of a IM solution in THF), under N . The mixture is stirred at ambient temperature overnight and, upon completion, is diluted with ether (25 mL). The solution is stirred for a half-hour, allowing the product to crystallize. The slurry is filtered through troyfelt and the solid residue is washed with ether to obtain Compound 10. To a solution of Compound 10 (1.4 g) in CH 2 C1 (85 mL) is added tetrakis(triphenyl-phosphine)palladium (0) (240 mg), under N 2 . The mixture is cooled (-10 to -5°C) and a cooled solution (<-10°C) of sodium ethylhexanoate (660 mg) in THF (42 mL) is added dropwise. The mixture is stirred for approximately 30 minutes, whereupon the resulting slurry is filtered and washed successively with CH 2 C1 and acetone, to obtain Compound 11. To a solution of Compound 11 (0.9 g) in absolute ethanol (126 mL) is added highly acidic ion-exchange resin (1.8g, Amberlite IR-120 - plus), under N . The mixture is stirred at ambient temperature for approximately 5 hours, whereupon it is filtered through a sintered glass filtration funnel to remove the resin. The filtrate is reduced in vacuo to approximately one third of its volume, whereupon water (45 mL) is added. The mixture is strirred for a few minutes and then filtered. The solid obtained is washed with water and dried in vacuo overnight to obtain [5R-[5α,6α(R*)]]-3-[[[4-(3-Carboxy- 1 -cyclopropyl-6-fluoro- 1 ,4-dihydro- 4-oxo-7-quinolinyl)- 1 -piperazinyl]carbonyloxy]methyl]-6-( 1 -hydroxyethyl)-7-oxo- 4-thia-l-azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid (Compound 12). EXAMPLE 3 Synthesis of [4R-[4α,5β,6β(R*)]]-3-[[[4-(3-Carboxy-l-cyclopropyl-6- fluoro- 1 ,4-dihydro-4-oxo-7-quinolinyl)- 1 -piperazinyl] carbonyloxy]methyl]-6-( 1 - hydroxyethyl)-7-oxo-4-thia- 1 -azabicyclo[3.2.0]hept-2-ene-2-carboxylic Acid, Disodium salt. Compound 3 (1.2 g), prepared in the same manner as Compound 5 in Example 11, is dissolved in CH 2 C1 2 (30 mL) and dried, under N , with activated molecular sieves. The solution is transferred to a second vessel, under N 2 , and cooled (-15°C). N,O-bis(trimethylsilyl)acetamide (1.5 mL) is added and the mixture is allowed to stir for 15 minutes under N 2 . In a third vessel, Compound 1 (1.12 g), prepared according to Schmitt et al., 41 J. Antibiot. 780-787 (1988) (incorporated by reference herein), is dissolved in CH C1 (30 mL) and dried, under N 2 , with activated molecular sieves. The solution is transferred, under N 2 , to a fourth vessel and N,N-diisopropylethylamine (0.58 mL) is added. The solution is stirred for 15 minutes at ambient temperature, under N , and cooled to -78°C. In a fifth vessel, to cooled (-78°C) CH C1 (25 mL) is added 20% phosgene in toluene (1.86 mL) under N 2 . The forementioned solution of Compound 1 is added dropwise while maintaining the solution temperature at less than -60°C. The reaction is stirred for 15 minutes and wanned to - 15°C to provide Compound 2 which is then reacted in situ by dropwise addition of the forementioned solution of Compound 3, while maintaining the temperature below -15°C. The reaction is stirred at -15°C under N 2 until complete. The reaction mixture is quenched with water (90 mL), warmed to 0°C and stirred 10 minutes. The organic portion is separated and dried with (Na SO4). The volatiles are evaporated in vacuo and the residue is subjected to column chromatography (silica) to give Compound 4. To a solution of Compound 4 (2.15 g) in CH3CN (40 mL) is added N,0- bis(trimethylsilyl)acetamide (2.04 mL). The reaction mixture is stirred under N at ambient temperature until complete. The reaction is quenched with water (10 mL), and the resulting slurry is filtered and washed with a mixture of water and CH3CN (5:1) giving Compound 5. To a cooled (0°C) solution of Compound 5 (1.9 g) in CH 2 C1 2 (75 mL) is added bis(triphenylphosphine)palladium-dichloride (78 mg), followed by water (3.5 mL). To this solution is added tributyltin hydride (4 mL) in one portion. The mixture is stirred at 0°C for 2 hours, whereupon sodium ethylhexanoate (715 mg) is added. The mixture is stirred for 20 minutes and the precipitate is partitioned between CH 2 C1 (350 mL) and water (450 mL). The aqueous phase is separated and lyophilized to provide a crude residue which is triturated with acetone (450 mL) to provide a solid that is subjected to column chromatography (reverse-phase silica) to provide [4R-[4α,5β,6β(R*)]]-3-[[[4-(3-Carboxy-l-cyclopropyl-6-fluoro- 1 ,4-dihydro-4-oxo-7-quinolinyl)- 1 -piperazinyl] carbonyloxy]-methyl]-6-( 1 -hydroxy- ethyl)-7-oxo-4-thia-l-azabi-cyclo[3.2.0]hept-2-ene-2-carboxylic Acid, Disodium salt (Compound 6). EXAMPLE 4 Synthesis of [6R-[6α,7β]]-3-[[[4-(3-Carboxy-l-cyclopropyl-6-fluoro-l,4- dihydro-4-oxo-7-quinolinyl)- 1 -piperazinyl]carbonyloxy]methyl]-8-oxo-7-[(2- thienylacetyl)amino]-5-thia-l-azabicyclo[4.2.0]oct-2-ene-2-carboxylic Acid, Disodium Salt. To a cooled (-5°C) suspension of 7-aminocephalosporanic acid (20 g) (Compound 1) in methanol (38 mL) is added IN NaOH (73.5 mL) over 30 minutes. Additional IN NaOH (73.5 mL) is then added over 7 minutes at 2-5°C to provide Compound 2. Compound 2 is further reacted in si_u by addition of acetone (50 mL) and NaHCO3 (18.51 g) followed by dropwise addition of 2-thiopheneacetyl chloride (9 mL) over 30 minutes at 0-5°C, while maintaining a pH of 7 by simultaneous addition of NaHCO3. The solution is washed with EtOAc (100 mL) and the layers are separated. The aqueous phase is layered with EtOAc (160 mL) and the resulting mixture is acidified at 0°C with concentrated HC1. The layers are separated and the aqueous phase is extracted with EtOAc (160 mL). The combined EtOAc layers are filtered and the volatiles removed in vacuo to near dryness. The precipitate that results is filtered and dried in in vacuo to provide Compound 3. To a solution of benzophenone hydrazone (10 g) in CH C1 2 (51 mL) is added a 1% w/v solution of iodine in CH 2 C1 2 (2.05 mL) and 1,1,3,3- tetramethylguanidine (6.43 g). 3-Chloroperoxybenzoic acid (9.7 g) is then added in small portions at room temperature. The solvent is removed in vacuo to provide diphenyl diazomethane. A solution of diphen- diazomethane (8.78 g) in EtOAc (19 mL) is then added to a cooled (5°C) solution of Compound 3 in THF (150 mL) and EtOAc (150 mL). The mixture is stirred until completion whereupon it is evaporated to dryness in vacuo. THF (64 mL) is added and the insolubles are filtered off. The filtrate is evaporated in vacuo until crystals begin to form. EtOAc (64 mL) is then added and the mixture is stirred for 1.5 hours at 0-5°C. The resulting solid is filtered to provide Compound 4. Compound 6 (1.9 g), prepared in the same manner as Compound 5 in Example 2, is dissolved in CH 2 C1 2 (58 mL) and activated 4 A molecular sieves (500 mg) are added under N 2 . After stirring for 30 minutes at room temperature, the solution is transferred via canula to a second vessel. The solution is cooled (-15°C) and N,O-bis(trimetbylsilyl)acetamide (2.37 mL) is added under N 2 . The mixture is allowed to stir for 15 minutes under N 2 . Concurrent with this procedure, to a cooled (0°C) solution of Compound 4 (2.52 g) in CH 2 C1 (48 mL) in a third vessel is added activated 4A molecular sieves (500 mg), under N 2 . After stirring for 30 minutes, the solution is transferred via canula to a fourth vessel and N,N- diisopropylethylamine (0.93 mL) is added under N 2 . The solution is stirred for 15 minutes at 0°C and cooled to -78°C. In a fifth vessel, to cooled (- 78°C) CH C1 (40 mL) is added 20% phosgene in toluene (3 mL) under N 2 . The forementioned solution of Compound 4 is added dropwise while maintaining the solution temperature at less than -60°C. The reaction is stirred for 15 minutes and warmed to -15°C to provide Compound 5 which is then reacted in situ by dropwise addition of the forementioned solution of Compound 6, while maintaining the temperature below -15°C. The reaction is stirred at -15°C under N 2 until complete. The reaction mixture is quenched with water (30 mL), warmed to 0°C and stirred 10 minutes. The organic portion is separated and dried with (Na 2 SO4). The volatiles are evaporated in vacuo and the residue is subjected to column chromatography (silica) to give Compound 7. To a solution of Compound 7 (2.9 g) in CH3CN (55 mL) is added N,O- bis(trimethylsilyl)acetamide (2.27 mL). The reaction mixture is stirred under N at ambient temperature until complete. The reaction is quenched with water (55 mL), and the resulting slurry is filtered and washed with a mixture of water and CH3CN (5: 1) giving Compound 8. To a cooled (-15°C) solution of Compound 8 (2.2 g) in anhydrous anisole (22 mL) is added TFA (22 mL), dropwise. The cooling bath is removed and the mixture is stirred for 30 minutes. The volatiles are removed in vacuo and ether (75 mL) is added to the residue. The mixture is stirred under N 2 for 30 minutes and the resulting solid is filtered to obtain Compound 9. To a solution of Compound 9 (1.6 g) in CH 2 C1 2 (90 mL) is added tetrakis(triphenylphosphine)palladium (0) (246 mg), under N 2 . The mixture is cooled (-10 to -5°C) and a cooled solution (<-10°C) of sodium ethylhexanoate (708 mg) in THF (45 mL) is added dropwise. The mixture is stirred for approximately 30 minutes, whereupon the resulting slurry is filtered and washed successively with CH 2 C1 2 and acetone, to provide [6R-[6α,7β]]-3-[[[4-(3- Carboxy- 1 -cyclopropyl-6-fluoro- 1 , 4-dihydro-4-oxo-7-quinolinyl)- 1 -piperazinyl]- carbonyloxy]methyl]-8-oxo-7-[(2-thienylacetyl)amino]-5-thia-l-azabicyclo[4.2.0]- oct-2-ene-2-carboxylic Acid, Disodium Salt (Compound 10). aro lg 5 Synthesis of [6R-[6α,7β]]-3-[[[4-[3-Carboxy-l-(l, l-dimethylethyl)-6- fluoro- 1 ,4-dihydro-4-oxo- l,8-napthyridin-7-yl]- 1 -piperazinyl]carbonyloxy]-methyI]- 8-oxo-7-[(2-thienylacetyl)amino]-l-azabicyclo[4.2.0]oct-2-ene-2-carboxylic Acid, Disodium Salt. Oalyl i O. J 7 H Xalyl onr ' κ COχfcH χ ?χ Solid sodium ethoxide (424.5 g) is added in portions (20 min) via a Gooch tube to a vigorously stirred, cold (ice bath) solution of ethyl fluoroacetate (450 g) and ethyl formate (525 g) under argon. The ice bath is removed and the reaction mixture is stirred for 3.5 h at room temperature. Malondiamide (745.5 g) is added in portions over 10 min with the aid of 5.4 L of absolute EtOH to wash in the solid. The mixture is slowly heated to reflux where upon the mixture becomes a thick paste. The reaction mixture is cooled in an ice bath and water (4.23 L) is added over 10 min. followed by addition of cone. HC1 (843 mL), while stirring and cooling. The mixture is filtered and the solid is washed successively with H 2 O and EtOH to give Compound 1. In an argon purged 5-L 3-neck flask is added Compound 1 (300 g) and phosphorus pentachloride (1200 g). The mixture is stirred thoroughly and is slowly heated to 110°C and maintained at 110°C for about 1 h. The mixture is distilled under partial vacuum to remove POCI3. The concentrated residue is mixed with cold water (3L) and stirred. The mixture is filtered and the solid is washed successively with H 2 O (2 x IL) and isopropyl a!cohol-H 2 O (1:1) to give, after vacuum drying, Compound 2. A solution of Compound 2 (200 g) in concentrated sulfuric acid (1.35 L) is heated at 90°C for 1.5 h. The solution is cooled to about 60°C and H 2 O (2.67 L) is slowly added while maintaining the temperature below 95°C. The reaction mixture is heated at 100°C for 3 h and then stored overnight at 5C°. The mixture is filtered, and the solid is air dried to give crude Compound 3. Compound 3 is purified by mixing with 5 L of EtOAc and adding decolorizing carbon (100 g). The mixture is filtered, and the filtrate is concentrated in vacuo to 3 L. The solution is diluted with hexanes (7 L) and further evaporated to 2 L. An additional 4 L of hexanes is added. The solid is collected and washed with hexanes (1 L) to give Compound 3. A mixture of Compound 3 (140 g) and thionyl chloride (250 mL) is stirred and heated at reflux for 2 h. The solution is cooled and evaporated in vacuo. The residue is evaporated further with toluene (3 x 600 mL, freshly filtered through anhydrous Na 2 SO4) to give the crude Compound 4, which is used immediately in the subsequent step. A 2.5M solution of n-butyl lithium (1270 mL) in hexanes is added over 2.5 h to a stirred solution of ethyl hydrogen malonate (197.1 g) in THF (3.4 L) at -50 to - 65°C under an Ar atmosphere. The cooling bath is replaced with warm water to bring the temperature to -5°C. The pasty mixture is recooled in the dry ice-acetone bath, and the crude Compound 4 in THF (250 mL) is added dropwise (1.5 h) while keeping the temperature below -50°C. After the addition is complete, the cooling bath is removed, and the reaction mixture is left to warm to room temperature overnight. The mixture is poured in about 4 equal portions to a rapidly stirred solution of cone. HC1 (270 mL) and H 2 O (2.5 L). The mixture is stirred for about 30 min and the temperature rises to 34°C. The layers are separated, and the aqueous layer is extracted (by stirring) with EtOAc (2 x 2 L). The combined organic material is washed with saturated aqueous NaHCO3 (1.8 L and 2 x 1 L). These aqueous washes are back extracted with EtOAc (800 mL). The combined EtOAc solutions are dried over Na 2 SO4 then concentrated in vacuo to a residue. This material is chromatographed on a 1.4 kg silica gel column eluted with CH 2 C1 . The fractions containing purified product are combined and concentrated in vacuo to give (after cold hexane trituration) Compound 5 as crystals. To a solution of Compound 5 (18.0 g) in THF (360 mL) is added piperazine (22 g). The mixture is refluxed under N 2 until complete and the THF is removed under reduced pressure. The residue is slurried in EtOAc (175 mL), and the excess piperazine is filtered off and rinsed with EtOAc. The EtOAc filtrate is washed with water (2 x 175 mL) and the combined aqueous layers are extracted with EtOAc (100 mL). The combined EtOAc layers are dried (MgSO4) an ^ treated with activated charcoal. The solvents are evaporated in vacuo and the residue is crystallized from isopropyl ether to give Compound 6. To a solution of allyl alcohol (84 g) in toluene (120 mL) is added 4- dimethylaminopyridine (2.2 g), under N 2 . Compound 6 (20 g) is added and the mixture is heated to reflux. Upon completion, the reaction mixture is cooled and saturated ammonium chloride (300 mL) is added, followed by the addition of EtOAc (350 mL). The layers are separated and the EtOAc portion is washed with water (4 x 100 mL) and brine (2 x 75 mL), and dried (MgSO4). Th e solvents are removed in vacuo and the residue is subjected to column chromatography (silica) to provide Compound 7. To a solution of Compound 7 (21 g) in CHCI3 (400 mL) is added a solution of di-t-butylcarbonate (15 mL) in CHCI3 (75 mL), under N 2 . The reaction is stirred for 5 minutes under N 2 at ambient temperature and evaporated in vacuo. Hexanes are added to the residue to give Compound 8. To a solution of Compound 8 (17.8 g) in triethylorthoformate (10.9 mL) is added acetic anhydride (34.8 mL). The mixture is fitted with a Dean-Stark trap and stirred at 130°C for 1.5 hours under N . The volatiles removed in vacuo and the residue is dissolved in CH 2 C1 (65 mL). The solution obtained is cooled to 0°C and tert-butylamine is added (5.8 mL). The reaction is stirred at 0°C for 5 minutes under N 2 , allowed to warm to ambient temperature and stirred for 1 hour. The volatiles are removed in vacuo and the residue obtained is subjected to column chromatography (silica) to provide Compound 9. To a cooled solution of Compound 9 (12 g) in anisole (90 mL) at 5-10°C is added TFA (90 mL). After stirring for 5 minutes under N 2 , the ice bath is removed and the reaction is warmed to ambient temperature. After 2 hours, most of the TFA and some of the anisole is removed in vacuo. The residue is slurried in Et 2 O (300 mL) and filtered. The solid is dissolved in a mixture of CH 2 C1 2 (100 mL) and saturated NaHCO3 (100 mL) and stirred for 10 min. The CH 2 C1 portion is separated, dried (MgSO4), treated with activated charcoal, and evaporated in vacuo. The residue is crystallized with hexane to give Compound 10. To a cooled (-5°C) suspension of (±)-7β-amino-l- methylenedethiacephalosporanic acid (21.5 g) (Compound 11), prepared as described in R. Guthikonda et al., 96 J. Am. Chem. Soc. 7584 (1974), which is incorporated herein by reference, in methanol (44 mL) is added IN NaOH (84.53 mL) over 30 minutes. Additional IN NaOH (84.53 mL) is then added over 8 minutes at 2-5°C. Acetone (58 mL) and NaHCU3 (21.29 g) are added, followed by dropwise addition of 2-thiopheneacetyl chloride (10.4 mL) over 30 minutes at 0- 5°C, while maintaining a pH of 7 by simultaneous addition of NaHCO3- The solution is washed with EtOAc (110 mL) and the layers are separated. The aqueous phase is layered with EtOAc (170 mL) and the resulting mixture is acidified at 0°C with concentrated HC1. The layers are separated and the aqueous phase is extracted with EtOAc (170 mL). The combined EtOAc layers are filtered and the volatiles removed in vacuo to near dryness. The precipitate that results is filtered and dried in in vacuo to provide Compound 12. To a solution of benzophenone hydrazone (11.3 g) in CH 2 C1 2 (58 mL) is added a 1% w/v solution of iodine in CH 2 C1 2 (2.3 mL) and 1,1,3,3- tetramethylguanidine (7.29 g). 3-Chloroperoxybenzoic acid (11 g) is then added in small portions at room temperature. The solvent is removed in vacuo to provide diphenyl diazomethane. A solution of diphenyl diazomethane (10 g) in EtOAc (22 mL) is then added to a cooled (5°C) solution of Compound 12 (9.7 g) in THF (170 mL) and EtOAc (170 mL). The mixture is stirred until completion whereupon it is evaporated to dryness in vacuo. THF (73 mL) is added and the insolubles are filtered off. The filtrate is evaporated in vacuo until crystals begin to form. EtOAc (73 mL) is then added and the mixture is stirred for 1.5 hours at 0-5°C. The resulting solid is filtered to provide Compound 13. Compound 10 (7.1 g) is dissolved in CH 2 C1 2 (160 mL) and activated 4A molecular sieves (1.5 g) are added under N 2 . After stirring for 30 minutes at room temperature, the solution is transferred via canula to a second vessel. The solution is cooled (-15°C) and N,O-bis(trimethylsilyl)acetamide (8.17 mL) is added under N 2 . The mixture is allowed to stir for 15 minutes under N 2 . Concurrent with this procedure, Compound 13 (9.1 g) is dissolved in CH 2 C1 2 (160 mL) in a third vessel and activated 4 A molecular sieves (1.5 g) are added, under N 2 . After stirring for 30 minutes, the solution is transferred via canula to a fourth vessel and N,N- diisopropylethylamine (3.21 mL) is added under N 2 . The solution is stirred for 15 minutes at ambient temperature and cooled to -78°C. In a fifth vessel, to cooled (- 78°C) CH 2 C1 2 (150 mL) is added 20% phosgene in toluene (10.4 mL) under N . The forementioned solution of Compound 13 is added dropwise while maintaining the solution temperature at less than -60°C. The reaction is stirred for 15 minutes and warmed to -15°C to provide Compound 14, which is then reacted in £_ by dropwise addition of the forementioned solution of Compound 10, while maintaining the temperature below -15°C. The reaction is stirred at -15°C under N 2 until complete. The reaction mixture is quenched with water (150 mL), warmed to 0°C and stirred 10 minutes. The organic portion is separated and dried (Na 2 SO4). The volatiles are evaporated in vacuo and the residue is subjected to column chromatography (silica) to give Compound 15. To a solution of Compound 15 (12.1 g) in CH3CN (140 mL) is added N,O- bis(trimethylsilyl)acetamide (9 mL). The reaction mixture is stirred under N 2 at ambient temperature until complete. The reaction is quenched with water (140 mL), and the resulting slurry is filtered and washed with a mixture of water and CH3CN (5:1) giving Compound 16. To a cooled (-15°C) solution of Compound 16 (8.6 g) in anhydrous anisole (80 mL) is added TFA (80 mL), dropwise. The cooling bath is removed and the mixture is stirred for 30 minutes. The volatiles are removed in vacuo and ether (200 mL) is added to the residue. The mixture is stirred under N 2 for 30 minutes and the resulting solid is filtered to obtain Compound 17. To a solution of Compound 17 (6.4 g) in CH 2 C1 2 (340 mL) is added tetrakis(triphenylphosphine)palladium (0) (932 mg), under N 2 . The mixture is cooled (-10 to -5°C) and a cooled solution (<-10°C) of sodium ethylhexanoate (2.68 g) in THF (170 mL) is added dropwise. The mixture is stirred for approximately 30 minutes, whereupon the resulting slurry is filtered and washed successively with CH 2 C1 2 and acetone to provide [6R-[6α,7β]]-3-[[[4-[3-Carboxy- 1 -( 1 , 1 -dimethylethyl)-6-fluoro- 1 ,4-dihydro-4-oxo- 1 ,8-napthyridin-7-yl]- 1 - piperazinyl]carbonyloxy]methyl]-8-oxo-7-[(2-thienylacetyl)amino]-l-azabicyclo- [4.2.0]oct-2-ene-2-carboxylic Acid, Disodium Salt (Compound 18). The following compounds are prepared according to Examples 1 through 5, with substantially similar results. NOT TO BE TAKEN INTO CONSIDERATION FOR THE PURPOSES O F INTERNATIONAL PROCESSIN G NOT TO BE TAKEN INTO CONSIDERATION FOR THE PURPOSES O F INTERNATIONAL PROCESSING NOT TO BE TAKEN INTO CONSIDERATION FOR THE PURPOSES O F I N TERNATIONAL PROCESSING NOT TO BE TAKEN INTO CONSIDERATION FOR THE PURPOSES O F INTERNATIONAL PROCESSING NOT TO BE TAKEN INTO CONSIDERATION FOR THE PURPOSES O F INTERNATIONAL PROCESSING NOT TO BE TAKEN INTO CONSIDERATION FOR THE PURPOSES O F INTERNATIONAL PROCESSING NOT TO BE TAKEN INTO CONSIDERATION FOR THE PURPOSES O F I N TERNATIONAL PROCESSING NOT TO BE TAKEN INTO CONSIDERATION FOR THE PURPOSES O F INTERNATIONAL PROCESSING NOT TO BE TAKEN INTO CONSIDERATION FOR THE PURPOSES O F INTERNATIONAL PROCESSING NOT TO BE TAKEN INTO CONSIDERATION FOR THE PURPOSES O F INTERNATIONAL PROCESSING NOT TO BE TAKEN INTO CONSIDERATION FOR THE PURPOSES OF INTERNATIONAL PROCESSING NOT TO BE TAKEN INTO CONSIDERATION FOR THE PURPOSES O F INTERNATIONAL PROCESSING NOT TO BE TAKEN INTO CONSIDERATION FOR THE PURPOSES O F INTERNATIONAL PROCESSING NOT TO BE TAKEN INTO CONSIDERATION FOR THE PURPOSES O F INTERNATIONAL PROCESSING to in ro O in ro o in in Example 6 Synthesis of [5R-[5α,6α(R*)]]-3-[[4-(3-Carboxy-l-cyclopropyl-6-fluoro- 1 ,4-d-hydro-4-oxo-7-quinolinyl)- 1 -piperazinyl]methyl]-6-( 1 -hydroxyethyl)-7-oxo-4- thia-l-azabicyclo[3.2.0]hept-2-ene-2-carboxylic Acid, Disodium Salt. To a cooled (0°C) solution of Compound 1 (4.2 g), prepared according to U. S. Patent 4,631,150, Battistini et al., issued December 23, 1986 (incorporated by reference herein), in CH C1 2 (75 mL) is added methanesulfonyl chloride (1.05 mL), dropwise, followed by the dropwise addition of triethylamine (1.43 mL), under N 2 . The mixture is stirred at 0°C for 40 minutes whereupon a 5% solution of NaHCO3 (60 mL) is added. After stirring at 0°C for 10 minutes, the organic layer is separated and washed with dilute brine (2 x 30 mL). The organic portion is dried (Na 2 SO_j) and the volatiles are removed in vacuo to provide Compound 2. To a solution of Compound 2 (4.3 g) in DMSO (40 mL) is slowly added a solution of CaBr 2 (1.89 g) in DMSO (38 mL), under N 2 . The reaction mixture is stirred for 3 hours, whereupon the mixture is diluted with EtOAc (175 mL) and poured over an ice/water mixture (175 mL). The mixture is stirred for 5 minutes whereupon the organic layer is separated and the aqueous layer is extracted with EtOAc (2 x 40 mL). The organic portion is washed with brine (2 x 60 mL) and dried (Na 2 SO4). The solvents are removed in vacuo to provide Compound 3. To a solution of Compound 4 (1.9 g), prepared in the same manner as Compound 5 in Example 2, in a 1:1 mixture of DMF and CH 2 C1 2 (60 mL) is slowly added a solution of Compound 3 (2.32 g) in a 1:1 mixture of DMF and CH 2 C1 2 (30 mL), under N 2 . N,N-Diisopropylethylamine (0.98 mL) is added dropwise and the reaction is allowed to stir at ambient temperature until complete. Upon completion, methanol (15 mL) is added and the mixture is stirred for 15 minutes. The volatiles are removed in vacuo until a small amount of DMF remains whereupon methanol (150 mL) is added. The mixture is stirred for 5 minutes and filtered to obtain Compound 5. To a solution of Compound 5 (2.2 g) in CH3CN (35 mL) is added N,O- bis(trimethylsilyl)acetamide (2.17 mL). The reaction mixture is stirred under N 2 at ambient temperature until complete. The reaction is quenched with water (30 mL), and the resulting slurry is filtered and washed with a mixture of water and CH3CN (5: 1) giving Compound 6. To a solution of Compound 6 (1.7 g) in THF (15 mL) and acetic acid (1.18 mL) is added tetra-n-butyl ammonium fluoride (5.76 mL of a IM solution in THF), under N 2 . The mixture is stirred at ambient temperature overnight and, upon completion, is diluted with ether (25 mL). The solution is stirred for a half-hour, allowing the product to crystallize. The slurry is filtered through troyfelt and the solid residue is washed with ether to obtain Compound 7. To a solution of Compound 7 (1.32 g) in CH 2 C1 2 (80 mL) is added tetrakis(triphenylphosphine)palladium (0) (227 mg), under N 2 . The mixture is cooled (-10 to -5°C) and a cooled solution (<-10°C) of sodium ethylhexanoate (643 mg) in THF (40 mL) is added dropwise. The mixture is stirred for approximately 30 minutes, whereupon the resulting slurry is filtered and washed successively with CH 2 C1 2 and acetone, to obtain [5R-[5α,6α(R*)]]-3-[[4-(3- Carboxy- 1 -cyclopropyl-6-fluoro- 1 ,4-dihydro-4-oxo-7-quinolinyl)- 1 -piperazinyl]- methyl]-6-(l-hydroxyethyl)-7-oxo-4-thia-l-azabicyclo[3.2.0]hept-2-ene-2- carboxylic Acid, Disodium Salt (Compound 8). Example 7 Synthesis of [6R-[6α,7β]]-3-[[4-(3-Carboxy-l-cyclopropyl-6,8-difluoro- 1 ,4-dihydro-4-oxo-7-quinolinyl)- 1 -piperazinyl]]methyl]-8-oxo-7-[2- (phenoxyacetyl)amino]-l-azabicyclo[4.2.0]oct-2-ene-2-carboxyIic Acid, Disodium Salt. To a cooled solution of potassium ethyl malonate (20 g) (Compound 1) in water (12.5 mL) is added 12N HC1 (10.1 mL) at a rate which allows the temperature to be maintained between 5-10°C. Once the addition is complete, the KCl formed is filtered and rinsed with ether (40 mL). The ethereal portion of the filtrate is separated and the aqueous portion is extracted with Et 2 O (3 x 15 mL). The combined ether layers are dried (MgSU4) and the solvent removed in vacuo to give Compound 2. To a cooled (-30°C) solution of 2,2-biquinoline (7.9 mg) and Compound 2 (8.2 g) in THF (95 mL), under N 2 , is added 2.5 M n-BuLi in hexane until a pink color persists at -5°C (approximately 50 mL). The mixture is cooled to -50°C and a solution of 2,3,4,5-tetrafluorobenzoyl chloride (4.0 mL) (Compound 3) in THF (45 mL) is added dropwise so that the temperature is maintained at -50°C. After 30 minutes, the mixture is allowed to warm to ambient temperature and is quenched with IM HC1 (130 mL) at a rate which allows the temperature to be maintained at about 30°C. The organic layer is separated and the aqueous layer is extracted with Et 2 O (4 x 40 mL). The combined organic layers are washed with 10% aqueous NaHCO3 (3 x 100 mL) and brine (3 x 100 mL). The organic portion is dried (MgSO4) and treated with activated charcoal. After removal of the solvents in vacuo. the residue obtained is subjected to column chromatography (silica) to give a mixture of Compound 4 and its enol ether which is used directly in the next step. To a solution of Compound 4 (12.3 g) in THF (240 mL) is added piperazine (16 g). The reaction is heated at reflux, under N , until completion, whereupon the volatiles are removed in vacuo. The residue obtained is dissolved in EtOAc (150 mL), washed with water (4 x 50 mL), and dried (MgSO4). The solvent is removed i vacuo and the residue obtained is subjected to column chromatography (silica) to give a mixture of Compound 5 and its enol ether which is used directly in the next step. To a solution of allyl alcohol (24 mL) in toluene (70 mL) is added 4- diπiethylaminopyridine (1.3 g), under N 2 . Compound 5 (11.9 g) is added and the mixture is heated to reflux. Upon completion, the reaction mixture is cooled and saturated ammonium chloride (175 mL) is added, followed by the addition of EtOAc (200 mL). The layers are separated and the EtOAc portion is washed with water (4 x 60 mL) and brine (2 x 45 mL), and dried (MgSO4). The solvents are removed in vacuo and the residue is subjected to column chromatography (silica) to provide a mixture of Compound 6 and its enol ether which is used directly in the next step. To a solution of Compound 6 (10.1 g) in CHCI3 (150 mL) is added a solution of di-t-butylcarbonate (7.5 mL) in CHCI3 (25 mL). The reaction is stirred for 5 minutes under N 2 at ambient temperature and the volatiles are removed in vacuo. Hexanes are added to give Compound 7. To a solution of Compound 7 (10.6 g) in toluene (40 mL) is added dimethylformamide dimethylacetal (4.9 mL). The reaction is heated at reflux under N for 2 hours and the volatiles are removed in vacuo to give crude Compound 8. The crude compound is carried directly to the next step by dissolving in EtOH (47 mL) and adding cyclopropyl amine (2.65 mL). The mixture is stirred for 2 hours at ambient temperature under N 2 . The volatiles are removed in vacuo and the residue is crystallized from 20% EtOAc/hexanes to give Compound 9. To a cooled solution of Compound 9 (9.1 g) in anisole (70 mL) at 5-10°C is added TFA (70 mL). After stirring for 5 minutes under N 2 , the ice bath is removed and the reaction is warmed to ambient temperature. After 2 hours, most of the TFA and some of the anisole is removed in vacuo. The residue is slurried in Et 2 O (250 mL) and filtered. The solid is dissolved in a mixture of CH 2 C1 2 (100 mL) and saturated NaHCO3 (100 mL) and stirred for 10 min. The CH 2 C1 2 portion is separated, dried (MgSO4), and treated with activated charcoal. The volatiles are removed in vacuo and the residue obtained is crystallized with hexane to give Compound 10. To a cooled (0°C) solution of allyl (7S, 6R)-7-(phenoxyacetamido)-3- (acetoxymethyl)-l-carba-l-dethia-3-cephem-4-carboxylate (4.2 g)(Compound 11), prepared as described in L. Blaszczak et al., 33 J. Am. Chem. Soc. 1656 (1990), in CH 2 C1 2 (30 mL) is added iodotrimethylsilane (2.07 mL). The mixture is stirred at 0°C for 0.5 hour and then at ambient temperature for 1 hour. The volatiles are removed in vacuo to provide crude Compound 12 which is used directly in the next step. In a second vessel, to a solution of Compound 10 (4 g) in DMF (30 mL) and CH 2 C1 2 (30 mL) is added activated molecular sieves (1 g), under N 2 . After stirring for 30 minutes, the solution is transferred to a third vessel and diisopropylethylamine (1.72 mL) is added, under N 2 . The mixture is cooled (- 40°C) and, after stirring for 0.5 hour, a solution of the forementioned crude Compound 12 in DMF (30 mL) and CH 2 C1 2 (30 mL) is slowly added. The mixture • L OD is stirred for 1 hour at -40°C and then stirred at 0°C for 1 hour and allowed to warm to ambient temperature. Upon completion, the reaction is diluted with CH 2 C1 2 (100 mL) and washed with IM HC1 (2 x 80 mL) and brine (2 x 80 mL). The organic portion is separated and the solvents are removed in vacuo to provide a residue that is subjected to column chromatography (silica) to provide Compound 13. To a solution of Compound 13 (4.1 g) in CH3CN (60 mL) is added N,O- bis(trimethylsilyl)acetamide (3.9 mL). The reaction mixture is stirred under N 2 at ambient temperature until complete. The reaction is quenched with water (60 mL), and the resulting slurry is filtered and washed with a mixture of water and CH3CN (5:1) to provide Compound 14. To a solution of Compound 14 (3.8 g) in CH 2 C1 2 (210 mL) is added tetrakis(triphenylphosphine)palladium (0) (580 mg), under N 2 . The mixture is cooled (-10 to -5°C) and a cooled solution (<-10°C) of sodium ethylhexanoate (1.67 mg) in THF (105 mL) is added dropwise. The mixture is stirred for approximately 30 minutes, whereupon the resulting slurry is filtered and washed successively with CH 2 C1 2 and acetone, to obtain [6R-[6α,7β]]-3-[[4-(3-Carboxy- 1 -cyclopropyl-6, 8-difluoro- 1 ,4-dihydro-4-oxo-7-quinolinyl)- 1 -piperazinyl]]- methyl]-8-oxo-7-[2-(phenoxyacetyl)amino]- 1 -azabicyclo[4.2.0]oct-2-ene-2- carboxylic Acid, Disodium Salt (Compound 15). The following compounds are prepared according to Examples 6 and 7, with substantially similar results. O O ■ S f ^ \ o lo 30 35 > \O* ιo& HO HI to in o ro in ro o tτι to in ro o ro in O in I IH Example 8 Synthesis of [4S-[3(R*),4α,5β,6β(S*)]]-3-[[[l-[3-Carboxy-l-(2,4- difluorophenyl)-6-fluoro- 1 ,4-dihydro-4-oxo- 1 , 8-napthyridin-7-yl]-3 -pyrroli- dinyl]amino]methyl]-6-(l-hydroxyethyl)-4-methyl-7-oxo-l-azabicyclo-[3.2.0]hept- 2-ene-2-carboxylic Acid, Disodium salt { ( (> To a solution of Compound 2 (12.5 g) (prepared in the same manner as Compound 5 in Example 5 above) is added (S)-(-)-3-(tert- butoxycarbonylamino)pyrrolidine (33.25 g) (Compound 1). The mixture is refluxed under N2 until complete and the THF is removed under reduced pressure. The residue is slurried in EtOAc (125 mL), and the excess pyrrolidine is filtered off and rinsed with EtOAc. The EtOAc filtrate is washed with water (2 x 125 mL) and the combined aqueous layers are extracted with EtOAc (70 mL). The combined EtOAc layers are dried (MgSO-j) and treated with activated charcoal. The solvents are evaporated in vacuo and the residue is crystallized from isopropyl ether to give Compound 3. To a solution of allyl alcohol (17 mL) in toluene (75 mL) is added 4- dimethylaminopyridine (0.95 g), under N2. Compound 3 (13.1 g) is added and the mixture is heated to reflux. Upon completion, the reaction mixture is cooled and saturated ammonium chloride (125 mL) is added, followed by the addition of EtOAc (150 mL). The layers are separated and the EtOAc portion is washed with water (4 x 50 mL) and brine (2 x 40 mL), and dried (MgSO4). The solvents are removed in vacuo and the residue is subjected to column chromatography (silica) to provide Compound 4. To a solution of Compound 4 (8.65 g) in triethylorthoformate (4.6 mL) is added acetic anhydride (14.6 mL). The mixture is fitted with a Dean-Stark trap and stirred at 130°C for 1.5 hours under N2. The volatiles removed in vacuo and the I I " ? residue is dissolved in CH2C-2 (30 mL). The solution obtained is cooled to 0°C and 2,4-difluoroaniline is added (2.4 mL). The reaction is stirred at 0°C for 5 minutes under N2, allowed to warm to ambient temperature and stirred for 1 hour. The volatiles are removed in vacuo and the residue obtained is subjected to column chromatography (silica) to provide Compound 5. To a cooled solution of Compound 5 (6.1 g) in anisole (40 mL) at 5-10°C is added TFA (40 mL). After stirring for 5 minutes under N2, the ice bath is removed and the reaction is warmed to ambient temperature. After 2 hours, most of the TFA and some of the anisole is removed in vacuo. The residue is slurried in Et2θ (125 mL) and filtered. The solid is dissolved in a mixture of CH2CI2 (75 mL) and saturated NaHCO3 ( 50 ™L *~- stirred for 10 min. The CH2CI2 portion is separated, dried (MgSO.}), treated with activated charcoal, and evaporated in vacuo. The residue is crystallized with hexane to give Compound 6. To a cooled (-78 °C) solution of Compound 7 (3.56 g), prepared as described in Schmitt et al., J. Antibiot., 4_L 780-787, 1988 (incorporated by reference herein), in CH2CI2 (14 mL) is added diisopropylethylamine (1.54 mL), followed by the dropwise addition of trifluoroacetic anhydride (1.49 mL). The reaction is stirred at -78°C for 1.5 hours to provide Compound 8 which is reacted ώ Si u by the dropwise addition of a solution of Compound 6 (4.9 g) and diisopropylethylamine (1.54 mL) in CH2CI2 (18 mL). The reaction is stirred at -78°C until completion, whereupon the cooling bath is removed and water (2 mL) is slowly added. When the temperature reaches -40°C, more water (40 mL) and CH2CI2 (150 mL) is added. The mixture is quickly separated and the organic portion is quickly washed successively with cold water (2 x 50 mL), 10% N-1HCO3 (3 x 50 mL) and water (50 mL). The organic portion is dried (Na2SO4) and the volatiles are removed m vacuo. The residue obtained is subjected to column chromatography (silica) to obtain Compound 9. To a solution of Compound 9 (4.1 g) in CH3CN (55 mL) is added N,O- bis(trimethylsilyl)acetamide (3.35 mL). The reaction mixture is stirred under N2 at ambient temperature until complete. The reaction is quenched with water (55 mL), and the resulting slurry is filtered and washed with a mixture of water and CH3CN (5: 1) giving Compound 10. To a solution of Compound 10 (3.3 g) in CH2CI2 (160 mL) is added tetrakis(triphenylphosphine)palladium (0) (433 mg), under N2. The mixture is cooled (-10 to - 5°C) and a cooled solution (<-10°C) of sodium ethylhexanoate (1.25 g) in THF (80 mL) is added dropwise. The mixture is stirred for approximately 30 minutes, whereupon the resulting slurry is filtered and washed successively with CH2CI2 and acetone to provide Compound 11. Example 9 Synthesis of [6R-[3(S*),6ot,7β]]-3-[[[l-[3-Carboxy-l-(l,l-dimethylethyl)- 6-fluoro- 1 ,4-dihydro-4-oxo- 1 , 8-n^thyridm-7-yl]-3-py-τo dinyl]amino]methyl]-8- oxo-7-[(2-thienylacetyl)an-u-rio]-5-thia-l-azabicyclo[4.2.0]oct-2-ene-2-carboxylic Acid To a solution of 2-(trimethylsilyl)ethanol (33 mL) in toluene (80 mL) is added 4-dimethylaminopyridine (0.82 g), under N2- Compound 1 (11.4 g) (prepared in the same manner as Compound 3 in Example 8) is added and the mixture is heated to reflux. Upon completion, the reaction mixture is cooled and saturated ammonium chloride (125 mL) is added, followed by the addition of EtOAc (150 mL). The layers are separated and the EtOAc portion is washed with water (4 x 50 mL) and brine (2 x 40 mL), and dried (MgSO ). The solvents are removed in vacuo and the residue is subjected to column chromatography (silica) to provide Compound 2. To a solution of Compound 2 (10.2 g) in triethylorthoformate (4.8 mL) is added acetic anhydride (15.4 mL). The mixture is fitted with a Dean-Stark trap and stirred at 130°C for 1.5 hours under N2. The volatiles removed in vacuo and the residue is dissolved in CH2CI2 (35 mL). The solution obtained is cooled to 0°C and tert-butylamine is added (2.6 mL). The reaction is stirred at 0°C for 5 minutes under N2, allowed to warm to ambient temperature and stirred for 1 hour. The volatiles are removed in vacuo and the residue obtained is subjected to column chromatography (silica) to provide Compound 3. To a cooled solution of Compound 3 (9.8 g) in anisole (60 mL) at 5-10°C is added TFA (60 mL). After stirring for 5 minutes under N2, the ice bath is removed and the reaction is warmed to ambient temperature. After 2 hours, most of the TFA and some of the anisole is removed i vacuo. The residue is slurried in Et2θ (175 mL) and filtered. The solid is dissolved in a mixture of CH2CI2 (110 mL) and saturated NaHCO3 ( 75 ""L) ^ stirred for 10 min. The CH2CI2 portion is separated, dried (MgSO4), treated with activated charcoal, and evaporated in vacuo. The residue is crystallized with hexane to give Compound 4. To a cooled (0°C) solution of tert-butyl 7-aminocephalosporanate (30 g) (Compound 5), prepared as described in R J. Stedman, 9 J. Med. Chem. 444 (1966), which is incorporated by reference herein, in THF (1.5L) is added a solution of sodium bicarbonate (12.93 g) in water (1.5 L). To this mixture is added a solution of 2-thiopheneacetyl chloride (13.1 mL). The ice bath is removed and the reaction is stirred at room temperature until complete. The volatiles are removed m vacuo until an aqueous mixture is obtained. This mixture is extracted with EtOAc (4 x 500 mL) and the combined EtOAc layers are dried (MgSO4). The EtOAc is removed in vacuo until approximately 200 mL of EtOAc remains. Hexane is added to this solution, until a precipitate begins to form. The mixture is then cooled to -20°C and held at this temperature for 16 hours. The resulting slurry is filtered and washed with hexanes to provide Compound 6. To a solution of Compound 6 (10 g) in CH2CI2 (150 mL) is slowly added iodotrimethylsilane (3.5 mL), under N2. After stirring for 30 minutes, additional iodotrimethylsilane (1.85 mL) is added and stirring is continued for 30 minutes more. The reaction is quenched by slowly adding a cold 5% solution of sodium thiosulfate (50 mL). The CH2CI2 portion is washed with a cold 5% solution of sodium thiosulfate (50 mL), a cold solution of 5% NaHCO3 (50 mL), cold water (50 mL) and brine (2 x 50 mL). The CH2CI2 solution is dried and the volatiles are removed in vacuo until about one third of the solvent remains. The resulting solution is cooled and product crystallized by the addition of hexanes to provide Compound 7. To a cooled (-40°C) solution of Compound 4 (2.26 g) in DMF (13 mL) and CH2CI2 (13 mL) is added diisopropylethylamine (0.71 mL) is added, under N2. After stirring for 30 minutes, a solution of Compound 7 (2.1 g) in DMF (13 mL) and CH2CI2 (13 mL) is slowly added. The mixture is stirred for 1 hour at -40°C and then stirred at 0°C for 1 hour, and allowed to warm to ambient temperature. Upon completion, the reaction is diluted with CH2CI2 (100 mL) and washed with cold IM HC1 (2 x 80 mL) and cold brine (2 x 80 mL). The organic portion is separated and the solvents are removed in vacuo to provide a residue that is subjected to column chromatography (silica) to provide Compound 8. To a solution of Compound 8 (3.45 g) in CH3CN (40 mL) is added N,O- bis(trimethylsilyl)acetamide (3.56 mL). The reaction mixture is stirred under N2 at ambient temperature until complete. The reaction is quenched with water (40 mL), and the resulting slurry is filtered and washed with a mixture of water and CH3CN (5: 1) to provide Compound 9. To a cooled (0°C) solution of Compound 9 (2.7 g) in THF (50 mL) is added a solution of tetra-n-butyl ammonium fluoride (10.4 mL of a IM solution in THF), under N2. The mixture is stirred at 0°C for 30 minutes and then warmed to ambient temperature. Upon completion, hexamethyldisiloxane (2.27 mL) is added and the mixture is stirred for an additional 30 minutes. The volatiles are removed in vacuo to provide a residue which is crystallized by the addition of ether to provide Compound 10. To a cooled (-15°C) solution of Compound 10 (1.6 g) and triethylsilane (1 22 mL) in CH2CI2 (30 mL) is slowly added trifluoroacetic acid (33 mL), under N2. After 30 minutes at -15°C, the mixture is allowed to warm to ambient temperature. Upon completion, the mixture is cooled to 0°C and is crystallized by the addition of cold ether to provide Compound 11. The following compounds are prepared according to Examples 8 and 9, with substantially similar results. 35 35 ■ H ∑ N^ ^NH O O OH A 13& The following are examples of the novel intermediates of the present in invention. While illustrated in the acid form, those skilled in the art will recognize that the intermediates are preferably in a protected form. \1 ( * ^ 35 <M3 \G lfc'i. 164 All publications mentioned hereinabove are hereby incorporated in their entirety by reference. It is understood that the examples and embodiments described herein are for illustrative purposes only and that various modifications or changes in light thereof will be suggested to one skilled in the an and are to be included in the spirit and purview of this application and scope of the appended claims.

Claims: WHAT IS CLAIMED IS: 1 A process for making a compound of the formula (Q - L1) - L - (L2 - B) the method comprising the steps of: (1) coupling a compound having a structure according to Formula (III) characterized in that (A) (1) A 1 is N or C(R 7 ); where (a) R 7 is hydrogen, hydroxy, alkoxy, nitro, cyano, halogen, alkyl, or -N(R^)(R^), and (b) R8 and R 9 are, independently, hydrogen, alkyl, alkenyl, a carbocyclic ring, or a heterocyclic ring; or R° and R" together comprise a heterocyclic ring including the nitrogen to which they are bonded; (2) A- is N or C(R2); where R- is hydrogen or halogen; (3) A^ is N or C(R^); where R^ is hydrogen; (4) R! is hydrogen, alkyl, a carbocyclic ring, a heterocyclic ring, alkoxy, hydroxy, alkenyl, arylalkyl, or -N(R 8 )(R 9 ); (5) R- is hydrogen, halogen, alkyl, a carbocyclic ring, or a heterocyclic ring; (6) R is hydroxy; (7) R6 is hydrogen, halogen, nitro or -N(R^)(R 9 ); and (8) X is a leaving group (B) and ( 1 ) when A- is C(R2), R2 and R 3 may together comprise -O-(CH2)n- 1 -, where n is from 1 to 4; (2) when A 3 is C(R 5 ), R 4 and R 5 may together comprise a heterocyclic ring; and (3) when A* is C(R 7 ), R 7 and R 3 may together comprise a heterocyclic ring including A^ and the carbon atom to which R 3 is bonded; or a protected form, salt, ester, or solvate thereof; with a lactam-containing compound having a structure according to Formula (II), to form an intermediate compound; and (2) cyclizing the intermediate compound by reaction with an organosilicon compound to give a compound of the formula (Q - i ) - L - (L^ - B), characterized in that (I) Q has a structure according to Formula (I) wherein (A) (1) A 1 is N or C(R 7 ); where (a) R 7 is hydrogen, hydroxy, alkoxy, nitro, cyano, halogen, alkyl, or -N(R 8 )(R 9 ), and (b) R 8 and R 9 are, independently, R a where R 8a is hydrogen, alkyl, alkenyl, a carbocyclic ring, or a heterocyclic ring; or R 8 and R 9 together comprise a heterocyclic ring including the nitrogen to which they are bonded; (2) A- is N or C(R^); where R- is hydrogen or halogen; (3) A 3 is N or C(R 5 ); where R 5 is hydrogen; (4) R! is hydrogen, alkyl, a carbocyclic ring, a heterocyclic ring, alkoxy, hydroxy, alkenyl, arylalkyl, or -N(R 8 )(R 9 ); (5) R J is hydrogen, halogen, alkyl, a carbocyclic ring, or a heterocyclic ring; (6) R 4 is hydroxy; and (7) R 6 is hydrogen, halogen, nitro or -N(R 8 )(R 9 ); (B) and (1) when A- is C(R2), R- and R 3 may together comprise -O-(CH2) n -O-, where n is from 1 to 4; (2) when A 3 is C(R^), R 4 and R^ may together comprise a heterocyclic ring; and (3) when A' is C(R 7 ), R 7 and R 3 may together comprise a heterocyclic ring including A^ and the carbon atom to which R 3 is bonded; (C) and provided that one of R\, R 3 , or R^ is a covalent bond to Ll; (II) B has a structure according to Formula (II): characterized in that (A) RIO is hydrogen, halogen, alkyl, alkenyl, heteroalkyl, a carbocyclic ring, a heterocyclic ring, R 8 -O-, R 8 CH=N-, (R 8 )(R 9 )N-, R 17 -C(=CHR 20 )-C(=O)NH-, R 17 -C(=NO- R 19 )-C(=O)NH-, or R 18 -(CH 2 ) m -C(=O)NH-; where (1) m is an integer from 0 to 9; (2) Rl7 is hydrogen, alkyl, alkenyl, heteroalkyl, heteroalkenyl, a carbocyclic ring, or a heterocyclic ring; (3) R 18 is R 17 , -Y 1 , or -CH(Y 2 )(R 17 ); ( 1 (4) R! 9 is R 17 , arylalkyl , heteroarylalkyl , -C(R 2 2)(R23). COOH, -C(=O)O-Rl 7 , or -C(=O)NH-Rl 7 , where R and R2 are, independently, R^ 7 or together comprise a carbocyclic ring or a heterocyclic ring including the carbon atom to which R22 an d R23 are bonded; (5) R20 is Rl9 halogen, -Y 1 , or -CH(γ2)(Rl 7 ) ; (6) γl is -C(=O)OR21, -C(=O)R21, -N(R 4 )R21, -S(O) p R 29 , or -OR2 9 ; and Y 2 is γl or -OH, -SH, or -SO 3 H; (a) p is an integer from 0 to 2; (b) R24 is hydrogen; alkyl; alkenyl; heteroalkyl; heteroalkenyl; a carbocyclic ring; a heterocyclic ring; -SO3H; -C(=O)R 25 ; or, when R 18 is -CH(N(R 2 4)R21 )(R17) R 24 may comprise a moiety bonded to R^l to form a heterocyclic ring; and (c) R25 is Rl 7 , NH(R 17 ), N(R 17 )(R26), O(R26), or S(R26) ; where R 2 ^ . s alkyl, alkenyl, a carbocyclic ring, a heterocyclic ring, or when R 25 is -N(R 17 )(R 2 6), R26 may be a moiety bonded to R^ to form a heterocyclic ring; and (7) R21 is R2 or hydrogen; where R 9 is alkyl; alkenyl; arylalkyl; heteroalkyl; heteroalkenyl; heteroarylalkyl; a carbocyclic ring; a heterocyclic ring; or, when Y is - N(R24)R21 and R 1 is R 29 , R21 and R 24 may together comprise a heterocyclic ring including the nitrogen atom to which R 4 is bonded; (B) R- - is hydrogen, halogen, alkoxy, or R2 C(=O)NH-, where R2 7 is hydrogen or alkyl; (C) bond "a" is a single bond or is nil; and bond "b" is a single bond, a double bond, or is nil; except bond "a" and bond "b" are not both nil; (D) R 1 2 is -C(R 8 )-, or -CH 2 -R 28 -; where R 28 is -C(R 8 ), -O-, or -N-, and R2 is directly bonded to N" in Formula (II) to form a 5-membered ring; except, if bond "a" is nil, then R*2 is (1) -C^XX 1 )-, where (a) X 1 is -R21 ; -OR 30 ; -S(O) r R 30 , where r is an integer from 0 to 2; -OC(=O)R 30 ; or -N(R 30 )R 3 l ; and (b) R 30 and R 3 1 are, independently, alkyl, alkenyl, a carbocyclic ring or a heterocyclic ring; or R 30 and R 3 * together comprise a heterocyclic ring including the nitrogen atom to which R 30 and R 3 ■ are bonded; or (2) -CH 2 -R 32 -; where R 32 is -C(R 8 )(R 2 1), -O-, or -NR 8 , and R 32 is directly bonded to N" in Formula (II) to form a 5-membered ring; (E) (1) if bond "b" is a single bond, R 13 is -CH(R 33 ); or, -C(O)NHSO 2 -, if bond "a" is nil; or -C*(R 33 )- if ; Rl4 contains a R 3 ^ moiety; where R 33 is hydrogen or COOR 46 where R 46 is hydrogen, alkyl or alkenyl, and C* is linked to R 3 ^ to form a 3- membered ring; (2) if bond "b" is a double bond, R 13 is -C(R 33 )=; or (3) if bond "b" is nil, R 13 is hydrogen, -SO 3 H, -PO(OR 34 )OH, -C(O)NHSO 2 N(R 34 )(R35) I -OSO3H, -CH(R 35 )COOH, or -OCH(R 3 )-COOH; where R 3 is hydrogen, alkyl, alkenyl, a carbocyclic ring, or a heterocyclic ring; and R ^ is hydrogen, alkyl, alkenyl, or -NHR 8 ; or, if R 13 is -C(O)NH- SO 2 N-(R 3 4)(R 3 5), R34 and R 35 may together comprise a heterocyclic ring including the nitrogen to which R 34 and R 3 ^ are bonded; and (F) (1) if bond "a" or bond "b" is nil, then R 14 is a covalent bond; (2) if bond "a" and "b" are single bonds, R 14 is -VV- C"=C(R 8a )-R 37 -, or -W-C"(R 36 )-R 37 -; or (3) if bond "a" is a single bond and bond "b" is a double bond, R 14 is -C(R 8 )(R 38 )-W-C"'-R 37 -; -W-C(R 8 )- (R 38 )-C"'-R 37 -; or -W-C' M -R 37 -; (4) where (a) W is O, S(O) s , where s is an integer from 0 to 2, or C(R 3 ), where R 38 is hydrogen, alkyl or alkoxy, (b) R 36 is hydrogen, alkyl, alkenyl, -COOH, or, if R 13 is -C*(R 33 ), R 36 may be linked to C* to form a 3-membered carbocyclic ring, (c) R 37 is covalent bond, alkyl, alkenyl, a carbocyclic ring, or a heterocyclic ring, and (d) C" is directly bonded to R 13 to form a 5- or 6-membered ring, and (III) (A) L is -C(=Z)-, -S(O) v -, -N(R 44 )-, -N + (R 44 )(R 5 , -N(R 44 )-N(R 44 )-, -O-, =N-, or a covalent bond, and L is bonded to L 3 and L 4 , where (1) Z is O, S, or + N(H) 2 , (2) v is 0, 1 or 2, (3) R 44 is hydrogen, substituted or unsubstituted lower alkyl, aryl, acyl, hydroxy, alkoxy, aryloxy, or acyloxy, and (4) R 4 * is hydrogen, unsubstituted or substituted lower alkyl, or substituted or unsubstituted aryl, (B) L - is L 3 or R 15 L 3 ; where (1) when L is -C(=Z)-, L 3 is a covalent bond, oxygen, sulfur, or nitrogen, and when L is other than -C(=Z)-, L 3 is a covalent bond, (2) R!5 is alkyl, alkenyl, heteroalkyl, a heterocyclic ring, a carbocyclic ring, or R^ together with L 3 is a heteroalkyl or a heterocyclic ring, and (3) L^ is bonded to Q at the point of attachment of R^, R 3 or R^, whichever is a covalent bond, (C) L 2 is L 4 , -X 2 t -R 39 -L 4 , or -X 3 t -R 39 -L 4 , where (1) when L is -C(=Z)-, L 4 is a covalent bond, oxygen, sulfur, or nitrogen, and when L is other than -C(=Z)-, L 4 is a covalent bond, (2) χ2 is oxygen, or S(O) v , where v is 0, 1, or 2, (3) X 3 is nitrogen, -N(R 40 )-, -N + (R 41 )(R 42 )-, or R 43 - N(R41), and is linked to R^ 4 by a single or double bond, or, if R^ 4 j s covalent bond, X 3 is linked to B by a single or double bond, where (a) R40 is R 8 ; -OR 8 ; or -C(=O)R 8 ; (b) R4 ' and R 4 2 are, independently, hydrogen; alkyl; alkenyl; carbocyclic rings; heterocyclic rings; or, if R 6 is R 16 X, then R 4 1 an d R 4 2 together with "Q" may comprise a heterocyclic ring as R^; (c) R4 is N(R41), oxygen or sulfur; (4) t is O or l; (5) R 39 is alkyl, alkenyl, heteroalkyl, heteroalkenyl, a carbocyclic ring, or a heterocyclic ring; and (6) (a) if bond "a" or bond "b" is nil, then L- is bonded directly to R*2 0 r R^ 3 ; or (b) if bond "a" and bond "b" are not nil, then L 2 is bonded to R^ 4; (D) provided that if L-, L- and R 37 are each a covalent bond, then L cannot be a covalent bond; or a protected form, salt, pharmaceutically-acceptable salt, biohydrolyzable ester, or solvate thereof. 2. The process according to Claim 1, characterized in that the coupling step is carried out in a halocarbon solvent, an ether solvent, an aromatic solvent, a dialkylamide solvent, or a mixture thereof; preferably the solvent is methylene chloride, chloroform, dichloroethane, diethyl ether, tetrahydrofuran, benzene, toluene; N,N-dimethylformamide; or a mixture thereof. 3. The process according to Claim 1 , characterized in that the coupling step is performed at a temperature from about -78°C to about 50°C, preferably at a temperature of from about -50°C to about 25°C. 4. The process according to Claim 1, characterized in that an organosilicon compound is reacted with a compound of Formula (III) prior to the coupling step; and the coupling step is performed at a temperature of less than about -15°C; preferably at a temperature of from about -78°C to about -15°C. 5. The process according to Claim 1, characterized in that R* 4 is -W- C"'-R 37 - or -W-C(R 8 )(R 38 )-C"-R 37 -; wherein preferably W is S(O) s , where s is 0; or W is C(R 38 ). 6. The process according to Claim 1, characterized in that A^ is nitrogen. A 2 is C(R 2 ), and A 3 is C(R 5 ), or, preferably, A 1 is C(R 7 ), A 2 is C(R 2 ), and A 3 is C(R 5 ) 7. The process of Claim 6, characterized in that R- is alkyl, aryl, cycloalkyl, or alkylamino; R 7 is hydrogen or halogen; and R 3 is a heterocyclic ring, preferably a substituted or unsubstituted pyrrolidine or a substituted or unsubstituted piperazine. 8. The process according to Claim 1, characterized in that R 3 is a covalent bond to L* or R > is a covalent bond to L* . 9. The process according to Claim 1, characterized in that (a) L is -C(=Z)-, where Z is O; and wherein L 3 is nitrogen; or (b) L is -N(R 4 -, where R44 is hydrogen or unsubstituted or substituted lower alkyl. 10. The process according to Claim 1, characterized in that (a) the quinolone moiety is: 1 -Cyclopropyl-6-fluoro- 1 ,4-dihydro-4-oxo-7-piperazinyl- quinoline-3 -carboxylic acid; 1 -Cyclopropyl-6-fluoro- 1 ,4-dihydro-4-oxo-7-piperazinyl- quinoline-3 -carboxylic acid allyl ester; 1 -Cyclopropyl-6-fluoro- 1 ,4-dihydro-4-oxo-7-piperazinyl- quinoline-3 -carboxylic acid diphenylmethyl ester; 1 -Cyclopropyl-6-fluoro- 1 ,4-dihydro-4-oxo-7-piperazinyl- quinoline-3 -carboxylic acid t-butyl ester; 1 -Cyclopropyl-6-fluoro- 1 ,4-dihydro-4-oxo-7-piperazinyl- quinoline-3 -carboxylic acid 2,2,2-trichloroethyl ester; 7-(3-Amino- 1 -pyrrolidinyl)- 1 -cyclopropyl-6,8-difluoro- 1 ,4- dihydro-4-oxo-quinoline-3 -carboxylic acid; ι « 7-(3 -Amino- 1 -pyrrolidinyl)- 1 -cyclopropyl-6,8-difluoro- 1 ,4- dihydro-4-oxo-quinoline-3 -carboxylic acid allyl ester; 7-(3 -Amino- 1 -pyrrolidinyl)- 1 -cyclopropyl-6, 8-difluoro- 1 ,4- dihydro-4-oxo-quinoline-3 -carboxylic acid allyl ester; 5-Amino-7-(3-amino-l -pyrrolidinyl)- 1 -cyclopropyl-6, 8- difluoro-l,4-dihydro-4-oxo-quinoline-3-carboxylic acid allyl ester; 5-Amino- 1 -cyclopropyl-6,8-difluoro- 1 ,4-dihydro-7-(2,6- dimethyl-4-piperazinyl)-4-oxo-quinoline-3-carboxylic acid; 7-(3 -Amino- 1 -pyrrolidinyl)- 1 -(2,4-difluorophenyl)-6-fluoro- l,4-dihydro-4-oxo-l,8-naphthyridine-3 -carboxylic acid allyl ester; or 7-[3-(t-Butyloxycarbonyl)amino- 1 -pyrrolidinyl]- 1 - cyclopropyl-6, 8-difluoro- 1 ,4-dihydro-5-hydrazino-4-oxo- quinoline-3 -carboxylic acid allyl ester; and (b) the lactam moiety is: [5R-[5a,6a]]-6-[(R)- 1 -(t-butyldimethylsilyloxy)ethyI]-3- hydroxymethyl-7-oxo-4-thia- 1 -azabicyclo[3 2.0]hept-2-ene- 2-carboxylic acid allyl ester; [5R , 5a,6a]]-6-[(R)-l-[(allyloxycarbonyl)oxy]ethyl]-3- hydroxymethyl-7-oxo-4-thia-l -azabicyclo[3 2.0]hept-2-ene- 2-carboxylic acid allyl ester; [5R-[5a,6a]]-6-[(R)-l-[(2,2,2- trichloroethyloxycarbonyl)oxy]ethyl]-3-hydroxymethyl-7- oxo-4-thia- 1 -azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid 2, 2,2-trichloroethyl ester; [5R-[5a,6a]]-6-[(R)-l-(t-butyldimethylsilyloxy)ethyl]-3- hydroxymethyl-7-oxo-4-thia-l-azabicyclo[3.2.0]hept-2-ene- 2-carboxylic acid diphenylmethyl ester; [5R-[5a,6a]]-6-[(R)-l-(t-butyldimethylsilyloxy)ethyl]-3- hydroxymethyl-7-oxo-4-thia-l-azabicyclo[3.2.0]hept-2-ene- 2-carboxylic acid t-butyl ester; [5R-[4b,5a,6a]]-6-[(R)-l-(t-butyldimethylsilyloxy)ethyl]-3- hydroxymethyl-4-methyl-7-oxo- 1 -azabicyclo[3.2.0]hept-2- ene-2-carboxylic acid allyl ester; [5R-[5a,6a]]-6-[(R)-l-(t-butyldimethylsilyloxy)ethyl]-3-(2- hydroxyethylthio)-7-oxo-4-thia- 1 -azabicyclo[3 2.0]hept-2- ene-2-carboxylic acid allyl ester; or [5R-[4b,5a,6a]]-6-[(R)-l-(t-butyldimethylsilyloxy)ethyl]-3- (2-hydroxy-ethylthio)-4-methyl-7-oxo- 1 - azabicyclo[3.2.0]hept-2-ene-2-carboxylic acid allyl ester. 11. A process, according to Claim 1, characterized in that said compound is: [5R-[5a,6a]]-3-[[[4-(3-Carboxy- 1 -cyclopropyl-6-fluoro- 1 ,4-dihydro-4-oxo- 7-quinolinyl)- 1 -piperazinyl]carbonyloxy]methyl]-6-[(R)- 1 -hydroxyethyl]-7- oxo-4-thia-l-azabicyclo[3.2.0]hept-2-ene-2-carboxylic Acid, Disodium Salt; [5R-[4b,5a,6a]]-3-[[[4-(3-Carboxy- 1 -cyclopropyl-6-fluoro- 1 ,4-dihydro-4- oxo-7-quinolinyl)- 1 -piperazinyl]carbonyloxy]methyl]-6-[(R)- 1 - hydroxyethyl]-4-methyl-7-oxo-l-azabicyclo[3.2.0]hept-2-ene-2-carboxylic Acid, Disodium Salt; [5R-[5a,6a]]-3-[[[[4-(3-Carboxy-l-cyclopropyl-6,8-difluoro-l,4-dihydro-4- oxo-7-quinolinyl)-(S)-3-pyrrolidinyl]amino]-carbonyloxy]methyl]-6-[(R)-l- hydroxyethyl]-7-oxo-4-thia- 1 -azabicyclo[3 2.0]hept-2-ene-2-carboxylic Acid, Disodium Salt; [5R-[4b,5a,6a]]-3-[[[[4-(3-Carboxy-l-cyclopropyl-6,8-difluoro-l,4- dihydro-4-oxo-7-quinolinyl)-(S)-3-pyrrolidinyl]amino]- carbonyloxy]methyl]-6-[(R)- 1 -hydroxyethyI]-4-methyl-7-oxo- 1 - azabicyclo[3.2.0]hept-2-ene-2-carboxylic Acid, Disodium Salt; [5R-[5a,6a]]-3-[[[[4-[3-Carboxy-l-(2,4-difluorophenyl)-6-fluoro-l,4- dihydro-4-oxo- 1 ,8-naphthyridin- 1 -yl]-(S)-3-pyrrolidinyl]amino]- carbonyloxy]methyl]-6-[(R)- 1 -hydroxyethyl]-7-oxo-4-thia- 1 - azabicyclo[3.2.0]hept-2-ene-2-carboxylic Acid, Disodium Salt; [5R-[4b,5a,6a]]-3-[[[[4-[3-Carboxy-l-(2,4-difluorophenyl)-6-fluoro-l,4- dihydro-4-oxo- 1 ,8-naphthyridin- 1 -yl]-(S)-3-pyrrolidinyl]amino]- carbonyloxy]methyl]-6-[(R)- 1 -hydroxyethyl]-4-methyl-7-oxo- 1 - azabicyclo[3.2.0]hept-2-ene-2-carboxylic Acid, Disodium Salt; [5R-[5a,6a]]-3-[[[4-(5-Amino-3-carboxy-l -cyclopropyl-6, 8-difluoro-l, 4- dihydro-4-oxo7-quinolinyl)-2,6-dimethyl-4- piperazinyl]carbonyloxy]methyl]-6-[(R)- 1 -hydroxyethyl]-7-oxo-4-thia- 1 - azabicyclo[3.2.0]hept-2-ene-2-carboxylic Acid, Disodium Salt; [5R-[4b,5a,6a]]-3-[[[4-(5-Amino-3-carboxy-l-cyclopropyl-6,8-difluoro-l,4- dihydro-4-oxo-7-quinolinyl)-2,6-dimethyl-4- piperazinyl]carbonyloxy]methyl]-6-[(R)- 1 -hydroxyethyl]-4-methyl-7-oxo- 1 - azabicyclo[3.2.0]hept-2-ene-2-carboxylic Acid, Disodium Salt; [5R-[5a,6a]]-3-[[[2-[7-((S)-3-Amino-l-pyrrolidinyl)-3-carboxy-l- cyclopropyl-6, 8-difluoro- 1 ,4-dihydro-4-oxo-5-quinolinyl]- 1 -hydrazino]- carbonyloxy]methyl]-6-[(R)— hydroxyethyl]-7-oxo-4-thia- 1 - azabicyclo[3.2.0]hept-2-ene-2-carboxylic Acid, Disodium Salt; [5R-[4b,5a,6a]]-3-[[[2-[7-((S)-3-Amino-l-pyrrolidinyl)-3-carboxy-l-cyclo- propyl-6,8-difluoro-l,4-dihydro-4-oxo-5-quinolinyl]-l-hydrazino]-carbonyl- oxy]methyl]-6-[(R)- 1 -hydroxyethyl]-4-methyl-7-oxo- 1 -azabicyclo- [3.2.0]hept-2-ene-2-carboxylic Acid, Disodium Salt; [4R-[4α , 5β,6β(R*)]]-3-[[[4-(3-Carboxy-l-cyclopropyl-6-fluoro-l,4- dihydro-4-oxo-7-quinolinyl)- 1 -piperazinyl]carbonyloxy]methyl]-6-( 1 - hydroxyethyl)-7-oxo-4-thia- 1 -azabicyclo[3.2.0]hept-2-ene-2-carboxylic Acid, Disodium salt; [6R-[6α,7β]]-3-[[[4-(3-Carboxy-l-cyclopropyl-6-fluoro-l,4-dihydro-4-oxo- 7-quinolinyl)- 1 -piperazinyl]carbonyloxy]methyl]-8-oxo-7-[(2- thienylacetyl)amino]-5-thia- 1 -azabicyclo[4.2.0]oct-2-ene-2-carboxylic Acid, Disodium Salt; [6R-[6α,7β]]-3-[[[4-[3-Carboxy- 1 -( 1 , 1 -dimethylethyl)-6-fluoro- 1 ,4- dihydro-4-oxo- 1 ,8-napthyridin-7-yl]- 1 -piperazinyl]carbonyloxy]-methyl]-8- oxo-7-[(2-thienylacetyl)arnino]-l-azabicyclo[4.2.0]oct-2-ene-2-carboxylic Acid, Disodium Salt; * [5R-[5α,6α(R*)]]-3-[[4-(3-Carboxy-l-cyclopropyl-6-fluoro-l,4-dihydro-4- oxo-7-quinolinyl)- 1 -piperazinyl]methyl]-6-( 1 -hydroxyethyl)-7-oxo-4-thia- 1 - azabicyclo[3.2.0]hept-2-ene-2-carboxylic Acid, Disodium Salt; [6R-[6α,7β]]-3-[[4-(3-Carboxy-l-cyclopropyl-6,8-difluoro-l,4-dihydro-4- oxo-7-quinolinyl)- 1 -piperazinyl]]methyl]-8-oxo-7-[2- (phenoxyacetyl)amino]- 1 -azabicyclo[4.2.0]oct-2-ene-2-carboxylic Acid, Disodium Salt; [4S-[3(R*),4α,5β,6β(S*)]]-3-[[[l-[3-Carboxy-l-(2,4-difluorophenyl)-6- fluoro-l,4-dihydro-4-oxo-l,8-napthyridin-7-yl]-3-pyrroli- dinyl]amino]methyl]-6-( 1 -hydroxyethyl)-4-methyl-7-oxo- 1 -azabicyclo- [3.2.0]hept-2-ene-2-carboxylic Acid, Disodium salt; or [6R-[3(S*),6α,7β]]-3-[[[ 1 -[3-Carboxy-l -( 1 , l-dimethylethyl)-6-fluoro- 1 ,4- dihydro-4-oxo-l,8-napthyridin-7-yl]-3-pyrrolidinyl]amino]methyl]-8-oxo-7- [(2-thienylacetyl)amino]-5-thia-l-azabicyclo[4.2.0]oct-2-ene-2-carboxylic Acid. 12. A compound having a structure according to the formula QΛ - ) - L - L 2 - B) characterized in that (I) M has a structure according to Formula (IN) π* characterized in that (A) ( 1 ) A - is N or C(R 7 ); where (a) R 7 is hydrogen, hydroxy, alkoxy, nitro, cyano, halogen, alkyl, or -N(R 8 )(R 9 ), and (b) R 8 and R 9 are, independently, R a where R a is hydrogen, alkyl, alkenyl, a carbocyclic ring, or a heterocyclic ring, or R 8 and R 9 together comprise a heterocyclic ring including the nitrogen to which they are bonded; (2) A2 is N or C(R 2 ); where R 2 is hydrogen or halogen; ( 3 ) A 3 is N or C(R5); where R^ is hydrogen; ( ) R! is hydrogen, alkyl, a carbocyclic ring, a heterocyclic ring, alkoxy, hydroxy, alkenyl, arylalkyl, or -N(R 8 )(R 9 ); (5) R 3 is hydrogen, halogen, alkyl, a carbocyclic ring, or a heterocyclic ring; (6) R 4 is hydroxy; ( 7 ) R is hydrogen, halogen, nitro or -N(R 8 )(R 9 ); and (8) X is a leaving group; (B) and (1) when A2 is C(R2), R2 and R 3 may together comprise -O-(CH 2 ) n -O-, where n is from 1 to 4; (2) when A 3 is C(R^), R 4 and R^ may together comprise a heterocyclic ring; and (3) when A is C(R 7 ), R 7 and R 3 may together comprise a heterocyclic ring including A^ and the carbon atom to which R 3 is bonded; (C) and provided that one of R-, R 3 , or R^ is a covalent bond to (II) B has a structure according to Formula (II): characterized in that (A) RIO is hydrogen, halogen, alkyl, alkenyl, heteroalkyl, a carbocyclic ring, a heterocyclic ring, R 8 -O-, R 8 CH=N-, (R 8 )(R 9 )N-, R - 7 -C(=CHR20)-C(=O)NH-, R ] 7 -C(=NO- . R 19 )-C(=O)NH-, or R 18 -(CH 2 ) m -C(=O)NH-; where (1) m is an integer from 0 to 9; (2) R 7 is hydrogen, alkyl, alkenyl, heteroalkyl, heteroalkenyl, a carbocyclic ring, or a heterocyclic ring; (3) R 18 is R 17 , -γl, or -CH(Y )(R 17 ); (4) R 19 is R 17 , arylalkyl, heteroarylalkyl, -C(R 22 ). (R 23 )-COOH, -C(=O)O-R 17 , or -C(=O)NH-R 17 , where R22 and R2 are, independently, R^ 7 or together comprise a carbocyclic ring or a heterocyclic ring including the carbon atom to which R22 and R 23 are bonded; (5) R 20 is R 19 , halogen, -Y 1 , or -CH(Y 2 )(R 17 ); (6) Y 1 is -C(=O)OR21, -C(=O)R21, -N(R 4 )R21 -S(O) p R 29 , or -OR 29 ; and Y 2 is Y 1 or -OH, -SH, or -SO 3 H; (a) p is an integer from 0 to 2; (b) R24 is hydrogen; alkyl; alkenyl; heteroalkyl; heteroalkenyl; a carbocyclic ring; a heterocyclic ring; -SO3H; -C(=O)R 5 ; or, when R 18 is -CH(N(R24)R21)(R17) R 24 may comprise a moiety bonded to R21 to form a heterocyclic ring; and (c) R-S is RI 7 , -NH(R 17 ), -N(R 17 )(R 26 ), O(R 26 ), or S(R 26 ); where R 26 is alkyl, alkenyl, a carbocyclic ring, a heterocyclic ring, or when R 25 is -N(R 17 )(R 26 ), R 26 may be a moiety bonded to R^ 7 to form a heterocyclic ring; and (7) R 2 1 is R 29 or hydrogen; where R 29 is alkyl; alkenyl; arylalkyl; heteroalkyl; heteroalkenyl; heteroarylalkyl; a carbocyclic ring; a heterocyclic ring; or, when Y is N(R 24 )R 2 1 and R 21 is R 29 , R 21 and R 24 may together comprise a heterocyclic ring including the nitrogen atom to which R 4 is bonded; (B) R- - is hydrogen, halogen, alkoxy, or R 27 C(=O)NH-, where R 27 is hydrogen or alkyl; (C) bond "a" is a single bond or is nil; and bond "b" is a single bond, a double bond, or is nil; except bond "a" and bond "b" are not both nil; (D) R 12 is -C(R 8 )-, or -CH 2 -R 28 -; where R 28 is -C(R 8 )-, -O-, or -N-, and R 2 8 is directly bonded to N" in Formula (II) to form a 5-membered ring; except, if bond "a" is nil, then R^ 2 is (1) -C(R 8 )(χl)-, where (a) X 1 is -R 21 ; -OR 30 ; -S(O) r R 30 , where r is an integer from 0 to 2; -OC(=O)R 30 ; or N(R 30 )R 3 1 ; and (b) R 30 and R ^ are, independently, alkyl, alkenyl, a carbocyclic ring or a heterocyclic ring; or R 30 and R ^ together comprise a heterocyclic ring including the nitrogen atom to which R 30 and R 3 - are bonded; or (2) -CH 2 -R 32 -; where R 32 is -C(R 8 )(R 21 ), -O-, or -NR 8 , and R 32 is directly bonded to N" in Formula (II) to form a 5-membered ring; (E) (1) if bond "b" is a single bond, R 13 is -CH(R 33 ); or, -C(O)NHSO 2 -, if bond "a" is nil; or -C*(R 33 )- if Rl4 contains a R ^ moiety; where R 33 is hydrogen or COOR 46 , where R 6 is hydrogen, alkyl or alkenyl, and C* is linked to R ^ to form a 3- membered ring; (2) if bond "b" is a double bond, R 13 is -C(R 33 )=; or (3) if bond "b" is nil, R 13 is hydrogen, -SO 3 H, -PO(OR 34 )OH, -C(O)NHSO 2 N(R 34 )(R 5), -OSO3H, -CH(R 3 5)COOH, or -OCH(R 34 )-COOH; where R 3 4 is hydrogen, alkyl, alkenyl, a carbocyclic ring, or a heterocyclic ring; and R 3 ^ is hydrogen, alkyl, alkenyl, or -NHR 8 ; or, if R 13 is -C(O)NHSO 2 N-(R 34 )(R 5), R34 and R 35 may together comprise a heterocyclic ring including the nitrogen to which R 4 and R 3 ^ are bonded; and (F) (1) if bond "a" or bond "b" is nil, then R 14 is covalent bond; (2) if bond "a" and "b" are single bonds, R 14 is -W- C"'=C(R 8 )-R 37 -, or -W-C"'(R 36 )- R 37 -; or (3) if bond "a" is a single bond and bond "b" is a double bond, R 14 is -C(R 8 )(R 3 8)-W-C"'-R 37 -; -W-C(R 8 )- (R38). C » '-R37. ; or . -C"'-R 37 -; (4) where (a) W is O; S(O) s , where s is an integer from 0 to 2; or C(R 8 ), where R 38 is hydrogen, alkyl or alkoxy; (b) R 36 is hydrogen; alkyl; alkenyl; -COOH; or, if R 13 is -C*(R 33 ), R 36 may be linked to C* to form a 3-membered carbocyclic ring; (c) R 37 is covalent bond, alkyl, alkenyl, a carbocyclic ring, or a heterocyclic ring; and (d) C" is directly bonded to R 13 to form a 5- or 6-membered ring; and (III) (A) L is -C(=Z)-; -S(O) v -; -N(R 4 4)- ; -N + (R44)(R45 ); . N (R44). N(R44)-; -0-; =N-; or a covalent bond; and L is bonded to L 3 and L4; where (1) Z is O, S, or + N(H) 2 ; (2) v is 0, 1 or 2; (3) R44 is hydrogen, substituted or unsubstituted lower alkyl, aryl, acyl, hydroxy, alkoxy, aryloxy, or acyloxy; and (4) R4 is hydrogen, unsubstituted or substituted lower alkyl, or substituted or unsubstituted aryl; (B) L 1 is L 3 or R 15 L 3 ; where (1) when L is -C(=Z)-, L 3 is a covalent bond, oxygen, sulfur, or nitrogen; and when L is other than -C(=Z)-, L 3 is a covalent bond; (2) R! 5 is alkyl, alkenyl, heteroalkyl, a heterocyclic ring, a carbocyclic ring, or R^ together with L 3 is a heteroalkyl or a heterocyclic ring; and (3) L,l is bonded to Q at the point of attachment of R-, R 3 or R^, whichever is a covalent bond; (C) L 2 is L 4 , -X 2 t -R 39 -L 4 , or -X 3 t -R 39 -L 4 ; where (1) when L is -C(=Z)-, L 4 is a covalent bond, oxygen, sulfur, or nitrogen; and when L is other than -C(=Z)-, . L 4 is a covalent bond; (2) X 2 is oxygen, or S(O) v , where v is 0, 1, or 2; (3) X 3 is nitrogen; N(R 40 ); N + (R 4 1)(R 42 ); or R 43 - N(R 4 1); and is linked to R* 4 by a single or double bond; or, if R^ 4 is covalent bond, X 3 is linked to B by a single or double bond; where (a) R 40 is R 8 ; -OR 8 ; or -C(=O)R 8 ; (b) R 4 * and R 42 are, independently, hydrogen; alkyl; alkenyl; carbocyclic rings; heterocyclic rings; or, if R 6 is R 16 X, then R 41 and R 42 together with Q" may comprise a heterocyclic (c) R 43 is N(R 4 J ), oxygen or sulfur; (4) t is O or l; (5) R 39 is alkyl, alkenyl, heteroalkyl, heteroalkenyl, a carbocyclic ring, or a heterocyclic ring; and (6) (a) if bond "a" or bond "b" is nil, then L 2 is bonded directly to R^ 2 or R 13 ; or (b) if bond "a" and bond "b" are not nil, then L 2 is bonded to R^ 4 ; (D) provided that if L 1 , L 2 and R 37 is each a covalent bond, then L is not a covalent bond; form, salt, ester, or solvate thereof. v 22_- 13. The compound of Claim 12, characterized in that A^ is nitrogen, A 2 is C(R 2 ), and A 3 is C(R 5 ) or, preferably. A 1 is C(R 7 ), A 2 is C(R 2 ), and A 3 is C(R5), R- is alkyl, aryl, cycloalkyl, or alkylamino, R 7 is hydrogen or halogen, and R 3 is a heterocyclic ring, preferably a substituted or unsubstituted pyrrolidine or a substituted or unsubstituted piperazine 14 The compound of Claim 12, characterized in that ( ) R 3 is a covalent bond to L ■• or R*> is a covalent bond to L ■ , (b) (i) L is -C(=Z)-, where Z is O, and L 3 is nitrogen, or (ii) L is -N(R 44 )-, where R 44 is hydrogen or unsubstituted or substituted lower alkyl, and (c) R 14 is -W-C"'-R 37 - or -W-C(R 8 XR 38 )-C"-R 37 -, preferably W is S(O) s , where s is 0, or W is C(R 38 ) 15 A process for making the compound of Claim 12, Claim 13, or Claim 14, the method comprising reacting a compound having a structure according to Formula (III) characterized in that (A) (1) A 1 is N or C(R 7 ), where (a) R 7 is hydrogen, hydroxy, alkoxy, nitro, cyano, halogen, alkyl, or -N(R 8 )(R 9 ), and (b) R 8 and R 9 are, independently, hydrogen, alkyl, alkenyl, a carbocyclic ring, or a heterocyclic ring, or R 8 and R 9 together comprise a heterocyclic ring including the nitrogen to which they are bonded, (2) A 2 is N or C(R 2 ), where R 2 is hydrogen or halogen, (3) A 3 is N or C(R 5 ), where R 5 is hydrogen. (4) R- is hydrogen, alkyl, a carbocyclic ring, a heterocyclic ring, alkoxy, hydroxy, alkenyl, arylalkyl, or -N(R 8 )(R 9 ); (5) R 3 is hydrogen, halogen, alkyl, a carbocyclic ring, or a heterocyclic ring; (6) R 4 is hydroxy; (7) R6 is hydrogen, halogen, nitro or -N(R 8 )(R 9 ); and (8) X is a leaving group (B) and (1) when A 2 is C(R 2 ), R 2 and R 3 may together comprise -O-(CH 2 ) n -O-, where n is from 1 to 4; (2) when A 3 is C(R^), R 4 and R may together comprise a heterocyclic ring; and (3) when A^ is C(R 7 ), R 7 and R 3 may together comprise a heterocyclic ring including A^ and the carbon atom to which R 3 is bonded; or a salt or ester thereof; with a lactam-containing compound having a structure according to Formula (II).

Inventors: GODLEWSKI JANE ELLEN, RANDALL JARED LYNN, GODLEWSKI, JANE, ELLEN, RANDALL, JARED, LYNN
Applicants: PROCTER & GAMBLE, THE PROCTER & GAMBLE COMPANY
Application year: 1995
Main classification: C07D499
IPC codes: A61K31, A61P31, C07D215, C07D463, C07D477, C07D491, C07D499, C07D501