Patent GB-1505355-A (GB)
Title: Process for the production of 3'-deoxy derivatives of an aminoglycosidic antibiotic
IPC: C07H15/244
Filed: 1975-07-22
Abstract: 1505355 3<SP>1</SP>-Deoxy derivatives of aminoglycoside antibiotics MEIJI SEIKA KAISHA Ltd 22 July 1975 [1 Aug 1974] 30659/75 Heading C2C A 3<SP>1</SP>-deoxy derivative of an aminoglycosidic antibiotic selected from 3<SP>1</SP>-deoxyneamine, a 6<SP>1</SP>- N-alkyl-3<SP>1</SP>-deoxyneamine, 3<SP>1</SP>-deoxykanamycin B, a 6<SP>1</SP>- N - alkyl - 3<SP>1 </SP>- deoxykanamycin B, 3<SP>1</SP>- deoxyribostamycin, a 6<SP>1</SP>- N - alkyl - 3<SP>1 </SP>- deoxyritostamycin and 3<SP>1</SP>-deoxyparomamine, is prepared by : (a) reducing with hydrogen a 3<SP>1</SP>,4<SP>1</SP>-α-anhydro derivative of aminoglycoside selected from (i) a 3<SP>1</SP>,4<SP>1</SP>-α-anhydro derivative of neamine or 6<SP>1</SP>- N-alkylneamine represented by the formula (IX)  wherein either A and B each is a hydrogen atom; or A is a hydrogen atom and B is a mono-valent amino-protecting group; or A and B taken together form a di-valent amino-protecting group; and either A<SP>1</SP> and B<SP>1</SP> each is a hydrogen atom; or A<SP>1</SP> is an alkyl group and B<SP>1</SP> is a hydrogen atom; or A<SP>1</SP> is a hydrogen atom and B<SP>1</SP> is a mono-valent amino-protecting group; or A<SP>1</SP> is an alkyl group and B<SP>1</SP> is a mono-valent amino-protecting group; or A<SP>1</SP> and B<SP>1</SP> taken together form a di-valent amino-protecting group; and Y is a di-valent hydroxyl-protecting group or represents two separate hydrogen atoms so that the two hydroxyl groups to which Y is attached remain unprotected, (ii) a 3<SP>1</SP>,4<SP>1</SP>- α-anhydro derivative of kanamycin B or 6<SP>1</SP>-N- alkylkanamycin B represented by the Formula (X) wherein A, B, A<SP>1</SP>, B<SP>1</SP> and Y have the same meanings as defined above, respectively, Z is a hydrogen atom or an acyl group, and Z<SP>1</SP> is a hydrogen atom or an acyl or aryl-methyl hydroxyl-protecting group, (iii) a 3<SP>1</SP>,4<SP>1</SP>-α- anhydro derivative of ribostamycin or 6<SP>1</SP>-N- alkylribostamycin represented by the Formula (XI) wherein A, B, A<SP>1</SP>, B<SP>1</SP> and Y have the same meanings as defined above, respectively; Z<SP>11</SP> is a hydrogen atom or an acyl or aryl-methyl hydroxyl-protecting group; and Z<SP>111</SP> is a hydrogen atom or an acyl or aryl-methyl hydroxyl. protecting group; and (iv) a 3<SP>1</SP>,4<SP>1</SP>-α-anhydro derivative of paromamine represented by the Formula (XII) wherein A, B, Y and Z<SP>1</SP> have the same meanings as defined above, respectively, in an alkaline reaction medium consisting of a C 1-4  alkanol containing an alkali metal hydroxide or alkoxide and in the presence of a Raney catalyst to effect the ring-fission of the 3<SP>1</SP>,4<SP>1</SP>-α-epoxide group and thereby 3<SP>1</SP>-deoxygenation and concurrent formation of the 4<SP>1</SP>-α-hydroxyl group, and, if necessary, (b) removing the residual protecting groups from the protected 3<SP>1</SP>-deoxygenation product obtained in the reaction stage (a). A hydroxyl-protected and amino-protected 3<SP>1</SP>,4<SP>1</SP>-α-anhydro derivative of neamine or 6<SP>1</SP>-N- alkylneamine represented by the aforesaid Formula (IX); a hydroxyl-protected and amino-protected 3<SP>1</SP>,4<SP>1</SP>-α-anhydro derivative of kanamycin B or 6<SP>1</SP>-N-alkylkanamycin B represented by the aforesaid Formula (X); a hydroxyl-protected and amino-protected 3<SP>1</SP>,4<SP>1</SP>- α-anhydro derivative of ribostamycin or 6<SP>1</SP>-N- alkylribostamycin represented by the aforesaid Formula (XI); or a hydroxyl-protected and amino-protected 3<SP>1</SP>,4<SP>1</SP>-α-anhydro derivative of paromamine represented by the aforesaid Formula (XII) is prepared by treating (i) an amino-protected and partly hydroxyl-protected 3<SP>1</SP>-sulphonylated derivative of nearnine or a 61- N-alkylneamine represented by the Formula (IX<SP>1</SP>) wherein Aa is a hydrogen atom and Ba is a mono-valent amino-protecting group; or Aa and Ba taken together form a di-valent aminoprotecting group; A<SP>1</SP>a is an alkyl group and B<SP>1</SP>a is a hydrogen atom, or Aa is a hydrogen atom and B<SP>1</SP>a is a mono-valent amino-protecting group, or A<SP>1</SP>a is an alkyl group and B<SP>1</SP>a is a mono-valent amino-protecting group, or A<SP>1</SP>a and B<SP>1</SP>a taken together form a di-valent aminoprotecting group; W is an alkylsulphonyl group, benzylsulphonyl group or an arylsulphonyl group; and Ya is a di-valent hydroxyl-protecting group, (ii) an aminoprotected and partly hydroxyl-protected 3<SP>1</SP>- sulphonylated derivative of kanamycin B or a 6<SP>1 </SP>- N - alkylkanamycin B represented by the Formula (X<SP>1</SP>) wherein Aa, Ba, A<SP>1</SP>a, B<SP>1</SP>a, W and Ya have the same meanings as defined above, respectively, and Z<SP>1</SP>a is a hydrogen atom or an acyl or arylmethyl hydroxyl-protecting group, (iii) an amino-protected and partly hydroxyl-protected 3<SP>1</SP>-sulphonylated derivative of ribostamycin or a 6<SP>1</SP>-N-alkylribostamycin represented by the Formula (XI<SP>1</SP>) wherein Aa, Ba, A<SP>1</SP>a, B<SP>1</SP>a, W and Ya have the same meanings as defined above, respectively, Z<SP>11</SP>a is an acyl or aryl-methyl hydroxylprotecting group, and Z<SP>111</SP>a is a hydrogen atom or an acyl or aryl-methyl hydroxyl-protecting group, or (iv) an amino-protected and partly hydroxyl-protected 31-sulphonylated derivative of paromamine represented by the Formula (XII<SP>1</SP>) wherein Aa, Ba, W, Ya and Z<SP>1</SP>a have the same meanings as defined above, respectively, in a C 1-4  alkanol with an alkali metal hydroxide or alkoxide in an amount sufficient to render said alkanol alkaline to effect epoxidation between the carbon atom substituted by the 3<SP>1</SP>-sulphonic ester group and the 4<SP>1</SP>-hydroxyl group, and then, if desired or required, removing some or all of the amino-protecting groups as well as some or all of the hydroxyl-protecting groups from the resulting protected 3<SP>1</SP>,4<SP>1</SP>-α-epoxide product, and, if desired, protecting an unprotected hydroxyl group of said resulting 3<SP>1</SP>,4<SP>1</SP>-α-epoxide product with a known hydroxyl-protecting group as specified for Y, Z, Z<SP>1</SP>, Z<SP>11</SP> and Z<SP>111</SP>. Tri - N - ethoxycarbonyl - 6<SP>1</SP> - O - acetylparomaVine is prepared by treating tri-N-ethoxycarbonylparomamine with acetic anhydride.