Patent GB-1392732-A (GB)
Title: 14,19-dioxygenated steroid compounds and their 14-dehydro  analogues and processes for the preparation thereof
IPC: C07J1/00
Filed: 1972-04-10
Abstract: 1392732 14,19 - Functionalized steroids STEELE CHEMICALS CO Ltd 10 April 1972 [4 Jan 1972] 16385/72 Heading C2U The invention comprises compounds of formula wherein A and B represent the 14- and 15-carbon atoms respectively which are linked by a double bond, carry an α- or #-epoxy group, or carry a 14#-hydroxy group in which case B is CH 2 ; the dotted lines represent optional #<SP>7</SP>, #<SP>4</SP>'<SP>6</SP> or #<SP>4,6,8(9)</SP> unsaturation, any 5-hydrogen atom being α- or #-oriented ; R<SP>1</SP> is OH, OR<SP>4</SP> or OR<SP>5</SP>; Y is α-OH, #-OH, #-OR<SP>6</SP> or oxo; R is OR<SP>2</SP>, OR<SP>3</SP>, OH, oxo, CN, or one of the following groups wherein R<SP>2</SP> and R<SP>4</SP> are each C 1 _ 7  alkyl, 2-tetra-  hydropyranyl, 2- or 3-furyl, halomethyl, benzyl, allyl, 2-propynyl or methoxymethyl; and R<SP>3</SP>, R<SP>5</SP> and R<SP>6</SP> are each acetyl, tri(C 1-7  alkyl)acetyl, mono- or tri-haloacetyl, 2- or 3-furoyl, or 2,4-dimethyl-, 2,5-dimethyl- or 2,4,5-trimethylpyrrole-3-carbonyl. Compounds I are prepared from or via compounds of the formulµ as follows: Epoxidation of II (e.g. with a peracid) yields III (major product)+ in Example 9 some 8α,9α-epoxy isomer+ in Examples 1 and 42 some 8,19-epoxy-14a-ol isomer+ in Example 1 (as shown by Example 2) a 3-unsubstituted- 8,19-epoxy-14α-ol. Any acyloxy groups in III may be reduced or hydrolysed (Examples 7, 8) and any hydroxy groups acetylated. Rearrangement of III under hydrogenation or acidic conditions yields I (#<SP>7</SP>; 14#-OH) + in Example 44 14α- and 14#-hydroxy-8,19-epoxy saturated byproducts; or in Example 3, I (saturated; 14#- OH)+#<SP>8(14)</SP> and 14-unfunctionalized by-products. Epoxidation of IV yields VI (R<SP>1</SP> = OH) + in Example 16 some 8,19-epoxy-14α,19-diol byproduct. Epoxidation of IV 19-acetate is said to yield the 8α,9α-epoxy isomer of VI (R<SP>1</SP> OH). Acetylation of VI (R<SP>1</SP>=OH) yields VI (R<SP>1</SP> = acetoxy) acidification of which yields I (#<SP>4,1,6,8(9)</SP>; 3-oxo; 19-acetoxy; 14#-OH). Metal hydride reduction of VI yields the corresponding #<SP>4,6</SP>- 3# ol which after optional 3-acetylation (Example 17) is catalytically hydrogonated to yield I(#<SP>7</SP>; 14#-OH)+ in Example 19 some III. Reduction of VII or a corresponding 3-(2- tetrahydropyranyloxy) compound (Example 48) yields I (#<SP>14</SP>; R<SP>1</SP> = OH or alkanoyloxy). Hydrogenolysis of VIII yields IX, hydrogenation of which yields X, dehydration of which yields XI, reduction of which yields I (#<SP>14</SP>; R1 = OH). The thus-obtained products are converted into other compounds I by one or more steps selected from (i) reduction of 3-oxo to hydroxy; (ii) catalytic hydrogenation of 4(5)- and 6(7)- double bonds or of a 7(8)-double bond; (iii) conversion of #<SP>14</SP> to 14α,15α- or 14#,15#-epoxy; (iv) "conversion of 14,15-epoxy to 14#-OH; (v) dehydration of 14#-OH to #<SP>14</SP> (Example 34); (vi) hydrolysis of acyl groups; and (vii) acetylation of hydroxyl groups. Compounds IV are prepared from the corresponding 4,6-dienes by enolization followed by dehydrogenation, and may be converted to compounds II by NaBH 4  reduction followed by catalytic hydrogenation. Compounds I are said to be of use in the synthesis of compounds of Formula XII A description in general terms is given of conventional methods for synthesizing the cardenolide lactone ring from suitable values of R in Formula I.