19,8-LACTONE AND LACTOL STEROID DERIVATIVES AND PROCESSES OF PREPARATION THEREOF

摘要

1392731 Steroid 19,8-lactones and lactols STEELE CHEMICALS CO Ltd 10 April 1972 [4 Jan 1972] 16382/72 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 14α- or 14#-hydroxy group on which case B is CH 2 ; the 4(5)- and 6(7)-bonds are both saturated (with 5α- or 5#-H), or both unsaturated; Y is oxo or α- or #-OH; RSP1/SP is oxo, OH or OCOMe; and R is ORSP2/SP, CN, pivaloyloxy, or one of the following groups wherein RSP2/SP is C 1-7 alkyl, 2-tetrahydropyranyl, 2- or 3-furyl, halomethyl, benzyl, allyl, 2- propynyl, or methoxymethyl; and RSP3/SP is 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-trimethyl-pyrrole-3-carbonyl. The 14-hydroxy-#SP4,6/SP compounds I are prepared from or via compounds of formulµ (wherein Z is CHO or CO 2 H) as follows: Oxidation of II (e.g. with CrO 3 /H 2 SO 4 ) yields I (14α-OH; RSP1/SP=oxo; major produet)+ I (14#-OH; RSP1/SP=oxo)+III (Z=CHO)+III (Z = CO 2 H). Epoxidation of II (e.g. a peracid) yields V (major product) + the 8α,14α-isomer of V, both of which are convertible into 19-acetates (Examples 10, 11). Oxidation of V yields VI acidification of which yields I (14#-OH; RSP1/SP = OH)+ in Example 12 some 14α-isomer. Epoxidation of III (Z = CO 2 H) yields I (14α-OH; RSP1/SP=oxo)+ in Example 7 some 14#- isomer. Epoxidation of III (Z = CHO) yields IV, acidification of which yields I (14α-OH; RSP1/SP = OH), and oxidation of which yields I (14α-OH; R= oxo)+ in Example 5 some I (14α-OH; B=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 the 4(5)- and 6(7)-double bonds; (iii) dehydration of 14α-OH to #SP14/SP; (iv) conversion of #SP14/SP to 14#,15#-epoxy; (v) conversion of 14,15-epoxy to 14#-OH; and (vi) 19-acetylation. Compounds II are prepared from the corresponding 4,6-dienes by enolization followed by dehydrogenation, and may be converted to compounds III by oxidation. Compounds I are said to be of use in the synthesis of compounds of Formulµ VII and VIII (wherein RSP1/SP is as above, and RSP6/SP is H, CHO or CH 2 OH). A description in general terms is given of conventional methods for synthesizing the cardenolide lactone ring from suitable values of R in Formula I.