Tetra- and hexahydro derivatives of aldosterone and 18-hydroxycorticosterone by chemical and microbial reductions.
Preparative methods were developed for reduction with NaBH4 at 0 of 3 beta, 5 alpha- and 3 alpha, 5 beta-tetrahydroaldosterone (1) and (12) to their respective 20 alpha-ol derivatives 2a and 13a. Corroboration of structures was obtained by periodate oxidations to the lactols 3b and 14b and thence, by further oxidation, to the lactones 4 and 15 respectively; these lactones were also independently obtained from 1 and 12. Reduction with NaBH4 at 80 degrees C converted 1 and 12 into 18-hydroxy-3 beta, 5 alpha, 20- and 18-hydroxy-3 alpha, 5 beta, 20-hexahydrocorticosterone 6a and 17a respectively, which were mixtures of epimers at C-20. Compound 17a could also be prepared by reduction of the lactone 21 with sodium aluminum bis-(methoxyethoxy) hydride. Again, periodate oxidations of 6a and 17a gave the lactols 7b and 22b and thence, by Jones oxidation, the diketolactones 8 and 23, which were also prepared from 18-hydroxy-11-dehydrocorticosterone (10) and 18-hydroxycorticosterone (24) respectively. Improved conditions for reduction with Clostridium paraputrificum permitted convenient conversion of aldosterone (11), the corresponding 18 leads to 11 lactone 18a and 18-hydroxycorticosterone (24) into their 3 alpha, 5 beta-tetrahydro derivatives.
D015069:18-Hydroxycorticosterone / Q000031:analogs & derivatives* / Q000378:metabolism; D000450:Aldosterone / Q000031:analogs & derivatives* / Q000378:metabolism; D001711:Biotransformation; D055598:Chemical Phenomena; D002621:Chemistry; D003013:Clostridium / Q000378:metabolism*; D003345:Corticosterone / Q000031:analogs & derivatives*; D010084:Oxidation-Reduction; D013057:Spectrum Analysis
D000450:Aldosterone; D015069:18-Hydroxycorticosterone; D003345:Corticosterone