[3,3]-Claisen rearrangements in 24alpha-methyl steroid synthesis. Application to campesterol, crinosterol, and Delta25-crinosterol side chain construction.
This paper elaborates an improved synthesis of crinosterol and campesterol starting from stigmasterol. The proposed approach is based on Claisen rearrangement of Delta23-22-allylic alcohols with various configurations of the 22-hydroxy group and geometry of the Delta23-double bond. It allows complete use of the starting steroid for preparing 24alpha-methyl derivatives. It was possible to partially control the stereochemistry at C-25. Hydrogenation of the Delta22-double bond was shown to proceed with partial isomerization of the C-24 alkyl substituent. The Ireland ester enolate variant of the Claisen rearrangement was demonstrated to be useful for preparing 24alpha-methyl steroids containing the Delta22,25-system.
Khripach
Vladimir A
VA
Institute of Bioorganic Chemistry, National Academy of Sciences of Belarus, Kuprevich str., 5/2, 220141 Minsk, Belarus. khripach@iboch.bas-net.by
Zhabinskii
Vladimir N
VN
Konstantinova
Olga V
OV
Khripach
Natalya B
NB
Antonchick
Andrey P
AP
Schneider
Bernd
B
D000438:Alcohols / Q000737:chemistry; D002784:Cholesterol / Q000031:analogs & derivatives* / Q000737:chemistry*; D015394:Molecular Structure; D010840:Phytosterols; D013256:Steroids / Q000138:chemical synthesis*; D013261:Sterols / Q000737:chemistry*
D000438:Alcohols; D010840:Phytosterols; D013256:Steroids; D013261:Sterols; C467539:crinosterol; C021273:campesterol; D002784:Cholesterol