Synthesis of steroid intermediates via alkylation of dianion derived from acetoacetic ester.
A synthetic route for A-ring aromatic steroid intermediates starting from alkylation of dianion derived from acetoacetic ester with m-methoxyphenylethyl bromide to form benzene ring connected to a linear six-carbon fragment is described. This unit, after chemical modifications to 5, was condensed with 2-methylcyclopentan-1,3-dione (6a) to form prochiral trione, 7a, a key synthetic intermediate in A-ring aromatic steroid. Microbial reduction of 7a with Schizosaccharomyces pombe (NRRL Y-164) gave chiral (-)-11 in 65% yield. Starting from 2,2-dimethylsuccinic acid, 2,4,4-trimethylcyclopentan-1,3-dione (6a) was prepared, which was condensed subsequently with 5 to form racemic 7b trione intermediate. Asymmetric cyclization of 7b in the presence of L-(-)-phenylanlanine, followed by acidic cyclization led to regiospecific synthesis of 16,16-dimethyl tetracyclic steroid intermediate.
Wang
K C
KC
School of Pharmacy, College of Medicine, National Taiwan, University, Taipei, R.O.C.
Liang
C H
CH
Kan
W M
WM
Lee
S S
SS
D000090:Acetoacetates / Q000737:chemistry; D000478:Alkylation; D000838:Anions; D004951:Esterification; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D010084:Oxidation-Reduction; D012568:Schizosaccharomyces / Q000378:metabolism; D013237:Stereoisomerism; D013256:Steroids / Q000096:biosynthesis / Q000138:chemical synthesis* / Q000737:chemistry
D000090:Acetoacetates; D000838:Anions; D013256:Steroids; C016635:acetoacetic acid