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 wi...

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Bibliographic Details
Published in:Bioorganic & medicinal chemistry 1994, Vol.2 (1), p.27-34
Main Authors: Wang, K.C., Liang, Chang-Hsing, Kan, Wai-Ming, Lee, Shoei-Sheng
Format: Article
Language:English
Subjects:
A-Ring aromatic steroids
Acetoacetates - chemistry
Alkylation
Anions
asymmetric cyclization
dianion alkylation
Esterification
Magnetic Resonance Spectroscopy
microbial reduction
Molecular Structure
Oxidation-Reduction
Schizosaccharomyces - metabolism
Stereoisomerism
Steroids - biosynthesis
Steroids - chemical synthesis
Steroids - chemistry
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Summary: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-(-)-phenylalanine, followed by acidic cyclization led to regiospecific synthesis of 16,16-dimethyl tetracyclic steroid intermediate. Graphic
ISSN:0968-0896
1464-3391
DOI:10.1016/S0968-0896(00)82199-9