Asymmetric Total Syntheses of Cochliomycin A and Zeaenol

• Published in: European journal of organic chemistry Vol. 2012; no. 23; pp. 4313 - 4320
• Main Authors: Jana, Nandan, Nanda, Samik
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.08.2012; WILEY‐VCH Verlag; Wiley; Wiley-VCH
• Subjects: Asymmetric synthesis; Chemistry; Chemistry, Organic; Exact sciences and technology; Lactones; Macrocycles; Metathesis; Noncondensed benzenic compounds; Organic chemistry; Physical Sciences; Preparations and properties; Science & Technology; Synthetic methods; LL-Z1640-2; HSP90; RADICICOL; Metathesis; KINASE INHIBITOR; Macrocycles; MACROLIDES; Lactones; ESTROGENIC ACTIVITY; ALCOHOLS; RESORCYLIC ACID LACTONES; Asymmetric synthesis; AIGIALOMYCIN-D; Synthetic methods; CHLORIDE; Benzoic acid; Julia-Kocienski olefination; athesis Sy; Chiral compound; Tartaric acid; Total synthesis; Macrocycle; Benzoic acid derivatives; Cyclization; nthetic methods Macrocycles; Benzenic compound; Keck allylation; Met; Functional group
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/ejoc.201200241

The first asymmetric total syntheses of two resorcylic acid lactones (RALs) – cochliomycin A and zeaenol – have been achieved in a divergent way. The main highlight of our strategy involves successful application of stereoselecive Keck allylation and Julia–Kocienski olefination to access an advanced intermediate, by starting from L‐tartaric acid as a chiral pool compound. This intermediate is coupled with a trisubstituted benzoic acid to afford a common RCM precursor for both target molecules. Ring‐closing metathesis at a late stage, followed by functional group manipulation, yielded the target molecules in an efficient way. Two resorcylic acid lactones (RALs) – cochliomycin A and zeaenol – have been synthesized for the first time by an enantiodivergent route from the common chiral pool compound L‐tartaric acid.