Approach to the total synthesis of chlorothricolide: synthesis of (.+-.)-19,20-dihydro-24-O-methylchlorothricolide methyl ester ethyl carbonate

摘要: An approach to the total synthesis of the macrolide antibiotic aglycone chlorothricolide (lb) is presented. Herein is described the synthesis of the advanced intermediate (±)-19, 20-dihydro-24-O-methylchlorothricolide, methyl ester, ethyl carbonate (34) from the “bottom half" acid 4 and the “top half” alcohol 3 by the sequence esterification, macrolactonization, ester enolate Claisen rearrangement, and decarboxylation. Chlorothricin (la), one of some 500 known macrolide antibiotics, 3 was isolated in 1969 by W. Keller-Schierlein. 4 Active …