Development of a synthesis of lankacidins: an investigation into 17-membered ring formation

MATA, ERNESTO G.; THOMAS, ERIC J.

JOURNAL CHEMICAL SOCIETY PERKIN

Royal Society of Chemistry

Año: 1995

0300-922X

tudies are reported concerning the synthesis of macrocyclic analogues of the lankacidins. The long-chain trienylphosphonate 33 has been synthesized as a mixture of epimers at C(7), by a convergent route which involved alkylation of ethyl 2-methyl-3-oxobutanoate 10 by the 10-(tert-butyldimethylsilyloxy)-3,9-dimethyldeca-2,4,8-trienyl chloride 11 to give 27 followed by an aldol addition to the aldehyde 12. Stereoselective reduction then gave the 1,3-syn-diol 35 which was protected as its acetonide 36. However, it did not prove possible to hydrolyse the 1,3-dioxolane ring in 36 to reveal the keto phosphonate grouping and leave the acetonide component intact. To avoid this problem, acrolein was added to the alkylated keto ester 27 to give the aldol product 40 as a mixture of diastereoisomers.