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Pure Appl. Chem., 2013, Vol. 85, No. 6, pp. 1133-1147

Published online 2013-05-20

Total synthesis of (+)-spirastrellolide A methyl ester: Challenges and discoveries

Ian Paterson*, Philip Maltas and Edward A. Anderson

University Chemical Laboratory, Lensfield Road, Cambridge CB2 1EW, UK

Abstract: This review focuses on recent synthetic efforts by our group towards spirastrellolide A methyl ester, a complex marine macrolide containing two spiroacetal ring systems that shows promising anticancer properties. The evolution of a flexible, modular strategy leading to the first total synthesis of (+)-spirastrellolide A methyl ester, and the associated challenges overcome, are highlighted, particularly in dealing with the initial structural ambiguities. This work enabled the development of an improved second-generation synthesis, which revealed a critical dependence of the key macrolactonization step on the nature of the protecting groups in the linker region between the spiroacetal motifs.