Synthesis of the C(29)-C(45) bis-pyran subunit (E-F) of spongistatin 1 (altohyrtin A)

A synthesis of the C(29)-C(45) bis-pyran subunit 2 of spongistatin 1 (1a) is described. The synthesis proceeds in 19 steps from the chiral aldehyde ent-7, and features highly diastereoselective alpha -alkoxyallylation reactions using the gamma -alkoxy substituted allylstannanes 17 and 19, as well as a thermodynamically controlled intramolecular Michael addition to close the F-ring pyran. The E ring was assembled via the Mukaiyama aldol reaction of F-ring methyl ketone 3 and the 2,3-syn-aldehyde 4.