Synthetic studies of mycalolide B, an actin-depolymerizing marine macrolide: construction of the tris-oxazole macrolactone using ring-closing metathesis

Tris-oxazole macrolactone 2, a key intermediate of mycalolide B (1), which has 13 stereogenic centres, was synthesized through the use of ring-closing metathesis (RCM). The E/Z ratio of the RCM product 2 was reversed by the use of CH2Cl2 and toluene, whereas a cross-metathesis reaction yielded the C1-C35 long-chain compound 19 in a highly E-selective manner. Thus, the loss of flexibility in aliphatic carbon chains and the steric hinderance of β- and γ-substituents of the C20 olefin in the precursor 11 may affect the stereoselectivity in RCM reactions.

Tris-oxazole macrolactone 2, a key intermediate of mycalolide B, was synthesized through the use of ring-closing metathesis (RCM).