Synthesis of 8-(S)-methoxy-11-desmethyl laulimalide: a novel laulimalide analogue

A strategy is outlined which enables preparation of novel laulimalide analogues at C.8 and C.11. A representative analogue, 8-(S)-methoxy-11-desmethyl laulimalide, was synthesized via this route.     

Conformational studies and solution structure of laulimalide and simplified analogues using NMR spectroscopy and molecular modelling

The solution structures of the potent microtubule-stabilizing anti-cancer agent laulimalide and simplified analogues were determined by a combination of high field ¹H NMR spectroscopic studies (J-based configuration analysis and NOESY) and constrained molecular dynamics simulations and discussed in relation to their antiproliferative activity.     

Towards a simplified peloruside A: synthesis of C1-C11 of a dihydropyran analogue

A simplified analogue of the C1-C11 fragment of peloruside A has been synthesised starting from a monoprotected 2,2-dimethylpropane-1,3-diol. Oxidation, asymmetric allylation and acryloylation provided a substrate for ring-closing metathesis to a δ-lactone. Reduction, acylation and homologation with trimethyl(vinyloxy)silane provided a protected C3-C11 analogue in a stereoisomer manner. Introduction of the C1-C2 fragment and incorporation of the 2,3-syn stereochemistry was achieved by a boron-mediated Evans aldol reaction.     

Stereoselective synthesis of the C3–C12 subunit of laulimalide

A stereoselective synthesis of the C3–C12 subunit of the tumor growth inhibitors laulimalide is disclosed. The key steps of the synthesis include asymmetric alkylation using Oppolzer’s protocol and an asymmetric hetero-Diels–Alder reaction using Jacobsen’s catalyst. Substrate controlled diastereoselective Luche reduction followed by Ferrier type reactions are other key steps.     

Synthetic studies on a phenyl-laulimalide analogue

An analogue of the paclitaxel-like antimicrotubule agent laulimalide with a phenyl in place of the dihydropyran has been synthesized. The fragments C₁-C₁₄ and C₁₅-C₂₈ were coupled via a stereoselective intermolecular allylboration. Ring closure was achieved using Yamaguchi’s protocol.