The C3-C14 segment of the novel antitumor agent laulimalidehas been constructed enantioselectively by utilizing a catalytic asymmetric hetero Diels-Alder reaction of benzyloxyacetaldehyde and Danishefsky's diene followedby Ferrier rearrangementand asymmetric CO13JUgak reactionas the key steps.@1997 Elsevier Science Ltd.
Laulimalide 1 also known as figianolideB, is a 20-memberedmacrolideisolated from the IndonesianspongeHyatteZla Sp.1 Morerecently,laulimalidehas alsobeenisolatedfroman Okinawan spongeFasciospongia rinzosa.2 Laulimalide representsa new and novel class of macrolidewith potentcytotoxicityagainstthe KB cell line with an IC50 vaiueof 15 ng/mL.lb The cytotoxicityof laulimalideagainstP388,A549,HT29andMEL28celllinesis alsoin therangeof 10-50ng/mL(IC50 values).2b The gross structureof laulimalidewas establishedby NMR studiesand more recentlyits absoluteconfigurationhas been elucidatedby X-raycrystallographic analysis.2aIn viewof its limited supplyand unique structuralfeaturesas well as its potentialutility as an anticanceragent, synthetic studiesof laulimalidebecameof interestto us. Herein, we report on the asymmetricsynthesisof the C3-C14segmentof laulimalidein whicha chiralbis(oxazoline)-metal complexcatalyzedheteroDiels-Alder reaction, a Ferrier type rearrangementof the derivedglycal and diastereoselectiveconjugate additionwereutilizedto settheC-9,C-5andC-11asymmetriccenters.