Geodiamolide A (la) and jaspamide (2) have been efficiently synthesized by use of the Evans asymmetric allcylation, the Mitsunobu esterification, and the DPPA macrolactsmization as key steps.
Geodiamolide A (la), isolated from a Caribbean sponge Geodia sp.ta and a Papua New Guinean sponge Pseudaxinyssa sp.,lb is a cyclic depsipeptide containing the tripeptide and polypropionate units. The other geodiamohdes B-F (lb-M) which are different each other in the peptide parts are also known in addition to jaspami&a (jasplakinolide2b) (2). which has been isolated from a south Pacific sponge Jaspis sp. As shown in the formula 2, jaspamide is a cyclic depsipeptide containing the same polypropionate unit as that of geodiamolides.
Cytotoxic and antifungal activities have been reported as the biological properties of both geodiamolides and jaspamide, the latter of which has also been found to have insecticidal and anthelmintic properties. These intemsting biological activities as well as their structural uniqueness have led several groups to synthesize these depsipeptides. 3-7 However, the stereoefficiencies of these syntheses have not been satisfactory and the yields of the final cycIization through the lactone formation have been low in the synthesis of geodiamolides.3
These results will preclude the supply of enough quantities of these depsipeptides to investigate their biological profiles in detail. Now, we wish to report efficient stereoselective syntheses of geodiamolide A (la) and jaspamide (2). which will promise their large scale production. The key steps of our syntheses are: (1) the asymmetric alkylation using the Evans chiral oxazolidinone to construct the polypropionate unit, (2) the coupling of the tripeptide unit with the polypropionate by the Mitsunobu reaction, and (3) the intramolecular amide bond formation using diphenyl phosphorazidate (DPPA,