TOTAL SYNTHESIS OF THE ANNONACEOUS ACETOGENIN (-ASIMICIN - DEVELOPMENT OF A NEW BIDIRECTIONAL STRATEGY())

The total synthesis of the Annonaceous acetogenin (+)-asimicin is desc ribed. The approach employs the (R)-alpha-OSEM allylic stannane 7 of > 95% ee and the dialdehyde 8 obtained from (S,S)-diethyl tartrate. Addi tion of 7 to 8 in the presence of InCl3 afforded the bis-adduct 9 in 7 1% yield. Tosylation and treatment with TBAF led to the core bis-tetra hydrofuran intermediate, diol 11, in 78% yield. Mono tosylation (n-BuL i, TsCl, THF-DMSO) and subsequent hydrogenolysis with LiBEt3H gave alc ohol 14. The iodide 15 was coupled with the higher-order vinylcyanocup rate to afford olefin 30. This was converted to diol 31 of high ee by the Sharpless protocol. This diol yielded the epoxide 33 via the mono- trisylate 32. Addition of (R)-lithio-2-(OTBS)-3-butyne in the presence of BF3 . OEt2 afforded the alcohol 34. The SEM derivative 35 was trea ted with TBAF, and the resulting alcohol was converted to the butenoli de 38 by a sequence involving treatment with (CF3CO)(2)O, then Pd(PPh3 )(4), CO, THF-H2O, and finally AgNO3/silica gel. Cleavage of the SEM p rotecting group with PPTS in ethanol afforded (+)-asimicin (39).