Asimicin

The total synthesis of (+)-asimicin also uses this methodology for the introduction of the butenolide in one of the final steps, the formation of 117 from 116 (Scheme 15.34) [78], Owing to the small scale (18 pirn o 1), an excess of catalyst had to be used. 

Comparison of Pesticidal Activity of Asimicin (2) (Figure 13.1) and Paw Paw Extract (F005) vs. Standard Insecticides... 

The Annonaceous acetogenins offer a unique mode of action (ATP depletion) against MDR tumors and against insecticide-resistant pests and are predicted to become important future means of thwarting ATP-depleting-resistance mechanisms. Their SARs in several systems have been determined (Landolt et al., 1995 Alfonso et al., 1996 He et al., 1997 Oberlies et al., 1997 Miyoshi et al., 1998) and optimum structural features generally point to the bis-adjacent THF compounds such as bullatacin (1) and asimicin (2). 

Shimada, H., Grutzner, ]., Kozlowski, J.F., and McLaughlin, J.L. Membrane conformations and their relation to cytotoxicity of asimicin and its analogs. Biochemistry, 37, 854, 1998. 

In 1995, Hoye published total syntheses of (+)-asimicin (69) and (+)-bullatacin (70), which differ only in their configurations at C-24 [97J. Here, the AD was used for the synthesis of two key fragments, 81 and 82. 

Thus, 1.7-octadiene (79), which was subjected to monohydroboration followed by asymmetric dihydroxylation of the remaining double bond to give triol 80 with approximately 80% ee. Further transformations then afforded the desired butenolide 81. Double asymmetric dihydroxylation of diene 83 and subsequent protection gave hydroxy lactone 84 [98], which was then converted into acetylenic bis(hydroxy)bistetrahydrofuran 82 as the required intermediate for the (+)-asimicin synthesis. Mitsunobu inversion at C-24 gave rise to the diastereomeric (+)-bullatacin precursor. 

A synthesis of the Annonaceous acetogenin asimicin and a side-chain analogue has been achieved by a highly convergent route in which Grubbs cross-metathesis played a key role.98... 

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