42 抗腫瘍性セスキテルペン(+)-イバリンの不斉全合成

概要

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The development of methodology for the asymmetric total synthesis of the biologically active natural products is an area of fruitful and challenging current research. We have reported a highly efficient enantioselective and diasteroselective synthesis of 1,2-disubstituted cycloalkanecarboxaldehydes based on the controlling of the substrate conformation by virtue of chelation. Herein we wish to report successful application of the method to the first asymmetric total synthesis of (+)-ivalin 1, a representative of the class of antitumor eudesmane sesquiterpene lactones. The reaction of isopropenyl Grignard reagent with a chiral α,β-unsaturated imine 22 has been shown to undergo a highly enantioselective 1,4-addition-alkylation sequence, giving 6 in 95% e.e. Then 6 was converted into 5. Ene-carbonyl cyclization of 5 with SnCl_4 afforded selectively 30 in 61% yield. By the reaction of the corresponding mesylate 33 with KO_2 in DMSO followed by protection the stereoinversion of the OH group in 30 was carried out to give 34. Alkylation of 34 with BrCH_2CO_2CH_3 and epimerization afforded 36. Subsequent construction of α-methylene lactone moiety has culminated in a first asymmetric total synthesis of the optically pure eudesmane sesquiterpene (+)-ivalin 1.
天然有機化合物討論会の論文
1983-09-15