APPLICATION AND MECHANISTIC STUDIES OF THE [2,3]-WITTIG REARRANGEMENT - AN APPROACH TO THE BICYCLIC CORE STRUCTURE OF THE ENEDIYNE ANTITUMOR ANTIBIOTICS CALICHEAMICIN GAMMA(1)(I) AND ESPERAMICIN-A(1)

被引:27
作者
AUDRAIN, H [1 ]
SKRYDSTRUP, T [1 ]
ULIBARRI, G [1 ]
RICHE, C [1 ]
CHIARONI, A [1 ]
GRIERSON, DS [1 ]
机构
[1] CNRS,INST CHIM SUBST NAT,F-91198 GIF SUR YVETTE,FRANCE
关键词
D O I
10.1016/S0040-4020(01)80630-X
中图分类号
O62 [有机化学];
学科分类号
070303 ; 081704 ;
摘要
Starting from readily available beta,gamma-unsaturated cyclohexenone precursors the 13-membered bicyclic enediyne 8 was prepared as well as the corresponding ''dihydro'' analogs 11 and 42 lacking the C4-C5 double bond. [2,3]-Wittig ring contraction fo 8 to 9, possessing the bicyclo [7.3.1] tridecadiynene system, characteristic of the enediyne antibiotics calicheamicin and esperamicin,was obstructed by competing electron transfer reactions involving the planar enediyne system. However, [2,3]-Wittig rearrangement of the 1,5-diynes 11 and 42 proved efficient. Under mild base conditions (DBU, 20 degrees C) the 10-membered bicyclic 1,5-diyne 57, bearing a OMs group at C-4, was converted to enediyne 9. This product underwent spontaneous Bergman cyclization giving a series of products, several of which lacked the O-Me substituent which was introduced at C-8. These results, confirmed by deuterium labeling studies, brought to light the occurrence of an internal quenching process involving 1,5-radical translocation.
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页码:1469 / 1502
页数:34
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