Calicheamicin-Esperamicin

Scheme 20. Sonogashira couplings in Magnus s calicheamicin/esperamicin model study.

Further elaboration of models involved the design of water-soluble derivatives like diol 305, suitable for tests as DNA-affecting agents. It was rewarding to discover that the conversion 305 -> 306 can be carried out in water in the presence of DNA. As a result, a temperature- and time-dependent cleavage of double-stranded DNA was observed. Hence diol 305, the simplicity of its structure notwithstanding, can be properly considered as the synthetic mimic of the calicheamicin/esperamicin class of antibiotics. Most remarkably, it took less... 

Research by S.J. Danishefsky et al. has shown that calicheamicin/esperamicin antibiotics containing an allylic trisulfide trigger can undergo a mild Bergman cyclization when treated with benzyl mercaptan." ... 

Mantlo, N.B. Danishefsky, S.J. A core system that simulates the cycloaromatization and DNA cleavage properties of calicheamicin-esperamicin a correlation experiment, J. Org. Chem. 1989, 54, 2781-2783,... 

Semmelhack, M,F, Gallagher, J.J. Minami, T. Date, T, The enol-keto trigger in initiating arene diradical formation in calicheamicin/esperamicin analogs. J. Am. Chem. Soc. 1993, 115, 11618-11619. 

Simulation of the calicheamicin/esperamicin cascade has been amply demonstrated by Danishefsky and co-workers with a variety of compounds (Scheme 7-49) [219-221]. Furthermore, comparisons of ealicheamicin yj (2) and calicheamicinone (222) in DNA-cleavage experiments pointed to the importance of the carbohydrate fragment of the natural product in the molecular recognition of its target sequence [85]. 

J.3 Synthetic Approaches to the Calicheamicin/Esperamicin Carbohydrate Fragments... 

Scheme 7-62 The Kahne synthesis of the calicheamicin/esperamicin core trisaccharide fragment 300.

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