Calicheamicin aglycone

Crevisy, C. Beau, J.-M. The esperamicin-calicheamicin aglycones ring closure of a simple strained system mediated by chromium(II)-nickel(ll) salts. Tetrahedron Lett. 1991, 32, 3171-3174. 

In a model reaction for the preparation of the esperamicin/calicheamicin aglycones (Scheme 2-20) the enediyne alcohol 175 is converted into the terminal iodo derivative 176 by... 

A number of other strategies have been reported for constructing the enediyne core of the calicheamicin aglycone. These include the oxidative formation of the enediyne unit from a... 

The first total synthesis of the calicheamicin aglycone (222, calicheamicinone) was finally achieved in 1990 by Danishefsky and co-workers [217-223]. Their synthesis, shown in Scheme 7-48, was a major achievement in this field. Key steps in the sequence, which begins... 

Total synthesis of the calicheamicin aglycone (Danishefsky and co-workeis). 

As impressive as the oligosaccharide domain is, calicheamici-none, the aglycon sector 7 (see Scheme 3) is the most striking substructure of calicheamicin y. The rigid bicyclic framework of 7 accommodates an unusual allylic methyl trisulfide and a novel pattern of unsaturation that had not been encountered in natural products before. 

Clive and coworkers have reported a total synthesis of calicheamicinone, the aglycon of the antitumor agent calicheamicin starting from the Diels-Alder reaction of methyl 3-nitro-propenoate with ketene acetal (Eq. 8.32).54 An asymmetric Diels-Alder reaction between ketene acetal presented in Eq. 8.32 and 3-nitropropenoate derived from (-)-8-phenyl-menthol affords the optically pure adduct, which can be converted into either enantiomer of calicheamicinone (Eq. 8.33).55... 

Transformation of o-methoxyphenol (135) into o-quinone monoacetal (136) using PIDA was used for the initial step of the synthesis of the enediyne aglycone, ( )-calicheamicinone (10), of the potent antitumor agent calicheamicin [93] (Scheme 10). 

Halcomb, R L, Boyer, S H, Danishefsky, S J, Synthesis of the calicheamicin aryltetrasaccharide domain bearing a reducing terminus — coupling of fully synthetic aglycone and carbohydrate domains by the Schmidt reaction, Angew. Chem. Int. Ed. Engl, 31, 338-340, 1992. 

The reaction of calicheamicin with the double helix of DNA is significantly different from that with the isolated aglycon (Drak et al. 1991). 

The same substrate and the same technique make it possible to compare the efficiency of calicheamicin and its separated aglycon. In the presence of a reducing thiols, calicheamicin causes degradation at concentrations as low as 0.7 nM. At a concentration of 1.5 pM, only small nucleotides remain. Calicheamicinone causes cleavage observable at a concentration of 13 pM. 

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