Oligosaccharides calicheamicin

Synthesis of calicheamicin oligosaccharide dimers and their duplex DNA recognition 97YGK600. 

Liu, C B.M. Smith, K. Ajito, H. Komatsu, L. Gomezpaloma, T.H. Li, E.A. Theodorakis, K.C. Nic-olaou, and P.K. Vogt (1996). Sequence selective carbohydrate DNA interaction dimeric and monomeric forms of the calicheamicin oligosaccharide interfere with transcription factor function. Proc. Natl. Acad. Sci. USA 93 940-944. 

The syntheses of a modified carbohydrate moiety, a head-to-tail dimer of the calicheamicin oligosaccharide [176], the 1,1 -disaccharide (trehalose) containing the carbohydrate moiety of everninomycin [177], and the vancomycin disaccharide... 

The calicheamicin oligosaccharide 5 (Scheme 2) was shown to bind with low micromolar affinity to its target site with similar selectivity as compared to calicheamicin Yi (3) [38] (see also references in [39]). This unique property could be used to compete off specific transcripton factors from their target sequence at the expected concentrations [39]. The limited selectivity and potency, however, were not sufficient for a meaningful biological application and the recent progress in the synthesis of complex oligosaccharides allowed this approach to be explored further. 

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. 

Nicolaou s total synthesis of the enediyne antibiotic, calicheamicin 71 [19], (Scheme 12.15 to Scheme 12.19) involves several new aspects in carbohydrate chemistry. The calicheamicin 71 oligosaccharide synthesis began with the construction of the D-ring intermediate from L-rhamnose. Thus, L-rhamnose 112 was converted into the glycosyl donor, trichloroacetimidate 118, through the... 

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