Total synthesis of calicheamicinone: new arrangements for actuation of the reductive cycloaromatization of aglycon congeners

The carbohydrate domain of calicheamicin gamma I1 determines its sequence specificity for DNA cleavage.

“…Calicheamicin Yi was kindly provided by G. Ellestad (American Cyanamid); calicheamicinone was synthesized as described (10). To oligonucleotides, one of them containing a TCCT cleavage site for the natural product (5,6), whereas in the other one we modified that sequence to TACT, the assumption being that the latter would not be a cleavage site for calicheamicin yi and could be used as a control in our experiments (oligonucleotides B and C, Fig.…”

“…Our logic relies on a comparison with the corresponding aglycone, the synthetic analog calicheamicinone (10). We have shown that the sugars are responsible for the sequence selectivity of the natural compound and that the carbohydrate moiety increases the apparent binding affinity with respect to the core aglycone by -3 orders of magnitude.…”

Chemistry and biology of natural and designed enediynes.

“…Danishefsky (31,32), Kende (33), Magnus (34,35), and Schreiber (36) and their colleagues were among the first of many to demonstrate that the construction ofthe bicyclic framework of the aglycon is not as daunting as at first appeared. Meanwhile, Magnus et al (66) had studied the chemistry of the allylic trisulfide group, and Danishefsky and coworkers (67), in a magnificent achievement, had succeeded in assembling the full functionality to achieve the first synthesis of calicheamicinone (80) as its racemate. Thus at the beginning of 1991, we embarked upon a new approach to the aglycon which would hopefully provide the molecule in enantiomerically pure form and in sufficient quantities for coupling to the oligosaccharide and completing the total synthesis of calicheamicin 'y.…”

“…A selection of these model compounds covering the rather wide spectrum of structural types synthesized in this field is shown in Fig. 9 [63 (55), 64 (56), 65 (57), 66 (58), 67 (59), and 68 (60)]. …”

A New Nucleophilic Ring Opening of an Activated Cyclopropane and a Formal Synthesis of (±)-Carbovir

“…Cyclopropanationnucleophilic ring opening 6 ) would be one solution for this issue. In this paper, we wish to describe a novel opening reaction of doubly activated cyclopropane for introducing the hydroxy methyl group into the cyclopentane ring and its application for the synthesis of the potent anti-HIV agent carbovir (9). 7) At first we investigated homoconjugate addition of nucleophiles to activated cyclopropane 1 8 ) (Scheme 1).…”