The polyketide-derived C-aryl glycoside natural products have a variety of interesting biological activities, most notably antitumor activity. There is considerable variety in the structures of both the aglycone and the sugar moieties of these compounds. Our ability to modify these functionally complex naturally occurring materials is limited; furthermore, the natural products are difficult to obtain. Therefore, synthesis is not only intellectually challenging, it is also essential for the study of structure-activity relationships. Recognizing the potential importance of compounds with the aryl C-glycoside structural feature, we are driven by the following goals: (1) to develop new strategies and efficient methods for the synthesis of C-aryl glycosides and for the preparation of polycyclic aromatic systems with control of substitution pattern; (2) to demonstrate new strategies and methods by application to the synthesis of natural products; (3) to take advantage of efficient sequences to prepare new C-aryl glycosides with the eventual goal of developing a structure-activity picture for the C-aryl glycoside antibiotics. Our experience with quinone chemistry led us to consider a """"""""reverse polarity"""""""" or """"""""umpolung"""""""" approach to the synthesis of C-aryl glycosides. This approach has produced methodology which establishes the functional group patterns required for preparation of members of all four structural classes of these antibiotics. We have recently completed a synthesis of ent-C104 and are close to the completion of a synthesis of papulacandin D. These compounds represent two of the major structural classes of aryl C-glycosides. During the period which corresponds to this proposal, we plan to apply our new methodology to the synthesis of deacetylravidomycin and kidamycin, representatives of the remaining two major classes.
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