The synthesis of antitumor gilvocarcin antibiotics (la-h) is based on a novel strategy (Scheme 1, P. 18) in which a C-1 lithiated glycal is added to a quinone acetal (e.g. 6+7 -> 8). The concurrent aromatization of the adduct and antiMarkovnikov hydration of the glycal double bond is then accomplished with diborane; this reaction, developed during the course of work on this project affords a C-aryl glycoside (e.g. adduct 8 will be converted to 9). Appropriately substituted C-aryl glycosides 10 will be converted to chromium carbenes which will be added to the acetylene 11 (R=CH=CH2) (readily available by a five-step procedure) to afford the V series of gilvocarcins (la-c, and e).The M series of gilvocarcins can be prepared by parallel scheme. In addition to the model gilvocarcin 43 (from D-glucose) and the natural products la-e, the disaccharide analog 65 will be prepared. Ravidomycin (la, authentic natural product ) and synthetic gilvocarcins will be subjected to DNA binding studies in an effort to clarify the mechanism of action of the gilvocarcin series.
