The Synthesis of Desamido Analogs of Staurosporine, RK-286c, and TAN-1030a

The nanomolar kinase inhibitory activity of staurosporine (1) and K252a (5) has prompted a continuing effort to isolate and/or synthesize novel pyranosylated and furanosylated indolocarbazoles.l,2,3. 4 Recently, we reported the enantioselective synthesis of (+)-K252a via an approach involving the late-stage coupling of aglycon 8 and furanose 9 (Scheme 1). Although this approach proved efficient for the p r e p a r a t i o n of f u r a n o s y l a t e d indolocarbazoles (e.g., 5), attempts to access the corresponding pyranosylated structures (e.g., 1 3 ) via a s imi lar s ingle-s tep glycosidation strategy have met with limited success. 5 In fact, the stepwise procedures developed in Danishefsky ' s l andmark synthesis of staurosporine have stood as the only successful means of accessing the fully functionalized pyranosylated indolocarbazoles (Scheme 1, e.g. 7 --> 1). 2 Herein we report results from a model investigation that demonstrate the feasibility of an alternative approach wherein a ring expansion reaction is utilized to access a single pyranosylated intermediate that can be readily transformed into desamido analogs of staurosporine, RKS c h e m e 1