摘要：

Griseolic acid A (1) is a member of a family of related structures isolated from the culture broth of Streptomyces griseoaurantiacus. They have been shown to be potent, but nonselective, inhibitors of cyclic nucleotide phosphodiesterases from various tissues. The griseolic acids were of particular interest since they contain the highly unusual and strained 1,5-dioxabicyclo[3.3.0]oct-3-ene. Indeed this bicylic diacid is believed to act as a mimetic of the ribose phosphate in cyclic nucleotides. We have used the griseolic acids as a template to discover more selective and therefore therapeutically useful antihypertensive agents. The total synthesis of griseolic acid A, described in this Communication, presents stereochemical and structural challenges absent in our previous work. Thus the key steps of this synthesis are (a) the introduction of the two-carbon acid at 6′ on the hindered α face of the bicyclic system; (b) the formation of the β adenine nucleoside; (c) the stereoselective introduction of the 7′-hydroxyl; and (d) the efficient formation of the key bicyclic enol ether of the griseolic acids.

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