The objective of the proposed research is to develop a unique and mild synthetic technique to construct the labile [3.1.1.] bicyclic acetal ring system found in thromboxane A2 (TXA2). Thromboxane A2 is an unstable (t1/2 30-40 s at 37C) major metabolite of the arachadonic acid cascade in human platelets with potent thrombotic and vasoconstricting properties; the structure proposed has not been rigorously verified. This proposal outlines a mild and practical method for the overall dehydrative ring closure of 1,3-dihydroxypyronosides to the corresponding bicyclic [3.1.1.] acetals using polymer-supported reagents. In this way, the labile products can be cleanly recovered from the polymer-bound reaction by-products without a chromatographic separation. The present methodology is readily adaptable to the conversion of TXB2 (the stable hydrolysis product of TXA2) into TXA2. This shall provide a non-aqueous preparation of TXA2 for structure determination and that of simpler analogs for biological investigation.
