Synthesis of metabolites of S-1452, an orally active thromboxane A2 receptor antagonist

The synthesis of 16 metabolites of S-1452, an orally active thromboxane A2 (TXA2) receptor antagonist, is described. Regioselective hydroxylation at C-5 or C-6 of the bicyclo[2.2.1]heptane skeleton of the optically active intermediate 16 was attempted by using 9-borabicyclo[3.3.1]nonane followed by H2O2 or m-chloroperbenzoic acid (m-CPBA) and then LiA1H4, to obtain the hydroxylated product 17a or 17b, respectively. Modification of the C-2 substituent of 17a and 17b afforded eight metabolites of S-1452. Eight non-hydroxylated metabolites were synthesized by using a similar reaction sequence.