Synthesis of stable analogues of TXA2

Abstract

Intramolecular aldol condensations and intramolecular Lewis acid-catalysed alkylations are used in approaches to substituted bicyclo[3.3.1]nonanes and bicyclo[3.2.1]octanes, specifically the oxo esters (7), (8), and (9). A ring expansion to a cycloheptane derivative is observed on treatment of the cyclopentyl derivative (18) with acid, and the bicyclo[4.4.0]decane and bicyclo[4.3.0]nonane derivatives (34) and (36) are obtained from the prenyl derivatives (30) and (35) respectively. The oxo esters (7), (8), and (9) are converted into the stable TXA₂ analogues (10), (11), and (12) respectively, by a series of reactions which involve stereospecific functionalisation of their ketone and ester groups.