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.