Synthesis of Novel Discodermolide Analogues with Modified Hydrogen-Bonding Donor/Acceptor Sites.

Abstract A series of novel structural analogues of the potent microtubule-stabilizing anticancer agent discodermolide were synthesised, with modifications in the C16–C20 region to create new oxygenated H-bonding donor/acceptor sites for tubulin binding. By starting from an advanced C9–C24 intermediate, fully synthetic discodermolide analogues, incorporating either an additional hydroxyl group 3 , an oxetane 4 or a cyclic carbonate 5 , were obtained in 10 or 11 steps by using a versatile aldol construction of the C6–C7 bond.