Towards phorboxazole B : the C20-C32 fragment

• Main Author: Ermanis, Kristaps
• Other Authors: Clarke, Paul A.
• Published: University of York 2014
• Subjects: 540
• Online Access: http://ethos.bl.uk/OrderDetails.do?uin=uk.bl.ethos.634378

Phorboxazole A and phorboxazole B are two potent cytostatic polyketides isolated from Phorbas marine sponge found in the Indian Ocean. Because of their excellent cytostatic activity and unprecedented structure phorboxazoles have been a very attractive target for synthetic chemists and eleven total syntheses have been reported. A novel and efficient synthesis of the C20-C32 core fragment of phorboxazoles has been developed. Key steps were: an enantioselective aldol reaction, a diastereoselective crotylation and, a diastereoselective oxy-Michael reaction. The synthesis was 7 steps long with an overall yield of 31%. A stereodivergent oxy-Michael reaction was further investigated in a computational study and analogue study.