TOWARDS PHORBOXAZOLE B: THE C20-C32 FRAGMENT

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.