Chemo- and regioselective functionalization of nortrilobolide: application for semi-synthesis of the natural product 2-acetoxytrilobolide

TY - JOUR

T1 - Chemo- and regioselective functionalization of nortrilobolide: application for semi-synthesis of the natural product 2-acetoxytrilobolide

AU - Doan, Thi Quynh Nhu

AU - Crestey, François

AU - Olsen, Carl Erik

AU - Christensen, Søren Brøgger

PY - 2015/6/26

Y1 - 2015/6/26

N2 - The difference in reactivity of the hexaoxygenated natural product thapsigargin (1) and the pentaoxygenated nortrilobolide (3) was compared in order to develop a chemo- and regioselective method for the conversion of nortrilobolide (3) into the natural product 2-acetoxytrilobolide (4). For the first time, a stereoselective synthesis of 2-acetoxytrilobolide (4) is described, which involves two key reactions: the first chemical step was a one-pot substitution-oxidation reaction of an allylic ester into its corresponding α,β-unsaturated ketone. The second process consisted of a stereoselective α′-acyloxylation of the key intermediate α,β-unsaturated ketone to afford its corresponding acetoxyketone, which was converted into 2-acetoxytrilobolide (4) in a few steps. This innovative approach would allow the synthesis of a broad library of novel and valuable penta- and hexaoxygenated guaianolides as potential anticancer agents.

AB - The difference in reactivity of the hexaoxygenated natural product thapsigargin (1) and the pentaoxygenated nortrilobolide (3) was compared in order to develop a chemo- and regioselective method for the conversion of nortrilobolide (3) into the natural product 2-acetoxytrilobolide (4). For the first time, a stereoselective synthesis of 2-acetoxytrilobolide (4) is described, which involves two key reactions: the first chemical step was a one-pot substitution-oxidation reaction of an allylic ester into its corresponding α,β-unsaturated ketone. The second process consisted of a stereoselective α′-acyloxylation of the key intermediate α,β-unsaturated ketone to afford its corresponding acetoxyketone, which was converted into 2-acetoxytrilobolide (4) in a few steps. This innovative approach would allow the synthesis of a broad library of novel and valuable penta- and hexaoxygenated guaianolides as potential anticancer agents.

U2 - 10.1021/acs.jnatprod.5b00333

DO - 10.1021/acs.jnatprod.5b00333

M3 - Journal article

C2 - 26078214

SN - 0163-3864

VL - 78

SP - 1406

EP - 1414

JO - Journal of Natural Products

JF - Journal of Natural Products

IS - 6

ER -