Total synthesis of curvulone B and a proposed structure for dothiorelone B; determination of the configuration of curvulone B and structural revision of phomopsin A

The total synthesis of curvulone B was achieved, and its absolute configuration unambiguously established, as had been determined by TD-DFT ECD calculations on the computed solution conformers. Key features of the synthesis were an olefin cross-metathesis of an α,β-unsaturated ketone as a common key building block with (R)-6-triethylsilyloxyhept-1-ene, and an intramolecular oxy-Michael addition of the hydroxyl enone obtained therefrom. An intermolecular metathesis of the enone with (S)-5-benzyloxyhept-ene also enabled us to prepare a proposed structure for dothiorelone B, thus leading to the confirmation of the structural revision of phomopsin A, a novel nine-membered cyclic phenol ether.

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(R,E)-1-(2,4-Bis(benzyloxy)-6-(2,2-dimethoxyethyl)phenyl)-7-(triethylsilyloxy)oct-2-en-1-oneC38H52O6Si[α]D24=-3.1 (c 0.65, CHCl3)Absolute configuration: (R,E)

1-(2,4-Bis(benzyloxy)-6-(2,2-dimethoxyethyl)phenyl)-2-((2S,6R)-6-methyltetrahydro-2H-pyran-2-yl)ethanoneC32H38O6[α]D24=+10.8 (c 0.41, CHCl3)Absolute configuration: (2S,6R)

1-(2,4-Bis(benzyloxy)-6-(2,2-dimethoxyethyl)phenyl)-2-((2R,6R)-6-methyltetrahydro-2H-pyran-2-yl)ethanoneC32H38O6[α]D24=-1.3 (c 0.82, CHCl3)Absolute configuration: (2R,6R)

Methyl 2-(3,5-bis(benzyloxy)-2-(2-((2R,6R)-6-methyltetrahydro-2H-pyran-2-yl)ethanoyl)phenyl)ethanoateC31H34O6[α]D23=-0.7 (c 0.71, CHCl3)Absolute configuration: (2R,6R)

(S,E)-6-(Benzyloxy)-1-(2,4-bis(benzyloxy)-6-(2,2-di-methoxyethyl)phenyl)oct-2-en-1-oneC39H44O6[α]D22=+5.2 (c 0.43, CHCl3)Absolute configuration: (S,E)

(S,E)-Ethyl 2-(3,5-bis(benzyloxy)-2-(6-(benzyloxy) oct-2-enoyl)phenyl)ethanoateC39H42O6[α]D25=+4.9 (c 0.66, CHCl3)Absolute configuration: (S,E)