The first total synthesis of naturally occurring (+)-gymnasterkoreayne F and its enantiomer

The first total synthesis of naturally occurring (+)-gymnasterkoreayne F and its enantiomer is reported. The seven-step route to these two polyacetylenes in enantiomerically pure form involves the use of (+)-2,3-O-isopropylidene-l-threitol and (−)-2,3-O-isopropylidene-d-threitol, respectively, as the starting material and a Cadiot–Chodkiewicz reaction as a key step. The absolute configuration of (+)-gymnasterkoreayne F has been confirmed to be (2E,8S,Z). The natural product and its enantiomer have been found to exhibit modest cytotoxicity against the 60 human tumor cell lines of the National Cancer Institute.

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(2S,3S,4Z)-2,3-(Isopropylidenedioxy)-1-(p-methoxybenzyloxy)-dodeca-4,11-dieneC23H34O4[α]D28=+7.0 (c 3.17, CHCl3)Source of chirality: (+)-2,3-O-isopropylidene-l-threitolAbsolute configuration: (2S,3S,4Z)

(2S,3S,4Z)-2,3-(Isopropylidenedioxy)-dodeca-4,11-dien-1-olC15H26O3[α]D28=-11.3 (c 3.14, CHCl3)Source of chirality: (+)-2,3-O-isopropylidene-l-threitolAbsolute configuration: (2S,3S,4Z)

(2R,3S,4Z)-1-Chloro-2,3-(isopropylidenedioxy)-dodeca-4,11-dieneC15H25ClO2[α]D28=-7.65 (c 3.11, CHCl3)Source of chirality: (+)-2,3-O-isopropylidene-l-threitolAbsolute configuration: (2R,3S,4Z)

(3S,4Z)-Dodeca-4,11-dien-1-yn-3-olC12H18O[α]D28=+132.4 (c 1.14, CHCl3)Source of chirality: (+)-2,3-O-isopropylidene-l-threitolAbsolute configuration: (3S,4Z)

(S,2E,9Z)-Heptadeca-2,9,16-trien-4,6-diyne-1,8-diol[(+)-gymnasterkoreayne F]C17H22O2Ee = 98.5%[α]D28=+370.0 (c 0.525, CH3OH)Source of chirality: (+)-2,3-O-isopropylidene-l-threitolAbsolute configuration: (S,2E,9Z)