Formal synthesis of (−)-flustramine B and its absolute configuration assignment by vibrational circular dichroism exciton chirality

A formal synthesis of the natural product (−)-flustramine B (3) is described, together with an easy and reliable approach for the absolute configuration assignment of a series of (3R,14S)- and (3S,14S)-oxindolylacetylphenyloxazolidinones 4, 6, 13a–c, and amides (+)- and (−)-14 by evaluation of the vibrational circular dichroism bisignated couplet resulting from the interaction of the C2 and C9 carbonyl groups. The absolute configuration assignment was validated by 1H NMR spectra and X-ray diffraction, and therefore (−)-flustramine B 3 was established as (3aS,8aR)-3.

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(S)-3-(2-((R)-6-Bromo-1,3-bis(3-methylbut-2-en-1-yl)-2-oxoindolin-3-yl)acetyl)-4-phenyloxazolidin-2-oneC29H31BrN2O4Ee >98% (by 1H NMR)[α]D20 = −9.2 (c 1.20, CHCl3)Source of chirality: (S)-(+)-4-phenyl-2-oxazolidinoneAbsolute configuration: (3R,14S)

(S)-3-(2-((S)-6-Bromo-1,3-bis(3-methylbut-2-en-1-yl)-2-oxoindolin-3-yl)acetyl)-4-phenyloxazolidin-2-oneC29H31BrN2O4Ee >98% (by 1H NMR)[α]D20 = +92.6 (c 1.20, CHCl3)Source of chirality: (S)-(+)-4-phenyl-2-oxazolidinoneAbsolute configuration: (3S,14S)

(R)-2-(6-Bromo-1,3-bis(3-methylbut-2-en-1-yl)-2-oxoindolin-3-yl)acetic acidC20H24BrNO3Ee >98% (by 1H NMR)[α]D20 = +18.3 (c 1, CHCl3)Source of chirality: (3R,14S)-6Absolute configuration: (3R)

(S)-2-(6-Bromo-1,3-bis(3-methylbut-2-en-1-yl)-2-oxoindolin-3-yl)acetic acidC20H24BrNO3Ee >98% (by 1H NMR)[α]D20 = −18.3 (c 1, CHCl3)Source of chirality: (3S,14S)-6Absolute configuration: (3S)