Straightforward and Facile Synthesis of a Bioactive Component from Zingiber cassumunar Roxb.

Abstract

Straightforward and facile synthesis of a bioactive component A from Zingiber cassumunarRoxb. is described. The phenylbutenoid dimer A was reported to possess anti-inflammatory and cytotoxic activities. The optically active cyclohexene ring fragment was obtained via the highly diastereo- and enantioselective Diels–Alder reaction of chiral acryloyloxazolidinones (1a and 1b) and 1-(4-hydroxy-3-methoxyphenyl)butadiene (2). The enantiomeric excess of Diels–Alder adducts 3a and 3bwere determined via high-performance liquid chromatotography of the corresponding bis-acetate (6). The greatest enantiomeric excess (99.9% ee) was obtained when the 4-phenyloxazolidin-2-one (1a) chiral auxiliary was used in combination with TiCl4. The optically pure bioactive compound A was prepared from the optically active Diels–Alder adduct (3a) in two additional steps.

GRAPHICAL ABSTRACT

Keywords:

• phenyl-butenoid dimer
• Chiral auxiliaries
• Diels–Alder reaction
• enantioselective synthesis

ACKNOWLEDGMENT

The authors thank New Drug Development Research Institute and Central Laboratory of Kangwon National University for the use of analytical instruments and bioassay facilities.

Notes

^a Reaction conditions: dienophile 1 (1.0 equiv), diene 2 (1.5 equiv), Et₂AlCl (1.0 equiv), CH₂Cl₂, −78 °C, 5 h; or dienophile 1 (1.0 equiv), diene 2 (1.5 equiv), TiCl₄ (1.0 equiv), CH₂Cl₂, −20 °C, 2 h.

^b Isolated yield after chromatography.

^c Based on the chiral HPLC analysis of diacetate 6.

^d Not detected.