Chemoenzymatic construction of chiral alkenyl acetylenic alcohol, a key building block to access diastereoisomers of polyacetylenes

Abstract

Background

Enzymatic kinetic resolution is proved as an efficient strategy of accessing chiral secondary alcohols in organic synthesis. Although several synthetic methods have been developed for the preparation of chiral acetylenic alcohol, biotransformation remains as a direct approach in the synthesis of polyacetylene lipids, which represent an intriguing class of marine natural products featuring interesting biological profiles.

Results

Novozym 435, a commercial lipase immobilized on macroporous acrylic resin, is utilized in the kinetic resolution of 1-yn-3-ol-4-(E)-ene (alkenyl acetylenic alcohol), which exists as terminus in recently isolated isofulvinol (1) both from the mollusk Peltodoris atromaculata and the sponge Haliclona fulva. The kinetic resolution enabled by Novozym 435 resulted in acetylenic alcohol and the corresponding acetate both in excellent enantiomeric excess and high isolated yield. The optimized reaction conditions allow us to realize the reaction at room temperature in toluene. The reaction is readily scaled up for synthetic use.

Conclusions

The current investigation builds up a platform for future exploration on stereoisomers of isofulvinol, synthetic intermediates with different chain length, and natural product analogs.

Keywords

Enzymatic catalysis / Novozym 435 / Kinetic resolution / Polyacetylene / Total synthesis

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