Practical Synthesis of (±)-Nyasol

Abstract

A practical total synthesis of racemic nyasol (7) was explored. The α-hydroxyketo compound 3 was prepared from commercially available starting materials in two steps. Chelation-controlled reduction of the α-hydroxyketo compound 3 with Zn(BH₄)₂ gave the anti-1,2-diol compound 4 as the major product (anti/syn = 11.5:1). Stereospecific elimination reaction of a 1,3-cyclic thionocarbonate intermediate (5) exclusively yielded the Z-alkene compound 6. Our total synthesis is very concise (seven steps), uses commercially available starting materials, and offers good overall yield (40%).

GRAPHICAL ABSTRACT

Keywords:

• Anti-diol
• chelation-controlled reduction
• 1,3-cyclic thionocarbonate intermediate
• (±)-nyasol
• stereospecific cis-elimination

ACKNOWLEDGMENTS

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

Notes

^a Yield after chromatography.

^b Based on the ratio between compound 6 and its E-stereoisomer.