Stereoselective Synthesis of (+)-Nephrosteranic Acid by Ring-Closing Metathesis and Its Biological Evaluation

Abstract

A simple and efficient approach to (+)-nephrosteranic acid from dodecanol as a starting material is described, employing Sharpless asymmetric epoxidation, ring-closing metathesis, and Gilman addition of a vinyl group as key steps. These key reactions allow fast access to trisubstituted γ-butyrolactone. The molecule synthesized exhibits potent antifungal, antibacterial, and cytotoxic activities against all the tested strains.

Keywords:

• Antimicrobial activity
• chemoselective reduction
• Gilman 1,4 addition
• paraconic acids
• ring-closing metathesis
• sharpless asymmetric epoxidation

ACKNOWLEDGMENTS

We thank the director of the Indian Institute of Chemical Technology, project director of NIPER, and head of the Organic Chemistry Division II for their encouraging support. P.A.K. thanks the Council of Scientific and Industrial Research for fellowship.

Notes

^a MIC (minimum inhibitory concentration in μg/mL) was determined as 90% inhibition of growth with respect to positive growth control. Negative control: DMSO, no inhibition.

^b SA, Staphylococcus aureus; SE, Staphylococcus epidermis; EC, Escherichia coli; PA, Psudomonas aeruginosa.

^c SS, Saccharomyces serviseae; CA, Candida albicans; AN, Aspergillus niger; RA, Rhizopus orizae.

^a IC₅₀: Inhibitory concentration.

^b THP-1: Human acute monocytic leukemia cell line.

^c Human leukemic monocyte lymphoma cell line.