Total synthesis of (–)-negamycin from a chiral advanced epoxide

Abstract

A concise route for the total synthesis of (–)-negamycin is described. Key point features (a) Cu-mediated ring-opening reaction of the advanced epoxide with vinyl magnesium chloride leads to the introduction of the carboxyl synthon; (b) Consecutive placement of diamino groups via azides was designed, including an unexpected cleavage of the silyl protecting group; (c) removal of four hydrogenolytically labile groups in one step.

GRAPHICAL ABSTRACT

Keywords:

• Antibiotic
• enantioselective allylation
• gram negative bacteria
• hydrazine
• negamycin

Acknowledgments

We thank the Instrument Center at National Chung Hsing University (NCHU) for providing valuable assistance on LC-MS/MS (MOST 110-2731-M-005-001) and the access of ESI mass spectra of the diazide 7 by Prof. I-Chung Lu of the Department of Chemistry at the National Chung Hsing University.

Additional information

Funding

This work was supported by the Ministry of Science and Technology of Taiwan (grant no. MOST 109-2113-M-005-016-MY2) and the National Chung Hsing University.