Synthesis of tetracyclines and intermediates thereto

US9073829B2 · kind B2 · utility

Assignee

• President and Fellows of Harvard College · US

Inventors

• Andrew G. Myers · Boston, US
• David A. Kummer · San Diego, US
• Derun Li · Dedham, US
• Evan Hecker · Arlington, US
• Amelie Dion · Cambridge, US
• Peter M. Wright · Faringdon, GB

Key dates

• Filing date: Apr 30, 2010
• Grant date: Jul 7, 2015
• Expiry date: Aug 28, 2031

Classification

• Technology area (CPC C): Chemistry; Metallurgy
• CPC primary: C07C2603/66
• WIPO field: Organic fine chemistry
• WIPO sector: Chemistry

Abstract

The tetracycline class of antibiotics has played a major role in the treatment of infectious diseases for the past 50 years. However, the increased use of the tetracyclines in human and veterinary medicine has led to resistance among many organisms previously thought susceptible to tetracycline antibiotics. The recent development of a modular synthesis of tetracycline analogs through a chiral enone intermediate has allowed for the efficient synthesis of novel tetracycline analogs never prepared before. The present invention provides more efficient routes for preparing the enone intermediate and allows for substituents at positions 4a, 5, 5a, and 12a of the tetracycline ring system.