Georgetown University Medical Center

Synthesis, Structure and Use of Bisoxazolidines for Asymmetric Catalysis and Synthesis

Section: For Industry

Category(ies): Chemistry

Reference #: WOCH222002

OTC Contact: David Odelson (Directory Information | Send a Message)

Description

In recent years, the synthesis of enantiomerically pure compounds has become increasingly profitable in the pharmaceutical industry. Enantiomerically pure drugs allow the use of one entantiomer in situations where the other entantiomer is found to be toxic or inactive. While traditional methods of organic synthesis focused on racemic drug mixtures, the recent demand for enantiomerically pure chemicals has lead to advancements in asymmetric synthesis methods utilizing chiral catalysts. The present invention relates to method of synthesis, use and structure of chiral bisoxazolidines as catalysts in the production of enantiomerically pure compounds.

Applications

Chiral bisoxazolidines are a novel class of compounds that has application in asymmetric synthesis. An important use for these chiral, non-racemic compounds is as intermediates in synthesis of compounds. For example, chiral bisoxazolidines enable the catalytic enantioselective alkynylation and alkylation of a range of aromatic and aliphatic aldehydes and keto esters to form high yields of chiral propargylic alcohols and secondary alcohols.

The advantages associated with the present invention include:

  • Enantiomerically pure drugs have fewer side effects and greater potency as compared to racemic drug mixtures; available in both enantipoure forms.
  • Provides high yields (>87%) for a wide range of substrates in various reactions
  • The chiral catalysts are derived from readily accessible and inexpensive rigid C2-symmetric chiral bisoxazolidines in a single-step reaction that does not require chromatographic work-up.
  • Use of the compounds in asymmetric bond-forming reactions has been successfully demonstrated.
  •  Inexpensive to make in large gram quantities with inexpensive starting materials.
  • Recyclable if desired.
  • Laborious and time-consuming stepwise pre-mixing of chiral ligand, organozinc reagent and acetylene and lengthy periods of stirring before addition of the aldehyde substrate is not necessary in the method of use of the present invention. 

Advantages

Stage of Development

Stage of Development:  Small quantities of the compound have been produced in the lab

Inventors: Dr. Christian Wolf, Ph.D., and Shuanglong Liu, Dept. of Chemistry, Georgetown University

Relevant Publications

  • Liu S, Wolf C. Chiral Amplification based on enantioselective dual-phase distribution of a scalemic bisoxazolidine catalyst. Org Lett. 2007 Aug 2;9(16):2965-8.
  • Bisoxazolidine-catalyzed enantioselective alkynylation of aldehydes.  J Am Chem Soc. 2006 Aug 30;128(34):10996-7.

Patent Status

Published U.S. Patent Application US27265255A1 (filed on 4/19/06)