Available Technology
Practical, scaleable method of making optically pure unnatural amino acids provide new set of intermediates for research and commercial use
Technology:
Scaleable syntheses of unnatural alpha-amino acids with bulky groups on the alpha position with high-yield and enantiomeric excess
Markets Addressed
Alpha-amino acids, besides their role in proteins, are often used to make small molecule pharmaceuticals and organic catalysts. In general, there are practical and scaleable means available to make alpha-amino acids, natural or unnatural, of either enanatiomer, as chiral intermediates to make pharmaceuticals or catalysts. However, there is a family of amino acids that are not accessible by existing methods. This is the family of unnatural amino acids with bulky groups, such as aryl or quaternary alkyl groups, in the alpha-position. A well known example is (R)(tert)–leucine. This invention, from the lab of Eric Jacobsen, provides, for the first time, a practical, scaleable method of making these optically pure unnatural amino acids that will provide a whole new set of intermediates for research and commercial use.
Innovations and Advantages
The essence of the invention is new catalysts that are easier to make (3 steps) and work under conditions amenable to large scale production compared to the current state of the art. They work by asymmetric catalysis of the Strecker synthesis to provide alpha-amino acids with bulky side groups in high yield and high enantiomeric excess. The catalysts have one chiral center and the different enantiomers of the catalysts produce the different enantiomers of the resultant alpha-amino acids. The new catalysts are robust and can be used with aqueous cyanide salts which results in a much safer and practical industrial synthesis compared with the present method which requires HCN.
Additional Information
Intellectual Property Status: A provisional patent application is pending in the USPTO.
Publication:
Zuend et al., “Scaleable catalytic asymmetric Strecker syntheses of unnatural alpha-amino acids”, Nature, 461, 968-970, October, 2009
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Inventor(s):
Jacobsen, Eric N.
Zuend, Stephan J.
Categories:
For further information, please contact:
Mick Sawka, Director of Business Development
(617) 496-3830
Reference Harvard Case #3572