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United States Department of Agriculture

Agricultural Research Service

Title: Highly Selective Asymmetric Synthesis of 2-Hydroxy Fatty Acids Through Chiral Oxazolidinone Carboximides

Authors
item HWANG, HONGSIK
item ERHAN, SEVIM

Submitted to: Journal of the American Oil Chemists' Society
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: October 10, 2000
Publication Date: N/A

Interpretive Summary: Fatty acids are the major components in vegetable oils. There are many fatty acids showing biological activities and being used as drugs such as antibiotics, antifungi, tumor inhibitors, and gastric secretion inhibitors. Chemical modification has been used to improve their properties as drugs, and a chemical reaction called hydroxylation is most widely used for this purpose. The positions of fatty acids to be modified, however, have been restricted because of difficulty in reactions at specific positions of fatty acids. We have successfully developed a unique chemical method to modify fatty acids at a specific position (hydroxylation at 2-position of fatty acids). We found that the method is very effective and convenient and could be applied to many fatty acids. The method provides scientists with a new and convenient tool for improving biological activities of existing fatty acids to develop better drugs. Finding better drugs from fatty acids would not only benefit human health but also enhance the values of fatty acids and ultimately benefit the United States farmers.

Technical Abstract: Highly selective asymmetric synthesis of 2-hydroxy fatty acids has been accomplished through chiral imide enolates. Five chiral oleic acid imides were prepared by reaction of oleic acid with pivaloyl chloride followed by reaction with five different lithiated chiral oxazolidinones including (R)-(+)-4-benzyl-2-,(S)-(-)-4-benzyl-2-,(4R,5S)-(+)-4-methyl- 5-phenyl-2-, (4S,5R)-(-)-4-methyl-5-phenyl-2-, and (R)-(+)-4-isopropyl- 2-oxazolidinones in 88-92% yields. The chiral imides were reacted with NaN(Me3Si)2 at -78C to give enolates, which subsequently reacted with 2- (phenylsulfonyl)-3-phenyloxaziridine to give hydroxylated products in 78-83% yields. Methanolysis of the hydroxylated products with magnesium methoxide gave methyl 2-hydroxyoleate. Enantiomeric excesses (ee) of the products were determined to be very high (98-99% ee) by 1H NMR study after esterification of the hydroxy group with (S)-(+)-O-acetylmandelic acid. Enantioselective hydroxylation of other fatty acids including elaidic acid, petroselinic acid, vaccenic acid, and linoleic acid were evaluated under the similar conditions using (4R,5S)-(+)-4-methyl-5- phenyl-2-oxazolidinone as a chiral auxiliary to give 98% ee values for all cases.

Last Modified: 9/10/2014
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