Preparation of several homochirally similar unnatural amino acids from a common intermediate

ORGN 521

Douglas S. Masterson,, Department of Chemistry and Biochemistry, University of Southern Mississippi, 118 College Drive, #5043, Hattiesburg, MS 39406

We have developed a method for the preparation of a- and b-unnatural analogues of serine, cysteine, lysine, and tyrosine from a common intermediate for each. The common intermediate is prepared by Pig Liver Esterase (PLE) hydrolysis of a prochiral malonate. The methodology uses straightforward chemistry that provides good yields and moderate to excellent enantioselectivities. We start by adding an appropriate protected side chain of the amino acid of interest to either diethyl methylmalonate or dimethyl methylmalonate to provide the prochiral diester 1. Compound 1 is then subjected to PLE hydrolysis giving 2 in good yield. Compound 2 is the common intermediate which can then be transformed into a-amino acid 3 or b-amino acid 4. Protecting group manipulations allow for the preparation of the opposite enantiomers of the desired amino acids from the same intermediate 2. We will report on the synthesis, selectivities, and future uses of this methodology.


Peptides, Proteins and Amino Acids
1:00 PM-4:40 PM, Wednesday, April 9, 2008 Morial Convention Center -- Rm. R06, Oral

Division of Organic Chemistry

The 235th ACS National Meeting, New Orleans, LA, April 6-10, 2008