I. The stereoselective synthesis of (E)-alkene dipeptide isosteres. II. New methods for solid and solution phase synthesis of boc-protected guanidines from amines. III. The pathways leading to the racemization of (S)-2-aminophenylacetonitrile

Yaw Fui Yong, Purdue University

Abstract

A stereoselective synthesis of the (E)-alkene dipeptide isostere of L-Ala-L-Ala from L-alanine methyl ester has been developed, utilizing the stereoselective, chelation controlled addition of (Z)-1-lithiopropene to the Schiff base of alanine methyl ester and stereocontrolled (2,3) -Wittig rearrangement. The (E)-alkene dipeptide isostere was obtained in seven steps and 3.8% overall yield. Two new highly efficient guanylation methods, the use of 4-nitro-1-H-pyrazole-1- ($N,N\sp\prime$-bis(tert-butoxycarbonyl)) carboxamidine and the combination of $N,N\sp\prime$-bis(tert-butoxycarbonyl)thiourea and Mukaiyama's reagent have been developed to effect the guanylation of primary and secondary amines in solution and on a solid support. The new reagents afforded higher yields and reacted faster when guanylating amines. Analytical tools such as $\sp1$H, $\sp{13}$C NMR spectroscopy and polarimetry have been used to understand the mechanisms leading to the racemization of (S)-2-aminophenylacetonitrile. The proposed pathways: (1) the intermolecular deprotonation of $\alpha$ carbon of (S)-2-aminophenylacetonitrile and (2) elimination of cyanide ion do not account for the racemization of (S)-2-aminophenylacetonitrile.

Degree

Ph.D.

Advisors

Lipton, Purdue University.

Subject Area

Organic chemistry|Biochemistry

COinS