Abstract
An (alpha)-amino acid was used in the preparation of non-peptide materials. The use of the (beta)-hydroxy-(alpha)-amino acid serine (14) was demonstrated to be effective in the construction of 2-substituted-4-carboxy-(DELTA)('2)-oxazolines (5), 2-substituted-4-carboxyoxazoles (4), 2-substituted-4-carboxy-(DELTA)('2)-thiazolines (13), and 2-substituted-4-carboxythiazoles (12). Starting from L-serine (14), stable crystalline O-tosyl-L-serine esters 25 and 30 were prepared in 65% and 34% overall yields, respectively. Acylation of these serine synthons (25 and 30) gave N-acyl-O-tosyl-L-serine esters (28 and 34), which underwent cyclization upon treatment with pyridine in methylene chloride at reflux to provide 2-substituted-4-carboxy-(DELTA)('2)-oxazolines (5). Subsequent oxidation with NiO(,2) yielded the corresponding 2-substituted-4-carboxyoxazoles (4). The L-serine methyl ester hydrochloride salt (20), which was prepared from L-serine in 95% yield, allowed for the rapid construction of 2-substituted-4-carboxy-(DELTA)('2)-thiazolines (13) and 2-substituted-4-carboxythiazoles (12) by three different routes. First, the serine synthon 20 underwent thioacylation to give N-thioacyl-L-serine methyl esters (50), which were then ring cyclized under basic sulfonate ester preparation conditions to 2-substituted-4-carbomethoxy-(DELTA)('2)-thiazolines (48). Second, the serine synthon 20 was acylated to give N-acyl-L-serine methyl ester 38, which underwent direct thiation and ring cyclization to give 2-substituted-4-carbomethoxy-(DELTA)('2)-thiazolines (48). Third, carboxymethyldithiobenzoate (46a) was coupled with the O-tosyl-L-serine ester 25 to give the (DELTA)('2)-thiazoline 48a in 34% yield. Subsequent oxidation yielded the corresponding 2-substituted-4-carboxythiazole (12). For both the heterocyclic ring systems, the methodology allows for the incorporation of a wide array of alkyl and aryl groups at the C-2 position, introduction of the C-2 position substituent in a common intermediate before ring cyclization, and basic ring cyclization conditions to accommodate acid sensitive C-2 position substituents.
Willingham, Reginald Arnol (1983). The use of L-serine in the construction of carboalkoxy-substituted delta²-oxazoline, oxazole, delta²-thiazoline, and thiazole heterocyclic ring systems. Texas A&M University. Texas A&M University. Libraries. Available electronically from
https : / /hdl .handle .net /1969 .1 /DISSERTATIONS -777385.