Folate analogs altered in the C9-N10 bridge region: 11-thiohomofolic acid

Publisher Website
Google Scholar
Abstract
The synthesis of 11-thiohomofolic acid (2) was accomplished. Reaction of 1-chloro-4-[p-(carbomethoxy)thiophenoxy]-2-butanone with hydroxylamine under carefully controlled conditions gave the corresponding oxime. Conversion of the oxime to 1-phthalimido-4-[p-(carbomethoxy)thiophenoxy]-2-butanone oxime (4) was carried out by its reaction with potassium phthalimide using crown 18 ether as a catalyst. Hydrazinolysis of compound 4 gave 1-amino-4-[p-(carbomethoxy)thiophenoxy]-2-butanone oxime which was used for the construction of 2 by modification of the Boon and Leigh procedure. An alternate synthesis utilizing 1-hydroxy-4-[p-(carbomethoxy)thiophenoxy]-2-butanone and 4-hydroxy-2,5,6-triaminopyrimidine was carried out. Compound 2 did not exhibit any antifolate activity against Lactobacillus casei or Streptococcus faecium. The dithionite reduction product, 7,8-dihydro-11-thiohomofolic acid, functioned as a substrate of L. casei dihydrofolate reductase. The catalytic reduction product of 2 consisting of a mixture of diastereomers showed powerful antifolate activity against both organisms.

This publication has 2 references indexed in Scilit: