2-Thio-orotic acid

One group of compounds that have proved to be particularly effective in interfering with DNA synthesis of tumour cells are the mercapto-purines and pyrimidines and their alkyl derivatives 6-mercaptopurine (6-MP) blocks the de novo synthesis of purines 9-(jS-D-arabinofuranosyl)-—9H—purine—6-thiol (ara—6-MP) inhibits the incorporation of L-aspartic acid and orotic acid into DNA cystosine 9-OS-D-xylo-furanosyl)—9H—purine—6-thiol (xyl—6-MP) inhibits the utilization of exogenously administered guanine the periodic acid oxidation product of 9-(/S-D-ribosyl)—6-methyl—thio purine (MMPR—OP) blocks the incorporation of thymidine into DNA . The effective clinical use of thiols... 

Orotic acid derivatives belong to the group of pyrimidines. The pyrimidine ring is substituted by oxo, thio or amino groups in the positions 2 and 4. Several other groupings may be present (Fig. 209). 

It is natutal to assume that the pjrriniidine moiety is dmved from orotic acid as are the pyrimidine bases of the nucleic adds. This has not, however, been shown. It is more difficult to qieculate on the biogenesis of the thiazole moiety. The limited experimental information on this matter comes again from experiments with pea roots (i). In this organ the thiamine thiazole requirement can be replaced by a mixture of thio formamide and acetopropyl alcohol and the vitamin thiazole is in fact synthesized from such a mixture [Eq. (3)]. 

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