새로운 amethopterin 유도체를 합성하기 위해서 pteridine의 C-2 탈아미노화와 C-2 methyl로 치환된 새로운 pteroic acid 유도체인 4-[[(4-amino-2-desaminopteridin-6-yl)methyl]thio]benzoic acid와 4-[[(4-amino-2-methyl-teridin-6-yl)methyl]thio]benzoic acid 합성을 시도하였다. 즉 p-aminobenzoic acid의 amino기를 SH로 치환하고 이 화합물을 에스테르화하였다. 그리고 이것을 2-amino-3-cyano-5-chloromethylpyrazine (11)과 결합하여 benzylester 화합물인 pyrazine 유도체 (14)를 얻었다. 따라서 이 화합물 (14)를 formamidine HCl, acetamidine HCl과 각각 cyclization시켜 화합물 4-[[(4-amino-2-desaminopterindin-6-yl)methyl]thio]benzoic acid benzylester와 4-[[(4-amino-2-methylpteri-din-6-yl)methyl]ohio]benzoic acid benzylester를 얻었으며, 이를 알칼리 가수분해 하여 71％, 36％의 수율로 pteroic acid 유도체인 7a와 7b를 합성하였다.

In order to produce new amethopterin derivatives, We tried to synthesized 4-[[(4-amino-2-desaminopteridin-6-yl)methyl]thio]benzoic acid of and 4-[[(4-amino-2-methyl-pteridin-6-yl)methyl]thio]benzoic acid of new pteroic acid derivative substituted with C-2 desamino and C-2 desamino-2-methyl. That is, We substituted SH group for amino of p-aminobenzoic acid, and esterificated it. Then we coupled the compound with 2-amino-3-cyano-5-chloromethylpyrazine(11) and obtained a benzyl ester compound, pyrazine derivative(14). Consequently the compound (4) was cyclizated with formamidine HCl and acetamidine HCl respectively, and so a compound of 4-[[(4-amino-2-desaminopterindin-6-yl)methyl]thio] benzoic acid benzylester and a compound of 4-[[(4-amino-2-methylpteri-din-6-yl)methyl]thio]benzoic acid benzylester were obtained. Finally we hydrolyzed them and obtained (7a) and (7b) of pte roic acid derivative by yield 71％ and 36％ respectively.