Cyclic guanidines. IV. Synthesis of hypoglycemic N-benzhydryl bicyclic guanidines.

Abstract

Synthesis of N-benzhydryl bicyclic guanidines (12) was attempted. The key intermediates, 1-benzhydryl-2-N- or 3-(ω-hydroxyalkyl)-2-imino-1, 3-diazacycloalkanes (4) and (9) were prepared. The intramolecular cyclization of 4 to 12 was not advantageous because of the low yield. On the other hand, the intramolecular cyclization of 9 to 12 resulted in good success. In our synthetic course, imidazo [1, 2-a] [1, 3, 5] oxadiazocine derivative (11), a new ring system, and N1-benzhydryl-N1-[2-(1-pyrrolidinyl) ethyl] urea (13) were isolated as by-products. The N-benzhydryl bicyclic guanidines (12) showed potent hypoglycemic activity.