Quinazolines. Part XXI. Synthesis of cis-2-amino-8a-carboxymethyl-3,4,4a,5,6,7,8,8a-octahydroquinazoline and related compounds. Conversion of perhydroquinazolin-2-ones into 2-amino-3,4,4a,5,6,7,8,8a-octahydroquinazolines

Abstract

In a study of simple analogues of tetrodotoxin (1), it was found that the halogen atom in cis-8a-bromomethyl-perhydroquinazolin-2-one (4) was readily displaced by cyanide and acetate ions to yield cis-8a-cyanomethyl-(5) and cis-8a-acetoxymethyl-perhydroquinazolin-2-one (9). Acidic hydrolysis of the cyano-group gave the corresponding 8a-carbamoylmethyl (6) and 8a-carboxymethyl (7) derivatives. A general method was found for converting cis-perhydroquinazolin-2-one and its 1,3-dimethyl and 8a-cyanomethyl derivatives into the respective cis-2-amino-3,4,4a,5,6,7,8,8a-octahydroquinazolinium salts (22), (23), and (20). From the last-named compound cis-2-amino-8a-carboxymethyl-3,4,4a,5,6,7,8,8a-octahydroquinazoline (2) and its methyl ester salt were obtained. 1- and 3-methyl-trans-perhydroquinazolin-2-one [(13) and (14)] and -2-thione [(17) and (18)] and 1-and 3-methyl-cis- and -trans-2-amino-3,4,4a,5,6,7,8,8a-octahydroquinazolinium salts were also prepared. 1H N.m.r. spectra and preliminary biological evaluation (M.L.D. values in mice) of some of these compounds are briefly discussed. Show more