Synthesis of dihydroisotryptamines

Abstract

To enable exploration of the physiological activity of isotryptamine derivatives, a number of 1,3-di-hydroisotryptamines, isomers of known tryptamine derivatives possessing significant physiological activity, were synthesized for the first time. Ring-substituted 1-nitrosonaphthalen-2-ols on tosylation and alkaline treatment gave the appropriate (Z)-3-(2'-cyanopheny1)propenoic acids, and by hydration, cyclization and ring-opening these acids were converted into (3'-oxo-1',3'-dihydroisoindol-1'-yl)- acetic acids. Fusion of these products with ureas yielded the corresponding (3'-oxodihydroisoindol-1'-yl)acetamides, which, on simultaneous reduction of the amide and lactam functions by diborane, yielded 1,3-dihydroisotryptamines. Some features of their n.m.r. spectra are also discussed.