Alternative syntheses of [73,75Se]selenoethers exemplified for homocysteine[73,75Se]selenolactone

Abstract

The present work describes two radiosynthetic pathways to prepare homocysteine[75Se]selenolactone 1 starting from n.c.a. [75Se]selenite 2. It was achieved either by alkylation reaction of n.c.a. methyl[75Se]selenide 4 or by hydrolysis of alkylated 1,3-dicyclohexyl[75Se]selenourea 11. N.c.a. methyl[75Se]selenide 4 is available using sulfur as non-isotopic carrier. However, the radiochemical yield of the substitution of 2-tert.-butoxycarbonylamino-4-bromobutyric acid ethylester 5 with n.c.a. methyl-[75Se]selenide is only in the range of 15-20%. Birch reduction of protected n.c.a. [75Se]selenomethionine 6 formed leads to a RCY of 5-10% homocysteine[75Se]selenolactone 1. Alternatively, the synthesis of homocysteine[75Se]selenolactone 1 is possible by hydrolysis of the corresponding [75Se]selenouronium salt 11 available by addition of 2-tert.-butoxycarbonylamino-4-bromobutyric acid ethylester 5 to 1,3-dicyclohexyl[75Se]selenourea 10. A method was developed for the synthesis of 1,3-dicyclohexyl[75Se]selenourea 10 by addition of c.a. [75Se]SeH2 to 1,3-dicyclohexylcarbodiimide, which leads to 20-30% RCY of c.a. homocysteine[75Se]selenolactone 1.