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

Abstract

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

Labelling with positron emitters of pnicogens and chalcogens

“…However, the RCY of the substitution of 2-tertbutoxycarbonylamino-4-bromobutyric acid ethyl ester, a precursor for the synthesis of L-[ 75 Se]selenomethionine and homocysteine[ 75 Se]selenolactone, and the corresponding methionine derivative with nca methyl[ 75 Se]selenide is only in the range of 15% to 20%. 163 To avoid the addition of a (nonisotopic) carrier, new strategies for the nca radioselenation were developed.…”

“…This pathway offers the advantage of generating both aliphatic and aromatic radioselenoethers by using appropriate alkyl or aryl magnesium (Grignard) or lithium compounds. 166 These nca radioselenation methods, successfully applied for the synthesis of nca [ 75 Se]selenomethionine and nca homocysteine[ 75 Se]selenolactone, 163,165 were studied to synthesize selenium-containing radiotracers potentially applicable in PET studies when labelled with 73 Se.…”

“…It was converted with methyl lithium into a mixture of lithium methyl [ 75 Se]selenide and lithium methyl mercaptide. However, the RCY of the substitution of 2‐ tert ‐butoxycarbonylamino‐4‐bromobutyric acid ethyl ester, a precursor for the synthesis of l ‐[ 75 Se]selenomethionine and homocysteine[ 75 Se]selenolactone, and the corresponding methionine derivative with nca methyl[ 75 Se]‐selenide is only in the range of 15% to 20% …”

“…These nca radioselenation methods, successfully applied for the synthesis of nca [ 75 Se]selenomethionine and nca homocysteine[ 75 Se]selenolactone, were studied to synthesize selenium‐containing radiotracers potentially applicable in PET studies when labelled with 73 Se.…”

Isolation of high purity 73Se using solid phase extraction after selective 4,5-[73Se]benzopiazselenol formation with aminonaphthalene

“…However, the long half-life of this radionuclide leading to inacceptable high radiation doses prevents its utilization in clinical practice. Nonetheless, due to the long half-life and γ-ray emission it is ideally suited as a surrogate for short-lived 73 Se for the radiochemical development of novel processes and separation techniques [5].…”