Synthesis of novel, highly reactive 1-oxyl-2,2,6,6-tetramethyl-1,2,5,6-tetrahydropyridine derivatives

Abstract

New multipurpose spin labels and synthons can be synthesized from 1-oxyl-2,2,6,6-tetramethyl-1,2,5,6-tetrahydropyridine-4-carboxylic acid (1). Either 1, its pentafluorophenylester (2), or acylcarbonate (3) (prepared from 1 with ethyl chloroformate) can be reduced to 1-oxyl-2,2,6,6-tetramethyl-4-hydroxymethyl-1,2,5,6-tetrahydropyridine (4). The methanesulfonate (6) and the bromo compound (7) are highly reactive alkylating reagents due, in large part, to the allylic linkage in the nitroxide ring. The latter can be reacted with KSSO2CH3 to give methanethiolsulfonate (9). A novel side chain spin-labelled α-amino acid ester (11) is made by a phase-transfer alkylation of a Schiff base with 7. Compound 11 can be coupled with the protected L-phenylalanine in the presence of dicyclohexylcarbodiimide (DCC) to produce the nitroxide dipeptide (12).