BIOLOGICALLY ORIENTED ORGANIC SULFUR CHEMISTRY .19. SYNTHESIS AND PROPERTIES OF "2-AMINO-5-MERCAPTO-5-METHYLHEXANOIC ACID, A BISHOMOLOGUE OF PENICILLAMINE - USE OF BORON-TRIFLUORIDE ETHERATE FOR CATALYZING MARKOVNIKOV ADDITION OF A THIOL TO AN OLEFIN

Synthesis is reported of 2-amino-5-mercapto-5-methylhexanoic acid (2) as a bishomologue of penicillamine (1). In this synthesis, alkylation of diethyl acetamidomalonate gave ethyl 2-acetamido-2-carbethoxy-5-methyl-4-hexe-noate (4). Addition of α-toluenethiol to 4 using BF3-Et2O then gave ethyl 2-acetamido-2-carbethoxy-5-benzylthio-5-methylhex.anoate (6) in 63-74% yield; this reaction appears to be the first use of BF3-Et2O as a catalyst for effecting Markownikoff-type addition of a thiol to an alkene. The bishomologue 2 was obtained from 6 either by decarboxylation to the amide (5), debenzylation of 5 to 7, and hydrolysis, or (preferably) by decarboxylation and hydrolysis to the amino acid 8 in one step and debenzylation. The bishomologue 2 resisted hot strong acid. It reacts with formaldehyde, Fe(III), or Cu(II) much less readily than does 1 and therefore affords a promising means of probing biological properties of 1 where it is unclear whether these properties depend upon ring formation involving SH and NH2 or upon independent action of functional groups. © 1978, American Chemical Society. All rights reserved.