Biologically oriented organic sulfur chemistry. 19. Synthesis and properties of 2-amino-5-mercapto-5-methylhexanoic acid, a bishomolog of penicillamine. Use of boron trifluoride etherate for catalyzing Markovnikov addition of a thiol to an olefin

Abstract

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-hexenoate (4). Addition of -toluenethiol to 4 using BF3-Et20 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 BFg-EtaO 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.

Indium Triflate‐Catalysed Addition of Thio Compounds to Camphene: A Novel Route to 2,3,3‐Trimethyl‐2‐thiobicyclo[2.2.1]heptane Derivatives

“…[1] Generally, this reaction proceeds through a radical-type mechanism with initiators, such as peroxides, AIBN or photochemistry, resulting in the addition of thio derivatives to the double bond with antiMarkovnikov regioselectivity. [2,3] Electrophilic-type additions with strong protic [4][5][6] or Lewis [7,8] acids in over-stoichiometric amounts result in the formation of Markovnikov-type adducts with some olefin polymerisation. We recently reported on the catalytic and efficient use of "super" Lewis acids derived from triflates for the selective functionalisation of nonactivated olefins in hydroalkoxylation cycloisomerisations and hydrothiolations.…”

Evidence for formation of an S-[2-(N7-guanyl)ethyl]glutathione adduct in glutathione-mediated binding of the carcinogen 1,2-dibromoethane to DNA.

“…-, The radioactivity profile monitored with a flow liquid scintillation counter in line with the UV detector. The large peak, which eluted at 15 min in this system, was collected and desulfurized with nickel and NaBH4 (23). 3.…”

Forty-Five Years With a Hydra, Organosulfur Chemistry

“…16.2). 9 It is worth adding that a desulfurization for proof of structure in this work failed with Raney nickel, perhaps because of too strong an adsorption, but succeeded with NiC& + NaBH,,: a (more convenient) procedure of Truce …”

“…7 was the best of seven explored for the synthesis of various P-substituted ethyl acetyl di~ulfides.~~ Nevertheless, the fact that a thiosulfonate only monothioalkylated 9 to give 10, while dimethyl sulfate dialkylated 9 to give 11 (eq. 8), 23 indicates that the relatively A c S C~~~ + HS(CH2 ) 2 X -AcSS(CH2 ) 2 X (7) 9 low electrophilicity and reactivity of thiosulfonates sometimes may afford desirable selectivity. As with the unsymmetrical disulfides of Sec.…”