73154-79-7Relevant academic research and scientific papers
Analgesic Dipeptide Derivatives. 3. Synthesis and Structure-Activity Relationships of o-Nitrophenyl-Modified Analogues of the Analgesic Compound H-Lys-Trp(NPS)-OMe
Garcia-Lopez, M. Teresa,Gonzalez-Muniz, Rosario,Molinero, M. Teresa,Naranjo, Jose R.,Rio, J. Del
, p. 1658 - 1663 (2007/10/02)
A series of analogues of the analgesic dipeptide derivative H-Lys-Trp(NPS)-OMe has been designed to determine the influence of the (2-nitrophenyl)sulfenyl (NPS)moiety on the activity.The syntheses and antinociceptive effects of these analogues of general formula H-Lys-Trp(R)-OMe sulfenyl (AacCmES) (13); R = sulfenyl (AacPS) (17); R = tert-butylsulfenyl (t-BuS) (23); R = (2-carbomethoxyethyl)sulfenyl (CmES) (24)> are described.Reaction of Z-Lys(Z)-Trp-OMe (3) with PS-, CmPS-, pNPS-, DNPS-, and AacCmES-Cl afforded the corresponding 2-(sulfenyl)tryptophan derivatives, which on treatment with boron-tris(trifluoroacetate)/trifluoroacetic acid or trimethylsilyl iodide in acetonitrile (Me3SiI/CH3CN) provided 9-13, respectively.Sulfenylation of 3 with NPS-Cl gave Z-Lys(Z)-Trp(NPS)-OMe, which, on catalytic hydrogenation of the nitro group using 10percent Pd/C followed by acetylation of the resulting amino function and removal of the protecting Z group, gave 17.Condensation of 2-(ter-butylsulfenyl)- and 2-tryptophan methyl ester, obtained by reaction of methyl 3a -hydroxy-1,2,3,3a,8,8a-hexahydropyrroloindole-2-carboxylate with the corresponding thiol, with Z-Lys(Z)-OSu afforded Z-Lys(Z)-Trp(t-BuS)-OMe and Z-Lys(Z)-Trp(CmES)-OMe, which on treatment with Me3SiI/CH3CN provided 23 and 24, respectively.Intracerebroventricular administration of 10 elicited a naloxone-reversible antinociceptive effect in mice similar to that of H-Lys-Trp(NPS)-OMe.No analgesia was however found with the phenylsulfenyl or acyclic sulfenyl substituted dipeptides 9, 11, and 17 or 13, 23, and 24.The Trp(DNPS)-containing analogue was neurotoxic.Structure-activity studies indicate that the role of the NPS and CmPS moieties could be related to the adoption of a preferential active conformation.
The use of sulfenyl halides in the synthesis of mercapturic acids and their esters
Buijs, Wim,Eid, Mohammed I. A.,Onkenhout, Willem,Vermeulen, Nico P.E.,Gen, Arne van der
, p. 449 - 455 (2007/10/02)
A new method for the synthesis of mercapturic acids (N-acetyl-S-substituted-L-cysteines), based on the addition of sulfenyl halides to olefins, is described.Alkenes and alkynes of widely different structure have been converted in this way into fully characterzed mercapturic acids and their methyl esters.
