1 H and 13 C NMR analysis of 2-acetamido-3- mercapto-3-methyl-N-aryl-butanamides and 2-acetamido-3-methyl-3-nitrososulfanyl- N-aryl-butanamide derivatives Rafael Germano Santana, a Derisvaldo Rosa Paiva, b Roberto da Silva Gomes c and Adriana Karla C. A. Reis b * The complete assignment of the 1 H and 13 C NMR spectra of various 2-acetamido-3-mercapto-3-methyl-N-aryl-butanamides and 2-acetamide-3-methyl-3-nitrososulfanyl-N-aryl-butanamides with p-methoxy, o-chloro and m-chloro substituents is reported. Copyright © 2013 John Wiley & Sons, Ltd. Keywords: NMR; 1 H NMR; 13 C NMR; N-aryl-butanamides; S-nitrosothiol Introduction It is well-established that nitric oxide (NO), a gaseous free radical, regulates vascular tone and participates in cellular signaling events. [1] S-nitrosothiols have been implicated as major trans- ducers of NO bioactivity, acting as both potent vasodilators and inhibitors of platelet aggregation. However, the mechanisms by which these reactive nitrogen species affect cellular functions are not fully established. [2–4] Covalent attachment of NO to protein or to low molecular weight thiols (S-nitrosylation) is generally used in cells as a reversible signal. [1] Through S-nitrosylation, S-nitrosothiols modify a number of proteins, including protein kinases, phosphatases, and transcription factors. [5,6] A number of theoretical and experimental studies involving the formation of S-nitrosothiols are described in the literature. [7,8] The majority of these studies involved the structural characterization of the compound and its relationship with the biological properties. S-nitroso-N-acetyl-penicillamine is a widely characterized nitrosothiol [9] whose functionality and unique aqueous stability suggest that penicillamine derivatives are good substrates for the synthesis of novel and stable S-nitrosothiols. [10] These com- pounds must be fairly water soluble to facilitate biological testing. In this context, S-nitrosopenicillamine derivatives are worthy of synthesis and would include simple a-amino derivatives. Therefore, the aim of this work was to prepare a series of 2-acetamido-3-methyl-3-mercapto-N-aryl-butanamides (1–4) and S-nitrosothiol derivatives (5–8) (Scheme 1) and to characterize them through their 1 H NMR and 13 C NMR spectra. Experimental Compounds Initially, 3-acetamido-4,4-dimethylthietan-2-one was obtained from the reaction of () penicillamine in dry pyridine and acetic anhydride (1 : 3) at room temperature. [11] This compound was utilized to produce the 2-acetamide-3-methyl-3-mercapto-N- aryl-butanamides through a reaction with aniline and substituted anilines (o-Cl, m-Cl, and p-MeO) in chloroform. The S-nitrosothiol derivatives were produced by reacting 2-acetamide-3-methyl-3-mercapto-N-aryl-butanamides in acetone and tert-butyl-nitrite (1 : 2). [9] * Correspondence to: Adriana K. C. A. Reis, Departamento de Ciências Exatas e da Terra, Universidade Federal de São Paulo (UNIFESP), 09972-270 Diadema, São Paulo, Brazil. E-mail: adriana.amorim@unifesp.br a Departamento de Bioquímica, Universidade Federal de São Paulo (UNIFESP), São Paulo, São Paulo, Brazil b Departamento de Ciências Exatas e da Terra, Universidade Federal de São Paulo (UNIFESP), Rua Prof. Artur Riedel, 275, Jardim Eldorado, 09972-270 Diadema, São Paulo, Brazil c Universidade Federal do Mato Grosso do Sul (UFMS), Campo Grande, Mato Grosso do Sul, Brazil NH O HS O NH Y 1 2 3 4 5 6 7 8 9 10 11 12 13 14 16 15 NH O ONS O NH 1 2 3 4 5 6 7 9 10 11 12 13 14 16 15 1 Y=H 2 Y= o-Cl 3 Y= m-Cl 4 Y= p-OMe 5 Y=H 6 Y= o-Cl 7 Y= m-Cl 8 Y= p-OMe Y 17 17 Scheme 1. Structures and numbering of the compounds studied (1–8). Magn. Reson. Chem. 2013, 51, 316–319 Copyright © 2013 John Wiley & Sons, Ltd. MRC Letters Received: 6 October 2012 Revised: 9 February 2013 Accepted: 11 February 2013 Published online in Wiley Online Library: 11 March 2013 (wileyonlinelibrary.com) DOI 10.1002/mrc.3944 316