O-Nitrophenylsulfenyl group

The 2,4,6-trimethylbenzyl ester has been prepared from an amino acid and the benzyl chloride (Et3N, DMF, 25°, 12 h, 60-80% yield) it is cleaved by acidic hydrolysis (CF COOH, 25°, 60 min, 60-90% yield 2 N HBr/HOAc, 25°, 60 min, 80-95% yield) and by hydrogenolysis. It is stable to methanolic hydrogen chloride used to remove A-o-nitrophenylsulfenyl groups or triphenylmethyl esters. ... 

L Zervas, D Borovas, E Gazis. New methods in peptide synthesis. I. Tritylsulfenyl and o-nitrophenylsulfenyl groups as N-protecting groups. J Am Chem Soc 85, 3660, 1963. 

Introduction of the o-nitrophenylsulfenyl group is simple using commercially available 2-nitrobenzenesulfenyl chloride (mp 74-76 C) and aqueous base... 

Further work with diphenylmethyl, phenacyl, and p-methylthioethyl 5 esters disclosed useful combinations with K-protecting groups, particiilarly trityl and o-nitrophenylsulfenyl groups. 

Protection of amino group. The o-nitrophenylsulfenyl group has been used for protection of side-chain amino groups in peptide synthesis. The classical method for removal is treatment with acid, even acetic acid, but this method is not selective. The selective removal is now possible by cleavage with 2-mercapto-pyridine (2-thiopyridone) and 1 equiv. of HOAc in CH3OH, DMF, or CH2Cl2. ... 

Protection of thiols.1 The f-butyl group has been of limited service for protection of thiols because removal has involved rather drastic treatment with liquid HF. /-Butyl thioethers can be cleaved by treatment with o-nitrobenzene-sulfenyl chloride in acetic acid at 25° to give S-o-nitrophenylsulfenyl derivatives. These products are reduced to thiols with NaBH4, HSCH2C02H, or HOCH2CH2SH. 

The o-nitrophenylsulfenyl protective group proved very satisfactory in a large-scale synthesis of L-leucyl-L-methionine amide an added advantage was that on cleavage of the protective group the reagent could be recovered readily and used itgain. 

Selective removal of o-nitrophenylsulfenyl N-protective groups NSAr NH... 

The use of triphenylmethylsulfenyl, o-nitrophenylsulfenyl and 2,4-dinitrophenylsulfenyl as protecting groups in peptide synthesis, has been reported recendy . ... 

The application to peptide synthesis of the stepwise addition of NCAs at controlled pH in solution has also been carried out on a polymer support (Scheme 4-3). The addition of the NCA was controlled by the formation of the resulting carbamate at basic pH (Blecher and Pfaender, 1973). Another way of controlling the addition of the NCA is to use a suitably N-blocked NCA derived from N-o-nitrophenylsulfenyl (Krichel-dorf, 1973) or N-(4,4 -dimethoxybenzhydryl) (Halstrom and Kovacs, 1973) amino acids. After each NCA addition, the N-blocking group is cleaved and addition of the successive N-blocked NCA is repeated. Maher et aL, (1972) reported repetitive peptide synthesis using unsubstituted NCA, but the resin-bound amino acid was AT-silylated (Scheme 4-3). 

Trifluoromethanesulfonic acid in the presence of anisole cleaves at room temp, a number of protecting groups used in peptide chemistry without significant side reactions. - E N-(o-Nitrophenylsulfenyl)valine allowed to react 3-5 min. in methylene chloride with 5-10 equivalents trifluoromethanesulfonic acid and 1.5-3 equivalents anisole as scavenger valine. Y 99.9%. F. e., also in tri-fluoroacetic acid instead of methylene chloride, s. H. Yajima et al., Chem. Com-mun. 1974, 107. 

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