A Convenient, Large Scale Synthesis of N-CBZ-(S-Phenyl)-L-Cysteine

Syntheses of FDA Approved HIV Protease Inhibitors

“…25 Reiger's synthesis begins with N-Cbz-S-phe-nyl-L-cysteine (73), produced by a previously described method. 26 Synthesis of the N,N-dimethyl amide proceeded by exposure of 73 to pivaloyl chloride followed by in situ displacement of the mixed anhydride by dimethylamine and afforded amide 74 in 98% yield (Scheme 19). Addition of the anion derived from the treatment of 1,3dithiane with n-BuLi to dimethyl amide 74 followed by reduction with NaBH 4 afforded alcohol 75 in 70% isolated yield from a 4.5:1 mixture of diastereomers.…”

“…There have been many reports of syntheses of unnatural Sphenyl cysteine in the literature. Some of the methods described include: opening of a serine derived -lactone intermediate with a thiophenol based nucleophile, 26,30 displacement of a serine derived tosylate by a thiolate anion, 31 opening of an aziridinecarboxylic acid by thiophenol, 32 Michael addition of thiophenol to a chiral nickel complex incorporating an electrophilic alanine-type substituent, 33 and an enzymatic process using cysteine desulfhydrase. 34 One synthesis of nelfinavir created the isostere via a -lactone ring opening using a thiophenol nucleophile.…”

Highly efficient preparation of active S-phenyl-L-cysteine with tryptophan synthase using a chemoenzymatic method

“…The possibility that S-phenyl-L-cysteine can, like nelfinavir, act as an effective suppressant of HIV protease [1], has increased the importance of developing more tractable approaches for producing these chemical compounds. This is further underscored by the potential for the synthesis of phenyl-L-cysteine and its use in multiple biological activation mechanisms [2–4].…”

Synthesis of Two Novel Cysteine-Functionalized Thiophenes

“…S-Aryl and S-heteroaromatic cysteine derivatives are actively investigated as useful intermediates for the synthesis of antibacterials 1 and drugs, 2 such as inhibitors of HIV protease, 3 and for their potential anti-cancer activity. 4 At the same time, variously substituted oligothiophenes have been proposed and tested as anti-cancer agents and some of them have shown unusual strong activity against solid tumours. 5 Moreover, thiophenes substituted with aminoacidic side chains have been used for the generation of electroactive polymers possessing biomimetic characteristics.…”

“…7 The methods reported in the literature for the synthesis of S-arylcysteine analogues of 1 are based on the reaction between cysteine derivatives and suitably functionalized aromatic systems, 9 and on the reaction of thiophenol with aacetamidoacrylic acid 10 or serine derivatives. 2b, 4,11 In particular, the synthesis of a derivative closely related to 1, from 3-iodothiophene and N-acetyl-L-cysteine in the presence of Cu(I) iodide, has been reported. 9b…”