Homocysteine-y-thiolactone

The most commonly used y-thiolactone derivative is homocysteine-y-thiolactone 1, a five-membered cyclic thioester of homocysteine (Scheme 2). Large-scale preparation of 1 requires an acid-catalyzed intramolecular condensation of methionine [77] or homocysteine [78], both bioresource compounds. The hydrochloric acid salt of the racemate 1 is a white solid that displays long-term stability at room temperature and is readily available as a bulk chemical at low cost. 

Homocysteine-y-thiolactOTie 1 is a valuable synthetic building block however, its implementation in polymer science as a versatile functional handle requires some special attention. In order to take part in a PPM, thiolactone 1 needs to be transformed into monomers and/or initiators and subsequently used in a (controlled) polymerization, while maintaining the integrity of the thioester ring. Because the intrinsic instability of the neutral homocysteine-y-thiolactone 1 leads to the formation of the corresponding diketopiperazine adduct [79], an efficient... 

Scheme 2 Chemical structure of homocysteine-y-thiolactone 1 and synthetically valuable derivatives...

A first literature precedent describes the reaction of y-thiobutyrolactone with propiolic acid under basic hydrolysis conditions, generating the corresponding acrylic acid 4 (Scheme 3a) [113]. As an alternative to this sequential hydrolysis and conjugate addition (thio-Michael addition), the lysis of thiolactones under basic conditions is often carried out in the presence of an alkylating agent. Because of the high nucleophilic character of the liberated thiol, 5-alkylated compounds are the final products of these reactions [108]. Methanolysis of homocysteine-y-thiolactone hydrochloride l.HCI and subsequent alkylation by treatment with an alkyl halide in a one-pot fashion has been reported as a simple method for the synthesis of S-alkylhomocysteines 5 (Scheme 3b) [114, 115]. 

Scheme 10 Synthesis of two different types of vinylic thiolactone-containing monomers N-(4-vinylbenzenesulfonyl) homocysteine-y-thiolactone 6 and iV-(acryloyl) homocystei-ne-y-thiolactone 7...

Homocysteine, HSCH2CH2CH(NH2)C02H, is a toxic amino acid that is thought to acylate lysine residues on proteins via its corresponding thiolactone (72) (Scheme 19). Now, for the first time, the kinetics have been studied of the aminolysis of (72) and of two model compounds, y-thiobutyrolactone (72 H instead of NH2) and N-trimethylamino homocysteine thiolactone (72 Me3N+ instead of NH2). A Brpnsted plot for homocysteine thiolactone (72) gave ft = 0.66. This and other data supported... 

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