Thiazolidines ring opening

A. M. Davis, N. J. Layland, M. I. Page, F. Martin, R. M. O Ferrall, Thiazolidine ring opening in penicillin derivatives. Part 2 Enamine Formation , J. Chem. Soc., Perkin Trans. 2 1991, 1225-1229. 

Oxidation reactions on the sulfur atom of penicillins remain the most important reactivity of S-1 encountered in the literature. Penam sulfoxides and sulfones are indeed important compounds as they confer to the skeleton an ease of thiazolidine ring opening by weakening the C(5)-S(l) and S(l)-C(2) bonds (see Section 2.03.5.9) <2004CHE816>. In particular, the former constitute key intermediates in ring-expansion transformations from penams to cephems (see Section 2.03.5.9), while the latter have a special biological interest as /3-lactamase inhibitors (e.g., sulbactam, tazobactam see Sections 2.03.1, 2.03.5.2, and 2.03.12.4). Since CHEC-II(1996) covers all the aspects of these oxidation reactions on the S-1 atom of penicillins, this section focuses on the most relevant recent papers. As there is no particular change in the subject, only a few articles have been released since 1995. 

The total synthesis of penems from penams reported by Kametani <1986JOC624> is based on thiazolidine ring opening with an a-diazoacetate catalyzed by rhodium(n) as the key step to furnish 110 (Scheme 55). Further reactions allowed the fused ring cyclization via Woodward s strategy. 

Fast thiazolidine ring opening resulting from interactions with mercury ions enables voltammetric determinations of Thz and its derivatives. 

At hydroxide ion concentrations above 1 M elimination across C(6)-C(5) and thiazolidine ring-opening occurs to give the enamine, similar to (71). This is suggested by the observation of the appearance of the chromophore at 280 nm and deuterium-exchange at C(6) (Davis and Page, 1986). 

Sodium carbonate Thiazolidine ring opening of the penicillin ring skeleton via sulfonium salts... 

Fig. 1. The penicillin thiazolidine ring (a) open conformation (b) closed conformation.

The sulfonium ylide derived chemistry of penicillins continues to meet the interest of several research groups. It is well known that intermolecular carbenoid attack at the sulfur atom generates a sulfonium ylide which undergoes spontaneous opening of the thiazolidine ring to furnish a l,2-sm>-penicillin 326). Novel examples of this reaction type were found upon Rb2(0Ac)4-catalyzed decomposition of diazomalonic esters in the presence of various penicillins this transformation constituted the opening step of a synthetic sequence directed towards 2-alkoxycarbonyl-cephems 345 a) or modified penicillins 345 b). Similar to its reaction with 4-thio-2-azetidinone... 

Fig. 5.10. Base-catalyzed epimerization at C(5) in penicilloic acids involves opening the thiazolidine ring by CS bond fission, followed by reclosure with inversion of configuration at...

Fig. 11.15. Mechanisms of ring opening of (R)-thiazolidine-4-carboxylic acids (11.113) as derivatives of and chemical delivery systems for l-cysteine (11.114). Activation was shown to be by nonenzymatic, hydrolytic reaction (Pathway a), or by mitochondrial oxidation (Pathway b) to the (R)-4,5-dihydrothiazole-4-carboxylic acid (11.115), followed by a (presumably nonenzymatic) hydrolysis to the IV-acylcysteine, and then by cytosolic hydrolysis to cysteine [138].

The first cases of ring opening to be examined, involving loss ofC02, is observed during activation of the cysteine prodrug, L-2-oxo-l,3-thiazolidine-... 

Thiazolidine-4-carboxylic acid is not stable in the presence of reducing agents, e.g. sodium in liquid ammonia 193 and, in contrast to N-protected Thz, the N-unprotected forms are unstable under oxidizing conditions, e.g. slow ring opening occurs in air at pH 10 in the presence of traces of ferric chloride, or, more rapidly, with hydrogen peroxide, bromine, or iodine in aqueous solution. 190 ... 

In another system, a non-diffusible compound reacts with undeveloped silver ions to liberate a diffusible dye, producing a positive transferred image.141 Again, thiosulfate-containing developers are used. In this system, the silver ions catalyze the ring-opening hydrolysis of a thiazolidine (73), shown in equation (1). 

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