Properties and Reactions of Substituted 1,2‐Thiazetidine 1,1‐Dioxides: Chiral Mono‐ and Bicyclic 1,2‐Thiazetidine 1,1‐Dioxides from α‐Amino Acids

Abstract

New chiral mono-and bicyclic b-sultams, valuable building blocks for drug synthesis, have been prepared from l-Ala, l-Val, l-Leu, l-Ile, l-Phe, l-Cys, l-Ser, l-Thr, and d-penicillamine by transformation of the COOH group into a methylsulfonyl chloride function, followed by cyclization under basic conditions. Selected properties, derivatives, and reactions of the b-sultams are described.Introduction. ± 1,2-Thiazetidine 1,1-dioxide (b-sultam) is a sulfone analogue (bioisoster) of the b-lactam moiety found in many important drugs [1]. It is known that the sultam ring is much more reactive than the b-lactam ring [2], and that b-sultams can interact with serine proteases such as elastase [3]. Therefore, b-sultams might be useful building blocks for new synthetic drugs and, therefore, should be available not only as racemic or diastereoisomeric mixtures, but as pure isomers [4]. Here, we report the synthesis and properties of chiral, stereochemically pure mono and bicyclic 3-substituted 1,2-thiazetidine 1,1-dioxides and their substitution products.A few examples of chiral b-sultams have been described in the literature [5]. For example, (R)-1,2-thiazetidine-3-carboxylic acid was obtained from l-Cys, and (R)-1,2-thiazetidine-3-methanol from l-Ser. In both cases, compounds from the natural −chiral pool× were used as starting materials, a general approach that has also been followed in the present paper.

Diastereoselective Synthesis of cycloSaligenyl‐Nucleosyl‐Phosphotriesters

“…[20] Compounds 18 and 13 were obtained as a racemic mixture after esterification of two salicylalcohols 9 and 12 with P(O)Cl 3 in 61 and 76 % yields (Scheme 3).…”

Convenient One-Pot Synthesis of Sulfonamides from Thiols and Disulfides Using 1,3-Dichloro-5,5-dimethylhydantoin (DCH)

“…In turn, sulfonyl chlorides can be prepared from the corresponding thiols using a number of methods, commonly by bubbling Cl 2 gas into aqueous acid or a biphasic mixture containing the thiol. [5][6][7][8][9] Although this methodology is relatively general, issues associated with the use of excess oxidant and/or aqueous acid have prompted the development of alternative methods. 10,11 We describe here an oxidation/substitution sequence that is mild and minimizes both the amount of oxidant required and the aqueous component.…”

Expanding the Scope of Asinger Chemistry towards Enantiomerically Pure Secondary Amines and β-Aminothiols through Chemoenzymatic Derivatization of 3-Thiazolines

“…For example, even simple representatives of (enantiomerically pure) β-aminothiols are hardly commercially available (such as the thiol analogue of alaninol), thus indicating the tediousness of current approaches. A representative chemical approach towards β-aminothiols has been described by Otto et al converting at first l-amino acids to β-aminoethanols, which are then brominated and subsequently transformed with thiourea to the desired β-aminothiols in yields of up to 40% [15].…”