Herein we present short and cost-effective synthesis of alkyl isothiazolidine-1,1-dioxide 3-carboxylates starting from commercially available α-amino acid ester hydrochlorides. These compounds were designed as sulfonamide-containing bioisosteres of known pharmacological template – pyroglutamic acid (pGlu). Specifically, α-amino acid ester hydrochlorides were sulfonylated with (2-chloroethyl)sulfonyl chloride providing in one-pot manner the corresponding alkyl 2-((vinylsulfonyl)amino)carboxylates. The obtained vinyl sulfonamides possessing SO₂NH functionality were alkylated with either MeI or MeOCH₂Cl (MOMCl) prior to cyclization step. At the same time, vinyl sulfonamides derived from N-monosubstituted and cyclic amino acid esters were directly involved in NaH-mediated intramolecular carbo-Michael reaction affording the target alkyl isothiazolidine-1,1-dioxide 3-carboxylates. Further acid-promoted cleavage of MOM-protecting group led to NH-unsubstituted target compounds.

在这里，我们提出了从市售的 α-氨基酸酯盐酸盐开始合成烷基异噻唑烷-1,1-二氧化 3-羧酸盐的短且具有成本效益的合成方法。这些化合物被设计为已知药理学模板 - 焦谷氨酸 (pGlu) 的含磺酰胺生物等排体。具体而言，用(2-氯乙基)磺酰氯磺酰化α-氨基酸酯盐酸盐，以一锅法提供相应的2-((乙烯基磺酰基)氨基)羧酸烷基酯。获得的具有SO ₂ NH 官能团的乙烯基磺酰胺在环化步骤之前用MeI或MeOCH ₂ Cl (MOMCl)烷基化。同时，N衍生的乙烯基磺酰胺-单取代和环状氨基酸酯直接参与NaH介导的分子内碳-迈克尔反应，得到目标烷基异噻唑烷-1,1-二氧化物3-羧酸盐。进一步酸促进的 MOM 保护基团的裂解产生了NH未取代的目标化合物。