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Tetrahedron 2022, 124 133013

DOI: 10.1016/j.tet.2022.133013

Izhyk V. V.; Poliudov A. O.; Dobrydnev A. V.; Omelian T. V.; Popova M. V.; Volovenko Y. M.

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.

 

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