Synthesis of alkyl isothiazolidine-1,1-dioxide 3-carboxylates via the intramolecular carbo-Michael reaction strategy

Herein we present short and cost-effective synthesis of alkyl isothiazolidine-1,1-dioxide 3-carboxylates starting from commercially available a-amino acid ester hydrochlorides. These compounds were designed as sulfonamide-containing bioisosteres of known pharmacological template -pyroglutamic acid (...

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Published inTetrahedron Vol. 124; pp. 133013 - 133020
Main Authors Izhyk, Vitalii V., Poliudov, Anton O., Dobrydnev, Alexey V., Omelian, Taras V., Popova, Maria V., Volovenko, Yulian M.
Format Journal Article
LanguageEnglish
Published OXFORD Elsevier 08.10.2022
Subjects
Chemistry
Chemistry, Organic
Physical Sciences
Science & Technology
Heterocycles
ACID
ONE-POT SYNTHESIS
Amino acids
5-ENDO-TRIG RADICAL CYCLIZATIONS
SULFONAMIDE
DOS APPROACH
8-MEMBERED RING SULTAMS
Cyclization
Sulfonamides
NONSTEROIDAL ANTIINFLAMMATORY DRUGS
DIELS-ALDER REACTION
BIOLOGICAL EVALUATION
STEREOSELECTIVE-SYNTHESIS
Michael reaction
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Summary:Herein we present short and cost-effective synthesis of alkyl isothiazolidine-1,1-dioxide 3-carboxylates starting from commercially available a-amino acid ester hydrochlorides. These compounds were designed as sulfonamide-containing bioisosteres of known pharmacological template -pyroglutamic acid (pGlu). Specifically, a-amino acid ester hydrochlorides were sulfonylated with (2-chloroethyl)sul-fonyl chloride providing in one-pot manner the corresponding alkyl 2-((vinylsulfonyl)amino)carboxyl-ates. 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.(c) 2022 The Authors. Published by Elsevier Ltd. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
ISSN:0040-4020
1464-5416
DOI:10.1016/j.tet.2022.133013