Georges Dewynter

Synthesis of 1,2,5-Thiadiazolidines 1,1-dioxides (Cyclosulfamides) Starting from Amino Acids and Chlorosulfonyl Isocyanate

Abstract We report here a practical access to a series of five-membered cyclosulfamides (1,2,5-thiadiazolidines 1,1-dioxides) N2 substituted by the BOC group. These compounds are synthesized starting from chlorosulfonyl isocyanate and nitrogen mustards or amino acids. The derivatization of amino acids can lead to an alkyl group on C-4 with a well-defined configuration; in this case the N5 position was protected by a benzyl group. These compounds are valuable tools for asymmetric synthesis.

SYNTHESIS OF PSEUDONUCLEOSIDES CONTAINING CHIRAL SULFAHYDANTOINS AS AGLYCONE (II)

Abstract A series of chiral sulfahydantoins have been synthesized by alkaline cyclization starting from N-sulfamylaminoacid methyl esters. Regioselective glycosylation of these pseudopyrimidic heterocycles was carried out with a benzyl protecting group on the N-sulfonylcarbamic position. Best glycosylation results were obtained by preliminary silylation of sulfahydantoins, and their condensation with a tetraacylribofuranose which yielded the pseudonucleosides in a s-anomeric configuration.

Synthèse de “sulfahydatoïnes” chirales. Aspects stéréochimiques et protection régiospécifique.

Abstract The enantiospecific synthesis of N 2 -benzyl-1-thia-2,5-diazolidin-3-one dioxides (sulfa-analogues of hydantoins) was carried out through two convergent pathways starting from chlorosulfonyl isocyanate (CSI) and chiral α-amino- and hydroxyesters. The intermediate carboxylsulfamides (containing “activated sulfamoyl group”) react easily in the Mitsunobu conditions to give ultimately the N-protected sulfa-hydantoins , or symmetric and dissymmetric sulfones of bis-N-aminoesters. The non-racemization during the cyclization of N-sulfamylaminoesters in alkaline conditions was established by chemical and spectroscopic methods (nmr with chiral Eu(hfc) 3 ).

Expedient synthesis of 2-chloroethylnitrososulfamides (CENS) via the decarboxylative reopening of sulfamoyloxazolidinones

The synthesis of chloroethylnitrososulfamide, (CENS), was carried out starting from chlorosulfonyl isocyanate, amines and haloalcohols through heterocyclization and decarboxylative reopening of N-sulfamoyl-2-oxazolidinones. A total regioselectivity concerning CO2 versus SO2 site hydrolysis was observed. A related aminolysis of sulfamoyloxazolidinones gave N-carbamoylsulfamides. The specific nitrosation on the N-chloroalkyl moiety can be obtained after methylation of the sulfamoyloxazolidinones.

Synthesis of n-sulfamoyloxazolidinones and -perhydrooxazinones reactivity and use as donors in the transsulfamoylation reaction; application to the preparation of 2-chloroethylnitrososulfamides. IV

Starting from chlorosulfonyl isocyanate, successive addition of selected 1,2 and 1,3 haloalcohols, sulfamoylation with the nitrogen mustard and cyclization in alkaline conditions give title compounds in good yields. These sulfamoyloxazolidinones and sulfamoylperhydrooxazinones were revealed as efficient 2-chloroethylsulfamoyl donors in the 2-chloroethylnitrososulfamides synthesis; five new CENS (derivated from heterocyclic amines and amino acids) were thus synthezised. According to the experimental conditions, N-sulfamoylcyclocarbamates can be reopened by nucleophiles giving addition products by transcarbamoylation.

A new family of potential oncostatics: 2-chloroethylnitrososulfamides (CENS)—I. Synthesis, structure, and pharmacological evaluation (preliminary results)

A new series of alkylating agents, 2-chloroethylnitrososulfamides (CENS), were developed on the model of 2-chloroethylnitrosoureas. Starting from chlorosulfonyl isocyanate, a four-step synthesis (carbamoylation-sulfamoylation, Mitsunobu alkylation, deprotection, and nitrosation) gives the title compounds in a 47-58% overall yield. The selection of the nitrosation site can be directed through an alternative route. The pharmacological evaluation shows a significant oncostatic activity towards both A549 and MCF7 cell lines.

Synthese et cyclisation de carboxylsulfamides dérivés d'aminoacides

Abstract 3-Oxo-4-substituted-1,2,5-thiadiazolidine 1,1,-dioxides are synthesized from the carboxylsulfamides of aminoacids.

Selective synthesis of sulfonylureas and carboxysulfamides a novel route to oxazolidinones.

Abstract Starting with chlorosulfonylisocyanate (CSI) two new series of 2-haloethyl carboxysulfamides 5 and 2-haloethyl oxosulfonylureas 6 have been prepared. The haloethyl carboxylate 5 underwent a novel cyclisation in the presence of Et3N to furnish quantitative yields of N-substituted oxazolidin-2-ones. This procedure constitutes a new route to these heterocycles.

SYNTHESIS OF 2- CHLOROETHYLNITROSOSULFAMIDES (CENS) VIA A TRANSSULFAMOYLATION REACTION

Abstract In order to synthesize the series of 2-chloroethylnitrososulfamides (CENS), a procedure using the nucleophilic exchange of an activating group of both the sulfamoyl esters and amides by several amines was developed. The N-oxysuccinimide sulfamate ester was revealed as the most reactive sulfamoyl group donor. This transsulfamoylation procedure allows the preparation of title compounds, especially the derivatives of amino acid esters in two steps in a 75–80% yield.

SULFONYL BIS-N-OXAZOLIDINONE (SBO) : A NEW VERSATILE DIELECTROPHILE WITH SEQUENTIAL REACTIVITY

Abstract The sulfonybis-N-oxazolidinone (SBO) was designed as a biscarbamoylating reagent. Its synthesis was easily carried out starting from sulfuryl chloride, chlorosulfonyl isocyanate or sulfonylbis-isocyanate, using oxazolidinone and/or 2-haloethanol in one-pot procedures. The structure of SBO was established by X-ray crystallography. The difference of reactivity of both electrophilic carbonyl centers allows the formation of dissymetric linkages.