One-Pot Syntheses of Dissymmetric Diamides Based on the Chemistry of Cyclic Monothioanhydrides. Scope and Limitations and Application to the Synthesis of Glycodipeptides

Abstract

Opening cyclic monothioanhydrides by amines provides a convenient entry into amido thioacids that can be trapped in situ by 2,4-dinitrobenzenesulfonamides, by electron-deficient azides, or by amines in the presence of Sanger's reagent leading, in each case, to dissymmetric diamides in what can be considered a one-pot, three-component coupling sequence. The use of monothiomaleic anhydride and bifunctional nucleophiles such as amino thiols provides access to heterocyclic amides. The low reactivity of cyclic monothioanhydrides toward alcohols enables the use of methanol as solvent and obviates the need for the protection of alcohols in the various reaction components. Reaction of N-benzyloxycarbonyl-l-aspartic monothioanhydride with unprotected glycosyl amines, followed by capture of the thioacid intermediate with N-sulfonyl amino acid derivatives results in a three-component convergent synthesis of glycosylated peptides.

Dihydro-3-(triphenylphosphoranylidene)-2,5-thiophendione: a convenient synthon for the preparation of substituted 1,4-thiazepin-5-ones and piperidinones via the intermediacy of thioacids

“…By analogy with the chemistry of 2-(triphenylphosphanylidenesuccinic anhydride),44-51 we reasoned that treatment of monothiomaleic anhydride39,40,52,53 with triphenylphosphine would result in the formation of dihydro-3-(triphenylphosphoranylidene)-2,5-thiophendione 1 , and that this ylide would be stable, isolable, and a suitable partner for reaction with aldehydes to give substituted monothioitaconic anhydride derivatives. In the event, reaction of monothio maleic anhydride with triphenylphosphine in glacial acetic acid at room temperature provided the crystalline 1 in 86% yield (Scheme 1).…”

“…With a series of alkylidene monothiosuccinic anhydrides in hand, we turned our attention to tandem Michael addition – nucleophilic ring opening processes with suitably constituted mercapto amines, of the kind previously practiced on monothiomaleic anhydride,39,40 with subsequent trapping of the released thioacid by reaction with 2,4-dinitrobenzenesulfonamides 9-11,36. A series of reactions were conducted in which either 2-mercaptoaniline or 2-mercaptoethylamine were stirred in DMF at 0 °C overnight before the addition of cesium carbonate and a 2,4-dinitrobenzenesulfonamide leading, ultimately, to the isolation of a series of substituted 1,4-thiazepin-5-ones, or their benzo-fused analogues, as presented in Table 2.…”

Thiomaleic Anhydride: A Convenient Building Block for the Synthesis of α-Substituted γ- and δ-Lactones through Free-Radical Addition, Nucleophilic Ring Opening, and Subsequent Thiocarboxylate Manipulation

“…Finally, addition of cesium carbonate and a 2,4-dinitrobenzenesulfonamide3,4n-p capped the sequence by amide bond formation (Table 2). In each case the cyclization step took place to give the more kinetically favored smaller of the two possible rings (lactone or lactam), although for the substrates derived originally from iodoalanine approximately 10% of a minor regioisomer was observed in the crude reaction mixture.…”

Recent progress in the field of neoglycoconjugate chemistry

“…The most frequently occurring glycan types have been addressed by different groups. Thus, Crich et al (32) employed N-benzyloxycarbonyl-L-aspartic cyclic monothioanhydrides and unprotected glycosyl primary amines and N-sulfonyl amino acid derivatives in a one-pot synthetic strategy to generate N-glycosyl asparagine derivatives. With the use of sulfonamide-functionalized amino acids the glycan-containing building block could be further elongated to a glycopeptide following a linear strategy.…”