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In this work, we present a metal‐free coupling protocol for the regio‐ and stereoselective C3‐thioarylation of 6‐amino‐2,3,6‐trideoxy‐d‐manno‐oct‐2‐ulosonic acid (iminoKdo). The developed procedure enables the coupling of electron‐rich, electron‐deficient, and hindered arylthiols, providing a series of C3‐modified iminoKdo derivatives in moderate to good yields. Elucidation of active species through controlled experimental studies and time‐lapse 31P NMR analysis provides insights into the reaction mechanism. We demonstrate that, following a tandem Staudinger/aza‐Wittig reaction of an azido‐containing keto ester, an inseparable equimolar mixture of imine/enamine is formed. The enamine then undergoes a Stork‐like nucleophilic attack with the in situ‐formed disulfide reagent, resulting in the formation of the coupling products. Additionally, we describe a rarely reported acid‐promoted aromatization of the C3‐thioarylated iminoKdo skeleton into 3,6‐disubstituted picolinates, which are reminiscent of dichotomines. [ABSTRACT FROM AUTHOR]

Realization of the one-pot Staudinger/aza-Wittig/Castagnoli–Cushman reaction sequence for a series of azido aldehydes and homophthalic anhydrides is described. The reaction proceeded at room temperature and delivered novel polyheterocycles related to the natural product realm in high yields and high diastereoselectivity. The methodology has been extended to three other cyclic anhydrides. These further unravel the potential of the Castagnoli–Cushman reaction in generating polyheterocyclic molecular scaffolds. [ABSTRACT FROM AUTHOR]

Realization of the one-pot Staudinger/aza-Wittig/Castagnoli–Cushman reaction sequence for a series of azido aldehydes and homophthalic anhydrides is described. The reaction proceeded at room temperature and delivered novel polyheterocycles related to the natural product realm in high yields and high diastereoselectivity. The methodology has been extended to three other cyclic anhydrides. These further unravel the potential of the Castagnoli–Cushman reaction in generating polyheterocyclic molecular scaffolds.

Novel seven-membered iminosugars fused thiazolidin-4-one and benzthiazinan-4-one were conveniently synthesized by the tandem Staudinger/aza-Wittig/cyclization reaction under microwave radiation. Benzoyl group (Bz) migrations were found in the synthesis of 8c and 9b using D-galactoside or D-mannoside as starting materials, respectively, which was suggested by HMBC and X-ray. The new bi/tricyclic iminosugars 3~4 ( a–d ) and 5 ( b–d ) were examined for their HIV reverse transcriptase (RT) inhibitory activities. The result showed that all compounds except 5b could effectively inhibit RT activity. Among them, compounds 3c and 4c were the best ones with the IC 50 values of RT inhibitory activities of 2.11 µM and 2.73 µM, respectively. Structure–activity relationship analysis suggested that the phenyl group in the tricyclic azasugars was beneficial for their anti-HIV RT activity. [ABSTRACT FROM AUTHOR]

Novel bi-/tricyclic azasugars fused thiazinan-4-one were conveniently synthesized by the tandem Staudinger/aza-Wittig/cyclization reaction under microwave radiation. The aryl group (phenyl or pyridyl) in mercaptan acid had an important effect on the formation of the diastereomers of the tricyclic hybrids 12b – 15b . The new bi/tricyclic azasugars 3a – 8a , 4b , 6b , 8b and the known ones 2a , 2b were examined for their HIV reverse transcriptase (RT) inhibitory activities. The result showed that compounds 2a – b , 4a , 4b , 5a , and 6a could effectively inhibit RT activity. Among them, the tricyclic azasugar 5a was the best one with the IC 50 value of 0.49 μM. Structure–activity relationship analysis suggested that the phenyl group in the tricyclic azasugars was benefit for their anti-HIV RT activity. [ABSTRACT FROM AUTHOR]

Abstract: Sequential Ugi reaction between p-substituted arylglyoxals, alkylamines, cyclohexyl isocyanide and 3-azido-(S)-2-(tert-butoxycarbonylamino)propanoic acid, followed by a Staudinger/aza-Wittig cyclization in the presence of triphenylphosphine, gave rise to enantiomerically pure N-cyclohexyl 4-alkyl-2-aryl-5-oxo-(S)-6-(tert-butoxycarbonylamino)-4,5,6,7-tetrahydro-1H-1,4-diazepine-3-carboxamides, that can be useful for new drug design. By the same sequence, p-substituted benzaldehydes, 2-aminobenzophenone, cyclohexyl isocyanide and (S)-3-phenyl-2-azidopropionic acid gave rise to N-cyclohexyl 2-((S)-3-benzyl-2-oxo-5-phenyl-2,3-dihydro-1H-benzo[e][1,4]diazepin-1-yl)-(R/S)-2-arylacetamides. [ABSTRACT FROM AUTHOR]

Abstract: Sequential Ugi reaction between p-substituted benzaldehydes, 2-acetyl or 2-benzoylanilines, cyclohexyl or benzyl isocyanides, and 2-azidobenzoic acid, followed by a Staudinger/aza-Wittig cyclization in the presence of triphenylphosphine afforded pseudopeptidic [(5H)-6-oxodibenzo[b,f][1,5]diazocine-5-yl]arylglycinamides. [Copyright &y& Elsevier]