p-Nitrophenyl carbonate promoted ring-opening reactions of DBU and DBN affording lactam carbamates.

The amidine bases DBU (1,8-diazabicyclo[5.4.0]undec-7-ene) and DBN (1,5-diazabicyclo[4.3.0]non-5-ene) display nucleophilic behaviour towards highly electrophilic p-nitrophenyl carbonate derivatives with ring opening of the bicyclic ring to form corresponding substituted ε-caprolactam and γ-lactam derived carbamates. This simple method presents a unified strategy to synthesize structurally diverse ε-caprolactam and γ-lactam compounds with a large substrate scope.

Synthesis of D-fructose-derived spirocyclic 2-substituted-2-oxazoline ribosides.

The TMSOTf-mediated synthesis of ß-configured spirocyclic 2-substituted-2-oxazoline ribosides was achieved using a "Ritter-like" reaction in toluene through nucleophilic addition of electron-rich nitriles to the oxacarbenium ion intermediate of 1,2;3,4-di-O-isopropylidene-ß-D-psicofuranose derivatives with concomitant intramolecular trapping of the C2 hydroxymethyl group on the electrophilic nitrilium carbon. These carbohydrate-derived spirooxazolines are stable and were obtained in good yield with high stereoselectivity due to the conformational rigidity imparted by the 3,4-isopropylidene group.

Synthesis of an Immunologically Active Heptamannoside of Mycobacterium tuberculosis by the [Au]/[Ag]-Catalyzed Activation of Ethynylcyclohexyl Glycosyl Carbonate Donor.

Tuberculosis (TB) is one of the most dreadful diseases, killing more than 3 million humans annually. M. tuberculosis (MTb) is the causative agent for TB and has a thick and waxy cell wall, making it an attractive target for immunological studies. In this study, a heptamannopyranoside containing 1 → 2 and 1 → 6 α-mannopyranosidic linkages has been explored for the immunological evaluations. The conjugation-ready heptamannopyranoside was synthesized by exploiting the salient features of recently discovered [Au]/[Ag]-glycosidation of ethynylcyclohexyl glycosyl carbonate donors. The glycan was conjugated to the ESAT6, an early secreted protein of MTb for further characterization as a potential subunit vaccine candidate.

Expedient synthesis of the heneicosasaccharyl mannose capped arabinomannan of the Mycobacterium tuberculosis cellular envelope by glycosyl carbonate donors.

The global incidence of tuberculosis is increasing at an alarming rate, and Mycobacterium tuberculosis (Mtb) is the causative agent for tuberculosis, a disease with high mortality. Lipoarabinomannan (LAM) is one of the major components of the Mtb cellular envelope and is an attractive scaffold for developing anti-tubercular drugs, vaccines and diagnostics. Herein, a highly convergent strategy is developed to synthesize heneicosasaccharyl arabinomannan for the first time. The arabinomannan synthesized in this endeavour has several 1,2-trans or α-Araf linkages and three 1,2-cis or ß-Araf linkages end capped with 1,2-trans or α-Manp linkages. All the key glycosidations were performed with alkynyl carbonate glycosyl donors under [Au]/[Ag] catalysis conditions, which gave excellent yields and stereoselectivity even for the reactions between complex and branched oligosaccharides. The resultant allyl oligosaccharide was globally deprotected to obtain the heneicosasaccharyl arabinomannan as a propyl glycoside. In summary, heneicosasaccharyl mannose capped arabinomannan synthesis was achieved in 56 steps with 0.016% overall yield.

[Au]/[Ag]-catalysed expedient synthesis of branched heneicosafuranosyl arabinogalactan motif of Mycobacterium tuberculosis cell wall.

Emergence of multidrug-resistant and extreme-drug-resistant strains of Mycobacterium tuberculosis (MTb) can cause serious socioeconomic burdens. Arabinogalactan present on the cellular envelope of MTb is unique and is required for its survival; access to arabinogalactan is essential for understanding the biosynthetic machinery that assembles it. Isolation from Nature is a herculean task and, as a result, chemical synthesis is the most sought after technique. Here we report a convergent synthesis of branched heneicosafuranosyl arabinogalactan (HAG) of MTb. Key furanosylations are performed using [Au]/[Ag] catalysts. The synthesis of HAG is achieved by the repetitive use of three reactions namely 1,2-trans furanoside synthesis by propargyl 1,2-orthoester donors, unmasking of silyl ether, and conversion of n-pentenyl furanosides into 1,2-orthoesters. Synthesis of HAG is achieved in 47 steps (with an overall yield of 0.09%) of which 21 are installation of furanosidic linkages in a stereoselective manner.