Lipoarabinomannan (LAM) is one of the major constituents of the Mycobacterium tuberculosis cell wall and an attractive molecular scaffold for antituberculosis drug and vaccine development. In this paper, a convergent strategy was developed for the synthesis of LAM oligosaccharides with an α-1,2-linked dimannopyranose cap at the nonreducing end. The strategy was highlighted by efficient coupling of separately prepared nonreducing end and reducing end oligosaccharides. Glycosylations were mainly achieved with thioglycoside donors, which gave excellent yields and stereoselectivity even for reactions between complex oligosaccharides. The strategy was utilized to successfully synthesize tetra-, hepta-, and undecasaccharides of LAM from d-arabinose in 10, 15, and 14 longest linear steps and 7.84, 7.50, and 2.59% overall yields, respectively. The resultant oligosaccharides with a free amino group at their reducing end were effectively conjugated with carrier proteins, including bovine serum albumin and keyhole limpet hemocyanin (KLH), via a bifunctional linker. Preliminary immunological studies on the KLH conjugates revealed that they could elicit robust antibody responses in mice and that the antigen structure had some influence on their immunological property, thus verifying the potential of the oligosaccharides for vaccine development and other immunological studies.

We estimate exchange rate pass-through (PT) into import, producer and consumer price indexes for nine OECD countries, using a method proposed by Uhlig (2005). In a Vector Autoregression (VAR) model, we identify the exchange rate shock by imposing restrictions on the signs of impulse responses for a small subset of variables. These restrictions are consistent with a large class of theoretical models and previous empirical findings. We find that exchange rate PT is less than one at both short and long horizons. Among three price indexes, exchange rate PT is greatest for import price index and smallest for consumer price index. In addition, greater exchange rate PT is found in an economy which has a smaller size, higher import share, more persistent exchange rate, more volatile monetary policy, higher inflation rate, and less volatile aggregate demand.

A total of 29 novel quinazoline-2-aminothiazole hybrids containing a 4-piperidinylamide linker were designed, synthesized, and evaluated for their anti-microbial properties against phytopathogenic fungi and bacteria of agricultural importance. The anti-fungal assays indicated that some of the target compounds exhibited excellent inhibitory effects in vitro against Rhizoctonia solani. For example, 11 compounds within this series (including 4a, 4g, 4h, 4j, 4o, 4s, 4t, 4u, 4v, 4y, and 4b′) were found to possess EC50 values (effective concentration for 50% activity) ranging from 0.42 to 2.05 μg/mL against this pathogen. In particular, compound 4y with a 2-chloro-6-fluorophenyl substituent displayed a potent anti-R. solani efficacy with EC50 = 0.42 μg/mL, nearly threefold more effective than the commercialized fungicide Chlorothalonil (EC50 = 1.20 μg/mL) and also slightly superior to the other fungicide Carbendazim (EC50 = 0.53 μg/mL). Moreover, compound 4y could efficiently inhibit the growth of R. solani in vivo on the potted rice plants, displaying an impressive protection efficacy of 82.3% at 200 μg/mL, better than those of the fungicides Carbendazim (69.8%) and Chlorothalonil (48.9%). Finally, the mechanistic studies showed that compound 4y exerted its anti-fungal effects by altering the mycelial morphology, increasing the cell membrane permeability, and destroying the cell membrane integrity. On the other hand, some compounds demonstrated good anti-bacterial effects in vitro against Xanthomonas oryzae pv. oryzae (Xoo). Overall, the presented results implied that 4-piperidinylamide-bridged quinazoline-2-aminothiazole hybrids held the promise of acting as lead compounds for developing more efficient fungicides to control R. solani.

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