Combinatorial approach towards synthesis of 2',3'-dideoxynucleosides and enzyme-catalysed selective hydrolysis of diethyl acetamidomalonate and amides of polyacetoxy aromatic carboxylic acid

507-51

Aldehydes: magnificent acyl equivalents for direct acylation

From the viewpoint of meeting the current green chemistry challenges in chemical synthesis, there is a need to disseminate how the cocktail of acylation and activation can play a pivotal role in affording bioactive acylated products comprising substituted ketone motifs in fewer reaction steps, with higher atom-economy and improved selectivity. In recent years, a significant number of articles employing the title compounds “aldehydes” as magnificent acylation surrogates which are less toxic and widely applicable have been published. This review sheds light on the compounds use for selective acylation of arene, heteroarene and alkyl (sp3, sp2 and sp) C–H bonds by proficient utilization of the C–H activation strategy. Critical insights into selective acylation of diverse moieties for the synthesis of bioactive compounds are presented in this review that will enable academic and industrial researchers to understand the mechanistic aspects involved and fruitfully employ these strategies in designing novel molecules

Synthesis of macromolecular systems via lipase catalyzed biocatalytic reactions: applications and future perspectives

Enzymes, being remarkable catalysts, are capable of accepting a wide range of complex molecules as substrates and catalyze a variety of reactions with a high degree of chemo-, stereo- and regioselectivity in most of the reactions. Biocatalysis can be used in both simple and complex chemical transformations without the need for tedious protection and deprotection chemistry that is very common in traditional organic synthesis. This current review highlights the applicability of one class of biocatalysts viz. ‘‘lipases’’ in synthetic transformations, the resolution of pharmaceutically important small molecules including polyphenols, amides, nucleosides and their precursors, the development of macromolecular systems (and their applications as drug/gene carriers), flame retardants, polymeric antioxidants and nanocrystalline solar cells, etc

Synthetic and mass spectral fragmentation studies on trisubstituted 2H-pyran- 2-ones and comparative EIMS behaviour of biologically active 3,5- disubstituted pyrazoles and isoxazoles

872-87

Chemoenzymatic synthesis, nanotization and anti- aspergillus activity of optically enriched fluconazole analogues

Despite recent advances in diagnostic and therapeutic advances in antifungal research, aspergillosis still remains a leading cause of morbidity and mortality. One strategy to address this problem is to enhance the activity spectrum of known antifungals, and we now report the first successful application of Candida antarctica lipase (CAL) for the preparation of optically enriched fluconazole analogs. Anti-Aspergillus activity was observed for an optically enriched derivative, (-)-S-2-(2’ ,4’ -difluorophenyl)-1-hexyl-amino-3-(1‴,2‴,4‴) triazol-1‴-yl-propan-2-ol, which exhibits MIC values of 15.6 μg/mL and 7.8 μg/disc in microbroth dilution and disc diffusion assays, respectively. This compound is tolerated by mammalian erythrocytes and cell lines (A549 and U87) at concentrations of up to 1000 μg/mL. When incorporated into dextran nanoparticles, the novel, optically enriched fluconazole analog exhibited improved antifungal activity against Aspergillus fumigatus (MIC = 1.63 μg/mL). These results not only demonstrate the ability of biocatalytic approaches to yield novel, optically enriched fluconazole derivatives but also suggest that enantiomerically pure fluconazole derivatives, and their nanotised counterparts, exhibiting anti-Aspergillus activity may have reduced toxicity

Gold-Catalyzed Cyclization Processes : pivotal avenues for Organic Synthesis

Over the years, gold catalysis has materialized as an incredible synthetic approach among the scientific community. Due to the trivial reaction conditions and great functional compatibility, these progressions are synthetically expedient, because practitioners can implement them to build intricate architectures from readily amassed building blocks with high bond forming indices. The incendiary growth of gold catalysts in organic synthesis has been demonstrated as one of the most prevailing soft Lewis acids for electrophilic activation of carbon-carbon multiple bonds towards a great assortment of nucleophiles. Nowadays, organic chemists consistently employ gold catalysts to carry out a diverse array of organic transformations to build unprecedented molecular architectures. Despite all these achievements and a plethora of reports, many vital challenges remain. In this account, we describe the reactivity of various gold catalysts towards cyclization processes developed over the years. These protocols give access to a wide scope of polyheterocyclic structures, containing different medium-sized ring skeletons. This is interesting, as the quest for highly selective reactions to assemble diversely functionalized products has attracted much attention. We envisage that these newly developed chemo-, regio-, and diastereoselective protocols could provide an expedient route to architecturally cumbersome heterocycles of importance for the pharmaceutical industry.status: publishe

Novel aromatic ester from Piper longum and its analogues inhibit expression of cell adhesion molecules on endothelial cells

We report here the isolation and characterization of two active principles, ethyl 3',4',5'-trimethoxycinnamate (1) and piperine (2), from the combined hexane and chloroform extracts of Piper longum. Using primary human umbilical vein endothelial cells, we evaluated the activities of compound 1 on TNF-α-induced expression of cell adhesion molecules, viz., ICAM-1, VCAM-1, and E-selectin, which play key roles in controlling various inflammatory diseases. Both compounds 1 and 2 inhibited the TNF-α-induced expression of ICAM-1 in a dose- and time-dependent manner; however, the activity of ethyl 3',4',5'-trimethoxycinnamate (1) was ~1.3 times higher than that of piperine (2). As ethyl 3',4',5'-trimethoxycinnamate (1) has been isolated for the first time from a natural source, Piper longum, and it exhibited higher activity, we carried out further studies on it. To correlate its cell adhesion molecule inhibitory activity with its functional consequences, we showed that it significantly blocked the adhesion of neutrophils to endothelium in a time- and concentration-dependent manner. Importantly, the inhibitory effect of cinnamate 1 was found to be reversible. To elucidate its structure-function-activity relationship, we synthesized nine different analogues of ethyl 3',4',5'-trimethoxycinnamate, i.e., compounds 3-11, and compared the ICAM-1 inhibitory activity of compound 1 with those of its synthetic analogues as well as the corresponding acids 12-15. The structure-activity studies indicate that the chain length of the alcohol moiety, substituents in the aromatic ring, and a, β-double bond of the cinnamic acid ester have significant effects on the inhibition of TNF-α-induced expression of ICAM-1 on endothelial cells. These findings have implications in developing compounds with a better therapeutic index against various inflammatory diseases

Stone houses, England

Cataloguer's title.The Rorke Family Photograph Collection contains 301 black and white and 28 colour photographs of the Rorke Family of Carbonear, Newfoundland, as well as the Forward and Bemister families from that area who are linked to it by marriage. Although spanning from the 1840s-1970s, most photos are from 1900-45, showing family events, homes and Newfoundland and Labrador locations. There is also an album of photos taken while James Rorke attended the Leys School in Cambridge, England