Biologically active compounds analogue generator

Diversity oriented synthesis, which aims to produce a wealth of structural complexity, may prove to be an effective tools of exploring effective routes toward the link between chemistry and medicine.The key synthesis objective is to generate a collection of structurally complex and diverse compounds capable of modulating any biological pathway or process of interest.->1 In this lecture we will present our efforts in the discovery of Neuraminidase inhibitors, a possible drug candidates for Flu pandemics. Furthermore, the enantioselective synthesis of skeletally diverse compounds inspired by natural analogues and related biologically active compounds for many purposes will be presented. 

The Kabachnik Fields reaction, which involves the hydrophosphonylation of phos phites with imines generated in situ from carbonyl compounds and amines, is an attractive method for the preparation of a amino phosphonates. Optically active a amino phosphonic acids and their phosphonate esters are an attractive class of compounds due to their potent biological activities as nonproteinogenic analogues of a amino acids. Therefore, considerable attention has been given to their enantio selective synthesis by hydrophosphonylation of preformed imines, using either metal based catalysts or organocatalysis [107]. 

Pyridone and 2-quinolone analogues are well known biologically active heterocyclic scaffolds. In 2004 Kappe and coworkers generated libraries of 3,5,6-substituted 2-pyridone derivatives by rapid microwave-assisted solution-phase methods using a one-pot, two-step procedure [61]. This three-component condensation of CH-acidic carbonyl compounds, N,N-dimethylformamide dimethylacetal (DMFDMA), and methylene-active nitriles led to 2-pyridones and fused analogues in moderate to good yields (Scheme 10.26). 

A purely chemical system for NAD(P)H oxidation to biologically active NAD(P) has been developed by Paoletti et al. (1990). Mn is specifically required for activity, while both EDTA and thioetha-nol can be replaced by analogues. Optimal molar ratios of chelator/metal ion (2 1) yield an active coordination compound which catalyses thiol auto-xidation to thiyl radical. The latter is further oxidised to disulphide by molecular oxygen whose one-electron reduction generates superoxide radical. 

Acetyl-CoA as a central intermediate in the metabolism of all carbon compounds can be dissimilated to generate biologically useful energy or assimilated and used for growth and multiplication. But the shortest and quickest way to store this carbon skeleton is synthesis of poly(3HB) via formation of aceto-acetyl-CoA (Fig. 1). Since the enzymes involved in the metabolic route to poly(3HB) are unspecific, the synthesis of other homopolyesters and heteropolyesters is possible. Such analogues are formed if appropriate prefabricated substrates (which merely need to be activated and incorporated) are offered. Compounds of this type are called related substrates. 

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