Complexes medicinally important

Medicinally Important Cold Complexes, Their Analogs and Reactions 287... 

Table 6.1 Medicinally important chrysotherapy complexes. Adapted from Shaw [17].

The less money available for health care the more important is the role of clinical pharmacology. In hospitals providing specialised services, where constraints on the availability and affordability of complex medicines are often acutely felt, clinical pharmacology makes it possible to reduce substantially the drug budget. 

Indole is the parent of a very large number of alkaloids and medicinally important compounds. Its reactions, and particularly the synthesis of complex derivatives, occupy central stage in heterocyclic chemistry. 

The substantial progress made in synthesis of the complex carbohydrates occurring in medicinally important molecules68-72 is largely due to the discovery of new oxidative procedures that permit ready preparation of aldosuloses. Branched-chain sugars were obtained by nucleophilic additions to various lcetopentoses and ketohexoses subsequent condensation with purines and pyrimidines then afforded the desired natural, or synthetic, antibiotics (see, for example, Refs. 19 and 73). 

Arylamines are commonplace. They are part of molecules with medicinally important properties, of molecules with structurally interesting properties, of materials with important electronic properties, and of transition metal complexes with catalytic activity. An aryl-nitrogen linkage is present in nitrogen heterocydes such as indoles [1, 2] and benzopyr-azoles, conjugated polymers such as polyanilines [3-9], and readily oxidizable triarylamines used in electronic applications [10-13]. The ability of aryl halides and triflates to form arylamines allows a single group to be used as a synthetic intermediate in aromatic carbon-... 

Flavonoids and their metal complexes exhibit a unique redox chemistry, acting both as antioxidants to protect against potential oxidative damage, e.g. in the presence of ROS, and as prooxidant that may result in oxidative damage, depending on the reaction conditions. A fine balance of these two pathways thus determines the characteristic role of this biologically and medicinally important family of natural products. 

However, in contrast to arsenic, antimony compounds remain of medicinal importance, particularly in the treatment of various parasitic infections including leishmaniasis, schistosomiasis, and trypanosomasis. Coordination compounds used include the sodium or potassium antimony tartrates and substituted catecholate complexes, which are O-donor complexes, whilst S-donors are utilized in 2,3-dithiosuccinate derivatives.While the mode of action is unclear in many cases, the attraction of these compounds, in addition to their clinical effectiveness, is their simplicity of manufacture and low cost. 

In the first two trends, we recognize indications of ripeness and fertility that awaits us in exploring the gap between "simple" chemistry and "complex" medicine. The third observation re-emphasizes the important role of evolving rigorous kinetic models which become essential, first for "keeping track" of, and subsequently for "making sense" out of the many interactive events in a multicomponent system, of promoters, inhibitors,... 

The utility of the Paal-Knorr reaction allows it to stiU remain at the forefront of organic chemistry for the preparation of highly complex substrates and drug-like compounds. The Paal-Knorr reaction was used to synthesize iV-aryl pyrroles 25 with an azide group on the aryl ring. These substrates were subsequently employed in a tandem azide-alkyne 1,3-dipolar cycloaddition reaction to synthesize medicinally important molecules with a diazepine scaffold 27 (14OL560). 

Constructing molecular complexity and diversity Total synthesis of natural products of biological and medicinal importance 12CSR5185. Design and synthesis of novel opioid ligands and their pharmacologies 12H(85)1821. 

Transition metal-mediated cycloaddition and cyclization reactions have played a vital role in the advancement and applications of modem synthetic organic chemistry. Rhodium-catalyzed cycloadditions/cyclizations have attracted significant attention because of their versatility in the transformations of activated and unactivated acetylenes, olefins, allenes, etc. These reactions are particularly valuable because of their ability to increase molecular complexity through a convergent and highly selective combination of acyclic components. In addition, these reactions allow for the preparation of molecules with chemical, biological, and medicinal importance with greater atom economy. Recent developments in rhodium-catalyzed cycloaddition and cyclization reactions are described in this section. 

The catalytic version of this type of reaction was realized by using acetoacetate derived O-silyl dienolate as nucleophiles in the presence of Carreira s catalyst, giving acetoacetate y-adducts in high yields and enantiomeric excesses [119] (Scheme 14.42). The products are ubiquitous structural subunits in biologically active natural products such as the polyene macrolide antibiotic and medicinally important HMG-CoA reductase inhibitors. This aldol addition can also be catalyzed by BINOL-Ti complex in the presence of 4A MS with moderate to good enantioselectivity [120]. The same catalyst system was also efficient in the asymmetric aldol reaction between the aldehydes and Chan s diene [ 1,3-bis-(trimethylsilyloxy)-l-methoxy-buta-1,3-diene] and other related silyl enol ethers [121, 122] (Scheme 14.43) or the functionalized silyl enol ether such as 2-(trimethylsilyloxy)furan with good to excellent enantioselectivities [123]. 

In the future, metabolic engineering and biotechnological approaches can be used as an alternative production system to overcome the limited availability of biologically active, commercially valuable and medicinally important secondary metabolite compounds. Advancement in culture techniques may provide new means for the culturing of non-cultured/exotic lichens and production of then-secondary compounds as they produce in nature. This may create an ultimate advantage to provide a continuous, rehable source of natural products from this complex organism. 

The utilization of copper(I) catalysis in asymmetric transformations is universal due to the special valence electron, Lewis acidity, and coordination characteristic of the metal. Copper salts are easily available, cost-efficient, and nontoxic. Copper(l)-catalyzed asymmetric cycloaddition and cascade addition-cyclization reactions are straightforward methodologies for the stereoselective construction of various biologically and medicinally important heterocyclic compounds. In the past 5 years, main endeavors have been paid into catalytic asymmetric [3+2] cycloadditions other types of cycloaddition protocols are relatively less developed. The examples described in this chapter clearly demonstrate the potential of chiral Cu(I) complexes in the synthesis of enantioenriched heterocycles. Further studies may lie in the diversification of catalytic system, reaction type, and catalysis mode. Research in this field is still challenging and highly desirable, and it would be expected that more discoveries will come in the near future. 

Yang, C.T. Sreerama, S.G. Hsieh, W.Y. Liu, S. (2008) Synthesis and Characterisation of a Novel Macrocyclic Chelator with 3-Hydroxy-d-Pyrone Chelating Arms and Its Complexes with Medicinally Important Metals. Inorg. Chem., Vol.47, pp.2719-2727. 

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