Generation methods natural products

The 2(lH)-pyrazinone system has received increased interest in the past two decades by both synthetic and biological research, due to its presence in a variety of natural and non-natural products as well as pharmacologically active compounds. The easy and diverse methods for the generation of this versatile scaffold make it a prime choice for the current pharmaceutical research hke thrombin inhibitors, substance P antagonists, etc. The rich 1,4-azadiene... 

The intriguing structural complexity and often potent biological activity exhibited by many polyacetate-derived natural products have generated a continuing interest in the development of efficient, stereoselective approaches to the assembly of repeating l -diol subunits. One such method is the alkylation and reduc-... 

New synthetic methods are the lifeblood of organic chemistry. Synthetic efforts toward natural products often provide the impetus for the development of novel methodology. Reactive synthons derived from 1,3-dioxanes have proven to be valuable intermediates for both syn- and anfz-1,3-diols found in many complex natural products. Coupling reactions at the 4-position of 1,3-dioxanes exploit anomeric effects to generate syu-1,3-diols (cyanohydrin acetonides), autz-1,3-diols (4-acetoxy-1,3-dioxanes), and either syn- or azztz-1,3-diols (4-lithio-1,3-dioxanes). In the future, as biologically active polyol-containing natural products continue to be discovered, the methods described above should see much use. 

Aziridines are important compounds due to their versatility as synthetic intermediates. In addition, aziridine rings are present in innumerable natural products and biologically active compounds. Nitrene addition to alkenes is one of the most well established methods for the synthesis of aziridines. Photolysis or thermolysis of azides are good ways to generate nitrenes. Nitrenes can also be prepared in situ from iodosobenzene diacetate and sulfonamides or the ethoxycarbonylnitrene from the A-sulfonyloxy precursor. 

This synthetic sequence for an olefin synthesis has been further developed by Kocienski who has shown that eliminative desulphonylations carried out on / -acyloxysulphones are remarkably stereoselective for the synthesis of trans-disubstituted-olefins. The method has wide applicability in that a-lithio phenyl sulphones are readily generated, and are readily coupled to aldehydes or ketones, to give j8-hydroxysulphones. The hydroxyl function of these is then esterified and the synthesis is completed by the reductive elimination with sodium amalgam. Kocienski has prepared two reviews that summarize his syntheses of a range of natural products - one of which is diumycinoP obtained... 

In recent years, the related C-H insertion chemistry of nitrenes has gained considerable momentum.36 Effective chiral catalysts have been developed as well as new methods for generation of the nitrene precursors. Even more impressive has been the application of this chemistry to the synthesis of complex natural products. The scope of this chemistry is described in Section 10.04.4. 

Acyl nitroso compounds react with 1, 3-dienes as N-O heterodienophiles to produce cycloadducts, which have found use in the total synthesis of a number of nitrogen-containing natural products [21]. The cycloadducts of acyl nitroso compounds and 9,10-dimethylanthracene (4, Scheme 7.3) undergo thermal decomposition through retro-Diels-Alder reactions to produce acyl nitroso compounds under non-oxidative conditions and at relatively mild temperatures (40-100°C) [11-14]. Decomposition of these compounds provides a particularly clean method for the formation of acyl nitroso compounds. Photolysis or thermolysis of 3, 5-diphenyl-l, 2, 4-oxadiazole-4-oxide (5) generates the aromatic acyl nitroso compound (6) and ben-zonitrile (Scheme 7.3) [22, 23]. Other reactions that generate acyl nitroso compounds include the treatment of 5 with a nitrile oxide [24], the addition of N-methyl morpholine N-oxide to nitrile oxides and the decomposition of N, O-diacylated or alkylated N-hydroxyarylsulfonamides [25-29]. 

DKPs, and 2,6-DKPs can be distinguished on the basis of intramolecular C-N cyclization, tandem reactions, and synthetic methods used. 2,3-DKPs have been used in medicinal chemistry and are found in natural products such as antibiotics (piperacillin), cefoperazone, and bicyclomycin. 2,5-DKPs are common namrally occurring peptide derivatives and are frequently generated as unwanted by-products in the synthesis of oligopeptides. " ... 

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