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A model considering various steric and stereoelectronic factors involved in transition state of the reductive elimination step is proposed and used to interpret results of systematic studies of arylcuprate conjugate addition reactions with cis and trans gamma-alkoxy-alpha,beta-enoates. While stereoselectronics disfavor syn-addition, a judicious choice of properly sized gamma-substituents might lead to the predominant formation of syn-products, especially with cis enoates.

The article explains the chemistry, as well as the mechanisms associated with synthesis of structurally simplified analogues of pancratistatin. These pancratistatin analogues are shown to be synthesized with a truncated cyclical portion of the molecule.

The study describes a newly developed one-step synthesis of several heterocyclic privileged medicinal scaffolds by employing the multicomponent reactions of the malonitrile with different aldehydes and thiols. The results show that the process is extremely efficient, as it can lead to the development of a large number of diverse libraries of such compounds without involving any kind of chromatography in the process.

Fifteen aromatic analogues of conduritol F., L-chiro-inositol, and dihydroconduritol F that possess four of the six pancratistatin stereocenters are synthesized and evaluated for anticancer activity. The analysis of the compounds reveal that they possess four of the six pancratistatin stereocenters and serve as truncated pancratistatin analogues lacking the lactam ring B, but retaining the crucial C10a-C10b bond with the correct stereochemistry.

Formal synthesis of (+)- and (-)-cyclophellitol from D-xylose is accomplished through utilization of the latent plane of chirality present in the starting carbohydrate. This synthetic pathway is suitable for the preparation and biological evaluation of cyclophellitol analogues in both enantiomeric series.

Current models used to predict the stereochemical outcome of organocopper conjugate addition processes focus on the nucleophilic addition step as stereochemistry-determining. Recent kinetic, NMR, kinetic isotope effect, and theoretical density functional studies strongly support the proposal that stereochemical preferences in these processes are dictated by the reductive elimination step, transforming CuIII to CuI intermediates. A new model that considers various steric and stereoelectronic factors involved in the transition state of the reductive elimination step is proposed and then used to interpret the results of systematic studies of arylcuprate conjugate addition reactions with cis and trans γ-alkoxy-α,β-enoates. The results give rise to the following selectivity guidelines for this process. To achieve high anti-addition diastereoselectivities the use of trans esters with a bulky nonalkoxy substituent at the γ-position is recommended. While stereoelectronics disfavor syn-addition, a judicious choice of properly sized γ-substituents may lead to the predominant formation of syn-products, especially with cis enoates. However, high syn-selelectivities may be achieved by using γ-amino-α,β-enoates. [ABSTRACT FROM AUTHOR]

Twenty-nine Amaryllidaceae alkaloids and their derivatives belonging to the five most common groups, including lycorine, lycorenine, tazettine, crinine, and narciclasine types, were evaluated for antiproliferative, apoptosis-inducing, and anti-invasive activities in vitro. The antiproliferative properties of each test compound are in agreement with those reported in the literature, while the high potency of amarbellisine is reported for the first time. It was also found that with the exception of ungeremine, amarbellisine, and hippeastrine, the antiproliferative effect of the potent compounds is apoptosis mediated. Thus, apoptosis in Jurkat cells was triggered by narciclasine, narciclasine tetraacetate, C10b-R-hydroxypancratistatin, cis-dihydronarciclasine, trans-dihydronarciclasine, lycorine, 1-O-acetyllycorine, lycorine-2-one, pseudolycorine, and haemanthamine. With the exception of narciclasine, lycorine, and haemanthamine, the apoptosis-inducing properties of these compounds are reported for the first time. The collagen type I invasion assay revealed potent anti-invasive properties associated with N-methyllycorine iodide, hippeastrine, clivimine, buphanamine, and narciclasine tetraacetate, all of which were tested at non-toxic concentrations. The anti-invasive activity of buphanamine is particularly promising because this alkaloid is not toxic to cells even at much higher doses. This work has resulted in the identification of several novel leads for anticancer drug design.

Privileged medicinal scaffolds based on the structures of 2-amino-3,5-dicyano-6-sulfanylpyridines and the corresponding 1,4-dihydropyridines have been prepared via a single-step, three-component reaction of structurally diverse aldehydes with various thiols and malononitrile. Mechanistic studies revealed that 1,4-dyhidropyridines undergo oxidation by the intermediate Knoevenagel adducts rather than by air oxygen. Although the latter process undermines the yields of pyridines, it results in the formation of substituted enaminonitriles, promising antiinflammatory agents.