Synthetic RCM approaches to enantiopure polyhydroxylated pyrrolizidine alkaloids

RCM approach to hindered 5-5-fused bicyclic pyrrolizidine system starting from chiral pyrrolidine, obtained from d-(+)-mannose, has been achieved in convenient yield.     

Synthesis of enantiopure chloroalcohols by enzymatic kinetic resolution

3-Alkenyl and heteroaryl chloroalcohols have been obtained in excellent enantiomeric excess (>99%) by enzymatic kinetic resolution using the haloalcohol dehalogenase HheC. Yields were close to the theoretical maximum for all substrates employed. Furthermore, the applicability of this methodology on multigram scale has been established.     

Practical and convenient enzymatic synthesis of enantiopure alpha-amino acids and amides

Catalyzed by the nitrile hydratase and the amidease in Rhodococcus sp. AJ270 cells under very mild conditions, a number of alpha-aryl- and alpha-alkyl-substituted DL-glycine nitriles 1 rapidly underwent a highly enantioselective hydrolysis to afford D-(-)-alpha-amino acid amides 2 and L-(+)-alpha-amino acids 3 in high yields with excellent enantiomeric excesses in most cases. The overall enantioselectivity of the biotransformations of nitriles originated from the combined effects of a high L-enantioselective amidase and a low enantioselective nitrile hydratase. The influence of the substrates on both reaction efficiency and enantioselectivity was also discussed in terms of steric and electronic effects. Coupled with chemical hydrolysis of D-(-)-alpha-phenylglycine amide, biotransformation of DL-phenylglycine nitrile was applied in practical scale to produce both D- and L-phenylglycines in high optical purity.     

Modern approaches to chemical toxicity screening

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Synthesis of enantiopure 2-amino-1-phenyl and 2-amino-2-phenyl ethanols using enantioselective enzymatic epoxidation and regio- and diastereoselective chemical aminolysis

Several enantiopure 1,2-amino alcohols have been prepared by combining a stereoselective enzymatic epoxidation of styrenes with regio- and stereoselective chemical reactions. An interesting reactivity has been noted concerning the reaction of epoxides and NH₃ under microwave activation.     

Flexible enzymatic and chemo-enzymatic approaches to a broad range of uridine-diphospho-sugars

Enzymatic and chemo-enzymatic approaches provide straightforward access to uridine diphospho sugars irrespective of the relative and absolute configuration of the sugar, its ring size and substitution pattern.     

New synthetic approach to enantiopure bicyclic sulfonium salts: swainsonine analogues

The enantioselective synthesis of bicyclic sulfonium salts 8 or 9, thioanalogues of swainsonine derivatives, is described. The synthetic strategy is based on a stereo- and regiospecific transannular cyclization reaction of nine-membered cyclic sulfides, mediated by Me(3)SiI or carried out under acidic catalysis.     

The first direct enzymatic hydrolysis of alicyclic beta-amino esters: a route to enantiopure cis and trans beta-amino acids

The first direct enzymatic method is reported for the synthesis of cis and trans beta-amino acid enantiomers through the lipase-catalyzed enantioselective hydrolysis of alicyclic beta-amino esters in organic media. High enantioselectivities (E usually >100) were observed when the Candida antarctica lipase B catalyzed reactions were performed with H2O (0.5 equivalents) in iPr2O at 65 degrees C. The resolved products, obtained in good yields (>or=42%), could be easily separated.     

A green and expedient synthesis of enantiopure diketopiperazines via enzymatic resolution of unnatural amino acids

Dipeptides comprising a d-phenylglycyl moiety coupled to the l-enantiomer of 2-amino butyric acid, norvaline, norleucine, and homocysteine were successfully synthesized from d-phenylglycine amide and the racemate of the corresponding unnatural amino acid. The reaction is catalyzed by an immobilized form of penicillin G acylase in an aqueous medium. The dipeptides were subsequently converted into the corresponding enantiopure diketopiperazines in overall isolated yields of 22–33%.     

New approaches to geochemical analysis and sampling

Methods are now being devised for the design of sampling schemes and for data evaluation promise to increase the certainty with which large, inhomogeneous, and segregated masses of material (mountains) may be analysed for interesting constituents. These methods are directed toward the integration of work originating within several disciplines, and utilize different kinds of sampling constant to control error.     

Chemical and enzymatic approaches to carbohydrate-derived spiroketals: di-D-fructose dianhydrides (DFAs)

Di-D-fructose dianhydrides (DFAs) comprise a unique family of stereoisomeric spiro-tricyclic disaccharides formed upon thermal and/or acidic activation of sucrose- and/ or D-fructose-rich materials. The recent discovery of the presence of DFAs in food products and their remarkable nutritional features has attracted considerable interest from the food industry. DFAs behave as low-caloric sweeteners and have proven to exert beneficial prebiotic nutritional functions, favouring the growth of Bifidobacterium spp. In the era of functional foods, investigation of the beneficial properties of DFAs has become an important issue. However, the complexity of the DFA mixtures formed during caramelization or roasting of carbohydrates by traditional procedures (up to 14 diastereomeric spiroketal cores) makes evaluation of their individual properties a difficult challenge. Great effort has gone into the development of efficient procedures to obtain DFAs in pure form at laboratory and industrial scale. This paper is devoted to review the recent advances in the stereoselective synthesis of DFAs by means of chemical and enzymatic approaches, their scope, limitations, and complementarities.     

New synthetic routes toward enantiopure nitrogen donor ligands

New polypyridylic chiral ligands, having either C3 or lower symmetry, have been prepared via a de novo construction of the pyridine nucleus by means of Kr?hnke methodology in the key step. The chiral moieties of these ligands originate from the monoterpen chiral pool, namely (-)-alpha-pinene ((-)-14, (-)-15) and (-)-myrtenal ((-)-9, (-)-10). Extension of the above-mentioned asymmetric synthesis procedure to the preparation of enantiopure derivatives of some commonly used polypyridylic ligands has been achieved through a new aldehyde building block ((-)-16). As an example, the synthesis of a chiral derivative of N,N-bis(2-pyridylmethyl)ethylamine (bpea) ligand, (-)-19, has been performed to illustrate the viability of the method. The coordinative ability of the ligands has been tested through the synthesis and characterization of complexes [Mn((-)-19)Br2], (-)-20, and [RuCl((-)-10)(bpy)](BF4), (-)-21. Some preliminary results related to the enantioselective catalytic epoxidation of styrene with the ruthenium complex are also presented.     

New medicines and approaches to treatment of atherosclerosis

Prerequisites for the use of photodynamic therapy (PDT) to treatment of atherosclerosis, as well as the development and structure of atherosclerotic vascular lesions in humans are analyzed. The basic requirements for PDT components, specifically photosensitizers (PS), and the radiation source, and the current state of their development are overviewed. Some original results of in vitro studies of the effect of PS on the basis of phthalocyanines and radiation on cells from the atherosclerotic plaques are presented.     

Cellular biosensing: chemical and genetic approaches

Biosensors have been developed to determine the concentration of specific compounds in situ. They are already widely employed as a practical technology in the clinical and healthcare fields. Recently, another concept of biosensing has been receiving attention: biosensing for the evaluation of molecular potency. The development of this novel concept has been supported by the development of related technologies, as such as molecular design, molecular biology (genetic engineering) and cellular/tissular engineering. This review is addresses this new concept of biosensing and its application to the evaluation of the potency of chemicals in biological systems, in the field of cellular/tissular engineering. Cellular biosensing may provide information on both pharmaceutical and chemical safety, and on drug efficacy in vitro as a screening tool.     

Accessibility of the carbohydrate moiety of membrane-boound rhodopsin to enzymatic and chemical modification

Galactose was specifically inserted into the carbohydrate moiety of rhodopsin by incubating retinal disk membranes with UDP-galactose: N-acetylglucosamine galactosyltransferase. The stoichiometry of labeling ranged from 1.2 to 1.8 (average = 1.5) residues of galactose per molecule of rhodopsin, indicating that some or all of the oligosaccharide chains of membrane-bound rhodopsin are readily accessible to enzymatic modification. These modified membranes were treated with galactose oxidase to generate an aldehyde at the C-6 position of the inserted galactose units. The enzymatically-oxidized membranes were then reacted with dansyl hydrazide to yield a fluorescent hydrazone which is sufficiently stable to permit spectroscopic analysis. This procedure for the specific attachment of a spectroscopic probe should be applicable to a wide variety of membrane glycoproteins.