Chemoenzymatic synthesis of boron-containing chiral amines and amides

The first application of lipases as catalysts to obtain optically active boron-containing amines and amides is described. We studied several reaction conditions to achieve the kinetic resolution of boron-containing amines via enantioselective acylation mediated by Candida antarctica lipase B (CAL-B). Excellent enantioselectivity (E>200) and high enantiomeric excess (up to >99%) of both the remaining amines and amides were obtained. (C) 2010 Elsevier Ltd. All rights reserved.

A Ring Contraction Strategy toward a Diastereoselective Total Synthesis of (+)-Bakkenolide A

A diastereoselective route to (+)-bakkenolide A is presented from the readily available optically active Wieland-Miescher ketone. This novel synthesis of this sesquiterpene lactone features the following as key stereoselective transformations: (i) the ring contraction reaction of a octalone mediated by thallium(III) nitrate (TTN); (ii) a hydrogenation to create the cis-fused junction; and (iii) the formation of the C7 quaternary center through an enolate intermediate. Furthermore, during this work, the absolute configuration of a trinorsesquiterpene isolated from Senecio Humillimus was assigned.

Synthesis of new fluorous modular chiral ligand derivatives from amino alcohols and application in enantioselective carbon-carbon bond-forming alkylation reactions

N-Trifluoracyl beta-chalcogeno amides and N-perfluoracyl beta-thio amide ligands were prepared by a simple and efficient reaction sequence. These new ligands were evaluated in palladium-catalyzed alkylation of rac-(E)-1,3-diphenyl-2-propenyl acetate in the presence of dimethyl malonate and an enantioselectivity of up to 99% was obtained. After catalysis, the fluorous ligand can be easily recovered by liquid-liquid extraction and reused without loss in the activity. (C) 2010 Elsevier Ltd. All rights reserved.

Practical synthesis of chiral beta-telluro amines by ring-opening reaction of aziridines

A set of chiral beta-tellurium amines and their selenium and sulfur-containing derivatives have been efficiently synthesized in good to excellent yields via the ring-opening reaction of chiral aziridines by chalcogen nucleophilic species. (C) 2008 Elsevier B.V. All rights reserved.

A Diastereoselective Total Synthesis of trans-Trikentrin A: A Ring Contraction Approach

A new route to obtain the polyalkylated indole (+/-)-trans-trikentrin A was developed. The synthesis of this natural alkaloid features a thallium(III)mediated ring contraction reaction to obtain the trans-1,3-disubstituted five-membered ring in a diastereoselective manner. Thallium(III) is chemoselective in this rearrangement, reacting with the olefin without oxidation of the indole moiety. Other key transformations are the Bartoli`s reaction to construct the heterocyclic ring and a Heck coupling to add the carbons atom that will originate the nonaromatic cycle.

Mild and efficient one-pot synthesis of chiral beta-chalcogen amides via 2-oxazoline ring-opening reaction mediated by indium metal

A simple and efficient procedure for the synthesis of beta-seleno and beta-thio amides via the ring-opening reaction of chiral 2-oxazolines in the presence of indium metal has been developed. Features of this method include the following: (i) easily and accessible starting materials; (ii) indium metal is more stable and less expensive then its respective salts; (iii) useful to excellent yields of beta-chalcogen amides derivatives. (C) 2008 Elsevier B. V. All rights reserved.

Stereoselective synthesis of azetidine-derived glutamate and aspartate analogues from chiral azetidin-3-ones

The stereoselective syntheses of cis conformationally constrained glutamate and aspartate analogues, containing an azetidine framework were accomplished from (S)-N-tosyl-2-phenylglycine in moderate overall yields. The key steps in these syntheses involved an efficient Wittig olefination of an azetidin-3-one, followed by a highly stereoselective rhodium catalyzed hydrogenation. The route could also be applied to the synthesis of a trans glutamate analogue, since epimerization of cis to trans isomer could be performed using DBU in toluene at reflux. (C) 2008 Elsevier Ltd. All rights reserved.

Kinetic resolution of iodophenylethanols by Candida antarctica lipase and their application for the synthesis of chiral biphenyl compounds

The kinetic resolution of (+/-)-iodophenylethanols was carried out using lipase from Candida antarctica and in some cases the enantiomeric excesses were high (up to >98%). Enantiomerically enriched (S)-iodophenylethanols produced by the enzymatic resolution process were used in the synthesis of chiral biphenyl compounds by the Suzuki reaction with good yields (63-65%). (C) 2010 Elsevier Ltd. All rights reserved.

Synthesis of the Macrolactone of Migrastatin and Analogues with Potent Cell-Migration Inhibitory Activity

The synthesis of the macrolactone core of migrastatin 2, its potent anti-metastasis analogue 34, and ester derivatives 35 and 38 are reported. The approach involves the use of a dihydroxylation reaction to establish the desired C-8 stereocenter followed by a metathesis cyclization reaction. The effects of the compounds on the migration and invasion of human breast cancer cells were evaluated by using the wound-healing and the Boyden-chamber cell-migration and cell-invasion assays. The results revealed a high potency of the macrolactones 2 and 34 and the ester analogues 35 and 38, which suggests they have potential as antimetastatic agents.

Synthesis of alpha,beta-unsaturated aryl esters via Heck reaction of unsymmetrical aryl tellurides

A variety of alpha,beta-unsaturated aryl esters were prepared by the direct reaction of unsymmetrical aryltellurides and ethyl acrylate, catalyzed by PdCl(2) via a Heck cross-coupling reaction. (C) 2009 Elsevier Ltd. All rights reserved.

Chemoselective screening for the reduction of a chiral functionalised (+/-)-2-(phenylthio)cyclohexanone by whole cells of Brazilian micro-organisms

The use of whole cells of micro-organisms to bring about the biotransformation of an organic compound offers a number of advantages, but problems caused by enzymatic Promiscuity may be encountered upon With Substrates hearing more than one functional group. A one-pot screening method, in which whole fungal cells were incubated with a Mixture of 4-rnethylcyclohexanone I and phenyl methyl Sulfide 2, has been employed to determine the chemoselectivity of various biocatalysts. The hyphomycetes, Aspergillus terreus CCT 3320 and A. terreus URM 3571, catalysed the oxidation of 2 accompanied by the reduction of I to 4-methylcyclohexanol 1a and, for strain A. terreus CCT 3320, the Baeyer-Villiger oxidation of 1. The Basidomycetes, Trametes versicolor CCB 202, Pycnoporus sanguineus CCB 501 and Trichaptum byssogenum CCB 203, catalysed the oxidation of 2 and the reduction 1, but no Baeyer-Villiger reaction products were detected. In contrast. Trametes rigida CCB 285 catalysed the biotransformation of 1 to 1a, exclusively, in the absence of any detectable Sulfide oxidation reactions. The chemoselective reduction Of (+/-)-2-(phenylthio)cyclohexanone 3 by T. rigida CCB 285 afforded exclusively the (+)-cis-(1R,2S) and (+)-trans-(1S,2S) diastereoisomers of 2-(phenylthio)cyclohexan-1-ol 3a in moderate yields (13% and 27%, respectively) and high enantiomeric excesses (>98%). Chemoselective screening for the reduction of a ketone and/or the oxidation Of a Sulfide group in one pot by whole cells of micro-organisms represents an attractive technique with applications in the development of synthesis of complex molecule hearing different functional groups. (C) 2008 Published by Elsevier Ltd.

First chemoenzymatic synthesis of organoselenium amines and amides

A series of organoselenium amines have been synthesized and submitted to the enzymatic kinetic resolution by acetylation mediated by CAL-B (Novozym 435) to give the corresponding chiral amides in an enantiomerically pure form. After evaluating the appropriate lipase, solvent, temperature,and lipase/substrate ratio in the kinetic resolution, the chiral organoselenium amides were obtained with enantiomeric excess of up to 99%. (C) 2008 Elsevier Ltd. All rights reserved.

Efficient synthesis of selenol esters from acid chlorides mediated by indium metal

This article describes an efficient and easy one-pot route for the synthesis of a wide range of selenol esters from acyl chloride with diselenides in the presence of indium metal. A variety of functional groups can be tolerated within the diorgano diselenide and the acyl chloride coupling partner. (C) 2009 Elsevier Ltd. All rights reserved.