[bmim]Br3 as a new reagent for regioselective monobromination of arylamines under solvent-free conditions

Reaction of arylamines with 1-butyl-3-methylimidazolium tribromide ([bmim]Br3) under solvent-free conditions, gave selectively the corresponding monobromination products with excellent, yields.

Organic reactions in ionic liquids:A simple and highly regioselective N-substitution of pyrrole

In ionic liquids [Bmim][PF6] or [Bmim][BF4], pyrrole replaced the halogen atom of an alkyl halide to give the corresponding N-substituted pyrrole in excellent yield. Benzenesulfonyl chloride, p-methylbenzenesulfonyl chloride and benzoyl chloride reacted similarly with pyrroles to afford the N-substituted pyrroles in quantitative yield. Michael addition reaction of pyrrole with electrophilic olefins was completed in a highly regioselective manner to afford the N-alkylpyrroles.

Organic reactions in ionic liquids: a simple highly regioselective or regiospecific substitutions of benzotriazole

In the absence of any added base in ionic liquids [Bmim][BF4], benzotriazole replaces the halogen atom of an a-halogenated ketone or a-halogenated carboxylic ester to give the corresponding N-1-substituted benzotriazole as the only isomer, and 1-chloro-2,4-dinitrobenzene reacted similarly with benzotriazole to afford the N-1-substituted benzotriazole in a good yield. Alkyl halides reacted regioselectively to afford the N-1-alkylbenzotriazole in ratios of more than 15 to 1 over the N-2-isomer.

Chemoenzymatic synthesis: a strategy to obtain xylitol monoesters

BACKGROUND: Fatty acid sugar esters are used as non-ionic surfactants in cosmetics, foodstuffs and pharmaceuticals. In particular, monoesters of xylitol have attracted industrial interest due to their outstanding biological activities. In this work, xylitol monoesters were obtained by chemoenzymatic synthesis, in which, first, xylitol was made soluble in organic solvent by chemo-protecting reaction, followed by enzymatic esterification reaction using different acyl donors. A commercial immobilized Candida antartica lipase was used as catalyst, and reactions with pure xylitol were carried out to generate data for comparison. RESULTS: t-BuOH was found to be the most suitable solvent to carry out esterification reactions with both pure and protected xylitol. The highest yields were obtained for reactions carried out with pure xylitol, but in this case by-products, such as di- and tri-esters isomers were formed, which required a multi-step purification process. For the systems with protected xylitol, conversions of 86%, 58% and 24% were achieved using oleic, lauric and butyric acids, respectively. The structures of the monoesters were confirmed by (13)C- and (1)H-NMR and microanalysis. CONCLUSION: The chemoenzymatic synthesis of xylitol monoesters avoided laborious downstream processing when compared with reactions performed with pure xylitol. Monoesters production from protected xylitol was shown to be a practical, economical, and clean route for this process, allowing a simple separation, because there are no other products formed besides xylitol monoesters and residual xylitol. (C) 2009 Society of Chemical Industry

Regiospecific synthesis of 5-trichloromethyl-1H-pyrazole and 1H-pyrazole-5-carboxylic ester derivatives

Reaction of 1,1,1-trichloro-4-methoxy-3-penten-2-one (1) with hydrazines (2a-h) (NH2NHR, R = H, Me, t-Bu, Ph, 4-NO2-C6H4, C6F5, CO2Me, CONH2) under differing conditions regiospecifically affords different pyrazole derivatives, 3-methyl-5-trichloromethyl-5-hydroxy-4,5-dihydropyrazoles (3a, d-h), 3-methyl-5-trichloromethyl-1H-pyrazoles (4a,b,d-g) and 5-carboxyethyl-3-methyl-1H-pyrazoles (5a-e). The structural assignments were based on the analysis of their H-1/C-13 NMR and ESI-MS data.

Ultrasound-assisted synthesis of symmetrical biaryls by palladium-catalyzed detelluration of 1,2-diaryiditellanes

An ultrasound-assisted synthesis of functionalized symmetrical biaryls with electron-withdrawing or electron-donating substituents is described and illustrated by the palladium-catalyzed detelluration of 1,2-diarylditellanes. This procedure offers easy access to symmetrical biaryls in short reaction time and the products are achieved in good to excellent yields. (c) 2009 Published by Elsevier Ltd.

Synthesis of indole derivatives by domino hydroformylation/indolization of 2-nitrocinnamaldehydes

The present work furnishes an innovative preparation of substituted indoles based on tandem hydroformylation, where the chemo- and the regio-selectivities are good, so the yield of the reaction. The novelty has been established in the four-step transformation of substituted alpha nitrocinnamaldehydes into desired indoles in a one-pot reaction. Under hydroformylation reaction conditions we have been able to trigger off a cascade of reactions, which gave substituted indoles in high yields. Useful intermediates are prepared by using this technique for the synthesis of well-known biologically active molecules. (C) 2008 Elsevier B.V. All rights reserved.

Oxidation of oxa and thia fatty acids and related compounds catalysed by 5-and 15-lipoxygenase

The modified fatty acids, (Z,Z,Z)-(octadeca-6,9,12-trienyloxy)acetic acid, (Z,Z,Z)-(octadeca-9,12,15-trienyloxy)acetic acid, (all-Z)-(eicosa-5,8,11,14-tetraenyloxy)acetic acid, (all-Z)-(eicosa-5,8,11,14-tetraenylthio)acetic acid, 3-[(all-Z)-(eicosa-5,8,11,14-tetraenylthio)]propionic acid, (all-Z)-(eicosa-5,8,11,14-tetraenylthio)succinic acid, N-[(all-Z)-(eicosa-5,8,11,14-tetraenoyl)]glycine and N-[(all-Z)-(eicosa-5,8,11,14-tetraenoyl)]aspartic acid, all react with soybean 15-lipoxygenase. The products were treated with triphenylphosphine to give alcohols, which were isolated using HPLC. Analysis of the alcohols using negative ion tandem electrospray mass spectrometry, and by comparison with compounds obtained by autoxidation of arachidonic acid, shows that each enzyme catalysed oxidation occurs at the omega -6 position of the substrate. In a similar fashion, it has been found that (Z,Z,Z)-(octadeca-6,9,12-trienyloxy)acetic acid, (Z,Z,Z)-(octadeca-9,12,15-trienyloxy)acetic acid, (all-Z)-(eicosa-5,8,11,14-tetraenylthio)acetic acid and N-[(all-Z)-(eicosa-5,8, 11.14-tetraenylthio)]propionic acid each undergoes regioselective oxidation at the carboxyl end of the polyene moiety on treatment with potato 5-lipoxygenase. Neither (all-Z)-(eicosa-5,8,11,14-tetraenylthio)succinic acid nor N-[(all-Z)-(eicosa-5,8,11,14-tetraenoyl)]aspartic acid reacts in the presence of this enzyme, while N-[(all-Z)-(eicosa-5,8,11,14-tetraenoyl)]glycine affords the C11' oxidation product. The alcohol derived from (Z,Z,Z)-(octadeca-6,9, 12-trienyloxy)acetic acid using the 15-lipoxygenase reacts at the C6' position with the 5-lipoxygenase. (C) 2001 Elsevier Science Ltd. All rights reserved.

Synthesis of new amphiphilic chlorin derivatives from protoporphyrin-IX dimethyl ester

A simple synthesis of new amphiphilic chlorin derivatives from protoporphyrin-IX dimethyl ester is reported.The preparation Of Such compounds is based in a straightforward methodology, which involves the Diels-Alder reaction of protoporphyrin-IX dimethyl ester with maleic anhydride followed by addition of nucleophilic species to the initially formed cycloadducts, a transformation, which is highly regioselective. Preliminary photophysical studies with the new compounds show that they meet adequate features for PDT applications. (c) 2008 Elsevier Ltd. All rights reserved.

One-pot synthesis of mixed (Z)-1,2-bis(organylchalcogene)-1-alkenes precursors of the novel beta-organylthio vinyllithium intermediates

One-pot hydrochalcogenation of 1-phenylthioacetylenes using organylselenolate and organyltellurolate anions generated by the insertions of selenium and tellurium in n-organyl lithium produced (Z)-1,2-bis(organylchalcogene)-1-alkenes. The chemical reactivity of these mixed 1,2-bis(organylchalcogene)-1-alkenes was studied by Te/Li and Se/Li stereoretentive exchanges carried out with n-butyl lithium, furnishing the new intermediate species (Z)-beta-organylthio vinyllithium anions, which were trapped with aldehydes, to give the (Z)-3-hydroxy vinyl thioethers with total control of the regio- and stereochemistry. (c) 2010 Elsevier Ltd. All rights reserved.

HOMO-raising strategies in aminocatalysis, from Enamine to Tetraenamine

Dissertação para obtenção do Grau de Mestre em Bioorgânica

Synthesis and structure - Activity relationship study of potent cytotoxic analogues of the marine alkaloid Lamellarin D

The marine alkaloid, Lamellarin D (Lam-D), has shown potent cytotoxicity in numerous cancer cell lines, and was recently identified as a potent topoisomerase I inhibitor. A library of open lactone analogs of Lam-D was prepared from a methyl 5,6-dihydropyrrolo[2,1-a]isoquinoline-3- carboxylate scaffold (1) by introducing various aryl groups through sequential and regioselective bromination, followed by Pd(0)-catalyzed Suzuki cross-coupling chemistry. The compounds were obtained in a 24-44% overall yield, and tested in a panel of three human tumor cell lines, MDA-MB- 231 (breast), A-549 (lung), and HT-29 (colon), to evaluate their cytotoxic potential. From these data the SAR study concluded that more than 75% of the open-chain Lam-D analogs tested showed cytotoxicity in a low micromolar GI50 range.

Synthesis and structure - Activity relationship study of potent cytotoxic analogues of the marine alkaloid Lamellarin D

The marine alkaloid, Lamellarin D (Lam-D), has shown potent cytotoxicity in numerous cancer cell lines, and was recently identified as a potent topoisomerase I inhibitor. A library of open lactone analogs of Lam-D was prepared from a methyl 5,6-dihydropyrrolo[2,1-a]isoquinoline-3- carboxylate scaffold (1) by introducing various aryl groups through sequential and regioselective bromination, followed by Pd(0)-catalyzed Suzuki cross-coupling chemistry. The compounds were obtained in a 24-44% overall yield, and tested in a panel of three human tumor cell lines, MDA-MB- 231 (breast), A-549 (lung), and HT-29 (colon), to evaluate their cytotoxic potential. From these data the SAR study concluded that more than 75% of the open-chain Lam-D analogs tested showed cytotoxicity in a low micromolar GI50 range.

Total synthesis of lamellarin D and analogs library

Larnellarins are a group of marine natural products isolated from the prosobranch mollusc Lamellaria sp., the ascidian Didemnum sp., and the sponge Dendrilla Cactos. Several of them exhibit interesting biological activities. Natural as well as synthetic lamellarins should be excellent candidates for the development of new drugs due to their unique skeletal structure and their important biological activities especially as antitumor agents. Lamelarin O has been recently characterized as a topoisomerase 1-targeted anti tumor agent. A variety of synthetic approaches have been developed for this family of alkaloids. Herein we describe a new route to the synthesis of Lamellarin D, from a methyl 2-pyrrolecarboxylate. Transformation of the starting material into the scaffold, a substituted 5,6-dihydropyrrolo (2,l ­a)isoquinoline (5,6-DHPl), was afforded by N-alkylation followed by intramolecular Heck cyclization. From this scaffold the synthetic strategy is based on two sequential regioselective bromination!Suzuki cross-coupling reactions which permitted the introduction of differently substituted aryl groups on positions 1 and 2 followed by oxidation, deprotection, and lactonization.

Enantiodivergent chemoenzymatic synthesis of codeine

The present thesis describes our latest results in the chemistry of morphine alkaloids. An enantiodivergent synthesis of codeine utilizing a cis-cyclohexadiene diol derived from microbial whole cell oxidation of ~-bromoethylbenzene,as starting material is discussed. The total synthesis of (+)-codeine in 14 steps featuring a Mitsunobu inversion and two intramolecular Heck cyclizations is presented. Investigation of a regioselective nucleophilic opening of a homochiral vinyl oxirane, which led to a total synthesis of the natural isomer of codeine, is detailed. Furthermore, described herein are novel methodologies designed for the transformation of naturally occurring opiates into medicinally relevant derivatives. Two studies on the conversion of thebaine into the commercially available analgesic hydrocodone, two novel ·transition metal catalyzed N-demethylation procedures for opioids, and the development of a catalytic protocol for N-demethylation and Nacylation of morphine and tropane alkaloids are presented. In addition, reactions of a menthol-based version of the Burgess reagent with epoxides are discussed. The synthetic utility of this novel chiral derivative of the Burgess reagent was demonstrated by an enantiodivergent formal total synthesis of balanol. ii