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Possible Mechanistic Pathways (possible + mechanistic_pathway)

Distribution by Scientific Domains
Chemistry75%

Selected Abstracts

Nickel-Catalyzed Mizoroki,Heck- versus Michael-Type Addition of Organoboronic Acids to ,,,-Unsaturated Alkenes through Fine-Tuning of Ligands

CHEMISTRY - AN ASIAN JOURNAL, Issue 11 2007
Pao-Shun Lin
Abstract Various arylboronic acids reacted with activated alkenes in the presence of [Ni(dppe)Br2], ZnCl2, and H2O in CH3CN at 80,°C to give the corresponding Mizoroki,Heck-type addition products in good to excellent yields. Furthermore, 1,equivalent of the hydrogenation product of the activated alkene was also produced. By tuning the ligands of the nickel complexes and the reaction conditions, Michael-type addition was achieved in a very selective manner. Thus, various p- and o- substituted arylboronic acids or alkenylboronic acid reacted smoothly with activated alkenes in CH3CN at 80,°C for 12,h catalyzed by Ni(acac)2, P(o -anisyl)3, and K2CO3 to give the corresponding Michael-type addition products in excellent yields. However, for m- substituted arylboronic acids, the yields of Michael-type addition products are very low. The cause of this unusual meta -substitution effect is not clear. By altering the solvent or phosphine ligand, the product yields for m- substituted arylboronic acids were greatly improved. In contrast to previous results in the literature, the present catalytic reactions required water for Mizoroki,Heck-type products and dry reaction conditions for Michael-type addition products. Possible mechanistic pathways for both addition reactions are proposed. [source]

Interstrand crosslink inducing agents in pretransplant conditioning therapy for hematologic malignancies

ENVIRONMENTAL AND MOLECULAR MUTAGENESIS, Issue 6 2010
Benigno C. Valdez
Abstract Despite successful molecularly targeted, highly specific, therapies for hematologic malignancies, the DNA interstrand crosslinking agents, which are among the oldest and least specific cytotoxic drugs, still have an important role. This is particularly true in stem cell transplantation, where virtually every patient receives conditioning therapy with a DNA-alkylating agent-based program. However, due to concern about serious additive toxicities with combinations of different alkylating drugs, the last several years have seen nucleoside analogs, whose cytotoxic action follows vastly different molecular pathways, introduced in combination with alkylating agents. The mechanistic differences paired with different metabolic pathways for the respective drugs have clinically translated into increased safety without appreciable loss of antileukemic activity. In this report, we review pre-clinical evidence for synergistic antileukemic activity when nucleoside analog(s) and DNA-alkylating agent(s) are combined in the most appropriate manner(s), without a measurable decrease in clinical efficacy compared with the more established alkylating agent combinations. Data from our own laboratory using combinations of fludarabine, clofarabine, and busulfan as prototype representatives for these respective classes of cytotoxic agents are combined with information from other investigators to explain how the observed molecular events will result in greatly enhanced synergistic cytotoxicity. We further present possible mechanistic pathways for such desirable cytotoxic synergism. Finally, we propose how this information-backed hypothesis can be incorporated in the design of the next generation conditioning therapy programs in stem cell transplantation to optimize antileukemic efficacy while still safeguarding patient safety. Environ. Mol. Mutagen., 2010. © 2010 Wiley-Liss, Inc. [source]

Palladium(II)-catalyzed catalytic aminocarbonylation and alkoxycarbonylation of terminal alkynes: regioselectivity controlled by the nucleophiles

APPLIED ORGANOMETALLIC CHEMISTRY, Issue 1 2010
Rami Suleiman
Abstract The aminocarbonylation and alkoxycarbonylation reactions of terminal alkynes took place smoothly and efficiently using a catalyst system Pd(OAc)2,dppb,p -TsOHCH3CNCO under relatively mild experimental conditions. The catalytic system was tested and optimized using two different nucleophiles: alcohols and amines. Phenylacetylene (1a) was considered as an alkyne along with diisobutylamine (2b1) and methanol (2c1) as nucleophiles. The results showed significant differences in the conversion of 1a and in the selectivity towards the gem or trans unsaturated esters or amides with these nucleophiles. The effects of the type of palladium catalysts, the type of ligands, the amount of dppb and the solvents were carefully studied. With diisobutylamine (2b1), excellent regioselectivity towards the 2-acrylamides (gem isomer, 3ab1) was almost always observed, while trans -,,,-unsaturated esters 4ac1 was the predominant product with methanol (2c1) as a nucleophile. This remarkable sensitivity in the selectivity of the reaction indicates two different possible mechanistic pathways for these carbonylation reactions. Copyright © 2009 John Wiley & Sons, Ltd. [source]

An Unexpected Michael,Aldol,Smiles Rearrangement Sequence for the Synthesis of Versatile Optically Active Bicyclic Structures by Using Asymmetric Organocatalysis

CHEMISTRY - A EUROPEAN JOURNAL, Issue 14 2010
Nicole Holub Dr.
Abstract A facile and simple organocatalytic procedure to generate optically active 6-alkyl- and 6-aryl-substituted bicyclo[2.2.2]oct-5-en-2-ones is presented. The reaction is catalysed by a 9-amino-9-deoxyepiquinine trifluoroacetic acid salt, which activates ,,,-unsaturated cyclic ketones for the 1,4-addition of ,-keto benzothiazoyl sulfones in a stereoselective fashion. Subsequent intramolecular aldol reaction and Smiles rearrangement gives rise to important optically active bicycles, which are a common motif in natural products, ligands in asymmetric catalysis and substrates for Cope rearrangements, photochemical reactions, radical cyclisations and metathesis. Different bicyclic structures were obtained by utilisation of various cyclic enones or by performing ring-expanding reactions. Furthermore, two possible mechanistic pathways are outlined and discussed. [source]