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Biomedical subjects

Ahmed M Hafez

Publications and source records attributed to Ahmed M Hafez.

9 recordsLinked to original sources
PubMed2004

Development of a new dimeric cyclophane ligand: application to enhanced diastereo- and enantioselectivity in the catalytic synthesis of beta-lactams.

We detail the synthesis of a new C(2)-symmetric bis(cyclophane) ligand system that can be thought of as electronically analogous to binol, but which possesses the added "third dimension" of cyclophane chirality. The ligand synthesis involves a spontaneous (but unexpected) atropisomerization to the desired product. We have employed this ligand to form a metal complex that is an effective cocatalyst for the highly enantio- and diastereoselective catalytic asymmetric synthesis of a beta-lactam.

Catalysis↗
PubMed2004

Catalytic, asymmetric alpha-chlorination of acid halides.

We present a full account of a tandem catalytic, asymmetric chlorination/esterification process that produces highly optically enriched alpha-chloroesters from inexpensive, commercially available acid halides using cinchona alkaloid derivatives as catalysts and polychlorinated quinones as halogenating agents. We have performed kinetics and control experiments to investigate the reaction mechanism and establish conditions under which the reactions can be best performed. We have developed NaH and NaHCO3 shuttle base systems as the easiest and most cost-effective ways of conducting the reactions, rendering the methodology economically competitive with known chiral halogenation procedures. We have also demonstrated the utility of our reactions by converting the products to synthetically useful derivatives.

Journal Article↗
PubMed2003

A multistage, one-pot procedure mediated by a single catalyst: a new approach to the catalytic asymmetric synthesis of beta-amino acids.

A catalytic asymmetric procedure for the preparation of beta-amino acids (specifically beta-substituted aspartic acid derivatives) is reported. The cinchona alkaloid catalyst benzoylquinine (BQ) mediates up to five distinct steps of a reaction pathway, all in one reaction vessel. The products of this reaction, highly optically enriched beta-substituted aspartic acid derivatives, were prepared from N-acyl-alpha-chloroglycine esters and acid chlorides in the presence of the catalyst. This approach was also amenable to the synthesis of small polypeptides containing beta-substituted aspartic acid units, including a non-natural fragment of the antibiotic lysobactin. The addition of Lewis acids to this system was found to accelerate the rate of specific steps in the reaction pathway. Mechanistic aspects of this reaction, such as imine formation and Lewis acid chelation to the beta-lactam intermediate, were investigated through comparison of IR, NMR, and other physical data.

Amino Acids↗
PubMed2003

Alpha-imino esters: versatile substrates for the catalytic, asymmetric synthesis of alpha- and beta-amino acids and beta-lactams.

The catalytic asymmetric addition of organic nucleophiles to alpha-imino esters has emerged as one of the most promising and intensely investigated routes to optically enriched alpha- and beta-amino acid derivatives and beta-lactams. The importance of alpha-imino esters stems not only from the vast appeal of the potential product classes,(1) but also from their remarkable reactivity as highly electrophilic imines. With each passing year, the number of publications concerning the asymmetric alkylation of imino esters grows significantly. The asymmetric alkylation of imines(2) and N,O-acetals has been in itself a subject of intense interest.(3) In this Account, we wish to illustrate our contribution to this timely field, as well as to highlight the seminal contributions of others.

Alkylation↗
PubMed2002

Sequential column asymmetric catalysis.

Since the introduction of catalysts and reagents on solid-support, researchers have developed new reaction systems to take advantage of their insoluble nature by designing multistep reaction sequences, high-throughput purification techniques, and combinatorial synthesis methods. The continuous flow system is one of these advancements and represents the foundation of a new technique termed sequential column asymmetric catalysis (CAC). In this strategy, reagents and catalysts are attached to a solid-phase support and loaded onto sequentially-linked columns. The substrates are present in the liquid phase that flows through the column. As a substrate encounters each successive column, it grows in complexity. Consequently, one can imagine a number of flow systems that consist of columns attached in series and/or in parallel that synthesize a fairly complex molecule. Herein, we discuss the development of the sequential CAC technique, beginning with the most relevant antecedents.

Catalysis↗
PubMed2002

The development of the first catalyzed reaction of ketenes and imines: catalytic, asymmetric synthesis of beta-lactams.

We report practical methodology for the catalytic, asymmetric synthesis of beta-lactams resulting from the development of a catalyzed reaction of ketenes (or their derived zwitterionic enolates) and imines. The products of these asymmetric reactions can serve as precursors to a number of enzyme inhibitors and drug candidates as well as valuable synthetic intermediates. We present a detailed study of the mechanism of the beta-lactam forming reaction with proton sponge as the stoichiometric base, including kinetics and isotopic labeling studies. Stereochemical models based on molecular mechanics (MM) calculations are also presented to account for the observed stereoregular sense of induction in our reactions and to provide a guidepost for the design of other catalyst systems.

Anti-Bacterial Agents↗
PubMed2002

Generation of ketenes from acid chlorides using NaH/crown ether shuttle-deprotonation for use in asymmetric catalysis.

[reaction: see text] We describe methodology for the in situ generation of reactive monosubstituted ketenes from acid chlorides through a shuttle deprotonation process using NaH as an inexpensive stoichiometric base and a crown ether cocatalyst. We have successfully applied this new procedure to the catalytic, asymmetric synthesis of beta-lactams and alpha-haloesters.

Alkenes↗
PubMed2002

A catalyst that plays multiple roles: asymmetric synthesis of beta-substituted aspartic acid derivatives through a four-stage, one-pot procedure.

We report a new method for the catalytic, asymmetric synthesis of beta-substituted aspartic acid derivatives in which the nucleophilic catalyst serves up to four discrete roles in a one-pot procedure: catalytic dehydrohalogenation of acid chlorides to form ketenes; catalytic dehydrohalogenation of alpha-chloroamines to form the corresponding imines; catalyzed [2 + 2]-cycloaddition to produce intermediate acyl beta-lactams; and finally, nucleophilic ring opening to afford optically enriched beta-substituted aspartic acids in high enantioselectivity and diastereoselectivity.

Aspartic Acid↗