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Penicillins and cephalosporins have a long history in combating bacterial infections. Despite new infectious diseases and occurring resistance, beta-lactam antibiotics will for many years to come continue to play a prominent role in our therapeutic arsenal. This book covers the industrial development of the chemical and biochemical processes used to manufacture these products, as well as looking ahead to possible future processes. The interplay between synthetic organic chemistry with the understanding and application of enzymes, modeling of fermentation processes and integration through (bio-) chemical process engineering is illustrated. In-depth scientific approaches to biocatalysis and biocatalyst development including enzyme kinetics, enzyme crystal studies and semi-rational enzyme mutations are also presented. Metabolic pathway analysis and modeling of fermentation process are treated as well as molecular precision in synthetic approaches to beta-lactams, their precursors and derivatives. Process technology studies including new reactor concepts, possible short-cut routes and improved down-stream-processing methods complete a broad view on the scope and limitations of the presently developed industrial processes including an intriguing insight into future process possibilities. This book represents an excellent case study on the transformation of traditional, stoïchiometric, organic synthesis and classical fermentations into modern (bio-) catalysis and biosynthesis based on insights in metabolic pathways and enzyme actions.
The use of antibiotics in the treatment by antibacterial and antifungal chemo therapy, has become standard practice since the end of World War Two and has had an enormous impact on healthcare throughout the world. Compounds belonging to this class have also reached an important place in the medical treatment of human cancer. Although, the discovery of most of these agents came from more or less sophisticated screening programs of soil microrganisms, many of the important antibiotics used today in clinical practice are derived from the original biosynthetic products by the application of often novel and generally elaborated chemical synthetic methodologies. In fact the antibiotics have represented (and still represent) for a generation of organic chemists an endless source of molecular structures whose varied assemblage of carbon atom backbones and chemical functions was beyond any possibility of imagination. Perhaps a similar repertoire of chemotypes was formerly offered by the natural products, namely the alkaloids, the terpenes, the vitamins and hormones as well as the pigments of the animal and plant kingdoms, albeit the chemical arrange ments of the antibiotic molecules appeared much more surprising and diverse to the admiring eyes of cultivated organic chemists. The idea of this book, certainly a landmark in the field, came during the Symposium of EUCHEM on Chemical Synthesis of Antibiotics, that was held at Aussois in Savoy, France (May 2-6, 1988), the initiative being taken by Gabor Lukacs to whom Masaji Ohno readily associated as a co-editor.
This book presents a thorough and authoritative overview of the multifaceted field of antibiotic science – offering guidance to translate research into tools for prevention, diagnosis, and treatment of infectious diseases. Provides readers with knowledge about the broad field of drug resistance Offers guidance to translate research into tools for prevention, diagnosis, and treatment of infectious diseases Links strategies to analyze microbes to the development of new drugs, socioeconomic impacts to therapeutic strategies, and public policies to antibiotic-resistance-prevention strategies
This volume provides an excellent survey of the chemistry, microbiology, pharmacology and clinical use of the oral cephalosporins in general and the newer agents in particular. The cephalosporins have long provided satisfactory treatment for many disorders without causing serious side effects; and over the past fifty years forms with different antimicrobial, pharmacologic and toxicologic properties have been developed. Despite the broad spectrum of their activity against a large variety of gram-positive and gram-negative bacteria, the third-generation oral cephalosporins including the prodrug esters do not work against Pseudomonas aeruginosa, methicillin-resistant staphylococci, enterococci or Bacteroides species. Many, however, are suitable for treating infections of the respiratory and urinary tracts and of the skin and its structure, as well as certain sexually-transmitted diseases. Authors consider other possible uses, against multi-resistant Enterobacteriaceae for instance, but also point out the limitations of the oral cephalosporins. For those working in the fields of infectious disease, bacteriology, chemotherapy, pharmaceutics and pharmacokinetics, this book is a valuable source of authoritative information.
Chemistry and Biology of ?-Lactam Antibiotics, Volume 1: Penicillins and Cephalosporins provides information pertinent to the study of antibiotics containing the ?-lactam moiety. This book discusses the occurrence of a group of ?-lactam antibiotics structurally related to cephalosporin C. Organized into five chapters, this volume begins with an overview of the mechanism of action of ?-lactam antibiotics that caused many microbiologists to develop screening tools for the detection of the ?-lactam moiety. This text then discusses the discovery of the nocardicins, the thienamycins, and olivanic acids. Other chapters provide a summary of the essential penicillin sulfoxide chemistry that gave rise to many compounds. This book discusses as well the ability of chemists to predict the level of biological activity of a compound from knowledge of its structure through theoretical and physicochemical studies. The final chapter deals with quantitative structure–activity relationships. This book is a valuable resource for microbiologists, chemists, and scientists.
Antimicrobial agents are essential for the treatment of life-threatening infections and for managing the burden of minor infections in the community. In addition, they play a key role in organ and bone marrow transplantation, cancer chemotherapy, artificial joint and heart valve surgery. Unlike other classes of medicines, they are vulnerable to resistance from mutations in target microorganisms, and their adverse effects may extend to other patients (increased risk of cross-infection). As a consequence, there is a constant requirement for new agents, as well as practices that ensure the continued effective prescribing of licensed agents. Public awareness and concerns about drug resistant organisms has led to widespread publicity and political action in the UK, Europe and worldwide. The control of drug resistance and the implementation of good prescribing practice are now legal requirements in the UK as a result of the UK Health Act (2008). These fundamental changes underscore the need for a thorough understanding of the advantages and risks associated with specific antibiotic choices. This sixth edition of Antimicrobial Chemotherapy continues to be a valuable resource for undergraduates and graduates requiring a thorough grounding in the scientific basis and clinical application of these drugs. This new edition is updated to include the most recently licensed agents, notably in the treatment of viral infections including HIV/AIDS, and contains new guidance on prescribing practice and infection control practices that limit the development and spread of resistant organisms.
This book presents an essential overview of beta-lactams and their medicinal value and use in the preparation of other biologically active compounds. Written by internationally respected authors, the individual chapters explore beta-lactams’ synthesis, their mechanism of formation, biological effects, and function as base materials for other heterocycles of major importance.
Contents: B. Alcaide ∙ P. Almendros: Novel Aspects on the Preparation of Spirocyclic and Fused Unsual β-Lactams.- S.S. Bari ∙ A. Bhalla: Spirocyclic β-Lactams: Synthesis and Biological Evaluation of Novel Heterocycles.- L. Troisi ∙ C. Granito ∙ E. Pindinelli: Novel and Recent Synthesis and Applications of β-Lactams.- C. Palomo ∙ M. Oiarbide: β-Lactams Ring Opening: A Useful Entry to Amino Acids and Relevant Nitrogen-Containing Compounds.- B. Mandal ∙ P. Ghosh ∙ B. Basu: Recent Approaches Towards Solid Phase Synthesis of β-Lactams.- A.Arrieta ∙ B. Lecea ∙ F.P. Cossio: Computational Studies on the Synthesis of β-Lactams Via [ 2+2] Thermal Cycloadditions.- B. K. Banik ∙ I. Banik ∙ F. F. Becker: Novel Anticancer β-Lactams
This book examines and evaluates the strategies utilized to design and synthesize pharmaceutically active agents. Significant updates over the last 10 years since the publication of the 1st edition include synthesis of enantiomerically pure isomers, novel chemical methodologies, and new pharmaceutical agents targeted at novel biological endpoints. Written by an experienced successful author, this book meets the needs of a growing community of researchers in pharmaceutical R &D, as well as medical professionals, by providing a useful guide for designing and synthesizing pharmaceutical agents. Additionally, it is a useful text for medicinal chemistry students.
Drug Stability for Pharmaceutical Scientists is a clear and easy-to-follow guide on drug degradation in pharmaceutical formulation. This book features valuable content on both aqueous and solid drug solutions, the stability of proteins and peptides, acid-base catalyzed and solvent catalyzed reactions, how drug formulation can influence drug stability, the influence of external factors on reaction rates and much more. Full of examples of real-life formulation problems and step-by-step calculations, this book is the ideal resource for graduate students, as well as scientists in the pharmaceutical and related industries. - Illustrates important theoretical concepts with numerous examples, figures, calculations, learning problems and questions for self-study and retention of material - Provides answers and explanations to test your knowledge - Enables you to better understand key concepts such as rate and order of reaction, reaction equilibrium, complex reaction mechanisms and more - Includes an in-depth discussion of both aqueous and solid drug solutions and contains the latest international regulatory requirements on drug stability