Table Of ContentTHE CHEMISTRY AND
BIOLOGY OF BETA-LACTAMS
THE CHEMISTRY AND
BIOLOGY OF BETA-LACTAMS
Zerong Wang, PhD
First edition published 2023
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Library and Archives Canada Cataloguing in Publication
Title: The chemistry and biology of Beta-Lactams / Zerong Wang, PhD.
Names: Wang, Zerong (Daniel Zerong), author.
Description: First edition. | Includes bibliographical references and index.
Identifiers: Canadiana (print) 20220443939 | Canadiana (ebook) 20220443971 | ISBN 9781774911716 (hardcover) |
ISBN 9781774911723 (softcover) | ISBN 9781003330288 (ebook)
Subjects: LCSH: Beta lactamases.
Classification: LCC QP609.B46 W36 2023 | DDC 579.3/5—dc23
Library of Congress Cataloging-in-Publication Data
CIP data on file with US Library of C ongress
ISBN: 978-1-77491-171-6 (hbk)
ISBN: 978-1-77491-172-3 (pbk)
ISBN: 978-1-00333-028-8 (ebk)
About the Author
Zerong Wang, PhD
Professor of Chemistry, College of Science and Engineering,
University of Houston-Clear Lake, Texas, USA
Zerong Wang, PhD, is a Full Professor at the University of Houston-Clear
Lake, Texas. Prior to that, he worked at the Institute for Biological Sciences
of the National Research Council of Canada for several years. Through his
career, the author has gained specific training and expertise in organic chem-
istry, particularly in physical and organic chemistry and other subdisciplines
that include photochemistry, spectroscopies, carbohydrate chemistry, sulfur
chemistry, nucleosides and heterocycles, material science, reaction meth-
odology, computational chemistry, among other. Dr. Wang has developed
research projects relating to sulfur chemistry, computational chemistry,
nucleoside analogs, heterocycle chemistry, materials science, and macro-
molecules (pillarene, calix[n]arene, and melamine-based dendrimers, etc.)
and has received 22 research grants, including from NSF-MRI, NSF-STEM,
Welch Research Grant, Welch Departmental Research Grant, and University
of Houston-Clear Lake’s Faculty Research and Support Fund (FRSF) Grants.
The author has developed two compendiums in organic chemistry:
Comprehensive Organic Named Reactions, with Detailed Mechanism
Discussions and Updated Experimental Procedures (3 volumes) (Wiley,
2009) and Encyclopedia of Physical Organic Chemistry (6 volumes) (Wiley,
2017), the PROSE Award winner in 2018.
While conducting research activities, the author also teaches courses for
both graduate and undergraduate students. To date, the author has taught
courses on General Chemistry, General Chemistry Laboratory, Analytical
Chemistry, Quantitative Chemical Analysis, Forensic Chemistry, Organic
Chemistry, Organic Chemistry Laboratory, Advanced Organic Chemistry,
Physical Organic Chemistry, Synthetic Organic Chemistry, Organometallic
Chemistry, Biochemistry, Biochemistry Laboratory, Polymer Chemistry,
Introduction to Chemical Engineering, Nutrition and Diet Chemistry,
Green Chemistry, Introduction to NMR Spectroscopy, Chemistry Seminar,
Graduate Research, and Chemistry for Non-Science Majors.
vi About the Author
Dr. Wang earned his BS degree in Chemistry from Lanzhou University,
PR China, and earned his MS and PhD degrees from the Shanghai Institute
of Organic Chemistry, Chinese Academy of Sciences. He conducted his
postdoctoral research at the Department of Chemistry, University of Cali-
fornia Berkeley and York University (Canada).
Contents
Abbreviations ...........................................................................................................ix
Acknowledgments ...................................................................................................xiii
Preface ....................................................................................................................xv
1. β-Lactams and Antibiotics ..............................................................................1
1.1 Brief Introduction ............................................................................................................1
1.2 Penicillin Antibiotics .......................................................................................................3
1.3 Cephalosporin Antibiotics .............................................................................................13
1.4 Carbapenem Antibiotics ................................................................................................14
1.5 Monobactam Antibiotics ...............................................................................................33
1.6 Clavam Antibiotics ........................................................................................................61
1.7 Miscellaneous β-Lactam Antibiotics .............................................................................63
Keywords ...............................................................................................................................73
References .............................................................................................................................74
2. Antimicrobial Activity of β-Lactams and Bacterial Resistance .................91
2.1 Brief Introduction of Bacteria .......................................................................................91
2.2 Nomenclature and Classification of Bacteria ................................................................93
2.3 Antibacterial Mechanism ..............................................................................................94
2.4 Resistance of Antibacterial Activity ............................................................................100
2.5 Mechanisms for Antibiotics Resistance ......................................................................101
2.6 β-Lactamases Databases .............................................................................................109
2.7 Other Biological Activities of β-Lactams ...................................................................120
Keywords .............................................................................................................................130
References ...........................................................................................................................130
3. Synthetic Methods of β-Lactams ................................................................139
3.1 Brief Introduction ........................................................................................................139
3.2 Formation of β-Lactams Through Cycloadditions ......................................................139
3.3 Intramolecular Substitutive Cyclization......................................................................204
3.4 Enzymatic Synthesis of β-Lactams .............................................................................300
3.5 Miscellaneous Methods...............................................................................................303
Keywords .............................................................................................................................321
References ...........................................................................................................................321
viii Contents
4. Reactions of β-Lactams ...............................................................................357
4.1 Brief Introduction ........................................................................................................357
4.2 Cleavage of the Amide Bond of β-Lactams ................................................................358
4.3 Preparation of Polyamides ..........................................................................................390
4.4 Application in the Synthesis of Unnatural α-Amino Acid Derivatives and
Relating Peptides ........................................................................................................399
4.5 Nucleophilic Substitution on C3 or C4 .......................................................................408
4.6 Cleavage of C3-C4 Bond ............................................................................................409
4.7 Cleavage of N1-C4 Bond ............................................................................................411
4.8 Function at N1 .............................................................................................................416
Keywords .............................................................................................................................419
References ...........................................................................................................................419
Index .....................................................................................................................431
Abbreviations
ACE angiotensin-converting enzyme
ADAC acyclic diaminocarbenes
AMR access antimicrobial resistance
APAF-1 apoptotic protease activating factor 1
ARDB antibiotic resistance genes database
ARDs antibiotic resistance determinants
ARGO antibiotic resistance genes online
ARO antibiotic resistance ontology
BHT butylated hydroxytoluene
BLAD beta-lactamase database
BLAST basic local alignment search tool
BLDB beta-lactamase database
BTPP tert-butylimino-tri(pyrrolidino)phosphorane
CAACs cyclic (alkyl)(amino)carbenes
CAL-B Candida Antarctica lipase B
CAN ceric ammonium nitrate
CARD comprehensive antibiotic resistance database
CBMAR comprehensive β-lactamase molecular annotation resource
CDC centers for disease control and prevention
CDD conserved domains database
CMPI 2-chloro-1-methylpyridinium iodide
CODLE comprehensive online database of β-lactamase enzymes
COG clusters of orthologous groups of proteins
CSI chlorosulfonyl isocyanate
DABCO 1,4-diazabicyclo[2.2.2]octane
DEAD diethyl azodicarboxylate
DIAD diisopropyl azodicarboxylate
DIPEA diisopropylethylamine
DMDO dimethyldioxirane
DME 1,2-dimethoxyethane
DMPU N,N’-dimethylpropyleneurea
EARS-Net European Antimicrobial Resistance Surveillance Network
ECDC European Center for Disease Prevention and Control
EDCI 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide
x Abbreviations
EDTA ethylenediaminetetraacetic acid
ESBL extended-spectrum beta-lactamases
FARME functional antibiotic resistant metagenomic element
FDA Food and Drug Administration
GES Guiana-extended-spectrum
HCMV human cytomegalovirus
HIV-1 PR human immunodeficiency virus type 1 proteinase
HMMs hidden Markov models
HWE Horner-Wadsworth-Emmons
IBC-Cl isobutyl carbonochloridate
IJSB international journal of systematic bacteriology
IJSEM International Journal of Systematic and Evolutionary
Microbiology
IMDs indwelling medical devices
IMP imipenemase
KEGG Kyoto Encyclopedia of Genes and Genomes
KOTMS potassium trimethylsilanolate
KPC Kiebsiella pneumoniae carbapenemase
LacED lactamase engineering database
LDL low-density lipoproteins
MBLs metallo-β-lactamases
MCR multi-component reaction
MDR multi-drug resistant
MIC minimal inhibitory concentration
MRIs mobile resistance integrons
MRSA methicillin-resistant staphylococcus aureus
NAAA N-acylethanolamine acid amidase
NCA N-carboxyanhydride
NCBI National Center for Biotechnology Information
NCS N-chlorosuccinimide
NDARO national database of antibiotic-resistant organisms
NDM New Delhi MBL
NHC N-heterocyclic carbene
NMI N-methylimidazole
OBHA·HCl O-benzylhydroxylamine hydrochloride
PASs poly(amido-saccharide)s
PATRIC pathosystems resource integration center
PBPs penicillin-binding proteins
PBS phosphate-buffered saline
