Добавил:
Sekretar
kiopkiopkiop18@yandex.ru
t.me/Prokururor I Вовсе не секретарь, но почту проверяю
Опубликованный материал нарушает ваши авторские права? Сообщите нам.
Вуз:
Предмет:
Файл:Ординатура / Хирургия / Библиотека им академика М.И. Перельмана / Книга_5872_Библиотеки_им_академика_М_И_Перельмана
.pdf
Chemistry and Biology of
Beta-Lactams
Due to their medicinal activity and potential use as synthetic starting materials, studies on beta-lactams
have increased signicantly. This unique volume takes readers on a tour de force from the concept of
antibiosis to the serendipity of antibiotics, evolution of beta‐lactam development, and molecular biology
of antibiotic resistance. These areas of research have culminated in a deeper understanding of microbiology, particularly in the area of bacterial cell wall synthesis and recycling. Considerable work has been
performed by chemists and biologists to continue updating their ndings about beta-lactam synthesis.
Feature s:
• Stereoselective synthesis of monocyclic, bicyclic, and polycyclic beta-lactams
• Microwave, ultrasound, and solid support-mediated preparation of beta-lactams
• Diverse medicinal activities including anticancer activities of beta-lactams and products
obtained from them
• Nanoparticles, articial intelligence, and dipole moments in beta-lactam science
• Synthesis and mechanism of formation of polyaromatic beta-lactams
Chemistry and Biology of
Beta-Lactams
Bimal Krishna Banik
Department of Mathematics and Natural Sciences, College of Sciences and Human Studies, Deanship of Research
Development, Prince Mohammad Bin Fahd University, Al Khobar 31952, Kingdom of Saudi Arabia
Department of Mathematics and Natural Sciences, College of Sciences and Human Studies, Prince Mohammad Bin Fahd
bimalbanik10@gmail.com; bbanik@pmu.edu.sa
Aparna Das
University, Al Khobar, Kingdom of Saudi Arabia.
aparnadasam@gmail.com
First edition published 2025
by CRC Press
2385 NW Executive Center Drive, Suite 320, Boca Raton FL 33431
and by CRC Press
4 Park Square, Milton Park, Abingdon, Oxon, OX14 4RN
CRC Press is an imprint of Taylor & Francis Group, LLC
© 2025 Bimal K. Banik and Aparna Das
Reasonable effor ts have been made to publish reliable data a nd information, but the author and publisher cannot assume responsibility for the validity of all materials or the consequences of their use. The authors and publishers have attempted to trace the
copyright holders of all material reproduced in this publication and apologize to copyright holders if permission to publish in this
form has not been obtained. If any copyright material has not been acknowledged, please write and let us know so we may rectify
in any future reprint.
Except as per mitted under the U.S. Copyright Law, no part of this book may be repr inted, reproduced, tra nsmitted, or utilized in
any form by any electronic, mechanical, or other means, now known or hereafter invented, including photocopying, microlming,
and recording, or in any information storage or retrieval system, without written permission from the publishers.
For permission to photocopy or use material electronically from this work, access
Clearance Center, Inc. (CCC), 222 Rosewood Drive, Danvers, MA 01923, 978-750-8400. For works that are not available on CCC,
please contact
Trademark notice: Product or corporate names may be trademarks or registered trademarks and are used only for identication
and explanation without intent to infringe.
ISBN: 9780367415242 (hbk)
ISBN: 9781032864556 (pbk)
ISBN: 9780367816339 (ebk)
DOI: 10.1201/9780367816339
Typeset in Times
by Deanta Global Publishing Services, Chennai, India
mpkbookspermissions @tandf .co .uk
www .copyright .com or contact the Copyright
Contents
https://t.me/med1917
Preface ......................................................................................................................................................vi
Authors ....................................................................................................................................................viii
1 Beta-Lactams: Classications, Biogenesis, Physical Characteristics, and Medicinal
Activities ............................................................................................................................................ 1
Aparna Das and Bimal Krishna Banik
2 Monocyclic Beta-Lactams: Stereocontrolled Synthesis by Diverse Methods ........................... 55
Bimal Krishna Banik and Aparna Das
3 Polycyclic Beta-Lactams: Synthesis by Diverse Methods ........................................................... 78
Aparna Das and Bimal Krishna Banik
4 Polyaromatic Beta-Lactams: Synthesisand Anticancer Activities ......................................... 131
Bimal Krishna Banik and Aparna Das
5 Microwave and Ultrasound in Beta-Lactam Chemistry ...........................................................161
Aparna Das and Bimal Krishna Banik
6 Solid Support-Mediated Beta-Lactam Synthesis ...................................................................... 193
Bimal Krishna Banik and Aparna Das
7 Mechanism of Beta-Lactam Synthesis by Cycloaddition Reaction ......................................... 224
Aparna Das and Bimal Krishna Banik
8 Beta-Lactams as Synthons for Diverse Heterocycles ................................................................ 243
Bimal Krishna Banik and Aparna Das
9 Medicinal Activities of Beta-Lactams as Antibacterials and Their Mechanism of Action .. 269
Aparna Das and Bimal Krishna Banik
10 Antibacterial Effects of Beta-Lactam Antibiotics with Nanoparticles ................................... 304
Bimal Krishna Banik and Aparna Das
11 The Effects of Dipole Moments on the Biological Activities of Diverse Beta-Lactams ......... 337
Aparna Das and Bimal Krishna Banik
12 Articial Intelligence on Beta-Lactam Research ...................................................................... 363
Bimal Krishna Banik and Aparna Das
Index ...................................................................................................................................................... 389
v
Preface
https://t.me/med1917
Chemistry and Biology of Beta-Lactams
Due to their medicinal activity, synthetic, biological, and clinical studies of β-lactams have been intensely
investigated for more than 100 years. Considerable work has been performed by scientists to continue
updating their ndings on the development of β-lactams in diverse areas.
The rst remarkably spectacular attempts to identify the active biochemicals found in antibacterial
mold follow the discovery of penicillin antibiotics. Since the discovery and synthesis of penicillin, many
other families of β-lactam antibiotics have been realized, and their extensive use continues to be a forefront line of action against infectious pathogens. Notably, β-lactams are found in other crucial applications to humans. These types of molecules are used as starting materials for the preparation of various
heterocycles of clinical signicance. For example, substituted hydroxy β-lactams are used in the semisynthesis of powerful cancer medicines, Taxol and Taxotere. Studies of human leukocyte elastase inhibitory mechanisms and the biological activity of this class of compounds are also available. As a result
of their signicant practical use in humans, many scientists in the world have contributed enormously
on β-lactams and have focused their active research program on this area for the past several decades.
Parallel to numerous researchers’ exceptional contribution, we have also been deeply engaged in
diverse β-lactam research for the past many years, and these endeavors have culminated in hundreds of
publications, patents, books, book chapters, and competitive US research grants. For example, we have
demonstrated and shown stereoselective synthesis by numerous methods, asymmetric synthesis, mechanism of reactions, biological and clinical activities, physicochemical properties, and contemporary articial intelligence research on β-lactams and products obtained from the methods in this book. Therefore,
special focus has been given to our contribution in this area.
This book has been divided into 12 chapters focusing on the diversity of research on beta-lactams:
1. Classications, Biogenesis, Physical Characteristics, and Types of Medicinal Activities (Aparna
Das and Bimal Krishna Banik)
2. Monocyclic Beta-Lactams: Stereocontrolled Synthesis by Diverse Methods (Bimal Krishna
Banik and Aparna Das)
3. Polycyclic Beta-Lactams: Synthesis of Diverse Methods (Aparna Das and Bimal Krishna
Banik)
4. Polyaromatic Beta-Lactams: Synthesis and Anticancer Activities (Bimal Krishna Banik and
Apa r n a Das)
5. Microwave and Ultrasound in Beta-Lactam Chemistry (Aparna Das and Bimal Krishna Banik)
6. Solid Support-Mediated Beta-Lactam Synthesis (Bimal Krishna Banik and Aparna Das)
7. Mechanism of Beta-Lactam Synthesis (Aparna Das and Bimal Krishna Banik)
8. Beta-Lactams as Synthons for Diverse Heterocycles (Bimal Krishna Banik and Aparna Das)
9. Medicinal Activities of Beta-Lactams as Antibacterials and Their Mechanism of Action
(Aparna Das and Bimal Krishna Banik)
10. Antibacterial Effects of β-Lactam Antibiotics with Nanoparticles (Bimal Krishna Banik and
Apa r n a Das)
11. Dipole Moment Studies on β-Lactams (Aparna Das and Bimal Krishna Banik)
vi
vii Preface
https://t.me/med1917
12. Articial Intelligence and/or Machine Learning on β-Lactam Research (Bimal Krishna Banik
and Aparna Das)
The authors expect that this book helps the students, scientists, and academic and business professionals
in their education, research, and professional careers. Information provided in this book may enhance
the curiosity of people about the benets of these types of compounds.
This book is published by CRC, Taylor & Francis. The authors are tremendously grateful to Ms.
Hilary Lafoe and Ms. Sukriti Singh for their knowledge in science, helping attitude, participation with
the authors, and encouragement. Respectfully,
Authors
https://t.me/med1917
Aparna Das obtained her Ph.D. degree in materials science/
nanophysics from Joseph Fourier University based upon the work
on “Semiconductor Quantum Dots for Opto-chemical Sensor
Application” at French Alternative Energies and Atomic Energy
Commission (CEA), France. Her postdoctoral experiences include
working as a research scientist at the California Nano Systems
Institute and Electric Engineering Department, University of
California, Los Angeles (UCLA), USA, and as an experienced
researcher at the Nanowiring-Marie Curie Initial Training Network,
Georg August Universität Göttingen, Germany. Currently, she is
working as an Assistant Professor at Prince Mohammad Bin Fahd
University, Saudi Arabia.
Dr. Das has published more than 130 peer-reviewed articles including 3 books (Elsevier and PMU
Press), 48 book chapters, 4 press release articles, 4 editorials, and 71 journal publications. She has made
53 contributions to international conferences. She has received several conference invitations to present her research works. Importantly, a signicant portion of her research contributions are undergoing
editorial reviews by many journals. Dr. Das has served as a guest editor of an international journal,
and she has acted as a reviewer. Dr. Das has obtained several competitive grants and has led a patent
application. She has received the Young Women Researcher Award, Outstanding Researcher Award,
European Microscopy Society (EMS) Outstanding Paper Award, and several international fellowships
such as Marie-Curie fellowship, CEA-CNRS research fellowship, and Brain Korea 21 fellowship. Dr.
Das’s research works have been recognized by Bentham publisher (Press release at the AAAS Site),
Heidelberg University, and Prince Mohammad Bin Fahd University.
Dr. Das’s research interests include computer-assisted physicochemical methods, quantum mechanical
calculations, interdisciplinary science (biology, chemistry, and physics) for drug development, computeraided drug design, microwave applications, photochemical reactions, III-nitride-based chemical sensors,
solar cells, optoelectronic devices, synthesis of thin layers and nanostructures including quantum wells,
quantum dots, and nanowires. Dr. Das has also experience in molecular beam epitaxy (MBE), plasmaenhanced chemical vapor deposition (PECVD), sputtering, atomic force microscopy (AFM), scanning
electron microscopy (SEM), X-ray diffraction (XRD) and spectroscopy, UV and IR photoluminescence,
transmission spectroscopy, time-resolved photoluminescence, Raman spectroscopy, Hall effect measurements, spin coating, reactive ion etching (RIE), electron beam evaporator, rapid thermal processing
(RTP), electron beam lithography, photolithography, wire bonding, prolometer and wafer saw, optical
bers (cleaving, cutting, splicing, launching light, loss measurements, and characterization of various
parameters), and operation of various lasers, light-emitting diodes (LEDs), spectrophotometers, uorometers, interferometers, and photomultiplier tubes.
viii
Professor Bimal Krishna Banik has a remarkable career, spanning signicant achievements in teaching, research, mentoring, and
professional service. He completed his Ph.D. degree in Chemistry
from the Indian Association for the Cultivation of Science, Calcutta.
Then, he pursued postdoctoral research at Case Western Reserve
University, Ohio, and Stevens Institute of Technology, New Jersey.
Dr. Banik was a Tenured Full Professor in Chemistry and First
President’s Endowed Professor in Science and Engineering at the
University of Texas-Pan American. He was the Vice President of
ix Authors
https://t.me/med1917
Research and Education Development at the Community Health Systems of Texas. Currently, Dr. Banik
is a Full Professor at the Prince Mohammad Bin Fahd University, Kingdom of Saudi Arabia. Notably,
he has been selected as a Fellow of Five International Scientic Societies and has been designated as a
Distinguished Researcher/Distinguished Scientist.
Professor Banik is engaged in synthetic chemistry and medicinal research on cancers, antibiotics,
natural products, hormones, and catalysis. His extensive and impactful contributions are reected
through $7.25 million grants from the US NIH, the US NCI, and US Private Foundations as principal
investigator. Dr. Banik is the author of more than 690 publications including books, book chapters,
name reactions, perspectives, reviews, and papers with 9344 citations. In addition, he has 520 presentation abstracts. Many of his international presentations at various conferences have been designated as
Keynote and Plenary Lectures. Notably, he has authored/edited 24 books, and these are published by
Elsevier, Springer, Springer Nature, Taylor & Francis (CRC), De Gruyter, ICS, PMU, and Nova.
Dr. Banik’s leadership roles in organizing international and national conferences highlight his inuence on scientic communities. He chaired 20 symposiums at the American Chemical Society National
Meetings and over 2 dozen conferences at the inter national level, including 1 at the Nobel Prize Celebration
Meeting in Germany. As the capacity of the Chair, he was able to introduce approximately 300 speakers.
He has been deeply involved in the publication process of other authors. For example, Dr. Banik has been
a reviewer of 93, editorial board member of 28, editor-in-chief of 12, founder of 8, and guest editor of
10 research journals. Due to his leading role in journal administration, Dr. Banik has recruited approximately 200 associate editors and editorial board members for journals. Importantly, he has served as a
reviewer of NSF, NIH-NCI, NRC, ACS, US Research Corporation, and international grant applications.
Dr. Banik has evaluated approximately 2500 research grants and manuscripts. He was the Chair of the
MD Anderson Cancer Center’s drug discovery symposiums and Director of their analytical chemistry
laboratory. He has served as a chair/member of more than 100 committees, reviewer of promotion and
tenure of faculties of the US and international universities, chair of the Faculty Research Council of the
UTPA, and an examiner of doctoral thesis.
Professor Banik has been involved in teaching science, medical, and engineering students on a regular basis for the past many years. He has taught more than 3000 students in the USA and in Saudi
Arabia. His brilliant teaching skills were reected and proven in several thousand students’, peers’, and
administrators’ outstanding evaluations as well as by independent comments posted on the “Rate My
Professor” Website by the US students. Numerous distinguished leaders in US universities constantly
rated Dr. Banik as a “Truly Exceptional Teacher” and “Excellent Teacher” by scaling him within excellent, good, average, and weak for the past many years. He has established two science societies that have
1400 students at the University of Texas. Many research students from his group have received Ph.D.,
M.D., D.D.S., D.Pharm., M.S., and P.A. degrees from US Universities. Some of his students are working
as university/hospital faculty members, clinicians, directors, and principal scientists of pharmaceutical/
chemical companies across the world. Dr. Banik has mentored 20 postdoctoral fellows, 8 research scientists, and approximately 300 students in research. Importantly, he has mentored 28 faculty members
in his research also.
Professor Banik was honored with several prestigious awards. He is consistently ranked among the
Top 2% Researchers in the World. He has received the Indian Chemical Society’s Lifetime Achievement
Award; Mahatma Gandhi Pravasi Honor Medal from the UK Parliament; the US National Society of
Collegiate Scholars’ Best Advisor Award for students; Professor P.K. Bose Endowment Medal; Dr. M.N.
Ghosh Gold Medal; University of Texas Board of Regents’ Outstanding Teaching Award; ACS Member
Service Award; and Best Researcher, Teacher, and Mentor Awards by the UTPA. He is recognized by
Burdwan University and Itachuna College as Distinguished Eminent Alumni and also by ACS News,
Elsevier, RSC, US NCI, US Research Foundation, University of Texas Board of Regents, Times of India,
Stevens Institute of Technology, ACS SEED, NCI, NIH, India and US newspapers, and Down to the
Earth magazine. Dr. Banik has received 200 invitations to deliver international lectures. He has also
been invited to write books by almost all reputed publishers in the world.
1
https://t.me/med1917
Beta-Lactams: Classications, Biogenesis, Physical
Characteristics, and Medicinal Activities
Aparna Das and Bimal Krishna Banik
Department of Mathematics and Natural Sciences, College of Sciences and Human Studies,
Prince Mohammad Bin Fahd University, Al Khobar 31952, Kingdom of Saudi Arabia.
*Corresponding authors: Aparna Das, email: aparnadasam @gmail .c om; Bimal
Krishna Banik, email: bimalbanik10 @gmail .c om; bbanik @pmu .edu .sa
1.1 Introduction
Lactams are cyclic amides. A β-lactam (beta-lactam) ring is a four-membered lactam, in which the carbonyl carbon atom is β to the ring nitrogen. The use of small heterocycles such as β-lactam in organic
chemistry and pharmaceutical chemistry as drugs is mainly due to their antimicrobial properties, and
they are well established in chemotherapeutics. The simplest β-lactam is 2-azetidinone. In many antibiotics, β-lactams are important structural units. Until the early 1970s, most of the research on the
β-lactam natural products was devoted to penicillin and cephalosporin groups; however, since then, a
variety of structures have been described.
It should be noted that the beta-lactam ring is a core component of many different antibiotic families.
A number of antibiotics have been discovered over the years, but the most outstanding ones are penicillins, cephalosporins, carbapenems, and monobactams, which are sometimes referred to as β-lactam
antibiotics. The mechanism of action of most of these antibiotics is that they inhibit the biosynthesis of
bacterial cell walls. It is known that this has a lethal effect on bacteria, although normally, any population
of bacteria will have some subgroup of bacteria that are resistant to these antibiotics. The formation of
bacterial resistance is caused by the expression of one of a number of genes involved in the production
of beta-lactamases, which are enzymes responsible for breaking the beta-lactam ring. Various types of
bacteria have a number of different beta-lactamases. It is important to note that the chemical structure
and catalytic efciency of these enzymes vary widely.
The use of beta-lactams can result in the resistance strains becoming more prevalent and therefore
becoming more virulent when bacteria populations have these resistant subgroups. There is no doubt that
beta-lactam-derived antibiotics are one of the most important antibiotic classes in the world, but they are
also one of the most resistant to clinical trials. It has been shown that beta-lactams exhibit their antibiotic
properties by imitating the naturally occurring d-Ala-d-Ala substrate of a group of enzymes known as
penicillin-binding proteins (PBPs), whose primary function is to cross-link the peptidoglycan part of the
bacterial cell wall with the beta-lactams. There are also some other drugs that contain the beta-lactam
ring, such as ezetimibe, a cholesterol absorption inhibitor. It was Hermann Staudinger who prepared the
rst synthetic beta-lactam in 1907 through the reaction between an aniline Schiff base and benzaldehyde
with diphenylketene in a [2+2] cycloaddition reaction.
In spite of the fact that more than 70 years have passed since the rst use of penicillin in medicine16
and more than a century has passed since Staudinger synthesized the rst beta-lactams,17 beta-lactams
1–15
DOI: 10.1201/9780367816339-1
1
Соседние файлы в папке Библиотека им академика М.И. Перельмана