Cutting-Edge Organic Synthesis and Chemical Biology of Bioactive Molecules: The Shape of Organic Synthesis to Come

371 Pages·2019·23.789 MB·English

by  Yuichi Kobayashi

Yuichi Kobayashi Editor
Cutting-Edge
Organic Synthesis
and Chemical
Biology of Bioactive
Molecules
The Shape of Organic Synthesis to Come
Cutting-Edge Organic Synthesis and Chemical
Biology of Bioactive Molecules
Yuichi Kobayashi
Editor
Cutting-Edge Organic
Synthesis and Chemical
Biology of Bioactive
Molecules
The Shape of Organic Synthesis to Come
Editor
Yuichi Kobayashi
Department of Biotechnology
Tokyo Institute of Technology
Yokohama, Japan
ISBN 978-981-13-6243-9 ISBN 978-981-13-6244-6 (eBook)
https://doi.org/10.1007/978-981-13-6244-6
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Preface
The purpose of organic synthesis is to provide target compounds by selective meth-
ods with high optical purity. Many transition metal-catalyzed asymmetric reactions
and reactions catalyzed by organocatalysts have been developed to efficiently reach
the goals. Reducing and oxidizing reagents that are highly chemoselective and/or
environmentally friendly are also indispensable tools toward the purpose. On the
other hand, analytical techniques have advanced to allow swift determination of the
efficiency of reactions and the structures. For example, LC-MS analysis equipped
with a chiral column could determine the chirality of the structure. Such new reac-
tions and the advances in analytical techniques produced new power for organic
synthesis to foray into fields, which used to be considered out of organic synthesis.
As a consequence, many interdisciplinary areas have emerged, attracted attention of
chemists, and rapidly grown.
This book was planned to grasp the latest and excellent achievements in organic
synthesis, which are expected to be grown more in the future. On the other hand, the
background of each chapter is explained. I hope that the chapters will be understood
easily by researchers, especially young, and stimulate research in the future.
Chapters “Microbial Fraction Library: A Screening Source for Drug Discovery”,
“Efficient Total Synthesis of Ōmura Natural Products”, “Enantioselective Total
Synthesis of the Antitumor Polycyclic Natural Products FR182877 and Taxol”,
“Synthetic Approaches on the Pluramycin-Class Antibiotics”, “Recent Progress
Toward the Total Synthesis of Duocarmycins A and SA, Yatakemycin, and PDE-I
and –II”, “Structure-Activity Relationship Studies of Maitotoxin Based on Chemical
Synthesis”, “Substitution of Allylic Picolinates with Various Copper Reagents and
Synthetic Applications”, “Total Synthesis of Ingenol” present isolation, elucidation,
and organic syntheses of several compounds that are naturally occurring. Organic
synthesis and biosynthesis of metabolites of polyunsaturated fatty acids are
described in chapters “Strategies for the Synthesis of Anti-inflammatory Metabolites
of Unsaturated Fatty Acids” and “Biosynthesis, Biological Functions, and Receptors
of Leukotriene B and 12(S)-Hydroxyheptadecatrienoic Acid”, respectively. Chapter
4
“Synthesis of Classical/Nonclassical Hybrid Cannabinoids and Related Compounds”
deals with natural and unnatural cannabinoids and would be helpful to design new
v
vi Preface
medical cannabinoids. Chapters “Exploring Bioactive Marine Natural Products and
Identification of Their Molecular Targets”, “Target Protein Chemical Modification”,
“Target Identification of Bioactive Compounds by Photoaffinity Labeling Using
Diazido Probes” explain chemical biology focusing on tools that are designed based
on organic reaction and/or interaction with target proteins.
The project of publishing this book began with an invitation of Mr. S. Koizumi,
Springer Japan. I sincerely acknowledge Ms. A. Komada of Springer and Ms.
M. Shimoda in our laboratory for checking the chapters carefully.
Yokohama, Japan Yuichi Kobayashi
Contents
1 Microbial Fraction Library: A Screening Source for Drug
Discovery . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
Toshihiko Nogawa, Julius Adam V. Lopez, and Hiroyuki Osada
2 Efficient Total Synthesis of Ōmura Natural Products . . . . . . . . . . . . . 21
Toshiaki Sunazuka, Tomoyasu Hirose, and Satoshi Ōmura
3 Enantioselective Total Synthesis of the Antitumor Polycyclic
Natural Products FR182877 and Taxol . . . . . . . . . . . . . . . . . . . . . . . . . 49
Masahisa Nakada
4 Synthetic Approaches on the Pluramycin- Class Antibiotics . . . . . . . . 75
Yoshio Ando, Kei Kitamura, Takashi Matsumoto,
and Keisuke Suzuki
5 Recent Progress on the Total Synthesis
of Duocarmycins A and SA, Yatakemycin, and PDE-I
and PDE-II . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 101
Juri Sakata and Hidetoshi Tokuyama
6 Structure-Activity Relationship Studies of Maitotoxin Based
on Chemical Synthesis . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 125
Tohru Oishi
7 Substitution of Allylic Picolinates with Various Copper
Reagents and Synthetic Applications . . . . . . . . . . . . . . . . . . . . . . . . . . 145
Yuichi Kobayashi and Miwa Shimoda
8 Total Synthesis of Ingenol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 171
Tyler F. Higgins and Jeffrey D. Winkler
9 Strategies for the Synthesis of Anti- inflammatory Metabolites
of Unsaturated Fatty Acids. . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 193
Yuichi Kobayashi and Masao Morita
vii
viii Contents
10 Biosynthesis, Biological Functions, and Receptors
of Leukotriene B and 12(S)-Hydroxyheptadecatrienoic Acid . . . . . . 233
4
Toshiaki Okuno and Takehiko Yokomizo
11 Synthesis of Classical/Nonclassical Hybrid Cannabinoids
and Related Compounds . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 247
Thanh C. Ho and Marcus A. Tius
12 Exploring Bioactive Marine Natural Products
and Identification of Their Molecular Targets . . . . . . . . . . . . . . . . . . . 291
Masayoshi Arai
13 Target Protein Chemical Modification . . . . . . . . . . . . . . . . . . . . . . . . . 305
Hiroyuki Nakamura
14 Target Identification of Bioactive Compounds
by Photoaffinity Labeling Using Diazido Probes . . . . . . . . . . . . . . . . . 335
Suguru Yoshida and Takamitsu Hosoya
List of Figures
Fig. 1.1 Screening strategy of interesting secondary metabolites ................ 2
Fig. 1.2 Morphological profiles of HeLa and srcts-NRK cancer
cells treated with pyrrolizilactone ................................................... 5
Fig. 1.3 Concept of the fraction library ........................................................ 7
Fig. 1.4 Culture condition and preparation of crude
extracts and fractions ...................................................................... 8
Fig. 1.5 A basic concept of 2D separation for the preparation
of fractions ...................................................................................... 9
Fig. 1.6 Mass distribution of fractions ......................................................... 9
Fig. 1.7 General activity profile of the fraction library evaluated
at 100 μg/mL ................................................................................... 10
Fig. 1.8 NPPlots and unusual alignments ..................................................... 11
Fig. 1.9 NPPlots and specific metabolite group of Streptomyces sp.
RK88–1355 ..................................................................................... 11
Fig. 1.10 Structure and putative biosynthetic pathway of verticilactam ........ 12
Fig. 1.11 Structures and putative biosynthetic pathway of spirotoamides ..... 13
Fig. 1.12 Structures of octaminomycins A and B .......................................... 14
Fig. 1.13 NPPlot of Streptomyces sp. RK88–1355 and new
antimycin-related metabolites ......................................................... 15
Fig. 1.14 Structural diversity of the antimycin class of metabolites .............. 16
Fig. 1.15 Variety of the functional group at C-3 position .............................. 17
Fig. 2.1 Our strategy ..................................................................................... 22
Fig. 2.2 Structures of novel Ōmura natural products ................................... 23
Fig. 2.3 Structures of pyripyropenes ............................................................ 24
Fig. 2.4 Biosynthesis of pyripyropene A ...................................................... 24
Fig. 2.5 Structures of pyripyropene analogues ............................................. 26
Fig. 2.6 Structure-activity relationships of pyripyropenes ........................... 27
Fig. 2.7 Structure of PP8201 (Afidopyropen) .............................................. 27
Fig. 2.8 Structures of arisugacins ................................................................. 28
Fig. 2.9 Computer simulation of arisugacin A 8 docking with AChE .......... 30
Fig. 2.10 Structures of lactacystin and salinosporamide A ............................ 31
ix
x List of Figures
Fig. 2.11 Regulatory functions of the eukaryotic proteasome and
target for lactacystin ........................................................................ 31
Fig. 2.12 Structures of lactacystin analogues ................................................. 32
Fig. 2.13 Inhibitory mode of macrosphelide A on cell adhesion ................... 33
Fig. 2.14 Structures of macrosphelides A and B ............................................ 34
Fig. 2.15 Structures of madindolines A 41 and B 42 ..................................... 36
Fig. 2.16 The mode of action of madindoline A ............................................ 39
Fig. 2.17 Structures of neoxaline 59 and oxaline 60 ...................................... 40
Fig. 2.18 Collaboration between the natural products and the
organic synthesis for drug discovery ............................................... 44
Fig. 3.1 Structures of (−)-FR182877 (1) and (−)-FR182876 ....................... 50
Fig. 3.2 X-ray crystal structure of 29 ........................................................... 58
Fig. 3.3 Immunostaining images obtained using control (I),
paclitaxel (10 nM) (II), and 31 (200 μM) (III) (left) and
the mitotic indexes (right) ............................................................... 59
Fig. 3.4 Structure of (−)-taxol ...................................................................... 60
Fig. 4.1 Pluramycins ..................................................................................... 77
Fig. 4.2 Hedamycin and conformation of α-C-glycosyl vancosamine ......... 78
Fig. 4.3 Synthetic challenges and lability of the pluramycins ..................... 78
Fig. 4.4 Strategies for the skeletal construction of the
pluramycin aglycon ......................................................................... 79
Fig. 4.5 The rare deoxyamino sugars on pluramycins ................................. 84
Fig. 4.6 Platforms for installing bis-C-glycoside ......................................... 90
Fig. 4.7 Further utilities of bis-C-glycosyl monocycles ............................... 92
Fig. 5.1 Structures of duocarmycins and the related compounds ................. 103
Fig. 5.2 Proposed mechanism of DNA alkylation ........................................ 103
Fig. 5.3 Structures of PDE-I (5) and PDE-II (6) .......................................... 104
Fig. 5.4 Proposed structure of yatakemycin (40) by
Igarashi and coworkers ................................................................... 109
Fig. 6.1 Structure of maitotoxin (MTX) ....................................................... 126
Fig. 6.2 Structure of brevetoxin B (BTXB) .................................................. 126
Fig. 6.3 Hypothesis of mode of action ......................................................... 127
Fig. 6.4 Partial structures of MTX ............................................................... 127
Fig. 6.5 Structure of artificial ladder-shaped polyether ALP7B ................... 139
Fig. 7.1 Synthetic targets using the allylic substitution ................................ 152
Fig. 7.2 Synthetic targets of the quaternary carbon-forming
allylic substitution ........................................................................... 159
Fig. 8.1 (a) Ingenol 1 alongside a 3-D model that highlights the
highly contorted trans-i ntrabridgehead stereochemistry,
(b) trans- and cis- intrabridgehead stereochemistry in
bicyclo[4.4.1]undecanes, and (c) the Paquette ingenane
analog with cis-intrabridgehead stereochemistry ............................ 172