Natural Products in the Chemical Industry

844 Pages·2014·50.09 MB·English

by  Professor Dr. Bernd Schaefer (auth.)

Bernd Schaefer
Natural
Products in
the Chemical
Industry
Natural Products in the Chemical Industry
Natural Products
in the Chemical
Industry
Bernd Schaefer
123
Professor Dr. Bernd Schaefer
BASF SE
Ludwigshafen
Germany
Extended and translated edition of the German textbook
Naturstoffe der chemischen Industrie
Translators
David Smith and Bernd Janssen
ISBN 978-3-642-54460-6 ISBN 978-3-642-54461-3 (eBook)
DOI 10.1007/978-3-642-54461-3
Springer Heidelberg New York Dordrecht London
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2
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To
Kathrin, Anselm, Heike,
Clara and Miriam
Preface to the second
edition
Every year, more than a million visitors travel to Washington, DC end of
March/early April to celebrate the National Cherry Blossom Festival (Fig. 0.1).
Are you surprised that the roots of this spectacular event are closely linked to a
discovery in natural products chemistry? You can find out more about this
topic in Chapter 6.3.
0.1 In March 1912, Tokyo
Mayor Yukio Ozaki gave the
gift of 3,020 Japanese cherry
trees to the city of Washing-
ton. They symbolize friendship
between nations, the renewal
of spring, and the ephemeral
nature of life.
During my career in the chemical industry, I was always fascinated by natural
products for two reasons:
1. They are a crucial factor in securing and enriching our livelihood not only
with food and medicine, but also by stimulating our senses with colour,
scent and flavour.
2. When industrial chemistry was called upon to satisfy an ever growing
d emand for such products, this became a challenging incentive for devel-
oping efficient and scalable processes to generate often rather complex
molecules. Here, the ingenuity and creativity of chemists in academia and
industry is displayed most prominently with admirable achievements.
My curiosity and my excitement for natural products from an industrial per-
spective led to questions about their discovery, early application and production,
their economic and sometimes social ramifications. When asked to prepare a
lecture course on “Natural Products in the Chemical Industry” at the University
of Heidelberg, I intended to share this multifaceted view on the subject with my
students, instead of conveying only the bare bones of chemical technology. Over
VIII Preface to the second edition
the past 12 years, the course has indeed sustained remarkable interest and sub-
sequently resulted in a German print edition of “Naturstoffe der chemischen
Industrie”. The current English version is based on its largely revised German
counterpart and aims at addressing a wider audience.
This is not a classical textbook, and even less a reference work. Whether you are
a teacher or a scholar, an undergraduate or graduate student, a professional
chemist in industry or academia, or someone just interested in natural sciences,
you will find plenty of food for thought – facts and information along with
e njoyable anecdotes, historical, political, biological and social considerations.
Of course, a large portion of this book is dedicated to the art of natural products
synthesis. Among many other conditions, it requires conceptual vision, as well
as profound knowledge of highly diverse compound classes and reaction mech-
anisms, but also persistence and often good luck to design a successful route and
construct the target molecules. Interdisciplinary know-how is necessary to find
adequate solutions, e.g. by embarking on biosynthetic strategies Nature itself has
employed or by using enzymatic transformations. Insight into physiology and
pharmacology may lead the way to simpler structures with the same or even
superior effects than its natural prototype.
The task to adopt a small-scale reaction to an economically viable and ecologi-
cally responsible manufacturing process, which yields large quantities of pure
material, poses particular challenges to chemists, engineers and experts from
many other disciplines. In this regard it is as well intriguing to witness the
a dvancements and elegance of modern chemical technologies.
Do you have to read this book to advance your professional career? Probably not.
But if you are looking for fun with science, you may want to consider placing it
on your night stand.
Most of the reaction schemes are presented in colour, which should facilitate the
easy recognition of building block fragments in the final products. From the
colour of the bonds, however, it is not always possible to draw conclusions on
the reaction mechanism. While this is in many cases rather complex, the reader
is therefore referred to the primary literature sources. A comprehensive index
section will assist in navigating through this book when searching for specific
topics, and the rich illustrations – many of them in colour – are meant to famil-
iarise with the origin and application of natural products, but also as a tool to
make a somewhat “arid subject” better digestible.
I am in particular grateful to three colleagues and friends of mine for their as-
sistance in this book project: Dr. Richard Riggs, Dr. David Smith and Dr. Bernd
Janssen. Without their commitment and their sound knowledge of the subject,
this book would not have found its way into print.
Preface to the second edition IX
Richard Riggs helped me to identify a freelance translator of my manuscript and
he read carefully the entire book. My warm thanks go to him for many valuable
suggestions and improvements.
David Smith, a chemist from Saint Andrews University and Richard’s former
PhD supervisor actually accepted the burden and challenges to provide a draft-
ed translation of my revised German textbook. I’m very grateful for David’s hard
work over some 18 months.
Last but not least I would like to express my deep gratitude to Bernd Janssen,
owner of the Massachusetts based Science&Management Consulting operation,
former colleague at BASF Pharma and friend for many years. Bernd had already
supported the earlier German edition of my book, and his unique diligence,
accuracy, perseverance and enthusiasm proved invaluable in compiling its cur-
rent English version. His careful proof-reading, suggestions for enhancements
and translation of parts of this book are especially acknowledged.
I warmly thank my editor Mrs. Elizabeth Hawkins of Springer Verlag, Heidel-
berg for her patience as well as the enjoyable and productive collaboration. Mrs.
Hawkins has supported the concept of this book from its early stages, and has
helpfully guided the development process through all phases.
My thanks go in particular to Fotosatz-Service Köhler GmbH in Würzburg,
Germany for their excellent design of the layout. They incorporated my numer-
ous requests for changing texts and illustrations in a very professional and
d iligent way. This was a marvellous collaboration.
I owe particular thanks to all those, who have made available to me excellent
illustration material, mostly even free of charge. I am delighted about such a
“worldwide” backing of my endeavour, which I would like to recognise by spe-
cifically naming the corresponding individuals and companies in the directory
of illustrations.
My final and most heartfelt thanks I want to give to my wife Wilgard, who has
encouraged and supported me wonderfully in so many ways during those count-
less evenings and weekends I had been engaged in this book project.
Bernd Schaefer
Dierbach, November 2014
Content
Preface to the second edition . . . . . . . . . . . . . . . . . . . . . . . . . VII
Content . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . X
1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 1
1.1 Important Fields of Application for Natural Product Chemistry 1
1.1.1 Population Growth . . . . . . . . . . . . . . . . . . . . . 1
1.1.2 Nutrition . . . . . . . . . . . . . . . . . . . . . . . . . . . 2
1.1.3 Healthcare . . . . . . . . . . . . . . . . . . . . . . . . . . 3
1.1.4 Fragrances . . . . . . . . . . . . . . . . . . . . . . . . . . 4
1.1.5 Colourants . . . . . . . . . . . . . . . . . . . . . . . . . . 5
1.1.6 Inspiration for Innovations . . . . . . . . . . . . . . . . . 6
1.2 Natural Product Chemistry in the Chemical Industry . . . . . . 6
1.2.1 A Short Selection of Elegant Syntheses . . . . . . . . . . 9
Summary in Bullet Points . . . . . . . . . . . . . . . . . . . . . . 10
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 10
2 Colourants . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 13
Summary in Bullet Points . . . . . . . . . . . . . . . . . . . . . . 17
2.1 Indigo . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 17
2.1.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . 17
2.1.2 Structure Determination . . . . . . . . . . . . . . . . . . 20
2.1.3 Biosynthesis . . . . . . . . . . . . . . . . . . . . . . . . . 22
2.1.4 Industrial Synthesis . . . . . . . . . . . . . . . . . . . . . 25
2.1.5 Modern Lab-scale Indigo Synthesis . . . . . . . . . . . . 28
2.1.6 Industrial Dyeing Process . . . . . . . . . . . . . . . . . . 29
2.1.7 Outlook . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
Summary in Bullet Points . . . . . . . . . . . . . . . . . . . . . . 30
2.2 Tyrian Purple . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 30
2.2.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . 30
2.2.2 Biosynthesis . . . . . . . . . . . . . . . . . . . . . . . . . 33
2.2.3 Structure Determination . . . . . . . . . . . . . . . . . . 34
2.2.4 Technical Application . . . . . . . . . . . . . . . . . . . . 35
2.2.5 Newer Developments . . . . . . . . . . . . . . . . . . . . 35
Summary in Bullet Points . . . . . . . . . . . . . . . . . . . . . . 36
2.3 Alizarin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 36
2.3.1 Introduction . . . . . . . . . . . . . . . . . . . . . . . . . 36
2.3.2 Structure Determination . . . . . . . . . . . . . . . . . . 38
Content XI
2.3.3 Industrial Synthesis . . . . . . . . . . . . . . . . . . . . . 40
2.3.4 Industrial Dyeing Process . . . . . . . . . . . . . . . . . . 40
2.3.5 Impact on the Development of the “Young” Chemical
Industry . . . . . . . . . . . . . . . . . . . . . . . . . . . . 41
2.3.6 Modern Developments . . . . . . . . . . . . . . . . . . . 41
Summary in Bullet Points . . . . . . . . . . . . . . . . . . . . . . 42
References . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 43
3 Flavours and Fragrances . . . . . . . . . . . . . . . . . . . . . . . . . 45
Summary in Bullet Points . . . . . . . . . . . . . . . . . . . . . . 52
3.1 Damascone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 52
3.1.1 Rose Scent from Rose Flowers . . . . . . . . . . . . . . . 53
3.1.2 Biogenesis of Damascone . . . . . . . . . . . . . . . . . . 55
3.1.3 Synthesis of Damascone . . . . . . . . . . . . . . . . . . . 58
3.1.4 Industrial Process . . . . . . . . . . . . . . . . . . . . . . 60
Summary in Bullet Points . . . . . . . . . . . . . . . . . . . . . . 62
3.2 Ionone . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 62
3.2.1 Violet and Iris Oil . . . . . . . . . . . . . . . . . . . . . . 63
3.2.2 Biosynthesis . . . . . . . . . . . . . . . . . . . . . . . . . 65
3.2.3 Industrial Syntheses . . . . . . . . . . . . . . . . . . . . . 66
3.2.4 Enantiomerically Pure Products . . . . . . . . . . . . . . 73
3.2.5 Importance for the Fragrance Industry . . . . . . . . . . 77
Summary in Bullet Points . . . . . . . . . . . . . . . . . . . . . . 77
3.3 Jasmonoids . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 77
3.3.1 Occurrence in Nature . . . . . . . . . . . . . . . . . . . . 79
3.3.2 Use in Perfumery . . . . . . . . . . . . . . . . . . . . . . 79
3.3.3 Nomenclature and Structure-Activity Relationships . . . 80
3.3.4 Biological Properties . . . . . . . . . . . . . . . . . . . . 80
3.3.5 Biosynthesis . . . . . . . . . . . . . . . . . . . . . . . . . 82
3.3.6 Chemical Syntheses . . . . . . . . . . . . . . . . . . . . . 84
3.3.7 Stereoselective Syntheses . . . . . . . . . . . . . . . . . . 87
3.3.8 Industrial Syntheses . . . . . . . . . . . . . . . . . . . . . 90
3.3.9 Magnolione(cid:112) . . . . . . . . . . . . . . . . . . . . . . . . . 94
Summary in Bullet Points . . . . . . . . . . . . . . . . . . . . . . 95
3.4 Menthol . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 95
3.4.1 Biosynthesis . . . . . . . . . . . . . . . . . . . . . . . . . 96
3.4.2 Structure and Activity . . . . . . . . . . . . . . . . . . . . 98
3.4.3 Industrial Syntheses . . . . . . . . . . . . . . . . . . . . . 100
3.4.4 Uses of Menthol . . . . . . . . . . . . . . . . . . . . . . . 107
Summary in Bullet Points . . . . . . . . . . . . . . . . . . . . . . 107
3.5 Vanillin . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . . 108
3.5.1 Occurrence . . . . . . . . . . . . . . . . . . . . . . . . . . 108
3.5.2 Odour and Taste . . . . . . . . . . . . . . . . . . . . . . . 109
3.5.3 Chemical Syntheses . . . . . . . . . . . . . . . . . . . . . 110
3.5.4 Modern Developments . . . . . . . . . . . . . . . . . . . 115
3.5.5 Applications . . . . . . . . . . . . . . . . . . . . . . . . . 118
Summary in Bullet Points . . . . . . . . . . . . . . . . . . . . . . 119