Active Pharmaceutical Ingredients in Synthesis

Catalytic Processes in Research and Development

Anthony J. Burke, Carolina Silva Marques, Nicholas J. Turner, Gesine J. Hermann

• Publisher: Wiley
• Year: 2018
• ISBN:
  9783527807260
• Edition: 1
• Topic: Physical Sciences
• Subtopic: Industrial & Technical Chemistry

Presents the most effective catalytic reactions in use today, with a special focus on process intensification, sustainability, waste reduction, and innovative methods This book demonstrates the importance of efficient catalytic transformations for producing pharmaceutically active molecules. It presents the key catalytic reactions and the most efficient catalytic processes, including their significant advantages over compared previous methods. It also places a strong emphasis on asymmetric catalytic reactions, process intensification (PI), sustainability and waste mitigation, continuous manufacturing processes as enshrined by continuous flow catalysis, and supported catalysis. Active Pharmaceutical Ingredients in Synthesis: Catalytic Processes in Research and Development offers chapters covering: Catalysis and Prerequisites for the Modern Pharmaceutial Industry Landscape; Catalytic Process Design - The Industrial Perspective; Hydrogenation, Hydroformylation and Other Reductions; Oxidation;; Catalytic Addition Reactions; Catalytic Cross-Coupling Reactions; Catalytic Metathesis Reactions; Catalytic Cycloaddition Reactions: Coming Full-Circle; Catalytic Cyclopropanation Reactions; Catalytic C-H insertion Reactions; Phase Transfer Catalysis; and Biocatalysis. -Provides the reader with an updated clear view of the current state of the challenging field of catalysis for API production
-Focuses on the application of catalytic methods for the synthesis of known APIs
-Presents every key reaction, including Diels-Alder, CH Insertions, Metal-catalytic coupling-reactions, and many more
-Includes recent patent literature for completeness Covering a topic of great interest for synthetic chemists and R&D researchers in the pharmaceutical industry, Active Pharmaceutical Ingredients in Synthesis: Catalytic Processes in Research and Development is a must-read for every synthetic chemist working with APIs.

1
Catalysis and Prerequisites for the Modern Pharmaceutical Industry Landscape

In the sum of the parts there are only the parts

Wallace Stevens, Poet

1.1 Introduction

The global market for active pharmaceutical ingredients (APIs) is in a very good state. The market was valued at US $119.7 billion in 2014 and is predicted to rise to US $185.9 billion by 2020 [1]. It is expected to increase at a compound annual growth rate (CAGR) of 6.50% from 2014 to 2020. The global API market is driven by the rising abbreviated new drug applications (ANDAs) [1]. It was also noted in 2011 that 90% of chemicals are derived from catalytic processes, and that the worldwide demand for catalysts was estimated to be about 850 000 tons in 2007 and the market value of products generated by catalysis reached about US $900 billion [2].

In the history of humanities' brief time on this planet, the need for more potent and efficient APIs has never been more critical than it is today. This has become a crucial issue particularly due to the exponential increase in the world population, the ever‐increasing aging world population, the impact of global climate change on world health, the ever‐diminishing set of natural resources, the greater propensity for the spread of disease, the rise in urban pollution, as well as lifestyle changes that are leading to serious health issues, such as obesity, and neurological problems, such as depression. For these reasons, there is an increased demand on world governments to improve their health care services. Within this context there is the requirement to provide new and efficacious drugs to treat a large panoply of diseases, including emerging ones, that are generally viral or spread by other microorganisms. This is no easy task, and two of the parameters that have to be considered are the cost of the drug (so that it can be acquired by governments and patients alike) and the speed of putting such entities on the market. However, quality is also a very important factor, and catalytic methods allowing for cleaner reaction conditions can make this an easier and more cost‐effective task. In both cases, catalysis can provide the answer as both economical and efficient/rapid catalytic routes can reduce the cost and accelerate the time to market.

Without a doubt during the past number of decades, catalysis has played a very important role in the development of APIs. When working at its optimum level, it is one of the most efficient and desirable ways of accessing APIs, particularly at the large scale over a prolonged period of time. Catalysis is desirable for accessing APIs, particularly in the pharmaceutical industry, for a number of reasons: it reduces waste, so the environmental footprint is reduced; the catalysts can be recycled, so that the process becomes more economical in the long run; low loadings can be attained for a number of metal‐based catalysts (like palladium), so that the overall cost is reduced; chiral catalysts can be used to afford enantiomerically pure chiral APIs [3]; specific catalysts that are eco‐friendly like enzymes (whether used as part of a whole cell, or as the isolated enzymes) with no metal contamination, organocatalysts can also be used which require facile working conditions (air reactions and water as solvent, and with no metal contamination issues); and catalysis can be easily integrated in continuous manufacturing processes, such as continuous‐flow chemistries (see subsequent text) that can really speed up production times.

However, with the new developments in enabling technologies, catalytic methods leading to APIs are undergoing a major revolution; the great advances in continuous‐flow methods in the context of continuous manufacturing [4] have certainly enhanced the effectiveness of catalytic routes in the past number of years (we return to this topic in Section 1.3) [5]. This technology is now highly integrated in an automatic or back‐to‐back setup, which includes not only the actual chemical transformation but the separations, crystallizations, drying, and formulations, as well! [4, 5].

It should also be noted that over the past three decades, there has been an increased application of the principles of green chemistry, particularly the incorporation of catalytic steps in API production [6, 7]. Catalysis is one of the 12 principles of green chemistry – i.e. principle 9 – [6] and for inherent sustainable catalytic processes it is crucial that it is integrated with the other key principles like atom economy (No. 2), safer solvents (No. 5), design for energy efficiency (No. 7), use of renewable feedstocks (No. 7), and inherently safer chemistry for accident prevention (No. 12). These ...

Table of contents

• Cover
• Table of Contents
• Dedication
• Foreword
• Preface
• Abbreviations
• Chapter 1: Catalysis and Prerequisites for the Modern Pharmaceutical Industry Landscape
• Chapter 2: Catalytic Process Design: The Industrial Perspective
• Chapter 3: Hydrogenation, Hydroformylation, and Other Reductions
• Chapter 4: Oxidation: Nobel Prize Chemistry Catalysis
• Chapter 5: Catalytic Addition Reactions
• Chapter 6: Catalytic Cross‐Coupling Reactions – Nobel Prize Catalysis
• Chapter 7: Catalytic Metathesis Reactions: Nobel Prize Catalysis
• Chapter 8: Catalytic Cycloaddition Reactions: Coming Full Circle
• Chapter 9: Catalytic Cyclopropanation Reactions
• Chapter 10: Catalytic C–H Insertion Reactions
• Chapter 11: Phase‐Transfer Catalysis
• Chapter 12: Biocatalysis
• Index
• End User License Agreement