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Asymmetric Synthesis of Non-Proteinogenic Amino Acids

ISBN: 978-3-527-34041-5
376 pages
November 2016
Asymmetric Synthesis of Non-Proteinogenic Amino Acids (3527340416) cover image

Description

Authored by two internationally recognized experts with an excellent track record, this much-needed reference summarizes latest research in the rapidly developing field of stereoselective synthesis of enantiomerically enriched amino acids, particularly of non-proteinogenic origin. It highlights several different catalytic and stoichiometric asymmetric methods for their synthesis and also provides information on origin, biological properties, different synthetic strategies and important applications in medicine and pharmacology.
Essential reading for synthetic chemists working in the field of asymmetric synthesis, natural products and peptide synthesis, stereochemistry, medicinal chemistry, biochemistry, pharmacology, and biotechnology.
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Table of Contents

List of Abbreviations IX

Introduction XI

1 Non-Proteinogenic α-Amino Acids, Natural Origin, Biological Functions 1

References 20

Part I Natural Synthesis of Amino Acids, Mechanisms, and Modeling 25

References 25

2 Some Regularities of Mechanisms for the Natural Synthesis of Amino Acids 27

References 33

3 Systems for Modeling Some Aspects of Pyridoxal Enzyme Action 35

References 40

4 Modeling of Processes Associated with Cleavage of Cα–H and Cα–Cβ Bonds 43

References 50

5 Modeling of α,β-Elimination Processes of PP-Catalysis, Kinetics, and Stereochemistry 51

References 60

6 Biomimetic Addition Reaction of Nucleophiles to CoΙΙΙ Complexes of Dehydroaminobutyric Acid 61

References 64

Part II Asymmetric Synthesis of Nonprotein α-Amino Acids 65

7 The Main Rules of Asymmetric Synthesis 67

References 70

8 Catalytic Asymmetric Synthesis 71

8.1 Achiral NiII Complexes of Schiff Bases of Amino Acids 90

8.1.1 The Alkylation of Achiral NiII Complexes Under Phase-Transfer Catalysis 94

8.1.2 Reactions of 1,4-Michael Addition to Achiral Glycine and Dehydroalanine Complexes 97

8.1.3 Synthesis of Enantiomerically Enriched α-Amino Acids 103

8.1.3.1 The Asymmetric Alkylation of Substrate 65a by Alkyl Halides Under Phase-Transfer Catalysis 103

8.1.3.2 Asymmetric Aldol Condensation of Achiral NiII Complexes of Amino Acids 111

8.1.3.3 The Asymmetric Michael Addition of Achiral NiII Substrates to Electron-Withdrawing Compounds 113

8.1.3.4 Catalytic Asymmetric Addition of Nucleophiles to an Achiral Dehydroalanine Substrate 125

8.2 Salen Complexes as Chiral Catalysts for PTC Alkylation 132

8.2.1 Structural Features of Salen Complexes 134

8.2.1.1 The Influence of the Structure of Salen Ligand 137

8.2.1.2 Chiral Diamine-Based Complexes 144

References 154

9 Stoichiometric Asymmetric Synthesis of α-Amino Acids 159

9.1 Synthesis of Chiral Auxiliary Reagents and Complexes Based on (S)-and (R)-Prolines 191

9.1.1 Effective Low-Waste Technology for Producing (S)-Proline 192

9.1.2 Preparation of (R)-Proline from (S)-Proline 198

9.1.3 Synthesis of Chiral Auxiliary Reagents and NiII Complexes of their Schiff Bases with Amino Acids 199

9.1.4 Preparation of NiII Complexes of Schiff Bases of Dehydroamino Acids 203

9.1.4.1 Synthesis of Chiral NiII Complexes of Dehydroalanine 204

9.1.4.2 Synthesis of Chiral NiII Complexes of Dehydroaminobutyric Acid 208

9.2 Stoichiometric Asymmetric Synthesis of α-Amino Acids 213

9.2.1 Synthesis of α-Substituted (S)-α-Amino Acids 213

9.2.2 Synthesis of α-Substituted (R)-α-Amino Acids 218

9.2.3 Diastereoselective Synthesis of β-Hydroxy-α-Amino Acids 220

9.2.4 The Asymmetric Synthesis of β-Substituted-α-Amino Acids 223

9.2.4.1 Asymmetric Addition of Nucleophiles to Chiral Dehydroalanine Complexes 224

9.2.4.2 Asymmetric Nucleophilic Addition to Chiral Complexes of Dehydroaminobutyric Acid 233

9.2.5 Asymmetric Synthesis of All Possible Stereoisomers of 4-Aminoglutamic Acid 239

9.2.6 Asymmetric Synthesis of Heterocyclic-Substituted α-Amino Acids 245

9.2.6.1 Addition of Heterocyclic Nucleophiles to Dehydroalanine Chiral Complexes 245

9.2.6.2 Asymmetric Synthesis of β-Heterocyclic-Substituted Derivatives of (2S,3S)-α-Aminobutyric Acid 253

9.3 Asymmetric Synthesis of Precursors for PET Radiopharmaceuticals 260

9.3.1 Preparation of Active Tyrosine Derivatives 261

9.3.1.1 Catalytic Methods of Substitution 261

9.3.1.2 Nucleophilic Substitution in Activated Arenechromiumtricarbonyl Complexes 265

9.3.1.3 A New Method for Synthesis of Precursors for Known Radiotracer (S)-O-2-([18F]Fluoroethyl) Tyrosine 269

9.3.2 Synthesis of Precursors for Producing a New Radiotracer (S)-4-[18F]Fluoroglutamic Acid 269

9.3.2.1 Catalytic Synthesis Method 271

9.3.2.2 Stoichiometric Approach to the Synthesis of 4-Fluoroglutamic Acid Precursors 273

9.3.3 Asymmetric Synthesis of 4-Fluoroglutamic Acid 277

9.4 Modified Chiral Auxiliary Reagents for Efficient Asymmetric Synthesis of Amino Acids 285

9.4.1 Chiral NiII Complexes of Amino Acids with Modified Aldimine Fragments 286

9.4.1.1 Synthesis and Research of Dehydroalanine Complexes with Modified Aldimine Fragment 292

9.4.1.2 Asymmetric Addition of Nucleophiles to Dehydroalanine Complex Modified by Aldimine Fragment 296

9.4.2 Chiral NiII Complexes of Schiff Bases of Amino Acids Modified by N-Benzylproline Moiety 304

9.4.2.1 New Modified Chiral Reagents and NiII Complexes of their Schiff Base with Amino Acids 306

9.4.2.2 Amino Acid Complexes with Modified N-Benzylproline Moiety in C-Alkylation Reactions 317

9.4.2.3 Dehydroamino Acid Complexes with Modified N-Benzylproline Moiety in Nucleophilic Addition Reactions 321

9.5 Stoichiometric Asymmetric Synthesis of Unsaturated α-Amino Acids 332

9.6 Universal Technology for Small-Scale Production of Optically Active Non-Proteinogenic α-Amino Acids 339

References 342

Index 353

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Author Information

Ashot Saghyan is Director of the Scientific and Production Center "Armbiotechnology" of the National Academy of Sciences of the Republic of Armenia. In 1985, he accomplished his post-graduate studies under the supervision of Prof. Yu. N. Belokon' at the A.N. Nesmeyanov Institute of Organoelement Compounds of the Academy of Sciences of the Soviet Union. In 1997, he defended his doctoral thesis. He has been working for the Institute of Biotechnology first as a researcher, head of the Laboratory of Asymmetric Synthesis and since 2000 as director. At the same time he is head of the Pharmaceutical Chemistry Department of Yerevan State University (since 2003). In 2006, he was elected Corresponding Member and, in 2010, Full Member of the National Academy of Sciences of the Republic of Armenia. Saghyan has authored over 400 scientific publications and has received a number of scientific awards, e.g. European R. Descartes Prize. He is a long-term editor-in-chief of the Chemical Journal of Armenia.

Peter Langer studied chemistry at the University of Hannover and at the Massachusetts Institute of Technology (MIT, USA). In February 1997 he obtained his Dr. rer. nat. at the University of Hannover. During a postdoctoral period in Cambridge (UK) he worked on the synthesis of oligosaccharides. In 1998 he moved to the University of Göttingen where he completed his habilitation in July 2001. In April 2002 he took a permanent position as a full professor (C4) at
the University of Greifswald. In December 2004 Peter Langer moved to a new position as a full professor (C4) at the University of Rostock. Since July 2005 he is
also affiliated to the Leibniz-Institute of Catalysis e. V. at the University of Rostock (LIKAT) as the head of the division `organic synthesis'. Prof. Langer is coauthor
of more than 600 research papers and reviews. His research is focused on the development of new synthetic methods and their application to the synthesis of biologically relevant ring systems. Professor Langer received several prestigious scholarships (Studienstiftung des Deutschen Volkes, Feodor-Lynen-scholarship, Liebig scholarship, Heisenberg-scholarship), international awards, and honorary doctorates of several universities. In 2015 Peter Langer has been elected foreign member of the National Academy of Science of Armenia.
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