اسیدهای آمینه: بینش‌ها و نقش‌ها در شیمی هتروسیکلیک، جلد دوم: هیدانتوین‌ها، تیوهیدانتوین‌ها و ۲،۵-دیکتوپیپرازین‌ها

This is the second volume of a first-of-its-kind four-volume book set that provides readers with up-to-date information on α-amino acids, the potential challenges in working with α-amino acids, the protecting groups for the carboxyl, amino and side chain groups of the amino acids, and the most popular heterocyclic compounds that are originating from alpha-amino acids. These heterocyclic compounds include hydantoins, thiohydantoins (including 2-thiohydantoins, 4-thiohydantoins, 2,4-dithiohydantoins), 2,5-diketopiperazines, N-carboxyanhydrides, N-thiocarboxyanhydrides, sydnones, sydnonimines, azlactones, pseudoazlactones, and oxazolidin-5-ones. This is the first resource to comprehensively collect all the heterocycles that can be directly prepared from α-amino acids. In addition, almost all kinds of synthetic methods for a particular type of heterocycles from alpha-amino acids are included, along with the detailed mechanistic discussions and experimental procedures. In Volume 2: Hydantoins, Thiohydantoins, and 2,5-Diketopiperazines compiles the three IUPAC accepted nomenclature systems for heterocyclic compounds, which will be very useful for readers working in the heterocyclic chemistry field for giving synthesized molecules their correct names. In addition, three groups of heterocyclic compounds, i.e., hydantoins, thiohydantoins (including 2-thiohydantoin, 4-thiohydantoin and 2,4-dithiohydantoin), and 2,5-diketopiperazines, have been organized with updated literature information. Particularly, all three groups of heterocyclic compounds have demonstrated many important biological activities, particularly anticancer and antibacterial activities. On the other hand, these three groups of heterocycles can be applied as substrates to make other chemical derivatives, particularly novel unnatural amino acids. All their reactivities have been compiled and updated. The other volumes include: Volume 1: Protecting Groups Volume 3: N-Carboxyanhydrides, N-Thiocarboxyanhydrides, and Sydnones Volume 4: Azlactones and Oxazolidin-5-ones All together, this unique 4-volume set thoroughly covers the two types of heterocyclic compounds that are originated from alpha-amino acids, providing carefully compiled updated information with detailed examples. The author has shared many thoughtful insights based on his strong background in physical organic chemistry. The volumes will be highly valuable for graduate students and senior students, as well as for professors and researchers working in the field of medicinal and pharmaceutical chemistry, organic chemistry, organic synthesis, heterocycles, and proteins and peptides. Cover Half Title Amino Acids: Insights and Roles in Heterocyclic Chemistry Series Amino Acids: Insights and Roles in Heterocyclic Chemistry, Volume 2: Hydantoins, Thiohydantoins, and 2,5-Diketopiperazines Copyright About the Author Contents Abbreviations Acknowledgments Preface 1. Heterocyclic Compounds 1.1 Introduction to Heterocyclic Compounds 1.2 Summary of Literature Reviews on Heterocycles 1.3 General Nomenclature Rules on Heterocycles 1.4 Heterocyclic Compounds from Α-Amino Acids Keywords References 2. Hydantoin 2.1 Introduction 2.1.1 Structure 2.2 Melting Points of α-Amino Acid Based Hydantoins 2.3 NMR and Infrared Data of α-Amino Acid Hydantoins 2.4 Polarity and Lipophilicity of Amino Acid Hydantoins 2.5 Natural Hydantoins 2.6 Biological Activities 2.6.1 Agonists and Antagonists of Protein Receptors 2.6.2 Protein Inhibitors or Ion Channel Blockers 2.6.3 Anticancer Agents 2.6.4 Antimicrobial Agents 2.6.5 Hydantoins of Medical Applications 2.7 Preparative Methods 2.7.1 General Description 2.7.2 Practical Preparation of Hydantoins 2.7.2.1 Preparation of Cystinehydantoin 2.7.2.2 Preparation of 3′,4′-Dihydro-6′-(N-Hexyl)-Spiro[Imidazolidine-4,3′(4′H)-Chroman]-2,5-Dione 2.7.2.3 Preparation of 5-(O-Carboran-1-Ylmethyl)Hydantoin 2.7.2.4 Preparation of 3-Carboxymethylhydantoin 2.7.2.5 Preparation of (S)-2-Butyl-5-(4-Nitrophenyl)-5,6,11,11A-Tetrahydro-1H-Imidazo[1’,5’:1,6]Pyrido[3,4-B] Indole-1,3(2H)-Dione 2.7.2.6 Preparation of [14C]SCH 900567 2.7.2.7 Preparation of 5-Heptyl-5-Phenylhydantoin 2.7.2.8 Preparation of (S)-2-(4-(3-guanidinopropyl)-2,5-dioxoimidazolidin-1-yl)acetic acid 2.7.2.9 Preparation of 4,6-Dichloro-3-[(3-isopropyl-2,4-dioxo-1-imidazolidinyl)-methyl]indole-2-carboxylic Acid Ethyl Ester 2.7.2.10 Preparation of E-Bromoaxinohydantoin and Z-Bromoaxinohydantoin 2.7.2.11 Rearrangement of Aminobarbituric Acids to Hydantoins 2.7.2.12 Preparation of Ethyl 2-(1,3-diisopropyl-2,5-dioxoimidazolidin-4-yl)-3,3,3-trifluoropropanoate 2.7.2.13 Preparation of 5-allyl-5-phenyl-hydantoin 2.7.2.14 Preparation of (4aS,8aS,9aR)-2-methyl-9A-phenyloctahydro-1H-imidazo-[1,5-a]indole-1,3(2H)-dione 2.7.2.15 Preparation of 1,3-dimethylimidazolidin-2,4-dione 2.7.2.16 Preparation of Hydantoin 2.7.2.17 Preparation of 1,3-di-tert-butyl-5-phenylimidazolidine-2,4-dione 2.7.2.18 Preparation of methyl 2-(2,5-dioxo-1,3-di-p-tolylimidazolidin-4-yl)-acetate 2.7.2.19 Preparation of 1-(p-toluenesulfonyl)-hydantoin 2.8 Reactions 2.9 Applications Acknowledgment Keywords References 3. Thiohydantoins 3.1 Introduction 3.1.1 Structure 3.1.2 Stability 3.1.3 Melting Points of Α-Amino Acid Based 2-Thiohydantoins 3.1.4 NMR and MS Data of Thiohydantoins 3.1.5 Polarity and Lipophilicity of Amino Acid-Based 2-Thiohydantoins 3.2 Biological Activities 3.2.1 Protein Ligands 3.2.2 Enzyme Inhibitors 3.2.3 Antibacterial Agents, Antiviral Agents, and Anti-Parasite Agents 3.2.4 Practical Medical Activities 3.3 Preparative Methods 3.3.1 Preparation of 2-thiohydantoins 3.3.2 Preparation of 4-thiohydantoins 3.3.3 Preparation of 2,4-dithiohydantoins 3.3.4 Practical Preparations of Thiohydantoins 3.3.4.1 Preparation of 2-thiohydantoins 3.3.4.1.1 Preparation of (S)-5-Benzyl-2-Thiohydantoin with NH4SCN/Ac2O 3.3.4.1.2 Preparation of (S)-5-Methyl-2-thiohydantoin with NH4SCN/Ac2O under Microwave Irradiation 3.3.4.1.3 Preparation of 1,5-Diphenyl-2-Thiohydantoin with KNCS/ Et3N 3.3.4.1.4 Preparation of 2-Thiohydantoin from α-Amino Acid Ester and Alkyl Isothiocyanate, Formation of (5R,9S)-9-(3,5-Dimethoxyphenyl)-3-Ethyl-7-Methyl-2-Thioxo-1,3,7-Triazaspiro[4.4]Nonan-4-One 3.3.4.1.5 Preparation of 5-Methyl-3-Phenyl-2-Thiohydantoin 3.3.4.1.6 Preparation of 3-(5-Chloro-2-Methylphenyl)-1-Ethyl-2-Thiohydantoin 3.3.4.1.7 Fluorous Phase-Based Preparation of 2-Thiohydantoin 3.3.4.1.8 Solid Support Based Preparation of 2-Thiohydantoin 3.3.4.1.9 One-Pot Synthesis of 2-Thiohydantoin 3.3.4.1.10 Ionic Liquid Supported Preparation of 2-Thiohydantoin 3.3.4.1.11 One-Pot Synthesis of 2-Thiohydantoin 3.3.4.1.12 Preparation of 2-Thiohydantoin from α-Isothiocyanato Ester 3.3.4.1.13 Preparation of 2-Thiohydantoin from Thiourea Protected with Recyclable Cyclododecanone 3.3.4.1.14 Preparation of 3,5-Substituted 2-Thiohydantoins 3.3.4.1.15 Preparation of 2-Thiohydantoin with CS2 as the Sulfur Source 3.3.4.1.16 Direction Formation of 2-Thiohydantoin from α-Amino Acid and Thiourea 3.3.4.1.17 Preparation of 2-Thiohydantoin from Benzil and Thiourea 3.3.4.1.18 Preparation of 2-Thiohydantoin from 2,4-Dithiohydantoin 3.3.4.2 Preparation of 4-thiohydantoin 3.3.4.2.1 Preparation of 4-Thiohydantoin from Hydantoin and P2S5 3.3.4.2.2 Preparation of 4-Thiohydantoin from Ethyl (Cyanomethyl)Carbamate 3.3.4.2.3 Preparation of 4-Thiohydantoin from 2,4-Dithiohydantoin 3.4 Reactions 3.4.1 Reaction of 2-thiohydantoins 3.4.1.1 Formation of 5-arylidene-2-thiohydantoins 3.4.1.2 Alkylation 3.4.1.2.1 N-Alkylation 3.4.1.2.2 S-Alkylation 3.4.1.3 Diels-Alder Reaction 3.4.1.4 Mannich Reaction 3.4.1.5 Multi-component Reaction 3.4.1.6 Reduction 3.4.2 Reaction of 4-thiohydantoins 3.4.3 Representative Reactions of Thiohydantoins 3.4.3.1 Preparation of (E)-5-((1-methyl-1H-indol-3-yl) methylene)-2-thiohydantoin 3.4.3.2 Preparation of (2-pyridinone-3-yl)methylene-2-thiohydantoin 3.4.3.3 The preparation of (E)-4-((5-oxo-2-thioxoimidazolidin-4-ylidene)methyl)phenyl Benzenesulfonate 3.4.3.4 PEG Supported Ni Nanoparticle Promoted N-Alkylation 3.4.3.5 Preparation of 2-(methylthio)-3,5-dihydro-4H-imidazol-4-one Derivative 3.4.3.6 The Mannich Reaction Involving 2-thiohydantoin 3.4.3.7 Preparation of Dimethyl 7-(cyclohexylimino)-3,5,6,7-tetrahydro-3-oxo-2,2-diphenyl-2H-imidazo[2,1-b] [1,3]thiazine-5,6-dicarboxylate by Multi-component Reaction of 2-thiohydantoin 3.4.3.8 General Procedure for the Diels-Alder Reaction 3.5 Applications Acknowledgment Keywords References 4. 2,5-Diketopiperazine 4.1 Introduction 4.1.1 General Introduction 4.1.2 Structure 4.2 Natural Abundance 4.2.1 Tryptophan-Based DKPS 4.2.1.1 Simple Tryptophan-containing DKPS 4.2.1.2 DKPS Containing Modified Tryptophan 4.2.1.3 DKPS Containing Spiro-Linked Tryptophan 4.2.1.4 DKPS Containing Annulated Tryptophan 4.2.1.5 Tryptophan-Containing DKPS with α,β-Unsaturation 4.2.1.6 Tryptophan-Containing DKPS with 2,5-diazabicyclo[2.2.2]octane-3,6-dione Moiety 4.2.1.7 Tryptophan-Containing DKPS with Sulfur Catenation 4.2.1.8 Homodimers and Heterodimers of Tryptophan-Containing DKPS 4.2.2 Phenylalanine and Tyrosine-Containing DKPS 4.2.2.1 Simple Phenylalanine- and Tyrosine-Containing DKPS 4.2.2.2 Phenylalanine or Tyrosine-Containing DKPS with α,β-Unsaturation 4.2.2.3 Phenylalanine- or Tyrosine-Containing DKPS with Catenated Sulfur Linkage 4.2.2.4 Phenylalanine Annulated DKPS 4.2.3 Proline-Containing DKPS 4.2.4 Other Important DKPS 4.3 Biological Activities 4.4 Preparative Methods 4.4.1 Cyclization of Dipeptide 4.4.2 Enzyme-Catalyzed Synthesis of DKPS 4.4.3 Direct Synthesis of DKPS from α-Amino Acids 4.4.4 UGI Multi-Component Reaction 4.4.5 Solid Phase-Based Synthesis of DKPS 4.4.6 Preparation of Alkylidene- and Arylidene-DKPS 4.4.7 Practical Preparations of DKPS 4.4.7.1 Synthesis of (3S,6S)-3,6-bis(hydroxymethyl)piperazine-2,5-dione 4.4.7.2 Synthesis of (S)-3-isopropylpiperazine-2,5-dione 4.4.7.3 Synthesis of (S)-3-methyl-1,4-bis((s)-1-phenylethyl) piperazine-2,5-dione and (R)-3-methyl-1,4-bis((S)-1-phenylethyl)piperazine-2,5-dione 4.4.7.4 Synthesis of (3S)-1,4-dibenzyl-3-methyl-6-phenylpiperazine-2,5-dione 4.4.7.5 Synthesis of 2,5-diketopiperazine-1,4-diacetate in Lanthanide-Based Coordination Polymers 4.4.7.6 Synthesis of 1-allyl-6-((Z)-benzylidene)-3-((Z)-3,4-dichlorobenzylidene)-piperazine-2,5-dione 4.4.7.7 Synthesis of (3R,6R)-3,6-bis(4-(dodecyloxy)phenyl)piperazine-2,5-dione 4.4.7.8 Synthesis of (3S,6S)-3,6-bis(2-methoxybenzyl) piperazine-2,5-dione, (3R,6R)-3,6-bis(2-methoxybenzyl) piperazine-2,5-dione and (3R,6S)-3,6-bis(2-methoxybenzyl)piperazine-2,5-dione 4.4.7.9 Synthesis of (R)-2-((3R,6R)-3-(2,3-dihydro-1H-inden-2-yl)-6-isobutyl-2,5-dioxopiperazin-1-yl)-N-isopropyl-2-phenylacetamide and (S)-2-((3R,6R)-3-(2,3-dihydro-1H-inden-2-yl)-6-isobutyl-2,5-dioxopiperazin-1-yl)-N-isopropyl-2-phenylacetamide 4.4.7.10 Synthesis of (5aS,10aS)-tetrahydro-3H,5H-dipyrrolo[1,2-A:1’,2’-D]pyrazine-3,5,8,10(2H,5aH)-tetraone (pyroglutamic diketopiperazine) 4.4.7.11 Synthesis of (2R,4aR,9aS)-2-methyl-2,4a,7,8,9,9a-hexahydro-5H,10H-pyrrolo[1’,2’:4,5]pyrazino[1,2-B][1,2] oxazine-5,10-dione) 4.4.7.12 Synthesis of (S,Z)-3-benzyl-6-((5-(tert-butyl)oxazol-4-yl)methylene)-piperazine-2,5-dione 4.5 Reactions of DKPS 4.5.1 Reactions AT 1,4-positions 4.5.1.1 Representative Examples for the Reactions AT 1,4-positions of DKPS 4.5.1.1.1 Preparation of 1-Allyl-3,6-di((Z)-Benzylidene)Piperazine- 2,5-Dione 4.5.1.1.2 Preparation of 1,4-Diallyl-2,5-Diketopiperazine 4.5.2 Reactions AT 2,5-positions 4.5.2.1 Representative Examples of Reactions AT 2,5-positions 4.5.2.1.1 Preparation of (3R)-3,6-Dihydro-2,5-Diethoxy-3- Isopropyl-Pyrazine 4.5.2.1.2 Preparation of 3-(((2S,5R)-3,6-Diethoxy-5-Isopropyl-2,5-Dihydropyrazin-2-yl)Methyl)-2-(Trimethylsilyl)-1H-2,5-Dihydropyrazin-2-yl)Methyl)-2-(Trimethylsilyl)-1HIndole 4.5.2.1.3 Preparation of (6R,13S,13aS)-13-Chloro-1,2,3,6,7,12,13,13a-Octahydro-5H-6,13-Epiminopyrrolo[1’,2’:1,2]Azocino[4,5-b]Indol-5-One 4.5.3 Reactions AT 3,6-positions 4.5.3.1 Preparation of (2R,5S)-5-isopropyl-1,4-bis((4-methoxybenzyl)oxy)-3,6-dioxopiperazin-2-yl acetate and (2S,5S)-5-isopropyl-1,4-bis((4-methoxybenzyl)oxy)-3,6-dioxopiperazin-2-yl acetate 4.5.4 Reactions AT α,β-Unsaturated π-Bond of Alkylidene- and Arylidene-DKPS 4.5.4.1 Preparation of (2S,3S,6S,8S)-4,9-dimethyl-2,8-diphenyl-1,7-dioxa-4,9-diazadispiro[2.2.26.23]decane-5,10-dione and (2R,3S,6S,8S)-4,9-dimethyl-2,8-diphenyl-1,7-dioxa-4,9-diazadispiro[2.2.26.23]decane-5,10-dione 4.6 Applications Keywords References Index "This first-of-its-kind four-volume book series, Amino Acids: Insights and Roles in Heterocyclic Chemistry, provides readers with up-to-date information on alpha-amino acids, the potential challenges in working with alpha-amino acids, the protecting groups for the carboxyl, amino and side chain groups of the amino acids, and the most popular heterocyclic compounds that are originating from alpha-amino acids. These heterocyclic compounds include hydantoins, thiohydantoins (including 2-thiohydantoins, 4-thiohydantoins, 2,4-dithiohydantoins), 2,5-diketopiperazines, N-carboxyanhydrides, N-thiocarboxyanhydrides, sydnones, sydnonimines, azlactones, pseudoazlactones, and oxazolidin-5-ones. This is the first resource to comprehensively collect all the heterocycles that can be directly prepared from alpha-amino acids. In addition, almost all kinds of synthetic methods for a particular type of heterocycles from alpha-amino acids are include, along with the detailed mechanistic discussions and experimental procedures. Volume 1: Protecting Groups, the first volume of this set, has collected the 260 protecting groups relating to amino acids, which have been organized by carboxyl group, amino group, and side chain group. The conditions to introduce these protecting groups as well as their deprotecting procedures have also been incorporated, along with the physical properties, solvent effect and temperature effect on the solubility of amino acids. It presents the solubility of glycine and phenylalanine in a variety of solvent systems to show the impact of solvent on the solubility of amino acid, where glycine generally represents the polar amino acid whereas phenylalanine represents the amino acid of non-polar side chain."-- Provided by publisher