Description
Validamycin and Its Derivatives: Discovery, Chemical Synthesis and Biological Activity presents, for the first time, a complete review of the underlying chemistry, synthesis, behavior and application of these compounds.
Beginning with an introduction to validamycin, the book then outlines the key elements of its discovery and production, including details of its structures, isolation, analysis, and issues relating to its large scale production.
Biological activities are then explored in more detail, followed by details of biosynthesis. Further to this, the chemical synthesis of validamycin and its intermediates, including valienamine, validamine, valiolamine, and validoxylamines is reviewed, before preparation of these derivatives and their biological activities are explored.
Finally, the book concludes with a discussion of the economic aspects of working with validamycin and its potential in future applications and trends. With its detailed chemical coverage from a team of expert authors, this detailed guide can be applied to the large-scale industrial production of antibiotics and the adaptation of bioactive agents, from agricultural, to novel pharmaceutical applications.
- Offers complete coverage of validamycin chemistry from a highly experienced team of authors
- Encourages the discovery of further novel drugs based on validamycin derivatives
- Presents an interesting model for establishing new pharmaceutical leads f
Chapter
2 Production of Validamycins
2.1 Discovery of Validamycins
2.2 Microbes for Producing Validamycins
2.2.1 General Characteristics for Microbes
2.2.2 Complete Genomes for the Two Microbes
2.2.2.1 General Features of the S. hygroscopicus var. jinggangensis 5008 Genome
2.2.2.2 General Features of the S. hygroscopicus subsp. limoneus KCTC 1717 Genome
2.3 Production and Isolation of Validamycins and Related Natural Compounds
2.3.1 Fermentation of Validamycins
2.3.1.1 Temperature of Submerged Culture
2.3.1.2 Effect of Medium Volume on Validamycin Production
2.3.1.3 Effect of Medium Composition on Validamycin Production
2.3.2 Isolation of Validamycins From the Broth
2.4 Structures, Characterization, and Properties of Validamycins and Related Natural Compounds
2.4.1 Structures of Validamycins and Related Natural Compounds
2.4.2 Characterization of Validamycins and Validoxylamines
2.4.3 Characterization of Valienamine, Validamine, Valiolamine, and Hydroxyvalidamine
2.5 Biosynthesis of Validamycins
2.6 Detection of Validamycin A
2.6.1 Reversed Layer Method
2.6.1.1 Procedure of Reversed Layer Method
2.6.2 Colorimetric Method
2.6.4 HPLC with Reverse Phase Chromatography
2.6.5 Liquid Chromatography with Ion Exchange Chromatography
2.6.6 Capillary Zone Electrophoresis
2.6.7 Liquid Chromatography–Atmospheric Pressure Chemical Ionization–Tandem Mass Spectrometry
2.7 Microbial Degradation of Validamycin A
2.7.1 Degradation of Validamycin A by Pseudomonas denitrificans
2.7.2 Degradation of Validamycin A by Flavobacterium saccharophilum
2.8 Cloning, Expression, and Deficiency of Genes in the Validamycin Biosynthesis and Their Applications
2.8.1 Cloning and Expression of valG Gene
2.8.2 Cloning and Expression of ugp Gene
2.8.3 Knocking Out valG Gene
2.8.4 Inactivation of valN Gene
2.8.5 Deletion of γ-Butyrolactone Receptor Genes
2.9 Fermentation Process for Production of Validamycins
2.9.1 Screening and Breeding High-Yield Strains
2.9.2 Optimization of Cultural Conditions
2.9.2.1 Optimization of Fermentation Medium
2.9.2.2 Application of Fermentation Strategies
2.9.2.3 Stimulator Addition
2.9.2.3.1 Addition of External Ethanol
2.9.2.3.2 Addition of External H2O2
2.9.2.3.3 Addition of Exogenous 1,4-Butyrolactone
3 Bioactivities of Validamycins and Related Natural Compounds
3.1 Antifungal Activities
3.1.1 Antifungal Activity Against Rhizoctonia solani
3.1.2 Antifungal Mechanism Against R. solani
3.1.2.1 Effect of Validamycins on the Morphology and Components of R. solani
3.1.2.1.1 Effect on the Morphology of P. sasakii (Nioh and Mizushima, 1974; Shibata et al., 1980, 1982; Trinci, 1985)
3.1.2.1.2 Effect of Validamycin A on Hyphal Extension and Hyphal Morphology of R. cerealis and R. solani (Trinci, 1985)
3.1.2.1.3 Effect of Validamycins on the Growth and Morphology of Other Fungi (Nioh and Mizushima, 1974)
3.1.2.1.4 Effect of Treatment with Validamycin A on the Pathogenicity of R. solani (Endo et al., 1983)
3.1.2.2 Induction of Validamycins for Endochitinase and β-1,3-Glucanase in Rice Plants
3.1.3 Antifungal Activity Against Fusarium oxysporum
3.1.4 Antibacterial Activity Against Pseudomonas solanacearum
3.1.5 Antibacterial Activity Against Xanthomonas campestris pv. campestris
3.1.6 Antimicrobial Activity Against Candida albicans
3.1.7 Antimicrobial Activity Against Other Microorganisms
3.2 Enzyme Inhibitory Activities
3.2.1 Inhibitory Activity Against Trehalase
3.2.2 Inhibitory Activities Against d-Glucose Hydrolases
3.2.3 Inhibitory Activity Against Tyrosinase
3.3 Insecticidal Activity of Validoxylamine A and Related Compounds
4 Chemical Synthesis of Validamycin and Related Natural Compounds
4.1 Synthesis of Valienamine
4.1.1 Synthesis From L-Quebrachitol
4.1.2 Synthesis From D-Glucose
4.1.3 Synthesis From 2,3,4,6-Tetra-O-Benzyl-D-Glucose
4.1.4 Synthesis From D-Xylose
4.1.5 Synthesis From Cyclohexane Skeleton
4.1.6 Synthesis From (−)-Quinic Acid
4.1.7 Synthesis From (1SR,2RS,3SR)-6-Methylenecyclohex-4-Ene-1,2,3-Triol
4.1.8 Synthesis From Tartaric Acid
4.1.9 Synthesis From L-Serine
4.1.10 Synthesis From Garner’s Aldehyde
4.1.11 Synthesis From (−)-Shikimic Acid
4.1.12 Synthesis From Acarbose, Validamycin, and Their Derivatives
4.2 Synthesis of epi-Valienamine
4.2.1 Synthesis of 1-epi-Valienamine
4.2.2 Synthesis of 2-epi-Valienamine
4.2.3 Synthesis of 4-epi-Valienamine
4.2.4 Synthesis of 1,2-bis-epi-Valienamine
4.3 Synthesis of Valiolamine
4.3.1 Synthesis From D-Glucose
4.3.2 Synthesis From (−)-Quinic Acid
4.3.3 Synthesis From Valienamine and Validamine
4.3.4 Synthesis From (−)-vibo-Quercitol
4.3.5 Synthesis From myo-Inositol
4.3.6 Synthesis From L-Tartaric Acid
4.3.7 Synthesis From (−)-Shikimic Acid
4.4 Synthesis of Validamine
4.4.1 Synthesis From (−)-7-endo-Oxabicyclo[2.2.1]-Hept-5-Ene-2-Carboxylic Acid
4.4.2 Synthesis From D-Glucose
4.4.3 Synthesis From Nitrofuranose
4.4.4 Synthesis From (−)-Quinic Acid
4.4.5 Synthesis From D-Xylose
4.5 Synthesis of Hydroxyvalidamine
4.6 Synthesis of Validoxylamines
4.6.1 Synthesis of Validoxylamine A
4.6.2 Synthesis of Validoxylamine B
4.6.3 Synthesis of Validoxylamine G
4.7 Synthesis of Validamycins
4.7.1 Synthesis of Validamycin A
4.7.2 Synthesis of Validamycin B
4.7.3 Synthesis of Validamycin C
4.7.4 Synthesis of Validamycin D
4.7.5 Synthesis of Validamycin E
4.7.6 Synthesis of Validamycin F
4.7.7 Synthesis of Validamycin G
4.7.8 Synthesis of Validamycin H
5 Voglibose: An Important Drug for Type 2 Diabetes
5.1 Chemical Structures of Various Pseudoaminosugar Glucosidase Inhibitors
5.2 α-d-Glucosidase Inhibitory Activity N-Substituted Valiolamine Derivatives and Related Compounds
5.3 Physicochemical Properties of Voglibose and Drug Summary
5.4 Preparation of Voglibose
5.4.1 Synthesis From Compound 35
5.4.2 Synthesis of Voglibose From Valiolamine
5.4.3 Synthesis of Voglibose From Glucose
5.5 Pharmacology, Pharmacokinetics, and Pharmacodynamics
5.5.1 Mechanism of Action
5.5.2 Pharmacokinetic Properties
5.5.3 Other Glycemic/Metabolic Effects
5.5.4 Voglibose in Combination With Mitiglinide for T2DM
5.6.1 Comparative Studies With Other Oral Antidiabetic Agents
5.6.2 Impaired Glucose Tolerance
5.6.3 Add-on Therapy to Insulin
5.6.4 Combination Therapy in Patients on Hemodialysis
5.6.5 Coronary Atherosclerosis
5.7 Safety and Tolerability
5.8 Comparison With Other Drugs of Acarbose and Miglitol
5.8.1 Drug Summary of Acarbose and Miglitol
5.8.2 Mechanism of Action
5.8.3 Pharmacokinetic Properties
5.8.4 Clinical Recommendations
5.8.6 Cost-effectiveness Ratio
5.8.7 Glycemic Control in Type 2 Diabetes Mellitus
5.8.8 Glycemic Excursions
5.8.11 Impaired Glucose Tolerance
5.8.12 Conclusion for Comparison of α-Glucosidase Inhibitors
5.9 Market and Development
6 N-Octyl-β-Valienamine and N-Octyl-4-epi-β-Valienamine: Two Highly Potent Drug Candidates for Chemical Chaperone Therapy
6.2 N-Octyl-β-valienamine for Chaperone Therapy of Gaucher Disease
6.2.1 Synthesis and Screening of N-Alkyl-β-Valienamine as β-Glucocerebrosidase Inhibitors
6.2.2 Chemical Modification of N-Octyl-β-Valienamine
6.2.3 Biological Activities of N-Octyl-β-Valienamine Derivatives
6.3 N-Octyl-4-epi-β-valienamine for Chaperone Therapy of GM1-Gangliosidosis
6.3.1 Synthesis and Screening of NOEV as β-Galactosidase Inhibitor
6.3.2 Chemical Modification of NOEV
6.3.3 Physicochemical and Biological Characteristics of NOEV
6.3.4 NOEV Effects on Cultured Human and Mouse Fibroblasts Expressing Mutant Human Genes
6.3.5 Chaperone Therapy in Genetically Engineered GM1-Gangliosidosis Model Mice
6.3.6 NOEV Effect on Model Mice: Clinical Assessment
6.4 Future Perspectives and Conclusion
7 Prospects and Concluding Remarks
Validamycin and Its Derivatives
：Discovery, Chemical Synthesis, and Biological Activity
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