Foreword xvii Preface xxi Introduction & Historical Background xxxi Part I Carbohydrates and Natural Products related to Carbohydrates 1 1 Carbohydrates 3 1.1 Polisaccarides 3 1.1.1 Gums and Mucilages 3 1.1.2 Mucilages 6 1.2 Carbohydrates as Antidiabetic Agents 6 1.2.

1 α-Glucosidase Inhibitors in Diabetes 6 A Appendix to Chapter 1 7 A.1 Non-Carbohydrates as Antidiabetic Agents 7 A.2 Type-II Antidiabetic Agents 9 A.3 Biguanides 12 2 Natural Products Related to Carbohydrates 15 2.1 Glycosides 15 2.1.1 Introduction 15 2.2 Anthraquinone Glycoside as Laxatives 16 2.

3 Phenol Glycosides 19 2.3.1 Phlorizin 19 2.4 Novel Strategy in the Treatment of Type-2 Diabetes 21 2.4.1 Glycoside Type-II Antidiabetic Agents 21 2.4.2 Gliflozins 21 2.

4.3 Gliflozins and Their Cardiovascular Benefits 23 References 24 Part II Polyphenols and Related Derivatives 27 3 Polyphenols and Related Derivatives 29 3.1 Introduction 29 3.1.1 Polyphenols 29 3.2 The Biosynthetic Shikimate Pathway 30 3.2.1 Aromatic Aminoacids 30 3.

2.1.1 Phenyl Propanoids 30 3.2.1.2 Gallic Acid and Tannins 30 3.2.1.

3 Galls 32 3.3 Phenylpropanes 33 3.3.1 Cinnamic Acid 33 3.3.2 Balsams 34 3.3.3 Cinnamon 36 3.

3.4 Essential (Volatile) Oils 36 3.3.5 Vanilla 38 3.3.6 Vanillin 40 3.4 Podophyllotoxin 41 References 44 Further Reading 44 4 Benzopyrane-Based Structures 45 4.1 Coumarins, Furochromones 45 4.

2 Coumarins 45 4.2.1 Anticoagulants from Sweet Clover 45 4.3 From Plant-Derived Coumarins to Modern Non Plant-Derived 47 4.3.1 Anticoagulant Therapeutic Agents 47 4.4 Furochromones 52 4.4.

1 Khellin as a Source of Coronary Dilators: Calcium Channel Blockers and Other Related Derivatives 52 4.5 BIS -Chromones as Mast Cell Stabilizers 59 4.5.1 Disodium cromoglicate. Chromolyn sodium as bronchodilator 59 4.5.2 Benzofuran Antiarrythmia 60 References 61 5 Flavonoids 63 5.1 Flavones 63 5.

2 Rutin (Rutoside) 68 5.3 Quercetin 70 5.4 Tea 71 5.5 Isoflavones 72 5.6 Flavone Alkaloids and Indol-based Natural Products as Cyclic-dependent Kinase Inhibitors (CDK-Inhibitors) 74 5.6.1 Flavone Alkaloid Rohituquine, Flavopiridol and Pyrimidine-related CDK Inhibitors 74 5.6.

1.1 The Cell Division Cycle 74 5.6.2 Development of CDK Inhibitors 76 5.6.2.1 Non-Plant Derived CDK Inhibitors 78 5.7 Indole-based Natural Products as Cyclic Dependent Kinase Inhibitors 83 5.

7.1 Indigo and Indirubine CDK Inhibitors 83 References 88 Part III Terpenes and Isoprenoids 91 6 Terpenes and Isoprenoids 93 6.1 Terpenes 93 6.1.1 Introduction 93 6.2 Monoterpenes 95 6.3 Cannabis and cannabinoids 95 6.3.

1 Cannabis 95 6.3.1.1 The Long Journey of a Controversial and Paradigmatic Plant 95 6.3.2 Cultivation 97 6.3.3 Chemistry 98 6.

3.4 Terpenes in Cannabis 100 6.3.5 Cannabis as a Crude Drug 101 6.3.6 Therapeutic Cannabinoids 102 6.3.7 Cannabidiol 103 6.

3.8 Endocannabinoids 105 References 107 Further Reading 108 7 Sexquiterpenes (C15) and Diterpenes (C20) 109 7.1 Sexquiterpenes: Artemisia 109 7.1.1 Diterpenes: Ginkgo 109 7.2 Santonine 109 7.3 Artemisinin 110 7.3.

1 From Ancient Recipes to Modern Drugs 112 7.3.1.1 Artemisinin Production 114 7.4 Diterpenes 117 7.4.1 Ginkgolides 117 References 122 8 Diterpenes II. Taxanes 125 8.

1 Taxanes: Paclitaxel, Docetaxel, Cabazitaxel 125 8.1.1 Semi-Synthesis of Taxanes 128 8.1.2 Production 130 References 133 Further Reading 133 9 Triterpenes 135 9.1 Triterpenes (C30) 135 9.2 Glycoside Pentacyclic Triterpenoid Saponines 135 9.2.

1 Triterpenoid Saponin Biosynthesis 137 9.2.2 Glycyrrhizin and Glycyrrhizic Acid 139 9.2.2.1 Liquorice Root 139 9.2.3 Quillaja Saponin 141 9.

3 Ginseng and Ginsenosides 142 9.3.1 Ginsenoside Biosynthesis 144 9.4 Siberiang Ginseng (Eleutherococcus) 146 9.5 Triterpene Carboxylic Acids 146 9.5.1 Betulinic Acid 147 References 148 Further Reading 149 Part IV Steroids and Plant Natural products as raw materials for Steroid production. Cardioactive Glycosides 151 10 Early Steroid Chemistry.

Introduction. Sexual Hormones I 153 10.1 Steroids 153 10.1.1 Introduction 153 10.1.1.1 A brief history 153 10.

1.2 Five Centuries Later. 155 10.2 Nomenclature/Structural Determination/ Stereochemistry 161 10.3 Structural Determination 162 10.3.1 Primitive Methods 162 10.4 Estranes.

Steroids in Which Ring a is Aromatic 164 10.4.1 Oestrogens. Oestrone. Estradiol 164 10.5 17α-Ethinyl Oestradiol 168 10.6 Early Pharmaceutical Production of Oestrogens 171 10.6.

1 Progynon B Oleosum 172 10.7 Androstanes 173 10.7.1 Androgens. Androsterone. Testosterone 173 10.7.1.

1 Androsterone 173 10.7.2 Testosterone 175 A Appendix to Chapter 10 179 A.1 Urinary Hormones in Medieval China 179 References 180 Further Reading 180 11 Early Steroid Chemistry. Sexual Hormones II, Progestagens. Pregnanes 181 11.1 Progesterone . The Hormone of Pregnancy , the Corpus Luteum Hormone 181 11.

2 Progesterone as a Drug. Isolation of Progesterone 181 11.2.1 Progesterone: Isolation and Structural Determination 181 11.2.2 Approaches to the Synthesis of Progesterone in Germany Before WorldWar II 183 11.2.3 Progesterone as an Active Ingredient in Gestagen Formulations 185 11.

2.4 Gestagens by the Oral Route: Ethistherone, the First Step 186 11.2.5 Progesterone as Prototype of Ovulation-Inhibiting Drugs: Synthetic Progesterone Analogues: Progestins 188 11.2.6 17α-hydroxyprogesterone 188 Further Reading 191 12 Steroid Chemistry III. Steroid Starting Materials 193 12.1 Phytochemicals as Raw Materials for the Semisynthesis of Steroidal Hormones 193 12.

2 Mexican ''Dioscoreas'', a Major Source of Steroids 194 12.2.1 From Saponin Diosgenin to Progesterone 194 12.2.1.1 Mexican Dioscoreas and Russell E. Marker 194 12.3 Rhizome of Mexican Dioscoreas as a Source of Steroids 198 12.

4 Other Dioscoreas 201 12.5 Soya-bean Oil. A Major Source of Raw Materials for the Semisynthesis of Steroid Molecules 201 12.5.1 The Phytosterol Route: From Stigmasterol to Progesterone 201 12.5.2 Stigmasterol 202 12.5.

3 Physostigmine, Stigmasterol and Percy Julian 202 12.6 Stigmasterol from Crude Soya Bean 203 12.7 Progesterone from Stigmasterol. Upjohn Process ( 1950 s- 1960 s) 204 12.8 Soya-bean Seed 209 References 210 Further Reading 210 13 Steroid Chemistry IV. From Oestrone to 19-Nor Steroids 211 13.1 Contraceptive Agents 211 13.1.

1 19-Nor Steroids 211 13.2 Norandrostane-based Steroids. Ethisterone 211 13.2.1 Industrial Production of Oestrone by Syntex. Production of Oestrone from Diosgenin 216 13.3 Androgenic-Anabolic Agents 219 13.3.

1 Gonane-based Androgens 219 A Appendix to Chapter 13 221 A.1 19-Norsteroids 221 A.1.1 Total Synthesis 221 References 223 Further Reading 223 14 Steroid Chemistry V. Corticosteroids and Analogues. Adrenal Cortical Hormones 225 14.1 Cortisone, the Glucocorticoid Hormone . The Beginnings of the Cortisone Era 225 14.

1.1 Cortisone from Bile Acids 227 14.2 Cortisone from Steroidal Sapogenins 229 14.2.1 Sarmentogenin 229 14.2.2 Hecogenin 230 14.2.

3 Hecogenin from Sisal 230 14.3 Cortisone from Progesterone (1955). The Commercial Synthesis of Cortisone 232 14.3.1 17α-acetoxy Progesterone 237 14.3.2 Cortexolone Diacetate 238 14.4 Adrenal Cortical Hormones 239 14.

4.1 Aldosterone, the Mineralocorticoid Hormone 239 14.5 Fluoro-Corticosteroids/Unsaturation Ring A 245 14.5.1 Fluorocorticoids: Fluodrocortisone 246 14.5.2 Methodology for Introducing Fluorine in 9α 247 14.6 Unsaturation Ring A.

Prednisone, Prednisolone 248 14.7 6α-Methyl Corticosteroids 249 14.7.1 Introduction of 6α Methyl Group. 6α-Methylprednisolone 249 14.7.2 Triamcinolone 250 14.8 C-16 Methylcorticosteroids 252 14.

8.1 Topical Corticosteroids 253 14.9 Corticosteroids. An Approach to an End. 256 14.10 Summary 257 References 260 Further Reading 260 15 Cardioactive Glycosides 261 15.1 Cardioactive Glycosides 261 15.1.

1 Digitalis and Strophantus Glycosides 261 15.2 Introduction 261 15.2.1 Congestive Heart Failure (CHF) 264 15.3 Digitalis: Chemistry and Pharmacy 266 15.3.1 The Legal Reaction 268 15.3.

2 Glycosides from Digitalis lanata 271 15.4 Glycosides from Digitalis Purpurea 271 15.5 Saponins on Digitalis Leaves 273 15.6 Strophantus 274 15.6.1 Convallaria 277 15.7 Squill (White Squill.