Asymmetric Synthesis of Drugs and Natural Products

Prof. Ahindra Nag is a Professor in the Chemistry Department at IIT Kharagpur. He has more than 3 decades of teaching and research experience. He has published 8 textbooks, 80 research papers in renowned journals and have guided 10 research scholars. He has also been granted with 3 industrial patents. He was invited as a Visting Professor in Academia Sinica (Taiwan), University of Molise ( Italy ) and Universty of Tennesse (USA).

Chapter 1 Basic Stereochemical Approaches to Natural Products and Drugs.

1.1Basic concept of Chirality.

1.2 Meso compounds.

1.3 Tautomerism and Valance Tautomerism.

1.4 Conformation.Fischer Projection and Absolute Configuration.

1.5 Chiral Resolution.

Application of Enantiomers in Drugs and Natural Products

1.7. References

Problems and answers

Chapter- 2: Diastereoselective Addition of Organometallic Reagents to Chiral Carbonyl Compounds

2.1. Introduction

2.2. Models for Asymmetric carbonyl compounds addition

2.3 Models for 1,3 Asymmetric carbonyl addition

2.4. Addition reactions of achiral reagent

2.5. Addition of aldehyde

2.6. Addition of Chiral ketones

2.7. Conclusion

2.8. References

Chapter- 3: Enantiomerically Pure Compounds by Enantioselective Synthetic Chiral Metal Complexes

3.1.Introduction

3.2 History

3.3. Mechanism of Dirhodium(II) – catalysed cycloprpanation reactions

3.4.Electronic modifications4.1.2.Steric modifications

3.5.Dirhodium ( II) carboxylate complexes

3.6.Dirhodium(II) catalysts-derived from chiral N-protected amino acid ligands

3.7.Dirhodium(II) catalysts derived from substituted cyclopropane carboxylate ligands

3.8.Dirhodium (II) carboxamidates complexes

3.9.Effects of axial ligands on Enantioselectivity

3.10. Conclusion

3.11. References

Chapter – 4: Chirality Organization of Peptide and -Conjugated Polyanilines

4.1. Introduction

4.2 Chirality Organization of Peptides

4.2.1 Chirality Organization of Peptides by Using Organic Molecular Scaffold

4.2.2 Chirality Organization of Peptides by Using Organometallic Molecular Scaffold

4.3 Synthesis of Optically Active Polyanilines

4.3.1 Polymerization of Anilines in the Presence of a Chiral Acid

4.3.2 Doping of Emeraldine Bases with a Chiral Acid

4.3.3 Introduction of Chiral Groups into Polyanilines

4.4 Chiral Complexation of Emeraldine Bases with Chiral Complexes

4.5 Application of Optically Active Polyanilines

4.6. Conclusion

4.7.Reference

Chapter -5: Diastereoselective Syntheses of Iminosugars

5.0. Introduction

5.1. Syntheses from the Chiral Pool

5.2. Bio-catalyzed syntheses.

5.3. Asymmetric Syntheses

5.4. Conclusion and Future Directions

5.5. References

Chaptere-6: The use of specific new artificial or semisynthetic bio-catalysts for synthesis of regio- and enantioselective compounds

6.1. Introduction

6.2. Regioselective preparation of monodeprotected esters

6.3. Refrences

Chapter – 7: Bioactive Natural Products and Their Structure-Activity Relationships Studies

7.1 Introduction

7.2 Anti-Microbial Natural Products

7.3 Glutathione S-Transferase Inhibitors

7.4 Acetylcholinesterase Inhibitors

7.5.-Glucosidase Inhibitors

7.6 Anti-Renin Natural Products

7.7. References

Chapter-8: Asymmetric Biocatalysis in Organic synthesis of Natural Products

8.1.Introduction

8.2.Prochirality. meso compounds

8.3.The enzymatic desymmetrization

8.4.Factors affecting an enzymatic reaction enantioselectivity

8.5.Hydrolases

8.6.Application of esterases and proteases in enzymatic desymmetrization of symmetrical compounds

8.7.Application of lipases in enzymatic desymmetrization of symmetrical compounds

8.8.Oxidoreductases

8.9. Application of dehydrogenases in enzymatic reduction of symmetrical compounds

8.10. Application of ene-reductases in enzymatic reduction of symmetrical compounds

8.11.Application of oxidases in enzymatic oxidation reactions of symmetrical compounds

8.12.Application of peroxidases in enzymatic oxidation reactions of symmetrical compounds

8.13. References

CHAPTER -9: Asymmetric Synthesis Of Biaryls And Axially Chiral Natural Products

9.1. Introduction

9.2.Chirality in biaryl compounds

9.3.Bridged and nonbridged biaryl compounds

9.4.Selective construction of biaryl axes

9.5.Oxidative homocoupling in the presence of chiral additives

9.6.Redox-neutral cross-coupling catalyzed by chiral metal complexes

9.7.Transformations of stable but achiral biaryls and conformationally unstable but chiralbiaryls

9.8.Desymmetrization of prostereogenicbiaryl compounds

9.9.Conversion of axially chiral but conformationally unstable biaryl compounds - introduction of additional substituent in the ortho position

9.10.Conversion of axially chiral but conformationally unstable biaryl compounds -bridge formation

9.11.Conversion of axially chiral but conformationally unstable biaryl compounds -cleavage of a bridge

9.12.Asymmetric axially chiral biarylsynthesis by construction of an aromatic ring

9.13.References

CHAPTER-10: Palladium-Catalyzed Asymmetric Transformations Of Natural Products And Drug Molecules

10.1. Introduction

10.2. Palladium-catalyzed asymmetric allylic alkylations

10.3. Asymmetric Intramolecular cyclization reactions

10.4. Palladium-catalyzed carbonylation reactions

10.5. Conclusion and Future Perspectives

10.6.Reference

Chapter-11: Enantioselective Organocatalysis from Concepts to Applications in the Synthesis of Natural Products and Pharmaceuticals

11.1.Introduction

11.2. Enamine Chemistry

11.3.Modes of activation: iminium catalysis

11.4.Cascade reactions based on iminium/enamine chemistry

11.5 Application in total synthesis of organocascade reactions: Synthesis of Strychnine

11.6.Conclusions

11.7.References

Chapter-12: Chiral Building Blocks for Drugs Synthesis via Biotransformations

12.1. Introduction

12.2. Anticancer Drugs

12.3 Small molecules

12.4 Antidiabetic Drugs.

12.5. Anti-inflammatory Drugs: Profens

12.6. Drugs for treatment of Cardiovascular diseases

12.7. Anticholesterol drugs

12.8 Antihypertensive drugs

12.8.1 β-BLOCKERS

12.9 ACE inhibitors

12.10 Calcium channel blockers

12.11. Conclusion

12.12.References

Chapter-13: Chiral Medicines

13.1 Introduction

13.2. Sitagliptin

13.3. Aprepitant

13.4. Simvastatin

13.5. Paroxetine

13.6. Levetiracetam

13.7 Pregabalin

13.8. Sertraline

13.9. Conclusions

13.10. References

Chapter -14: Drug Delivery Systems

14.1. Introduction

14.2. Classification of drugs

14.3. Prodrug

14.4.Mode of action of drug

14.5. Sites of Drug Action

14.6.Goal of Drug delivery

14.7. Safety considerations

14.8.Drug Distribution

14.9.Further reading

Problems to be solved