Signposts to chiral drugs organic synthesis in action - Sunjic, Vitomir; Parnham, Michael J.; SpringerLink (Online service). (Basel Springer Basel, 2011)
1. Organic synthesis in drug discovery and development 1. Introduction 2. Synthetic organic chemistry in drug R&D process 3. New concepts in drug discovery process 3.1. The impact of natural products upon modern drug discovery 3.2. Biology oriented and DNA-templated synthesis in drug discovery 3.3. Incorporation of genomics in drug discovery 4. Conclusion References 2. Aliskiren fumarate 1. Introduction 2. Renin and the mechanism of action of aliskiren 3. Structural characteristics and synthetic approaches to aliskiren 3.1 Strategy based on visual imagery, starting from Nature's chiral pool; a Dali-like presentation of objects 3.2 Fine-tuning of the chiral ligand for the Rh complex; hydrogenation of the selected substrate with extreme enantioselectivities 4. Conclusion References 3. (R)-K-13675 3.1 Introduction 3.2 Peroxisome proliferator-activated receptor a (PPARa) agonists. 3.2.1 b-Phenylpropionic acids 3.2.2 a-Alkoxy-b-arylpropionic acids 3.2.3 a-Aryloxy-b-phenyl propionic acids. 3.2.4 Oxybenzoylglycine derivatives. 3.3 Non-hydrolytic anomalous lactone ring-opening 3.4 Mitsunobu reaction in the ether bond formation 3.5 Conclusion References 4. Sitagliptin phosphate monohydrate 4.1 Introduction 4.2 Endogenous glucoregulatory peptide hormones and dipeptidyl peptidase IV (DPP4) inhibitors 4.3 Synthesis with C-acyl mevalonate as the N-acylating agent 4.4 Highly enantioselective hydrogenation of unprotected b-enamino amides and the use of Josiphos-ligands 4.5 Ammonium chloride, an effective promoter of catalytic enantioselective hydrogenation 4.6 Conclusion References 5. Biaryl unit in valsartan and vancomycin 5.1 Introduction 5.2 Angiotensin AT1 receptor, G-protein coupled receptors (GPCRs). 5.3 Cu-promoted catalytic decarboxylative biaryl synthesis, biomimetic type aerobic decarboxylation 5.4 Stereoselective approach to axially chiral biaryl system; the case of vancomycin 5.5 Conclusion References 6. 3-Amino-1,4-benzodiazepines 6.1 Introduction 6.2 3-Amino-1,4-benzodiazepine derivatives, g-secretase inhibitors 6.3 Configurational stability; racemization and enantiomerization 6.4 Crystallization induced asymmetric transformation 6.5 Asymmetric Ireland-Cleisen rearrangement 6.6 Hydroboration of the terminal C=C bond; anti-Markovnikov hydratation 6.7 Crystallization-induced asymmetric transformation in the synthesis of L-768,673 6.8 Conclusion References 7. Sertraline 7.1 Introduction 7.2 Synaptosomal serotonin uptake and its selective inhibitors (SSRI) 7.3 Action of sertraline and its protein target 7.4 General synthetic route 7.5 Stereoselective reduction of ketones and imines under kinetic and thermodynamic control 7.5.1 Diastereoselectivity of hydrogenation of rac-tetralone-methylimine; the old (MeNH2/TiCl4/toluene) method is improved by using MeNH2/EtOH-Pd/CaCO3, 60-65 oC in a telescoped process 7.5.2 Kinetic resolution of racemic methylamine; hydrosylilation by (R,R)-(EBTHI)TiF2 /PhSiH3 catalytic system 7.5.3 Catalytic epimerization of the trans- to the cis-isomer of sertraline 7.5.4 Stereoselective reduction of tetralone by chiral diphenyloxazaborolidine 7.6. Desymmetrization of oxabenzonorbornadiene, Suzuki coupling of arylboronic acids and vinyl halides 7.7 Pd-Catalyzed (Tsuji-Trost) coupling of arylboronic acids and allylic esters 7.8 Simulated moving bed (SMB) in the commercial production of sertraline 7.9 Conclusion References 8. 1,2-Dihydroquinolines 8.1 Introduction 8.2 Glucocorticoid receptor (GCR) 8.3 Asymmetric organocatalysis; introducing a thiourea catalyst for Petasis reaction 8.3.1 General consideration of the Petasis reaction 8.3.2 Catalytic, enantioselective Petasis reaction 8.4 Multicomponent reactions (MCRs); general concept and examples 8.4.1 General concept of MCRs 8.4.2 Efficient, isocyanide-based Ugi MCRs 8.5 Conclusion References 9. (-)-Menthol 9.1 Introduction 9.2. Natural sources and first technological production of (-)-menthol 9.3 Enantioselective allylic amine-enamine-imine rearrangement, catalysed by Rh(I)-(-)-BINAP complex. 9.4 Production scale synthesis of both enantiomers 9.5 Conclusion References 10. Fexofenadine hydrochloride 10.1 Introduction 10.2 Histamine receptors as biological targets for antiallergy drugs 10.3 Absolute configuration and "racemic switch" 10.4 Retrosynthetic analysis of fexofenadine 10.4.1 ZnBr2-Catalyzed rearrangement of a-haloketones to terminal carboxylic acids 10.4.2 Microbial oxidation of non-activated C-H bond. 10.4.3 Bioisosterism; silicon switch of fexofenadine to sila-fexofenadine 10.5 Conclusion References 11. Montelukast sodium 11.1 Introduction 11.2 Leukotriene D4 receptor (LTD4), CysLT-1 receptor, antagonists 11.3 Hydroboration of ketones with boranes from ?-pinenes and the non-linear effect (NLE) in asymmetric reactions 11.4 Ru(II) catalyzed enantioselective hydrogen transfer 11.5 Biocatalytic reduction with ketoreductase KRED (KetoREDuctase) 11.6 CeCl3-THF solvate as a promoter of the Grignard reaction; phase transfer catalysis 11.7 Conclusion References 12. Thiolactone peptides as antibacterial peptidomimetics 12.1. Introduction 12.2 Virulence and quorum sensing system of Staphylococcus aureus. 12.3 Development of chemical ligation (CL) in peptide synthesis 12.4 Development of native chemical ligation (NCL); chemoselectivity in peptide synthesis 12.5 Development of NCL in thiolactone peptide synthesis 12.6 Conclusion References 13. Efavirenz 13.1 Introduction 13.2 HIV-1 reverse transcriptase (RT) inhibitors 13.2.1 Steric interactions at the active site 13.3 Asymmetric addition of alkyne anion to C=O bond with formation of chiral Li+ aggregates 13.3.1 Mechanism of the chirality transfer 13.3.2 Equilibration of lithium aggregates and the effect of their relative stability on enantioselectivity 13.4 Scale-up of alkynylation promoted by the use of Et2Zn. 13.5 Conclusion References 14. Paclitaxel 14.1 Introduction 14.2 Disturbed dynamics of cellular microtubules by binding to ss-tubulin 14.2 Three selected synthetic transformations on the pathway to paclitaxel 14.3 Three selected synthetic transformations on the pathway to paclitaxel 14.3.1 Intramolecular Heck reaction on the synthetic route to baccatin III 14.3.2 Trifunctional catalyst for biomimetic synthesis of chiral diols; synthesis of the paclitaxel side-chain 14.3.3 Zr-complex catalysis in the reductive N-deacylation of taxanes to the primary amine, the key precursor of paclitaxel 14.4 Conclusion References 15. Neoglycoconjugate 15.1 Introduction 15.2 Human a-1,3-fucosyltransferase (Fuc-T) 15.3 Click chemistry, energetically preferred reactions 15.4 Target-guided synthesis (TGS) or freeze-frame click chemistry 15.5 Application of click chemistry to the synthesis of nucleoconjugate 1 15.6 Conclusion References 16. 12-Aza epothilones 16.1 Introduction 16.2 Epothilones; mechanism of action and structure-activity relationships 16.3. Extensive versus peripheral structural modifications of natural products 16.4 Ring closure metathesis (RCM), an efficient approach to mac rocyclic "non-natural natural-products" 16.5Diimide reduction of the allylic C=C bond 16.6Conclusion References.
Electronic reproduction.
Keywords: Chiral drugs; Electronic books