TAILIEUCHUNG - DRUG STEREOCHEMISTRY Analytical Methods and F'hannacology Second Edition_2

the beginning, medicinal therapy consisteodf concoctions coadministered with incantations. Little thought was given to dissecting out the contributions of the pharmacology of the concoction from the spiritual consequences of the incantations. Eventually, potions and extracts were recognized to have predictable activity that could be observed and described objectively. Then came the capacity to estimate potency,t o l eading concentration and purification. And finally came chemical identification and synthesis and the currently fashionable demand that a modern medicament must be a pure single chemical entity. With synthesis replacing nature, the chemical aspeocf t pharmaceutical scienceh ad gone as far as it could go-or had it?. | 7 Synthesis of Enantiomerically Pure Drugs John w. Scott Hoffmann-La Roche Inc. Nutley New Jersey The need to prepare a chiral organic molecule that is to be used as a drug in enantiomerically homogeneous form has been amply justified in other sections of this monograph. Here the synthetic chemical and biochemical methods available for preparing these compounds will be reviewed and illustrated. I. METHODOLOGY A. Synthetic Analysis and Design The synthesis of an organic molecule generally proceeds in a series of logically connected individual stages. Fữst obviously is definition of the target. For the medicinal chemist this includes in the case of a chiral molecule a decision on whether to prepare the compound in racemic or enantiomerically homogeneous form. The design of a synthesis is based on a careful analysis of the structure sought. This process termed retrosynthetic analysis by Corey who is responsible for its formalization can be performed manually or in a computer-aided fashion 1 . It involves consideration of all potential bond breakings thus retrosynthesis of the target. Each is evaluated in terms of the probability of success based on known reactions of the reverse synthetic transformation. In its more sophisticated forms the computer program will provide an estimate of the probability of success of the proposed transformation as well as relevant literature citations. The first generation retrosynthetic analysis provides the initial branches of a tree. Similar analysis of each branch representing a target precursor is then carried out. A judicious choice of which branches to terminate 183 184 Scott leads ultimately to a compound starting material that is commercially available or whose synthesis is known. Usually several routes to the target will be generated in this fashion. The choice of which one is to be attempted is often subjective based on the prejudices of the chemist involved. On a more logical basis the factors leading to the synthesis choice .

• Y học thường thức
• Enantiomer Analysis
• Direct Resolution
• Enantioselective Binding
• FDA Perspective
• Chiral Stationary
• Chromatography A
• Chiral HPLC
• Mode dedication
• Regeneration of chiral stationary phases
• Eluent history
• Hindered structural transition
• Cellulose based chiral stationary phases
• Hydro organic mobile phases compatible
• Retention behaviour
• Enantioresolution ability
• Tetrahydro ß carboline analogs
• Ion exchanger chiral stationary phases
• Enantioselective separation
• Numerous alkaloids
• Chiral separation techniques
• Preparative chiral separations
• Method development
• Glycopeptide chiral stationary phases
• Enantiomeric separations
• Liquid chromatography
• Macrocyclic glycopeptide based chiral
• Core shell particles
• Stationary phases
• Cinchona alkaloid based chiral stationary phases
• Fluorinated ß phenylalanine derivatives
• Thermodynamic characterization
• High performance liquid chromatography
• Cinchona alkaloid based weak
• Chiral stationary phases
• Mobile phase
• Chiral separation
• Enantiomer elution order
• Polar organic mode
• Neat methanol
• Tetrahydroisoquinoline analogues
• Benzazepine analogues
• High performance liquid chromatographic
• Subcritical fluid chromatographic
• Nonstandard solvents
• Reversed phase
• Anticancer drugs
• Isopulegol analogs
• Prodrug mechanism
• Novel antidiabetic drug
• Capillary electrochromatography
• Chiral stationary phase
• Amylose tris
• Nano liquid chromatography
• Bee pollen
• Enantiomeric separation
• Supercritical fluid chromatography