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Asymmetric Synthesis. Dr. Mirza Shahed Baig. MIROR IMAGE. What is Asymmetric Synthesis?.
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Asymmetric Synthesis Dr. Mirza Shahed Baig
What is Asymmetric Synthesis? Asymmetric synthesis is a method for preparation of chemical compounds which aims to bias the synthesis in favour of producing one stereoisomer over another stereoisomer. Stereoisomers are molecules with the same connectivity of atoms, but with different arrangements of atoms in three-dimensional space, and can have dramatically different properties from one another.
Chiral pool synthesis • Chiral pool synthesis is one of the simplest and oldest approaches for enantioselective synthesis. A readily available chiral starting material is manipulated through successive reactions, often using achiral reagents, to obtain the desired target molecule. This can meet the criteria for enantioselective synthesis when a new chiral species is created, such as in an SN2 reaction. • Chiral pool synthesis is especially attractive for target molecules having similar chirality to a relatively inexpensive naturally occurring building-block such as a sugar or amino acid. However, the number of possible reactions the molecule can undergo is restricted and tortuous synthetic routes may be required (e.g. Oseltamivir total synthesis). This approach also requires a stoichiometric amount of the enantiopure starting material, which can be expensive if it is not naturally occurring.
Sources of Natural Chiral Compounds 1) Amino Acids 2) Sugar/Carbohydrates 3) Terpenes
Why Chirality?? Thalidomide tragedy
Eudysmic ratio • The eudysmic ratio is a common term in pharmacology, chemistry, and molecular biology. The eudysmic ratio describes the difference in pharmacologic activity between the two enantiomers of a drug. When enantiomers are formed non-selectively and the resulting product contains an equal quantity of each enantiomer it is called a racemic mixture. In pharmacology it is frequently, though not always, the case that one enantiomer of a chiral drug has greater pharmacological activity than the other. • The eudysmic ratio is a mathematical equation that quantitatively measures the difference in this activity. A eudysmic ratio significantly differing from 1 means that there is a large difference in activity between the two enantiomers. • One way the eudysmic ratio is computed is by dividing the EC50 or the IC50 of the eutomer by the same measurement of the distomer.
Enantioselective synthesis • Enantioselective synthesis, also called chiral synthesis or asymmetric synthesis, is a form of chemical synthesis. It is defined by IUPAC as: a chemical reaction (or reaction sequence) in which one or more new elements of chirality are formed in a substrate molecule and which produces the stereoisomeric (enantiomeric or diastereoisomeric) products in unequal amounts. • Hence it is the synthesis of a compound by a method that favors the formation of a specific enantiomer or diastereomer. • Enantioselective synthesis is a key process in modern chemistry and is particularly important in the field of pharmaceuticals, as the different enantiomers or diastereomers of a molecule often have different biological activity.
Diastereomeric Excess (d.e) • The preferential formation in a chemical reaction of one stereoisomer over another. When the stereoisomers are enantiomers, the phenomenon is called enantioselectivity and is quantitatively expressed by the enantiomer excess; when they are diastereoisomers, it is called diastereoselectivity and is quantitatively expressed by the diastereoisomer excess. • This is defined by analogy with enantiomer excess, as D1 - D2 [and the percent diastereoisomer excess as 100(D1 - D2)], where the mole fractions of two diastereoisomers in a mixture or the fractional yields of two diastereoisomers formed in a reaction are D1 and D2 (D1 + D2 = 1). The term is not applicable if more than two diastereoisomers are present. Frequently this term is abbreviated to d.e.
