Chirality and Chiral Separations

Fischer Projections and the DL Nomenclature System:This was invented by Fischer in 1891. It works by having horizontal bonds in front of the plane and vertical bonds behind the plane.

Still used for sugars, but generally discouraged.

Definitions

Isomers: different compounds that have the same molecular formula.

Stereochemistry: the science that deals with structure in three dimensions.

Stereoisomers: isomers that are different from each other only in the way atoms are oriented in space. However. they are similar to one another in that the atom of each are joined in an identical order. There two types of stereoisomers: (1)enantiomers and (2)diastereomers.

Enantiomer: an isomeric compound that cannot be superimposed on its mirror image. In an isotropic environment, enantiomers have identical physical and chemical properties.

Diastereomers: stereoisomers that are not mirror images of each other. Diastereomers can have similar chemical properties since they have the same functional groups and are members of the same family. However. their chemical properties are not identical and they have different physical properties. There are two basic types of diastereomers. One containsno chiral center and is not optically active (e. g., geometrical isomers: cis- trans. syn- anti. etc.) The other type is optically active and often contains two or more chiral centers.

Epimer : two diastereomers that differ in configuration at only one chiral center. Carbohydrates. steroids. etc. exist as epimers. Epimcrs are optically active.

Meso Compound: a compound whose molecules are superimposable cn their mirror images even though they contain chiral centers . It is optically inactive.

Racemate or Racemic Mixture: a mixture composed of equal amounts of enantiomers (50/50). This mixture is not optically active. Frequently, the properties of the mixture arc slightly different than those of the pure enantiomers.

The 2n rule: The maximum number of stereoisomer that can exist for a compound containing more than one chital center is 2n. where n is the number of chital centers.

D-, L-: In the system invented by Fisher. These are the letters used to designate opposite enantiomers (relates back to glyceraldehydes). Amino acids, sugars and related compounds often use this system These letters have nothing to do with the direction of rotation of plane polarized light. This system actually is inconsistent and is considered archaic. Many feel this system will be disgarded soon.

d -, l - and (+) and (-): d is the abbreviation for dextrorotatory and l is for levorotatory. If plane polarized light (sodium D - line, 589.3 nm) is rotated to the right (clockwise) it is “d” or (+). If it is rotated to the left (counter clockwise) it is designated “l” or (-),

NOTE: the degree and direction of rotation of plane polarized light varies with the wavelength of the light used in the measurement. Sometimes (+) and (-) is used to refer to the direction of the Cotton effect in a circular dichroism measurement.

R-and S-: “R” is the abbreviation for rectus (Latin) right (clockwise). “S” is the abbreviation for sinister (Latin) left (counter clockwise). These are the terms coined by Cahn. Ingold and Prolog and are used to described the absolute conformation of a chiral compound according to their sequence rules.

Specific rotation: the number of degrees of rotation, , observed if a l - decimeter tube is used, and the compound being examined is present to the extent of l g/cc. This is usually calculated from observations with tubes of other lengths and at different concentrations by means of the equation.

specific rotation=

where d represents density for a pure liquid or concentration for solution

d

1][

ccgdmlength

reestationobservcdro

/)(

)(deg

% Optical Purity or = 100Enantiomeric Excess

Example: If the specific rotation of enantiomers “A” was +60° and a partially racemized mixture was +30°, what was the % optical purity of the enantiomeric excess? What are the relative amounts of ( + ) and ( - ) enantiomers in the mixture?

(a) % optical purity= (b) In the mixture there is 75% of the ( + ) enantiomer and 25% of th

e ( - )enantiomer. This can be calculated via two simultaneous equations:X + Y = 100%X – Y =50% Let X = % of ( + ) enantiomer Let Y = % of ( - ) enantiomer

Enantiomeric Excess (%e.e.):Enantiopurity is usually reported in terms of “enantiomeric excess”(e.e.). %e.e. = Major - minor x 100

major + minor

Pirkle 型 :又名 brush 型（ brush type ）、 π- 錯合物型（ π-complex type ）或電荷轉移型（ charge transfer type ）。其中影響分離的作用力形式有： π-π 作用力（ π-π interactions ） 氫鍵（ hydrogen bonds ） 立體障礙（ steric interactions ） 靜電作用力（ electrostatic interaction

s ）

表一常見之蛋白質靜相的種類及其適用的分析物特性

蛋白質種類 適用之分析物的特性

α1-Acid glycoprotein 適用於具芳香環的環狀二級胺，以及某些酸性或中性化合物

Bovine serum albumin 適用於某些芳香羥酸和離子型化合物

Human serum albumin 適用於某些芳香羥酸和離子型化合

Ovomucoid 適用於具芳香環的環狀二級胺，以及某些中性化合物

Cellobiohydrolase 一級胺和其他二級胺及胺基化合物

The structure of (R,R) P-CAP chiral stationary phase

J. Chromatogr. A 2005,1066 55

Hydrogen bond interactionDipolar interactionSolvophobic-driven attractionSteric repulsive

Proposed Structure of Vancomycin

-acceptor

ionic site

hydrogen bonding & dipole stacking sites

sugar moieties

amine

A, B, C are inclusion pockets (weak)

Multiple use

Covalent bonding

Broad applicability

H

A B

C

HO

HO

HOO

HOO

OCH3

CH3

OH

NH2

Cl

NH

HO

ONH

O

NH

HO OH

COOHO

O

OO

NHO

NH

NH2

O

HO O

NHO

NH

H3C

Cl

H

Proposed Structures of Glycopeptide CSPs

Teicoplanin

Teicoplanin Aglycone HO

O

NH2

O

HO

Cl

HHO

H

O

HN

NH

O

H

B

A

OCl

N

O

N

HO

HHO

C

OHOHO

NHH

NH

O

HOOC

HD

HO

H

H

H

OH

NHR

CH2OH

HO

O

HNCOCH 3

HO

O

NH2

O

HO

Cl

HHO

H

O

HN

NH

O

H

B

A

OCl

N

O

N

HO

HHO

C

OHOHO

NHH

NH

O

HOOC

HD

HO

OH

CH2OHOH

OH

O

CH2OH

HO

O

OH

Key sites

Proposed Structures of Glycopeptide CSPs

Ristocetin A

O

O O

N

O

O

OH

H2NCH3

H

HOH

O

OHHO

O

HO

COOCH 3

H

OH

NN N

O

O

H

NH2

HHO

HO O

HHH

HN

O

H

HO

CH3 OH

O

HOOH

OHOH

O

OHOH

OH

CH3

OO

OHHOOH

O

HO

HO

OH

B

O

N

DA

C

O

O