Page 226 - Chiral Separation Techniques

204 8 Nonchromatographic Solid-Phase Purification of Enantiomers

relatively low. An alternative to isomer separation is the synthesis of the pure isomer.
In many cases, this alternative is not practical because of the many and/or costly syn-
thetic steps involved in the preparation.
For chiral separations, it is desirable to increase the product throughput, reduce
the number of total separation stages, and minimize the use of operating chemicals.
An approach used by us to accomplish these aims is to design molecules that can dif-
ferentiate between enantiomers based on the preferential fit of the molecule to one
of the enantiomers. There has been an extensive body of work on the design and per-
formance of such molecules in single-phase homogeneous systems. These studies
have been particularly successful for the separation of enantiomeric primary amine
guests by chiral macrocyclic hosts. In these systems, ∆ log K values (Equation (1))
for the interaction of chiral hosts with enantiomeric guests exceeded 0.6, which cor-
responds to an α value (Equation (2)),

–
K = [host guest complex] (1)
[host][guest]

α = Κ enantiomer A
Κ enantiomer B (2)

log α = ∆ log K

of 4. Reviews of this work have been published [5, 6]. The symbol K, as used in this
paper, refers to an apparent equilibrium constant for single-phase homogeneous
solutions and for interactions between supported ligand hosts and guests.
A significant advance toward the use of these host–guest systems for separations
was the attachment of the host to a solid support, thereby making desired separations
possible using few stages [7–9]. This approach has several advantages. First, syn-
thetic methods of modern supramolecular chemistry can be used to design and con-
struct appropriate hosts capable of selective interaction with desired enantiomeric
guests. Second, attachment of the chiral host to a solid support allows the separations
system to be used many times before replacement of the host molecules is required.
Third, the supported system is easily incorporated into a conventional engineered
format that allows large quantities of enantiomers to be processed per relatively low
amounts of the separations material. Fourth, the separations system has demon-
strated high loading capacity and low solvent usage, along with high throughput.
Recently, a number of applications of this technology have begun to emerge in the
pharmaceutical and life science industries where more efficient and low-cost chiral
separations technology is desired. The attractiveness of the technology in these areas
lies in the ability to design synthetic organic ligands that can discriminate with high
factors among nearly identical molecular species. Because the separation agent is a
synthetic organic, it is highly selective, yet extremely rugged in its operation.
This chapter provides: (i) a brief review of the chemistry involved in chiral
host– chiral guest recognition involving primary amines; (ii) a description of a
nonchromatographic (equilibrium or bind-release based) separation process devel-