Chiral immobilization chemistry

Aldolases are a group of C—C bond forming enzymes with widespread applications. The stereoselective aldol addition reaction catalyzed by aldolases represents an attractive alternative to conventional chiral organic chemistry methods for chemical and pharmaceutical industries. Aldolases are classified according to both their proposed catalytic mechanism and the structure of the donor substrate, their sources and microbial production processes being presented in this chapter. To design appropriate bioreactors for aldol synthesis, the characteristics of aldolase biocatalysts obtained after purification procedures in free and immobilized form are discussed. 

Immobilized catalysts on solid supports inherently have benefits because of their easy separation from the products and the possibility of recycling. They are also expected to be useful for combinatorial chemistry and high-throughput experimentation. The polystyrene-bound BINAP/DPEN-Ru complex (beads) in the presence of (CH3)3COK catalyzes the hydrogenation of l -acetonaphthone with an SCR of 12 300 in a 2-propanol-DMF mixture (1 1, v/v) to afford the chiral alcohol in 97% ee (Fig. 32.35) [113]. This supported complex is separable... 

The detailed design of chiral reaction spaces for asymmetric catalysis on surfaces is still a serious challenge [1, 26, 27]. The chemistry of homogeneous metal complexes in solution can not straightforwardly be transferred to chemistry on solid surfaces, and both catalytic activity and enantioselectivity in homogeneous systems often decrease upon simple immobilization of the homogeneous meal complexes on surfaces. 

Enzymes have found frequent use in the synthesis of single isomer drugs from racemic or prochiral compounds at the larger manufacturing scales. The use of enzymes to effect chiral transformations in the medicinal chemistry laboratory has been far less frequent however, the increasing availability of immobilized and stabilized forms of enzymes has made their use easier and the resultant transformations more predictable. 

Inspired by the seminal report of Nagel [34], which described a very active and selective Rh-pyrphos catalyst attached covalently to sihca gel, Pugin and colleagues have developed the modular toolbox which his depicted schematically in Figure 12.4. The main elements of their system are functionalized chiral diphosphines, where three different hnkers are based on isocyanate chemistry and various carriers [37, 45, 58]. This approach allows for a systematic and rapid access to a variety of immobilized chiral catalysts, with the possibility of adapting their catalytic and technical properties to specific needs. 

Another QSERR was carried out by Kaliszan, Noctor and Wainer [86] who suggest many of the abstract and arbitrary indicator variables used by Norinder and Hermansson obscures the physical interpretation of the correlations. These authors measured retentions of 21 chiral and achiral 1,4-benzodiazepine derivatives, like 37 and 38 on an immobilized human serum albumin CSP. The variables used to determine the QSERR consisted of molecular descriptors derived from computational chemistry. 

PDMS has unique properties such as elastomeric, nontoxic, optically transparent down to 280 nm, and hydrophobic surface chemistry. However, due to the PDMS adsorption property of most of chemicals, it is a challenge to perform the monoliths in a PDMS channel. Lin s group [13] fabricated polyacrylamide (PAA) gel monolithic column in a PDMS microchip for chiral separation in p-CEC. The PDMS microchannel was first pretreated with 3-(trimethoxysilyl) propyl methaciylate, and the chiral selector, y-cyclodextrin (y-CD), was immobilized firmly into the PAA gel in the nficrochannel. The key to... 

The Naito laboratory has investigated the applicability of radical reactions in solid-supported chemistry. A pronounced effect of the solid support on the stereochemical outcome of a radical reaction was reported for the addition of an alkyl radical onto the chiral oxime 139, delivering a-amino acid derivatives 140 in good yield and with high stereoselectivity (Scheme 6.32). Higher diastereoselectivities were observed with the substrate 139 immobilized on the solid support (>90% de), compared to comparable solution-phase reactions of 139 (72-85% de). This effect was rationalized based on the lower reactivity and reduced reaction rate of the immobilized oxime, inducing an enhanced selectivity. ... 

Zech, G., Kunz, H. (2004). Synthesis of a polymeric-bound galactosylamine and its apph-cation as an immobilized chiral auxiliary in stereoselective synthesis of piperidine and amino acid derivatives. Chemistry - A European Journal, 10, 4136-4149. 

---