Chiral host synthetic

Stereoselective catalysis using biocatalysts (e.g. enzymes) and also of rationally designed small chiral molecules, deals essentially with the same principle the spatial and selective docking of guest molecules to a chiral host molecule to form complementary interactions to form reversible transient molecule associates (see the specific sections in this volume). The enantiomeric excess of a certain reaction and hence the result will be determined by the degree of chiral discrimination. Along the same theoretical lines the concepts of protein (enzyme, antibody, etc.) mimicks via imprinted" synthetic polymers should be mentioned and will be discussed further. 

From a totally different point of view, Morii and co-workers [70] have studied the utility of synthetic proteins as chiral hosts. They showed that a-helix bundle structures, formed by the folding of peptides such as 75, induced chirality in fluorescent dyes by forming inclusion complexes in the hydrophobic interior of the structures. Again these results can have implications for the development of optical materials and switches. 

Optical resolution of some hydrocarbonds and halogeno compounds by inclusion complexation with the chiral host (9a) has been accomplished.11,12 Preparation of optically active hydrocarbons is not easy and only a few example of the preparation of optically active hydrocarbons have been reported. For example, optically active 3-phenylcyclohexene has been derived from tartaric acid through eight synthetic steps.11 Although one-step synthesis of optically active 3-methylcyclohexene from 2-cyclo- hexanol by the Grignard reaction using chiral nickel complex as a catalyst has been reported, the enantiomeric purity of the product is low, 15.9%.11 In this section, much more fruitful results by our inclusion method are shown. 

Although some kinds of optically active compounds can be prepared by an asymmetric synthesis using a chiral catalyst, this method is not applicable for preparation of all kinds of compounds. Furthermore, optical yields of the product are not always very high. On the contrary, optical resolution method by inclusion complexation with a chiral host is applicable to various kinds of guest compounds as described in this chapter. When optically pure product cannot be obtained by one resolution procedure, perfect resolution can be accomplished by repeating the process, although asymmetric synthetic process cannot be repeated. Especially, optical resolutions by inclusion complexation with a chiral host in a water suspension medium and by fractional distillation in the presence of a chiral host are valuable as green and sustainable processes. 

Despite the excessive complexity from the synthetic viewpoint, the above-discussed supramolecular systems are of obvious interest for various application fields, especially for chiral recognition purposes. However, the specific host-guest matching, which is one of the key elements for enantioselective processes, requires fine design of the chiral host that in turn imposes limitations on the scope of the host s applicability. 

D2 and D3 vitamins (ergocalciferol and cholecalci-ferol) has not been equally successfulJ Vitamin D extracted from natural sources has a single conformational stereochemistry that is one of several isomers produced in synthetic preparations. To certify that the natural form is present in a synthetic product, where it can be accurately assayed in the presence of the other isomers, is a formidable analytical task. Whether direct CD detection can satisfactorily solve it is currently unknown. A prior non-selective derivati-zation reaction might be required on all isomers. The A and E vitamins are achiral and not subject to chiroptical detection unless first derivatized by reaction with a chiral host. 

PHTP is a chiral host which can be resolved into enantiomers DCA and ACA are (or derive from) naturally occurring optically active compounds. Using these hosts inclusion polymerization can be performed in a chiral environment and can be used for the synthesis of optically active polymers. This line of research has been very fruitful, both on the synthetic and on the theoretical plane. It has been ascertained that asymmetric inclusion polymerization occurs by a "through space" and not by a "through bond" induction only steric host-guest interactions (physical in nature) and not conventional chemical bonds are responsible for the transmission of chirality (W). 

Photochemical asymmetric synthesis with native and modified CDx s is certainly one of the most potentially successful examples of supramolecular photochirogen-esis, which is applicable in principle to most photoreactive substrates of appropriate size and shape. Despite this wide applicability, the enantiodifferentiating ability of CDx and hence the product ee obtained are not sufficiently high in many cases. Furthermore, the elucidation of the chiral discrimination mechanism and the rationalization of the product chirality and ee are generally more difficult in photochemical asymmetric induction. For more simple and well-defined host-guest interactions (in the ground as well as excited states), several approaches to photochemical asymmetric induction with newly designed synthetic chiral hosts have been reported. 

Preparation of enantiomerically active hydrocarbons is difficult and only a few examples of the preparation of chiral hydrocarbons have been reported. For example, chiral 3-phenylcyclohexene has been derived from tartaric acid through eight synthetic steps. Enantiomeric separation by host-guest complexation with a chiral host is more fruitful for the preparation of chiral hydrocarbons. For example, when a solution of fR,Rh( )-t ws-4,5-bis(hydroxydiphenylmethyl)-l,4-dioxaspiro[4.4]-nonane (lb) [2] (3 g, 6.1 mmol) and rac-3-methylcyclohexene (2a) (0.58 g, 6.1 mmol) in ether (15 ml) was kept at room temperature for 12 h, a 2 1 inclusion complex of lb and 2a (2.5 g, 75%) was obtained as colorless prisms in the yield indicated. The crystals were purified by recrystallization from ether to give the inclusion complex (2.4 g, 71%), which upon heating in vacuo gave (-)-2a of 75% ee by distillation (0.19 g, 71%) [3]. By the same inclusion complexation, (-i-)-4-methyl- (2b) (33% ee, 55%), (-)-4-vinylcyclohexene (2c) (28% ee, 73%), (-)-bicyclo[4.3]-nonane-2,5-diene... 

With catalytical amounts of chiral hosts hopefully enantio- and diastereoselective syntheses can be carried out. Regioselective reactions using cavity-enclosed guests have been already achieved using the cyclodextrins. This can most certainly be mimicked by synthetic hosts which are tailor-shaped to meet the specific problem. 

Considerable work has been done in the field of chiral hosts capable of discriminating between enantiomeric guest molecules. A variety of chiral residues either synthetic or derived from natural products l (sugars, tartaric acid, amino acids etc.) have been fused to macrocyclic rings. In most cases, chiral primary ammonium cations have been the guest species of choice, although the complexation of chiral carboxylates has been examined to some extent 2]. 

A major step toward synthetically useful enantioselectivities induced by chiral complexing agents was achieved by the introduction of rationally designed hosts. These chiral hosts serve as stoichiometric complexing agents, which differentiate the enantiotopic faces of the starting material by binding to it in... 

Metabolic pathways containing dioxygenases in wild-type strains are usually related to detoxification processes upon conversion of aromatic xenobiotics to phenols and catechols, which are more readily excreted. Within such pathways, the intermediate chiral cis-diol is rearomatized by a dihydrodiol-dehydrogenase. While this mild route to catechols is also exploited synthetically [221], the chirality is lost. In the context of asymmetric synthesis, such further biotransformations have to be prevented, which was initially realized by using mutant strains deficient in enzymes responsible for the rearomatization. Today, several dioxygenases with complementary substrate profiles are available, as outlined in Table 9.6. Considering the delicate architecture of these enzyme complexes, recombinant whole-cell-mediated biotransformations are the only option for such conversions. E. coli is preferably used as host and fermentation protocols have been optimized [222,223]. 

Chiral bicyclic guanidinium receptors (e.g. 12-14, S,S-configuration shown) have been developed in our group from aminoacid precursors [16]. Improved synthetic procedures for such compounds were later reported by Schmidtchen [17] (who in 1980 presented a first type of achiral bicycloguanidinium hosts [18] that form complexes with several oxoanions [19]). Most derivatives are highly... 

A similiar approach was performed by van de Velde (1999), using incorporation of vanadate into an acid phosphatase (phytase) to create a semi-synthetic peroxidase similar to the heme-dependent chloroperoxidase. The latter is a useful enzyme for the asymmetric epoxidation of olefins, but less stable due to oxidation of the porphyrin ring and difficult to express outside the native fungal host. The authors exploited the structural similarity of active sites from vanadate-dependent halo-peroxidases and acid phosphatases and have shown the useful application as an enantioselective catalyst for the synthesis of chiral sulfoxides (van de Velde, 1999). 

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