Chirality/Chiral nature

The potential for use of chiral natural materials such as cellulose for separation of enantiomers has long been recognized, but development of efficient materials occurred relatively recently. Several acylated derivatives of cellulose are effective chiral stationary phases. Benzoate esters and aryl carbamates are particularly useful. These materials are commercially available on a silica support and imder the trademark Chiralcel. Figure 2.4 shows the resolution of y-phenyl-y-butyrolactone with the use of acetylated cellulose as the adsorbent material. 

The example given above of the selection of deoxycholic acid as a SM for the synthesis of cortisol also illustrates the use of a chiral natural substance as synthetic precursor of a chiral TGT. Here the matching process involves a mapping of individual stereocenters as well as rings, functional groups, etc. The synthesis of helminthosporal (105) from (-i-)-carvone (106)21 and the synthesis of picrotoxinin (107) from (-)-carvone (108)22 amply demonstrate this approach employing terpenes as chiral SM s. 

The axially chiral natural product mastigophorene A (70) was synthesized via a copper-catalyzed asymmetric homocoupling of bromooxazoline 68. Treatment of 68 with activated copper in DMF afforded 69 in 85% yield as a 3 1 mixture of atropisomers. The major atropisomer was converted into mastigophorene A (70) the minor regioisomer was transformed into the atropisomeric natural product mastigophorene... 

Atroposelective cleavage of configurationally unstable lactone cycle in biaryl derivatives as effective route to chiral natural products and useful reagents 99S525. 

Progress in the synthesis of chiral natural macrolide antibiotics epothione B and tartrolonB 99JHC1421. 

Chiral enolates of 1,3-dioxalan-4-ones, methyl l,3-oxa2ohdine-4-carboxylates,and 1,3-iml-da2ohdine-4-ones derived from chiral natural sources such as fS -prohne, fS -serine, and fS -threonine are added to nltroalkenes in high diastereoselectivity fScheme 4,12, ... 

Four general methods have been used for obtaining chiral ligands resolution of a racemic mixture, use of a chiral naturally occurring product 33), and asymmetric homogeneous or heterogeneous hydrogenation. 

The guideline concludes with a note that there is no intention to require further data on established medicinal products which contain a racemic drug unless new evidence emerges concerning the safety or efficacy of one enantiomer. If new claims related to the chiral nature of the active substance are made, then supporting studies on the individual enantiomers will be required. 

In spite of the fact that biotechnology rather than chemical processing will probably provide the future greatly needed chirally pure compounds (ref. 1), we believe that simple chemical reactions starting from chiral natural compounds and proceeding under stereochemical control will eventually retain full importance. On the above grounds, we report on simple reactions which start from a-aminoacids, as an example of utilization of natural compounds, and move to related bromine containing compounds (Fig. 1). 

Several examples have been described in which a chiral natural polymer, such as silk fibroin or chitosan, act as chiral ligand and support at the same time. In such cases, the chiral ligand (the monomer or monomers coordinating... 

The reduction of nitro ketones with baker s yeast is a good method for the preparation of chiral nitro alcohols.89 The reduction of 5-nitro-2-pentanone with baker s yeast gives the corresponding (5)-alcohol, which is an important chiral building block. Various chiral natural products are prepared from it. In Scheme 7.16, the synthesis of the pheromone of Andrena haemorrhoa is described, where the acylation of the chiral nitro alcohol followed by radical denitration is involved as key steps.89a... 

Baker s yeast reduction of y-nitroketones offers the corresponding chiral nitro alcohols, which are useful building blocks for the synthesis of chiral natural compounds.120 For example, optically active 2-substituted pyrrolidine can be prepared using the chiral nitro alcohol (Eq. 10.75).121... 

Discotic liquid crystals based on carbohydrates are intrinsically chiral due to the chiral nature of their core.49,50 Numerous discotic liquid crystals derived from these mesogens have been reported however, the expression of chirality in the subsequent mesophases has only rarely been seen. An example of the latter is the a-anomer of penta- O -decanoylglucopyranosc (47), which forms a discotic mesophase in which the molecules pack helically in the columns... 

Several examples exist of the application of chiral natural N-compounds in base-catalyzed reactions. Thus, L-proline and cinchona alkaloids have been applied [35] in enantioselective aldol condensations and Michael addition. Techniques are available to heterogenize natural N-bases, such as ephedrine, by covalent binding to mesoporous ordered silica materials [36]. 

Modification of catalytic metal surfaces with chiral natural compounds has led - for particular combinations - to results varying from good to excellent in enantioselective hydrogenations. The field has been reviewed [39]. 

An irreversible consecutive reaction as a driving force to shift an unfavorable Cope rearrangement equilibria in the needed direction can be illustrated by the Cope-Claisen tandem process used for the synthesis of chiral natural compounds243. It was found that thermolysis of fraws-isomeric allyl ethers 484 or 485 at 255 °C leads to an equilibrium mixture of the two isomers in a 55 45 ratio without conversion into any other products (equation 184). Under the same conditions the isomer 487 rearranges to give the Cope-Claisen aldehyde 491 (equation 185). Presumably, the interconversion 484 485 proceeds via intermediate 486 whose structure is not favorable for Claisen rearrangement. In contrast, one of the two cyclodiene intermediates of process 487 488 (viz. 490 rather than 489) has a conformation appropriate for irreversible Claisen rearrangement243. 

The chiral nature of the chlorosulfinyl grouping was first demonstrated by NMR spectroscopy. King and Beatson (112) found that the proton NMR spectrum of a-chloroethanesulfinyl chloride 84 indicated clearly the presence of two diastereomers due to the... 

As noted above, molecules that are not superimposable on their mirror images are said to be chiral. Nature makes important distinctions between right-handed and left-handed molecules. 

In an extension of the work to chiral chemistry 244), the imidazolium cation of the ionic liquid was modified to carry a chiral substituent. The high cost of the chiral cation could be justified as the chiral ionic liquid, [MBMIM ] , can be reused. In the ATRP of soluble methyl acrylate, a small effect of the chiral ionic liquid on the polymer tacticity was observed. The use of a chiral ionic liquid as a solvent could lead to applications in other areas of catalysis. The synthesis of imidazolium-containing ionic liquids functionalized with chiral natural amino acids has already been reported 245), as have less expensive chiral ionic liquids(2- (5). 

Although most of the glycosides 6-12 showed some inhibition towards the j3-glycanases available to us (18], it was the epoxybutyl -cellobioside 7 (n = 2) that was an efficient inhibitor of one particular enzyme. Also, in view of the chiral nature of an enzyme, it seemed an especially good idea to prepare molecules such as 7 in optically-pure form. We therefore began a program to synthesize the pure diastereoisomers 6a,6b,7a and7b. 

The chiral nature of ( )-cycloalkenes, whose jump rope conformational interconversions are restricted because of non-bonding interaction across the ring, was first pointed out in 1952 when Blomquistpresented the enantiomeric figures of ( )-cyclononene in his paper describing the syntheses of cis- and trans-isomers of cyclononene. 

As mentioned earlier, preparation of (Z),( )-l, 5-cyclooctadiene (31) in an optically active modification 2) first demonstrated the chiral nature of ( )-cycloalkenes. In this classical experiment, Cope and coworkers obtained ( + )-31 by the Hofmann elimination of the (-l-)-ammonium salt 30. They were also successful in obtaining (+)-31 by optical resolution of racemic 31 through complexing with a chiral Pt(II)... 

The close relationship 44a b) between bridgehead olefins and ( )-cycloaikenes had been discussed solely with regard to their strained characteristics, but, a careful examination revealed that this relationship should be extended to their chiral natures. 

The same authors 83) used the chiral ketone (46) as substrate for the preparation of optically active cyclohexanol derivatives (47) which may be useful intermediates in the synthesis of chiral natural products, such as (—)-mesenbranoene, (+)-2-carene etc. 

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