Chiral design

Mori et al. have now synthesized the cfs-verbenols [(32) and its enantiomer] in optically pure state using essentially the same route as used for frans-verbenol (Vol. 7, p. 41) in connection with optical purity and stereochemical comparisons based upon optical rotations, it is of interest to note that optically pure (32) has [a]o = —9.8° in chloroform and [a]o = +11.4° in methanol and +6.2° in acetone, emphasizing the value of using chiral designations." ... 

In our laboratories, new highly selective asymmetric inductions featuring the functions of C4-chiral thiazolidines and oxazolidines were recently developed. An overview of these chiral designs, reactions, and applications will be discussed in this article. 

Attempts were made to develop a new chiral design based on the symmetry of organic molecules without using metal chelation. 

The C4-chiral thiazolidine-2-thiones and oxazolidine-2-thiones developed by us proved to be efficient for chiral induction. They should be applicable to practical syntheses of drugs. Novel chiral designs using these functional and chiral heterocycles seem likely in the future, especially when used in combination with organometallic reagents and/or molecular symmetry. Creative investigations employing such chiral heterocycles and related compounds will be extensively pursued. 

The R, S convention is a scheme which has largely superseded the D, i. system to denote configuration about a chiral centre in a molecule. The convention allows unequivocal designation of the absolute configuration in a description of the positions in space of ligands attached to a chiral centre, in relation to an agreed standard of chirality like a right-hand helix. 

Analogous definitions and designations apply to molecules containing a chiral centre and a prochiral tetrahedral or trigonal centre. The plane containing the chiral and prochiral centres is called a diastereo-zeroplane (Y. Izumi, 1977). 

Optically Inactive Chiral Compounds. Although chirality is a necessary prerequisite for optical activity, chiral compounds are not necessarily optically active. With an equal mixture of two enantiomers, no net optical rotation is observed. Such a mixture of enantiomers is said to be racemic and is designated as ( ) and not as dl. Racemic mixtures usually have melting points higher than the melting point of either pure enantiomer. 

FIGURE 1.19 Viewing angle as a means of designating the absolute configuration of compounds with a chiral axis, (a) (R )-2-Butanol (sequence clockwise) (b) (fi)-2-butanol (sequence counterclockwise). 

There is increasing pressure to develop homochiral dmgs (34). Growing demands are faced by the pharmaceutical industry in dmg development to consider chiral issues in the eady preclinical phases of dmg design and synthesis. 

When ofloxacin was first introduced it was made available as the racemate. Later the optical isomers were prepared and it was found that the (3)-enantiomer, DR 3355 (6b), was substantially more active (8—128-fold) than the (R)-isomer against a broad range of bacteria (47—50). This chiral preference is not unique to ofloxacin and has been demonstrated in other quinolones as well (51,52). This significant finding has already had an impact on the design of new quinolone antibacterials still in development (53). 

Design of chiral catalysis and asymmetric autocatalysis for diphenyl-(l-methyl-pyrrolidin-2-yl) methanol-catalyzed enantioselective additions of organozinc reagents 97YGK994. 

Binding of organic nitroso compounds to metalloporphyrins 99ACR529. Design and applications of chiral porphyrins 98YGK201. 

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