Stereospecific search

When stereospecific search options are used, only compounds that include stereochemical information are regarded. The stereo property of atoms is defined by specifying wedged and dashed bonds. The resulting stereo descriptor is calculated internally. If no stereo center has been specified, the stereo configuration is usually presumed as undefined. Stereo bonds can be defined in several ways  

The latter case can be used to specify racemic mixtures with a stereo either bond. Stereo either bonds are interpreted as a racemic mixture of R and S enantiomers and are also used for epimers. An atom is considered as a potential stereo center if it binds to at least three substituents the fourth may be an implicit hydrogen atom. The atom is handled as an explicit stereo center if at least three different nonhydrogen atoms are bonded. 

Recognition of stereochemical information can be restricted to several search modes, such as 

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Searching for particular stereochemical configurations is in principle just an extension of the methods for searching without stereochemistry additional conditions of bond orientation etc. need to be satisfied before a match is identified. A growing number of substructure search systems are now offering stereospecific searching. 

Progress is being made in the search for catalysts to hydrogenate aromatic systems (see Section VII). This area is likely to become increasingly important if coal, which contains polyaromatic compounds, is utilized more for production of petrochemicals. Stereospecific production of fully m-C6D6H6 from perdeuterobenzene has been reported catalysts for selective hydrogenation of benzene to cyclohexene would be valuable. 

This should open the search for novel stereospecificities for transaldolase mutant proteins. 

The strategy adopted for attacking this problem is, so to speak, an orthodox one. This can be divided into five distinct steps first, search for catalyst having a high degree of stereospecificity second, isolation and purification of the catalyst third, determination of structure and clarification of the chemical behavior of the catalyst fourth, elucidation of the mode of action of the catalyst on the monomer fifth, clarification of catalytic behavior in the polymerization reaction of the catalyst and its derivatives. 

Highly stereospecific catalysts for the polymerization of these monomers were found quite naturally along two lines of search starting from the triethylaluminum-water and triethylaluminum-alcohol catalyst systems, which were known to be stereospecific polymerization catalysts for these monomers when we started the experiments on this subject. Development and interrelation of these catalysts in our research are shown in Scheme 1 (8). 

Although such a definition is seemingly quite clear and unique, the practical exploitation of the above criterion is complicated by the fact that the scission and formation of bonds is a microscopic process, inaccessible to direct experimental observation. This, of course, suggests the necessity of searching other, more easily exploitable, criteria of concert. One such criterion is the remarkable stereospecificity accompanying the formation of products in allowed pericyclic reactions [60,61]. The fact that the origin of the synchronisation in the process of scission and the formation of the bonds was always intuitively related to a certain energetic stabilisation led to another widespread opinion that all allowed reactions are automatically concerted. On the other hand nonconcertedness, advocated by frequently observed stereo-randomization [60] was practically always expected in forbidden reactions. 

Fry, in a search for an intermediate capable of undergoing stereospecific cyclization to 11/3-alkylbenzomorphans, studied the 2,3-cis and trans isomers of 2-benzyl-l,3,4-trimethyl-l,2,3,6-tetrahydropyridine (Scheme 4.11). These were prepared from the iminium dienes (80 and 81) isolated as crystalline perchlorates from benzyl Grignard attack on 1,3,4-trimethylpyridinium bromide. The isomeric dienes were differentiated through their cyano derivatives (82 and 83), which on borohydride reduction gave the isomeric tetrahy-dropyridines, 84 and 85. Elimination of HCN from 82 gave the iminium diene (86) isomeric with 81. Addition of nitrile to 81 followed by borohydride reduction resulted in the appropriate trans tetrahydropyridine (88) that cyclized to the 11/3-methylbenzomorphan (89). 

Further investigations showed that the means of improving enantioselectivity consists not in searches for new modifier structures but in elaboration of the stereochemical mechanism of reaction based on concepts of dual sites, the existence of chiral modified and non-stereospecific centers, on the surface of catalysts (see, Sachtlei , Klabunovskii Smith - )... 

Hydrolytic enzymes such as proteases, esterases and lipases are ready-to-use catalysts for the preparation of optically active carboxylic acids, amino acids, alcohols, and amines. The area is sufficiently well researched to be of general applicabihty for a wide range of synthetic problems. Consequently, about two thirds of the reported research on biotransformations involves these areas. This is facilitated by the fact that a considerable collection of commercially available proteases and lipases is available in conjunction with techniques for the improvement of their selectivities. The development of simple models aimed at the prediction of the stereochemical outcome of a given reaction is still a challenge and will be the subject of future studies. A search for novel esterases to enrich the limited number of available enzymes and for lipases showing anti-Kazlauskas stereospecificities would be a worthwhile endeavor. 

The discovery, by Ziegler, et. si., (1, 2) of stereospecific polymerization, transformed isoprene into a monomer of great commercial importance. The continuing increase in world demand for synthe.tic poLy-isoprene has catalyzed the search for less costly isoprene processes. 

CAS has undertaken a multi-year effort to renovate the Registry System. As part of this effort, we are currently engaged in adding atom/bond specific stereodescriptors to the connection tables of stereospecific substances already on the Registry File. These extensions will, in turn, permit us to enhance structure display and substructure search to use accurately the stereochemical information available. 

The discovery of antiviral activity of oligo(nucleoside methane-phosphonate)s (44) and oligo(nucleotide phosphorothioate)s (45-47), so far chemically prepared by the nonstereocontrolled methods, attracted the attention of several research establishments to the search for stereospecific synthesis of those classes of oligonucleotide analogs. Since their routine synthesis via phosphoramidite or any other approach leads to the mixture of m diastereoisomers, the question may be asked whether desired antiviral activity is owing to all m components of diastereo-isomeric mixture or to the fraction possessing the proper sense of chirality at each modified phosphate. Moreover, since the seminal works of... 

The search for novel p-lactam antibiotics has been severely restricted by the relative inaccessibility of these ring systems by stereospecific total syntheses. Because of the availability of both the penicillin and, more recently, cephalosporin nuclei from fermentation processes, partial synthesis of new ring systems from these starting materials has been extensively investigated. The penicillin-cephalosporin interconversions continue to be studied while new degradative procedures have permitted the synthesis of useful snythons by complete removal of the thiazoline ring of penicillin. 

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