Congener approach

APPLICATION OF THE CONGENER APPROACH TO THE DESIGN AND SYNTHESIS OF PEPTIDE-CATECHOLAMINE CONJUGATES... 

Scheme 1. Schematic Representation of the Congener Approach for Drug Conjugate Design.

Bromoamides are interesting and versatile intermediates for substitution of bromine by a variety of nucleophiles and for other synthetic approaches. Whereas emphasis is given to chiral 2-bromoamides, congeners carrying a tertiary or primary C-Br function have also been investigated. 

Rice, K.C. (1980) Synthetic Opium Alkaloids and Derivatives. A Short Total Synthesis of (ib)-Dihydrothebainone, ( )-Dihydrocodeinone, and ( )-Nordihydrocodemone as an Approach to a Practical Synthesis of Morphine, Codeine, and Congeners. Journal of Organic Chemistry, 45, 3135-3137. 

Both approaches are useful and they are also complementary because it is important to know where a chemical that may be best in its class falls out with respect to hazard. For example, a surfactant that is best in its class will be rapidly biodegradable, but most surfactants have some aquatic toxicity because they are surface active. However, surfactants as a class are typically close to the green end of the hazard spectrum because they tend to have low hazard ratings for most other endpoints. It is also possible to have chemicals that are best in their class but that are still problematic. For example, some dioxin congeners are less toxic than others but one would not presume that a dioxin congener that is best in its class is green . Concurrent use of the best in class approach with the absence of hazard approach is also important because it drives continual advancement within a class toward the ideal green chemistry. Once innovation occurs and a chemical or product is developed that meets the same or better performance criteria with lower hazard, what was once considered best in class shifts. 

Jones, K.C. 1988. Determination of polychlorinated biphenyls in human foodstuffs and tissues suggestions for a selective congener analytical approach. Sci. Total Environ. 68 141-159. 

DeWeerd and Bedard [253] investigated novel approaches for enhancing microbial PCB dechlorination in aquatic sediments of the Housatonic River. They reported that PCB dechlorinating microorganisms were activated (i.e., primed) to dechlorinate the PCBs that have persisted for years in these sediments. Several PCB congeners, especially 2,3,4,5,6-pentachlorobiphenyl (23456-CB), 2,3,4,6-tetrachlorobiphenyl (2346-CB), and 2,3,6-trichloro-biphenyl (236-CB), were shown to prime and sustain mefa-dechlorination of Aroclor 1260 in the river sediment, whereas the PCB congener 245-CB primed para-dechlorination of PCBs in the same sediments. 

The information contained in karma s knowledge bases is based upon quantitative structure-activity relationships (QSAR), kinetic data, and structural chemistry. The combination of QSAR and kinetic data allows for the study of enzyme-ligand interactions. The Hansch approach to QSAR, based on a set of congeners, states ... 

A more promising approach to a synthesis of vinblastine-type compounds can be derived from the significant observation that reaction of one enantiomer of the carboline ester (-l- )-38 with p-nitrobenzyl chloro-formate and 3-methoxy-A/, A-dimethylaniline, at 25°C, gave a model (-t-)-congener of 39 in 72% yield and 55% enantiomeric excess, thus indicating a conformational retention in the nine-membered cationic intermediate formed on acylation of the carboline ester 38 (37b). 

Searches through more than one data base in combination would be very desirable. For example, one often possesses mass spectral and nmr data for an unknown and it would be very useful to be able to identify any compounds that match these data in a single search. Work is going on in this area do interface programs so that this approach can be tested. In another development, it is expiected that the CONGEN programs developed for the DENDRAL project [30] will be merged into CIS within the... 

The enantiomers of the naturally occurring lignans, schizandrin (5) and isoschizandrin (6), have been prepared from oxazoline 10 in 11 steps with 0.7% and 5.5% overall yield, respectively. Although both natural products are accessible by this strategy, the reported synthetic approach is basically a route to isoschizandrin (6). Schizandrin (5) was obtained only as minor congener and a selective synthesis of 5 has not been accomplished by the authors. 

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