Bioactivity relationships

VAILETAL. Strigol Syntheses and Structure-Bioactivity Relationship... 

The next challenge after the completion of the synthesis of racemic JHs was the synthesis of pure enantiomers of JHs to compare the bioactivities of natural and unnatural enantiomers of JHs. In the 1970s several groups reported the syntheses of optically active JHs. Although none of the attempts in this period could provide pure enantiomers of JHs, I summarize here the stereochemistry-bioactivity relationships reported in the 1970s and the early 1980s. 

It was clear in 1973 that the stereochemistry-bioactivity relationships among pheromones would be elucidated only after successful synthesis of both the pure enantiomers of pheromones. If a synthetic... 

Chiral pheromones whose stereochemistry-bioactivity relationships are diverse and complicated... 

The relationships between stereochemistry and bioactivity among pheromones are diverse and far from straightforward. Organisms utilize chirality to enrich and diversify their communication systems.8,9 It must be emphasized that such diversity could be found only through experiments by using pure pheromone enantiomers of synthetic origin. In this section, several examples will be given to illustrate the diverse stereochemistry-bioactivity relationships. 

In the case of ipsdienol (112), the stereochemistry-bioactivity relationship is much more complicated and interesting. My first synthesis of (/ )-(—)-ipsdienol (112 ) in 1976 from (fC j-glyccraldchyde allowed the assignment of S-configuration to (+)-ipsdienol isolated by Silverstein.115 Our second synthesis to provide both the enantiomers of ipsdienol employed the enantiomers of malic acid as starting materials.113 That synthesis, however, was lengthy and yielded the final products of 90% ee due to the partial racemization in the course of the synthesis. 

We became interested in synthesizing both the enantiomers of sporogen-AO 1 so as to clarify the stereochemistry-bioactivity relationship and also to provide a sufficient amount of material for its evaluation as a bioregulator useful in fermentation industry. To secure both enantiomers, we adopted the... 

Although ( )-138 had been synthesized in 1983 by I. Fleming et al. in the UK, the absolute configuration of the naturally occurring (+)-138 was unknown in 1985. We therefore started our work to synthesize both the enantiomers of trichostatin A so as to establish the absolute configuration of (+)-138 and also to clarity the stereochemistry-bioactivity relationship. 

Bioisosteric interchanges, of course, are not limited to univalent functions. In fact, divalent atoms and groups add the additional factor of steric similarity to the equation since the bond angles between the valencies are very similar. The angles for/CH2 (l 11.5°),/NHv(l 11°) /S (l 12°), and/Q(108°) illustrate this point. When a deviation of 3 degrees, depending on the full structural features of the compound, are taken into consideration, it becomes apparent how identical these features can be. A rather convincing example is seen when the bioactivity relationship between the isosteric ester and amide moieties is examined (Fig. 1-4). 

Although several hundred alkaloids have been isolated from Strychnos species, little work has been devoted to the evaluation of their biological activities. For the last five years, the biological results, in which preliminary structure-activity relationships can be drawn, include anticancer, antiprotozoal and chemosensitizing activities. They are reviewed here with focus on structure-bioactivity relationships whenever possible. 

Isolation and characterization of magnesium and calcium complexes (538) H and C NMR, structural investigations, structure-bioactivity relationship (559)... 

Of course when someone finds a successful molecule, the structural variation in order to establish structure-bioactivity relationship (SAR) is inevitable. In the course of that investigations we found some interesting relations in addition to SAR, between structure and chemical reactivity as well. 

A.R. El-Ghannam, Advanced bioceramic composite for bone tissue engineering design principles and structure-bioactivity relationship, J. Biomed. Mater. Res. A 69 (2004) 490-501. 

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