Aromatic quadrant rule

X-ray and CD analysis. The structure of procyanidin B-1 was unequivocally confirmed by x-ray analysis of its deca-(9-acetyl derivative by Weinges, one of the pioneers in the field of proanthocyanidin chemistry. One of the most powerful methods to establish the absolute configuration at C-4 of the T-unit in dimeric A- and B-type proanthocyanidins remains the chiroptical method via application of the aromatic quadrant rule. This has been repeatedly demonstrated by the author s own work and several other contributions listed in Refs. 7-12. 

DeAngelis, G.G. and Wildman, W.C., Circular dichroism studies. 1. A quadrant rule for the optically active aromatic chromophore in rigid polycyclic systems. Tetrahedron, 25, 5099, 1969. 

Subsequently, the application of a quadrant rule developed for compounds bearing an asymmetric center adjacent to the aromatic chromophore by means of considerations of the CD and ORD spectra of products of established absolute configuration to the alkaloids of the 5,10b-ethanophenanthridine series led to conclusions on their absolute stereochemistry at variance with those mentioned above 42). 

De Angelis, G.G., and W.C. Wildman Circular Dichroism Studies-1. A Quadrant Rule for the Optically Active Aromatic Chromophore in Rigid Polycyclic Systems. Tetrahedron, 25, 5099 (1968). 

Various strategies have been advocated in order to cover the physicochemical parameter space of a series of new compounds as well as possible. Familiar strategies go back to proposals by Topliss and Craig. Both are schemes used for substituent variation at a selected site. The Topliss substitution scheme can be used to optimize aromatic and aliphatic substituents using a fixed set of substituents and rules. A Craig plot is a 2D plot of selected descriptors, for example, Hammett electronic properties) and Hansch 7T values (lipophilicity). Substituents can be selected from each quadrant of this plot such that they vary widely in their properties, for example, lipophilic and hydrophilic, electron-donor and electron-acceptor, and to ensure the two properties are not correlated in the selected set which is preferable for the generation of stable QSAR models. 

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