Sila-procyclidine

Sila-procyclidine, (cyclohexyl)phenyl[2-pyrrolidin-l-yl]silanol, may be prepared by hydrolysis of the corresponding methoxysilane (220) and is interesting in that it can form two types of hydrogen-bonded structure depending on whether it is enantiomerically pure or a racemate. In the racemate, the compound forms centrosymmetric dimers of (R)- and (S)-configuration molecules with an 0---N distance of 1.791 A. In the pure (R)-compound, however, the molecules are linked into infinite chains via intermolecular 0-H---N hydrogen bonds (0---N distance 2.792 A) (221), again similar to those in (2-morpholinoethyl)diphenylsilanol shown in Fig. 3. 

Sila-biperidin rac-(SiRS, C2 SR), 35, can be prepared by hydrolysis of the corresponding methoxysilane and behaves in a similar way to sila-procyclidine The exo form has centrosymmetric dimers formed via a pair of intermolecular OH---N hydrogen bonds (0---N distance 2.810 A), while the endo form has intermolecular OH---N hydrogen bonds linking the molecules into infinite chains (222). 

As can be seen from Figure 2, the (/ )-enantiomers (eutomers) of the silanols 3 and 7 show a significantly higher affinity for muscarinic M2 and M3 receptors than the corresponding (S)-antipodes (distomers). To the best of our knowledge, this is the first example of a biological discrimination between enantiomeric silicon compounds, with the silicon atom as the center of chirality. The stereoselectivity indices SI [SI = Kn S)/Kd(R) for sila-procyclidine (3) are 1.8 (M2) and 4.1 (M3), respectively. For sila-tricyclamol iodide... 

In contrast to the enantiomers of the carbinols, e g. HHD or THP, the enantiomers of si-lanols, e.g. sila-procyclidin, racemize quickly in aqueous solution [40] and are therefore unsuitable for the pharmacological investigation of enantioselectivity. 

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