Comparative Analysis of the Olfactory Properties of Silicon/Germanium/Tin Analogues of the Lily-of-the-Valley Odorants Lilial and Bourgeonal.

The silicon/germanium/tin analogues of the lily-of-the-valley odorants lilial (rac-1a), compounds rac-1b, rac-1c, and rac-1d, and bourgeonal (2a), compounds 2b, 2c, and 2d, were synthesized and characterized for their olfactory properties, including GC-olfactometry studies. Compounds rac-1a-c and 2a-c possess a typical lily-of-the-valley odor, whereas the stanna-analogues rac-1d and 2d, despite some floral aspects, clearly no longer belong to the lily-of-the-valley family. In both series of the carbon/silicon/germanium/tin analogues studied, the lily-of-the-valley odor decreases in the order of carbon<silicon< germanium<tin. A HEK293 cell line with stable tetracycline-regulated expression of hOR17-4 was generated to analyze recombinant hOR17-4 activation by rac-1a-d and 2a-d by using Ca²⁺ imaging. Bourgeonal (2a) showed the highest activation potency, whereas lilial (rac-1a) and sila-bourgeonal (2b) exhibited lower activation potencies. Sila-lilial (rac-1b), germa-lilial (rac-1c), and stanna-lilial (rac-1d), as well as germabourgeonal (2c) and stanna-bourgeonal (2d), did not activate heterologously expressed hOR17-4 at the concentrations tested. The carbon/silicon/germanium/tin switch strategy thus showed that the stanna-derivatives clearly exceeded the molecular dimensions of the odorant receptor(s) responsible for the recognition of lily-of-the-valley odorants, although the receptor affinity was already affected with the sila- and germaanalogues. These data could later be used in the qualitative and quantitative evaluation of computational receptor models. [ABSTRACT FROM AUTHOR]