Structural functions of the sweet pharmacophore.

The relative sweetness, onset times, and durations of response of D-glucose, D-xylose, D-quinovose, D-galactose, L-arabinose, and D-fucose were determined at four temperatures. The results can be interpreted by simple concepts of intramolecular hydrogen bonding which indicate that the so-called gamma-function of the tripartite AH,B, gamma sweet pharmacophore plays little or no part in sugar sweetness. Probably the Lemieux effect (intramolecular hydrogen bonding between the hydroxymethyl substituent and the 4-hydroxy group) is of overriding importance in determining sugar sweetness, and the separate features of intensity and time of response indicate distinct functions of chemoreception. The absence of a gamma-function in simple hydrophilic molecules such as glucose has already been emphasized. This function distinguishes them from the artificial sweetners such as saccharin, which may be 500 times or more sweeter than sucrose, depending on their stereostructure and lipophilicity.