The Discovery of Stereoselectivity at Biological Receptors: Arnaldo Piutti and the Taste of the Asparagine Enantiomers—History and Analysis on the 125th Anniversary

Abstract

In 1886, Italian chemist Arnaldo Piutti isolated, for the first time, d-asparagine, the enantiomer of the known l-asparagine. He obtained 100 g of D-asparagine from 6500 kg of vetches. Using an ingenious synthetic scheme, Piutti established the chemical structure of asparagine and demonstrated that his isolation of D-asparagine from plants was not the result of the racemization of L-asparagine during the extraction procedure. He found a striking difference in the taste of asparagine: L-asparagine was without taste, while D-asparagine was intensely sweet. This was the first example of enantioselectivity in a receptor-mediated biological activity. Receptors constitute one of the most important and most intensively studied phenomena in biology, and enantioselectivity in receptor-mediated activity, including at the sweetness receptor, is today an important and commonly seen aspect of receptor function. Therefore, Piutti's discovery, although made ca. 15 years before the emergence of the receptor concept, was a milestone. The publication of Piutti's asparagine work prompted several eminent scientists, including Louis Pasteur and Arthur Cushny, a leading pharmacologist of the time, to remark on the importance of the discovery. Piutti also carried out investigations in many other fields, e.g., other organic compounds and reactions, pharmaceuticals, alimentary products, radioactivity, noble gases, and spectroscopy. Considerable progress has been made in recent decades concerning the biology and chemistry of sweet taste, but the details of the interactions of chiral molecules with the sweetness receptor remain poorly understood. Piutti and his discovery are largely forgotten today; they deserve the attention of the chirality and receptor "communities."

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Assessment and application of Marfey’s reagent and analogs in enantioseparation: a decade’s perspective

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