Abstract
When Louis Pasteur observed para tartaric acid crystals under the microscope, he noted right- and left-handed tiny crystals, which when manually separated resulted in the same optical activity but of opposite sign. This seminal observation was correctly interpreted indicating that para tartaric acid was the mixture of two different molecules: a finding that was later recognised as an essential code of molecular pharmacology based on the 3D spatial configuration of molecules. An immediate application of this concept refers to natural products such as morphine or ephedrine, both of which have the precise stereochemistry to fit and selectively activate the μ-opiate receptor or α-adrenoceptor mechanisms, respectively, and their associated intracellular signalling mechanisms. In this essay, we review the past, present and future of stereochemistry notions and its significance for adrenergic pharmacology, highlighting the relevance of optical isomers of sympathomimetics or β-adrenoceptor antagonists. The principle of optical activity revealed by Pasteur challenges the pharmaceutical industry to identify biologically active chemicals identifying the relevant stereochemical isomer responsible for drug efficacy and safety. It is no overstatement that pain is alleviated worldwide by a single stereochemical morphine isomer, that is synthesised by the poppy plant, which interacts stereospecifically with the relevant opioid receptor(s) highlighting Pasteur’s brilliant discovery to the principles of molecular pharmacology.
Highlights
For centuries humans have used botanical extracts as a medical source
Notwithstanding the multiple contributions of Pasteur to modern medicine, this essay will focus on his influence on the understanding of the spatial architecture of living molecules and his decisive inspiration to the fundamentals of molecular pharmacology development
From crystals to the 3D spatial configuration, Pasteur investigated the optical activity of molecules, laying the foundations of stereochemistry and chirality
Summary
For centuries humans have used botanical extracts as a medical source. Only during the past century, with the consolidation of a vigorous pharmaceutical industry, the development of drugs by industrial synthesis prevailed over natural product discoveries. This unexplained observation set a paradox that attracted young Pasteur’s imagination He wanted to understand why two apparently identical compounds, tartaric and para tartaric acids, differed in optical activity. Pasteur used a microscope to observe the crystals of para tartaric and tartaric acid; he noted two different crystal morphologies [1,2,3] as reported previously by Mitscherlich He undertook the painstaking job of separating these crystals (Figure 1) and analysed the optical activity of each crystal type distinctly. This observation explained and accounted for the observation that para tartaric acid was optically inactive, resolving the inconsistency This result allowed to further infer that the optical activity of asymmetric molecules is due to their spatial atomic arrangements, as summarised by [11,12]. Principles of stereochemistry and its application to adrenergic pharmacology: the case of natural and synthetic drugs
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
