Atropine chemistry

Esters of tropine have a venerable place in medicinal chemistry. One such compound, cocaine, the object of some current interest, was the natural product lead which led eventually to most of today s local anesthetics. A distantly related analogue is prepared by reaction of tropine (132) with 3,5-dimethylbenzoyl chloride. This leads to an ester structurally related to another ]ii ominent natural product, atropine (133). The product, tropanaerin (134), is described as an iinti.serotonergic agent intended for antimigraine use [34]. 

WILLSTATER, RICHARD (1872-1942). A German chemist who won the Nobel prize for chemistry in 1915 or his work on plant pigments, especially clilorophyll. His education was at the University of Munich where he studied and taught before going to Zurich, Switzerland. He researched chlorophylls and pigments of plants and the relationship of cornflower blue to rose red. Work included the study of alkaloids including cocaine, tropine, and atropine. His work perfected the process of chromatographic partition. 

Scopolia spp. (Solanaceae) Atropine studied by Richard Willstatter (Nobel Prize, Chemistry, 1915, plant pigments chlorophyll fled Nazis, 1938)... 

The traditional method of drag development, at least in this century, has been to develop leads by first using, and then by isolating and identifying, the active chemical constituents from natural products, some of which may have been medicinally in use since antiquity. With the advent of modem organic chemistry some of these purified compounds were used directly (e.g., morphine, cocaine, atropine, quinine), and, once their chemical structures were ascertained, they became leads for hoped-for chemical modifications to achieve improved efficacy, less toxicity, or, at least, higher potency (e.g., dihydromorphinone, homatropine, acetylsalicylic acid). 

Further recent contributions to the analytical chemistry of the tropane alkaloids include the selective determination by g.l.c. of atropine/hyoscyamine and scopolamine in admixture with other amines e.g. phenylpropanolamine and chlorpheniramine) often used in drug mixtures, the separation and identification of tropane alkaloids by g.l.c. of their trimethylsilyl ethers, and the separation of alkaloid mixtures by high-speed, high-pressure liquid chromatography. ... 

In many instances a useful purpose is served by presenting the chemistry of the alkaloids according to their occurrence in various plant families, genera and species (254). However, it is the opinion of the author that a more direct route to a knowledge of the chemistry of the tropane alkaloids is through (1) the presentation of the chemistry of the alkaloids whose structure is known with certainty (e.g., atropine, i-cocaine, i-hyoscyamine All R groups in formula I will be considered to be hydrogen unless otherwise stated. 

Historical The term A. was introduced by the apothecary C. F. W. Meissner in 1819 for alkali-like plant substances. The development of A. chemistry is illustrated by some dates and names morphine (1803 or 1816 Sertiimer), strychnine (1818 Pelletier and Caven-tou), solanine (1820 Desfosses), caffeine (1820 Runge), quinine (1820 Pelletier and Caventou), nicotine (1828 Posselt and Reimann), atropine (1831 Mein), codeine (1832 Robiquet), theobromine (1842 Woskresensky), cocaine (1860 Wohler), ephedrine (1887 Nagai), scopolamine (1881 Ladenburg and 1888 E. Schmidt), mescaline (1896 Heffter). The first A. synthesis was realized in 1886 by Ladenburg (coniine). In the 20th century A. chemistry is especially associated with the names Willstatter, Woodward, Schopf,... 

Figure 6.6a. Diurnal changes in atropine content of Atropa belladonna (Fairbaim and Wassel, 1967). Courtesy of Journal of Chemistry of the United Arab Republic, Cairo.

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