Scopolamine chemistry

The combinatorial decoration or derivatization of existing natural products is a popular method for library creation. Among targets for such exercises are the alkaloids yohimbine and scopolamine, terpenoids and steroids, and the heterocyclic peptide antibiotic GE-2270A (Figure 11). In the latter case, combinatorial variation was instrumental in the discovery of a developmental candidate now in clinical trials at Vicuron. Pfizer, the world s largest pharmaceutical company, recently acquired Vicuron for the sum of 1.9 billion, a mark of approval for natural product-based combinatorial chemistry. 

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. ... 

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,... 

Hashimoto T, Yamada Y (1983) Scopolamine production in suspension cultures and redifferentiated roots of Hyoscyamus niger. Planta Med 47 195-199 Hashimoto Y, Kawanishi K, Moriyasu M (1988) Forensic chemistry of alkaloids by chromatographic analysis, vol 32, chapter 1. In Brossi A (ed) The Alkaloids. Academic Press, New York... 

FIGURE 2.9 Three examples of combinatorial chemistry involving scaffold decoration of readily available natural products — yohimbine, scopolamine, and sorangicin (readily available to those who isolated it ). 

R. Whelpton and P.R. Hurst, HPLC-EC analysis of hyoscine (scopolamine) in urine, in Analysis of Drugs and Metabolites, Including Anti-infective Agents, R. Reid and I.D. Wilson, (eds) Royal Society of Chemistry, Cambridge, 1990, 279-284. 

Fig. 13.6. DESI mass spectrum of Atropa belladonna seeds using methanol water =1 1 as spray solvent. The insets show tandem mass spectra of the protonated alkaloids hyoscamine, m/z 290 and scopolamine, m/z 304. Both protonated alkaloids have the characteristic loss of tropic acid, 166 u, in common. Reprinted from Ref. [13] with permission. The Royal Society of Chemistry, 2005.

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