Tropane alkaloids as medicinally useful natural products and their synthetic derivatives as new drugs.

Secondary metabolites of Solanaceae plants, sharing tropane skeleton as a common structural feature, are sharply divided into two classes: tropine and ecgonine derivatives. The first group, represented by well known alkaloids: atropine and scopolamine, which are considered to be model anticholinergic drugs, continues to provide inspiration in the search for more selective muscarinic receptor antagonists. The second class accommodates one of the principal drugs of abuse, cocaine. Synthesis of much needed cocaine antagonists, despite extensive research, has not been particularly successful. Therefore, new concepts of cocaine abuse treatment resort to immunotherapy and biotechnology. Contemporary pharmaceutical industry manufactures over 20 active pharmaceutical substances containing tropane moiety in their structure, which are applied as mydriatics, antiemetics, antispasmodics, anesthetics and bronchodilators. There are two sources of raw materials for this industrial activity: natural products isolated from cultivated transgenic plants (mainly scopolamine and atropine from Australian Duboisia) and chemical synthesis based on common intermediate: tropinone, which can be further transformed by synthetic means to the following classes of compounds: tropine and its esters (tropeines), scopine and nortropine derivatives, and tropane quaternary ammonium salts. This survey focuses on new developments in chemistry and pharmacology of tropane derivatives, particularly in view of their prospective industrial applications as therapeutics.

Chemotaxonomy of the pantropical genus Merremia (Convolvulaceae) based on the distribution of tropane alkaloids.

The occurrence and distribution of tropane and biogenetically related pyrrolidine alkaloids in 18 Merremia species of paleo-, neo-, and pantropical occurrence have been studied. The extensive GC-MS study included members of almost all sections of the genus and has been carried out with epigeal vegetative parts as well as with roots. It comprises altogether 74 tropanes and 13 pyrrolidines including nicotine. Along with datumetine known already from a solanaceous species, the study led to the isolation (from M. dissecta and M. guerichii, respectively) and structure elucidation (spectral data) of four novel 3alpha-acyloxytropanes, merresectines A-D: 3alpha-(4-methoxybenzoyloxy)nortropane (A), 3alpha-kurameroyloxytropane (B), 3alpha-nervogenoyloxytropane (C), 3alpha-[4-(beta-D-glucopyranosyloxy)-3-methoxy-5-(3-methyl-2-butenyl)benzoyloxy]tropane (beta-d-glucoside of D). Moreover, the novel 3alpha,6beta-di-(4-methoxybenzoyloxy)tropane (merredissine) has been isolated from M. dissecta and structurally elucidated. In addition the structures of datumetine and merresectine A could be confirmed by synthesis. Spectral data for two known 3alpha-acyloxytropanes (merresectine E beta-D-glucoside, 4'-dihydroconsabatine) and one known 3beta-acyloxytropane (concneorine) are documented for the first time. The structures of three further merresectines (F-H) have been determined by mass spectrometry. Furthermore, the linkage (2',3- and 2',4-, respectively) of two position isomer N-methylpyrrolidinylhygrines was proven by synthesis. The results of the study contribute to the solution of infrageneric taxonomic problems. Whereas all species yield pyrrolidine alkaloids without suitably differentiating results the diverging occurrence of tropane alkaloids leads to three groups of sections: (1) taxa free of tropanes, (2) taxa with simple tropanes, and (3) taxa with merresectines in addition to simple tropanes.