Tropane Alkaloids: Chemistry, Pharmacology, Biosynthesis and Production

Abstract

Tropane alkaloids (TA) are valuable secondary plant metabolites which are mostly found in high concentrations in the Solanaceae and Erythroxylaceae families. The TAs, which are characterized by their unique bicyclic tropane ring system, can be divided into three major groups: hyoscyamine and scopolamine, cocaine and calystegines. Although all TAs have the same basic structure, they differ immensely in their biological, chemical and pharmacological properties. Scopolamine, also known as hyoscine, has the largest legitimate market as a pharmacological agent due to its treatment of nausea, vomiting, motion sickness, as well as smooth muscle spasms while cocaine is the 2nd most frequently consumed illicit drug globally. This review provides a comprehensive overview of TAs, highlighting their structural diversity, use in pharmaceutical therapy from both historical and modern perspectives, natural biosynthesis in planta and emerging production possibilities using tissue culture and microbial biosynthesis of these compounds.

Synthesis of Dicarbonyl Curcumin Analogues Containing the Tropane Scaffold

“…Tropane alkaloids usually have considerable water solubility, oral bioavailability and some of them (including scopolamine and cocaine) are able to penetrate the blood brain barrier ,…”

“…Tropane derivatives can be synthesized by a variety of approaches including stereoselective C‐C forming reactions such as acylation of tropinone enolate or alkylation of tropinone azaenolate . However, to this date no synthesis of tropane containing diarylheptanoids was published , , . The only described curcumin analogues containing tropane ring are limited to monocarbonyl derivatives and as such are lacking a salient feature of curcuminoids.…”

“…[10] Moreover, fusing the diarylheptanoid characteristic of curcumin with a structure representative of a group of natural products such as tropanes, [14] many of which possess biological activities, [15] could give interesting results. Therefore we aimed at merging diarylheptanoids with tropane core which is present in biologically active compounds like cocaine (an inhibitor of reuptake of dopamine, noradrenaline and serotonin) [16] or scopolamine (competitive muscarinic receptor antagonist) [17] (Figure 2). Tropane alkaloids usually have considerable water solubility, oral bioavailability and some of them (including scopolamine and cocaine) are able to penetrate the blood brain barrier.…”

“…Tropane alkaloids usually have considerable water solubility, oral bioavailability and some of them (including scopolamine and cocaine) are able to penetrate the blood brain barrier. [16,18] Tropane derivatives can be synthesized by a variety of approaches [19] including stereoselective C-C forming reactions [20] such as acylation of tropinone enolate [21] or alkylation of tropinone azaenolate. [22] However, to this date no synthesis of tropane containing diarylheptanoids was published.…”

“…[22] However, to this date no synthesis of tropane containing diarylheptanoids was published. [16,19,20] The only described curcumin analogues containing tropane ring are limited to monocarbonyl derivatives and as such are lacking a salient feature of curcuminoids. [9b,23] The synthetic route to these analogues was based on aldol condensation of tropinone 1 with aromatic aldehydes (Scheme 1).…”