New lead for pain treatment: the synthesis of conolidine, a scarce, naturally occurring compound, has enabled the first studies of its pharmacological properties to be carried out. Excitingly, conolidine is a painkiller that seems to have an unusual mechanism of action

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Date: May 26, 2011
From: Nature(Vol. 473, Issue 7348)
Publisher: Nature Publishing Group
Document Type: Article
Length: 875 words
Lexile Measure: 1410L

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Some of the most powerful painkillers, such as morphine, hydrocodone and oxycodone, belong to the opioid family of analgesics. Unfortunately, prolonged exposure to these analgesics can cause several adverse side effects, including physical and psychological addiction. As a result, there is a continued effort to identify painkillers that have different biological mechanisms from opioids and that elicit fewer side effects. With this in mind, a team of chemists, led by Glenn Micalizio, has joined forces with a group of neuroscientists, headed by Laura Bohn, to synthesize and study the analgesic properties of a rare, naturally occurring compound called conolidine. Their promising findings, reported in Nature Chemistry (Tarselli et at. (1)), might pave the way for the development of new non-opioid analgesics.

The natural product conolidine was originally isolated (2) in extremely small quantities--just 0.00014% yield--from the stem bark of the flowering tropical plant Tabernaemontana divaricata. The low natural abundance of the compound has hindered the study of its potential therapeutic properties. By completing the first total chemical synthesis of conolidine, Micalizio and co-workers provided Bohn's team with enough synthetic material to carry out the first in vivo studies of its analgesic properties.

A key challenge in the synthesis of conolidine is the construction of its bicyclic ring system (Fig. 1a), which consists of an eight-membered ring bridged by...

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Gale Document Number: GALE|A258357042