Anti-malarial drug synthesised

DAVID LIVINGSTONE called quinine "the most constipating of drugs". But without this extract of the cinchona tree which puts the bitter bite in tonic water he would probably have succumbed to malaria much sooner than he did. Now chemists have finally made synthetic quinine after more than a century of trying, reopening its file as a potential source of new anti-malarial drugs.

Gilbert Stork and co-workers at Columbia University have made quinine from scratch a process called `total synthesis'. Amos Smith of the University of Pennsylvania, who also synthesizes complex natural molecules, calls the achievement "an absolute classic" according to a repot in the Journal of the American Chemical Society.The work has "tremendous historic value" Smith points out: attempts at making quinine stretch back to the mid- nineteenth century when it was the only known protection against malaria, but was expensive to extract from cinchona bark. In 1856 the 18-year-old William Perkin, a student at the Royal College of Chemistry in London, ended up making the mauve dye that launched the entire modern chemicals industry while attempting to make quinine in his home laboratory.

In 1944 U.S. chemists Robert Woodward and William Doering almost cracked it, but they could not control the shape of the molecule's carbon- atom framework precisely enough to synthesize quinine alone, instead making a blend of closely related variants of it.

This was because, at several places, quinine's molecular framework can have either a left-handed or right-handed arrangement of atoms: identical except for being mirror images. The difficulty of making the right combinations of these has dogged attempts at a total synthesis ever since. It is by plucking the fruits of earlier work, particularly that conducted at the Hoffmann-La Roche company in the 1970s, that Stork's team has at last made the quinine molecule in pure form.

Quinine does not by itself cure malaria, it simply interferes with the growth of the malaria parasite Plasmodium falciparum. So more effective antimalarial drugs such as chloroquine were developed in the 1940s. But by the 1960s, resistance to chloroquine had become widespread in P. falciparum, and some regions started to use quinine once more. Now even newer drugs, such as mefloquine, have become useless on their own in several areas, including Thailand. Most of Africa and Asia are afflicted with drug-resistant strains.

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