Isomeric surprise

An unexpected route for producing specific isomers of stilbenes has been found by UK scientists.

Richard Taylor’s group from the University of York has modified the Ramberg-B?cklund reaction, where SO₂ is eliminated from a sulfone to give an alkene. This leads to the formation of both cis- and trans-isomers where previously the trans-isomer would predominate.

Stilbenes are found extensively in nature and as synthetic biologically-active compounds. They are widely used in drugs, particularly in cancer and HIV treatments. The active isomer in these drugs, such as the anti-tumour agent combretastatin, is the cis-form, also known as the Z-form.

Taylor’s group was working on the synthesis of an anti-HIV drug when it made a remarkable discovery. The researchers found that a particular sulfone underwent the Ramberg-B?cklund reaction to give the cis- and trans-isomers of the stilbene in a 1:1 ratio.

Previously, experiments had yielded the trans-isomer exclusively; an isomerisation reaction occurred during the process to give the single product. In addition, the reaction conditions tended to promote the creation of solely the trans-form.

The group believes that this Z-stereoselectivity arises from a base-promoted intramolecular SO₂ elimination before isomerisation, ensuring the cis-conformation is retained. Using the cis-intermediate, new analogues of anti-HIV natural products have been made.

Taylor says, ’we next hope to apply this new method to the preparation of analogues of the anti-cancer drugs’.

Sophia Anderton