SELECTIVE SEMIREDUCTION OF ALKYNES AS PART OF AN ENVISAGED CONTINUOUS FLOW SYNTHESIS OF COMBRETASTATIN A-4

Combretastatin A-4 (1) is a natural product isolated from the South African bushwillow tree Combretum caffrum. It is endowed with a powerful inhibitory activity on microtubule formation as well as a related antiangiogenic activity. [1-2] As such, 1 has a strong potential in the anticancer therapy, prompting the development of new derivatives. [3-6] We have turned our attention to the design of a synthetic procedure for 1 performed entirely in
flow, which should enable continuous and rapid production of this useful compound and its derivatives in significant quantities.
Presented in this poster is a crucial step in this synthetic strategy - a selective semi-reduction of the triple bond of an alkyne precursor to the Z-double bond in the final product. The Lindlar-type hydrogenation in flow has been described only scarcely and for products typically more stable than Z-stilbenes. [7] We therefore set out to explore this technique and decided to expand it to a wider range of structurally various alkynes.