A Scalable Synthesis of the C14-C23 Fragment of Eribulin

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Eribulin, also known as Halaven, is an anticancer drug that has been approved for use in treating pretreated metastatic breast cancer and inoperable liposarcoma. While not itself a natural product, eribulin is a synthetic analogue of the natural product halichondrin, which was originally isolated from a marine sponge. Due to the incredible complexity of the structure of eribulin, its commercial production is one of the most challenging of any approved drug. As a result, there is real interest in identifying improvements to the eribulin synthesis that would ultimately impact the financial and environmental costs of drug production. Towards this goal, the Britton research group at Simon Fraser University has spent several years developing new chemical reactions that enable the rapid and reliable synthesis of tetrahydrofurans, which are small molecules also found in the complicated molecular structure of eribulin. Eurofins-Alphora, a contract research organization located outside of Toronto, has independently spent several years developing a manufacturing route for eribulin. The proposed industry-academic partnership will take advantage of these uniquely aligned interests. Specifically, this collaboration will partner the Britton research groups unique expertise in tetrahydrofuran synthesis with the production capabilities at Eurofins-Alphora to support and improve the large-scale synthesis and commercial production of eribulin. In addition to impacting the various costs of eribulin production, this Canadian academic-industry partnership which is focused on the most complex fully synthetic marketed drug, is an excellent example of innovation and leadership in complex molecule synthesis and will showcase Canada's leading role in this area.