A Scalable Synthesis of the C14-C23 Fragment of Eribulin

Eribulin，也被称为Halaven，是一种抗癌药物，已被批准用于治疗预先治疗的转移性乳腺癌和不可手术的脂肪肉瘤。虽然它本身不是一种天然产品，但它是天然产品软海绵素的合成类似物，软海绵素最初是从海绵中分离出来的。由于艾里布林的结构极其复杂，其商业化生产是所有获批药物中最具挑战性的之一。因此，人们真正感兴趣的是确定对伊曲布林合成的改进，这些改进最终将影响药物生产的财务和环境成本。为了实现这一目标，西蒙弗雷泽大学的布里顿研究小组花了几年时间开发新的化学反应，使四氢呋喃的快速可靠合成成为可能。四氢呋喃是一种小分子，在复杂的分子结构中也发现了四氢呋喃。Eurofins-Alphora是一家位于多伦多郊外的合同研究机构，它独立地花了几年时间开发了一种制造eribulin的路线。拟议中的产学研伙伴关系将利用这些独特的一致利益。具体来说，这次合作将使布里顿研究小组在四氢呋喃合成方面的独特专业知识与Eurofins-Alphora的生产能力相结合，以支持和改进埃瑞布林的大规模合成和商业生产。除了影响艾里布林生产的各种成本外，这一专注于最复杂的全合成上市药物的加拿大学术-工业伙伴关系是复杂分子合成创新和领导的一个很好的例子，并将展示加拿大在这一领域的领导作用。

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.