三萜角鲨烯的乳液((6E,10E,14E,18E)-2,6,10,15,19,23-六甲基四萨-2,6,10,14,18,22-己烯,CAS111-02-4)自1990年代以来已被用作流感疫苗的佐剂。传统上来自鲨鱼肝油,鲨鱼的过度捕捞和随之而来的大洋鲨种群减少引发了疫苗佐剂级角鲨烯的可持续性问题。我们报告了一种半合成的角鲨烯路线,符合当前用于疫苗的药典规范,该路线利用了反式-β-法尼烯((6E)-7,11-二甲基-3-亚甲基-1,6,10-十二碳三烯的现成可用性,CAS18794-84-8),通过酵母发酵过程从可持续的甘蔗制造。通过千克规模的GMP合成验证了所提出的路线的可扩展性。我们还报告了证明合成的半合成角鲨烯用于疫苗佐剂制剂时的物理稳定性和生物活性的数据。
Emulsions of the triterpene squalene ((6E,10E,14E,18E)-2,6,10,15,19,23-hexamethyltetracosa-2,6,10,14,18,22-hexaene, CAS 111-02-4) have been used as adjuvants in influenza vaccines since the 1990s. Traditionally sourced from shark liver oil, the overfishing of sharks and concomitant reduction in the oceanic shark population raises sustainability issues for vaccine adjuvant grade squalene. We report a semisynthetic route to squalene meeting current pharmacopeial specifications for use in vaccines that leverages the ready availability of trans-β-farnesene ((6E)-7,11-dimethyl-3-methylene-1,6,10-dodecatriene, CAS 18794-84-8), manufactured from sustainable sugarcane via a yeast fermentation process. The scalability of the proposed route was verified by a kilo-scale GMP synthesis. We also report data demonstrating the synthesized semi-synthetic squalene\'s physical stability and biological activity when used in a vaccine adjuvant formulation.