Improved Synthesis of the C16鈥揅20 Segment of Resolvin E1 Using Enantioselective Ketone Reduction and Lipase-Catalyzed Resolution
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- 作者：Rasidul Amin ; Jian-Xie Chen ; Ian C. Cotterill ; Daniel Emrich ; Daniel Ganley ; Yuri L. Khmelnitsky ; Mark D. McLaws ; Peter C. Michels ; C. Eric Schwartz ; Deb Thomas ; Jun Yan ; Qiang Yang
- 刊名：Organic Process Research & Development
- 出版年：2013
- 出版时间：June 21, 2013
- 年：2013
- 卷：17
- 期：6
- 页码：915-920
- 全文大小：245K
- 年卷期：v.17,no.6(June 21, 2013)
- ISSN：1520-586X
文摘
A practical synthesis targeting the C16鈥揅20 segment of the endogenous metabolite Resolvin E1 (RvE1) is described. The original route was revised to avoid the use of source-constrained raw materials and chemistries that were problematic on larger scale. The revised route utilizes commercially available (E)-1-chloropent-1-en-3-one as the key raw material to replace (S)-glycidol. The (E)-vinyl iodide functionality was installed by an addition/elimination sequence to prepare the segment required for a subsequent Sonogashira coupling. The chiral secondary hydroxyl group at C18 was established by Corey鈥揃akshi鈥揝hibata (CBS) reduction followed by lipase-catalyzed acetylation to achieve chiral purity in excess of 98% ee. The revised route offered a viable multikilogram process to support early clinical production of this pro-resolution therapeutic agent.