School of Pharmacy, Department of Pharmaceutical Chemistry, University of Oslo, PO Box 1068 Blindern, N-0316 Oslo, Norway.
Org Biomol Chem. 2014 Jan 21;12(3):432-7. doi: 10.1039/c3ob41902a. Epub 2013 Nov 19.
A convergent stereoselective synthesis of the potent anti-inflammatory, proresolving and neuroprotective lipid mediator protectin D1 (2) has been achieved in 15% yield over eight steps. The key features were a stereocontrolled Evans-aldol reaction with Nagao's chiral auxiliary and a highly selective Lindlar reduction of internal alkyne 23, allowing the sensitive conjugated E,E,Z-triene to be introduced late in the preparation of 2. The UV and LC/MS-MS data of synthetic protectin D1 (2) matched those obtained from endogenously produced material.
已实现具有强大抗炎、促修复和神经保护作用的脂类介质保护素 D1（2）的收敛性立体选择性合成，总产率为 15%，历经 8 步反应。关键特征在于采用 Nagao 手性辅基的立体控制 Evans-aldol 反应，以及内部炔烃 23 的高选择性 Lindlar 还原，从而可以在 2 的制备后期引入敏感的共轭 E,E,Z-三烯。合成保护素 D1（2）的紫外和 LC/MS-MS 数据与内源性产生的物质一致。
