Yang Hao, Liebeskind Lanny S
Department of Chemistry, Emory University, 1515 Dickey Drive, Atlanta, Georgia 30322, USA.
Org Lett. 2007 Aug 2;9(16):2993-5. doi: 10.1021/ol070991m. Epub 2007 Jul 4.
A short and efficient synthesis of high enantiopurity (-)-D-erythro-sphingosine has been achieved in 71% yield over 6 steps from N-Boc-L-serine. The key steps are high yield, racemization-free, palladium-catalyzed, copper(I)-mediated coupling of the thiophenyl ester of N-Boc-O-TBS L-serine with E-1-pentadecenyl boronic acid and the highly diastereoselective reduction of the resulting peptidyl ketone with LiAl(O-t-Bu)3H. By using this concise route (-)-D-erythro-sphingosine can be prepared on large scale and in high enantio- and diastereopurity (ee >99%, de up to 99%).
以N - Boc - L - 丝氨酸为原料，经6步反应，以71%的产率实现了高对映体纯度的(-)-D - 赤藓糖神经鞘氨醇的短程高效合成。关键步骤包括：N - Boc - O - TBS L - 丝氨酸的硫代苯酯与E - 1 - 十五碳烯基硼酸的高产率、无消旋化、钯催化、铜(I)介导的偶联反应，以及用LiAl(O - t - Bu)3H对所得肽基酮进行高度非对映选择性还原。通过这条简洁的路线，可以大规模制备高对映体和非对映体纯度的(-)-D - 赤藓糖神经鞘氨醇（对映体过量>99%，非对映体过量高达99%）。
