A concise and scalable synthesis of high enantiopurity (-)-D-erythro-Sphingosine using peptidyl thiol ester-boronic acid cross-coupling
A concise and scalable synthesis of high enantiopurity (-)-D-erythro-Sphingosine using peptidyl thiol ester-boronic acid cross-coupling
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DOI：
10.1021/ol070991m
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发表时间：
2007-08-02
期刊：
影响因子：
5.2
通讯作者：
Liebeskind, S.
中科院分区：
文献类型：
--
作者：
Lanny, Hao Yang;Liebeskind, S.
以N-叔丁氧羰基-L-丝氨酸为起始原料，经6步反应合成了高纯度的（-）-D-β-神经鞘氨醇，产率为71%。关键步骤是N-Boc-OTBS L-丝氨酸的噻吩酯与E-1-十五烯基硼酸的高产率、无外消旋化、钯催化、铜（I）介导的偶联，以及所得肽基酮与LiAl（O-t-Bu）H-3的高度非对映选择性还原。用此路线可以大规模制备高纯度（ee > 99%，de高达99%）的（-）-D-β-鞘氨醇。
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-OTBS L-serine with E-1-pentadecenyl boronic acid and the highly diastereoselective reduction of the resulting peptidyl ketone with LiAl(O-t-Bu) H-3. 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%).