紫草素与阿卡宁的不对称全合成

Asymmetric synthesis of shikonin and alkannin

目的采用不对称氢化还原的方法实现紫草素和阿卡宁的全合成。方法以1,4,5,8-四甲氧基-2-萘甲醛为原料,通过与异戊烯溴化锌进行Reformatsky反应、Dess-Martin氧化和手性二异蒎烯基硼烷氯化物的不对称还原,得到光学纯的四甲氧基紫草素或四甲氧基阿卡宁,最后经侧链羟基乙酰化-硝酸铈铵氧化、羰基还原乙酰化-硝酸铈铵氧化和水解后,得到对映体过量分别为96%e.e.的紫草素和95%e.e.的阿卡宁。结果与结论以41.9%的总收率合成了具有光学活性的紫草素与阿卡宁,该合成路线步骤少、收率高,反应条件温和、操作简便。

Objective To invent a convient route for total synthesis of shikonin and alkannin in excellent en- antiomeric excess and high yield. Methods The key intermediate （ R ） or （S） -4-methyL- 1- （ 1,4,5,8-tetra- methoxynaphthalen- 2-yl） pent-3-en-1 -ol （4） was synthesized from 1,4,5,8-tetramethoxy-2-naphthaldehyde via Reformatsky reaction, Dess-Martin oxidization and asymmetric hydrogenation by chiral chlorodiisopinoc- ampheylborane （DIP-Cl）. After compound 4 was in hand, shikonin and alkanin can be obtained respectively by three chemical redections, including acetylation-oxidation, reduction-acetylation and oxidation-hydrolysis. Results and Conclusions Structures of the target compounds and other intermediates are confirmed by 1H-NMR. The total yield reaches 41.6% with excellent enantiomeric excesses （96% e. e. for shikonin and 95 % e. e. for alkannin）.