Synthesis of (R)-Boc-2-methylproline via a Memory of Chirality Cyclization. Application to the Synthesis of Veliparib, a Poly(ADP-ribose) Polymerase Inhibitor
Synthesis of (R)-Boc-2-methylproline via a Memory of Chirality Cyclization. Application to the Synthesis of Veliparib, a Poly(ADP-ribose) Polymerase Inhibitor
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DOI：
10.1021/acs.joc.8b02866
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发表时间：
2019-04-19
影响因子：
3.6
通讯作者：
Schellinger, Adam
中科院分区：
文献类型：
--
作者：
Kolaczkowski, Lawrence;Barkalow, Jufang;Schellinger, Adam
以丙氨酸苄酯盐酸盐11为原料，在良好的立体化学控制下，以较高的产率合成了(R)-Boc-2-甲基脯氨酸(3a)。该方法是对Kawabata所述方法的改进，分四步进行，不需要层析。然后将产物(R)-Boc-2-甲基脯氨酸(3a)分三步进行生产，得到一种聚(ADP-核糖)聚合酶抑制剂veliparib1。
(R)-Boc-2-methylproline (3a) was synthesized in good yield with excellent stereochemical control from alanine benzyl ester hydrochloride 11. The process, which is based on a modification of one described by Kawabata, proceeds in four steps and requires no chromatography. The product (R)-Boc-2-methylproline (3a) was then carried forward in three steps to produce veliparib 1, a poly(ADP-ribose) polymerase inhibitor.