Organocatalytic Site-Selective Acylation of Avermectin B2a, a Unique Endectocidal Drug.
Organocatalytic Site-Selective Acylation of Avermectin B2a, a Unique Endectocidal Drug.
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DOI：
10.1248/cpb.c16-00205
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发表时间：
2016-07
影响因子：
1.7
通讯作者：
Takeshi Yamada;Koh Suzuki;T. Hirose;T. Furuta;Y. Ueda;T. Kawabata;S. Ōmura;T. Sunazuka
中科院分区：
文献类型：
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作者：
Takeshi Yamada;Koh Suzuki;T. Hirose;T. Furuta;Y. Ueda;T. Kawabata;S. Ōmura;T. Sunazuka
以阿维菌素B2 a为原料，采用有机催化的方法，对阿维菌素B2 a进行了定点单酰化反应。虽然使用4-二甲氨基吡啶（DMAP）作为催化剂的乙酰化阿维菌素B2 a得到差的位点选择性，使用我们的有机催化剂增加了在C-5-OH的酰化的位点选择性以及单乙酸酯的产率。该催化剂在其它酰化反应中也是有效的。有趣的是，在相同条件下的三卤乙酰化得到差的位点选择性。然而，我们的有机催化剂的对映体的使用提供了C-4″-O-三卤代乙酰基阿维菌素B2 a具有优异的位点选择性。这些结果表明，阿维菌素B2 a的位点选择性酰化可以通过合适的有机催化剂和酸酐的组合来控制。
The organocatalytic site-selective monoacylation of avermectin B2a, an insecticidal and anti-parasitic drug, was accomplished. Although an acetylation of avermectin B2a using a 4-dimethylaminopyridine (DMAP) as a catalyst gave poor site-selectivity, use of our organocatalyst increased site-selectivity of the acylation at the C-5-OH as well as the yield of monoacetate. This catalyst was also effective in other acylations. Interestingly, trihaloacetylation under same conditions gave poor site-selectivity. However, the use of an enantiomer of our organocatalyst provided the C-4″-O-trihaloacetyl avermectin B2a with excellent site-selectivity. These results indicate that the site-selective acylation of avermectin B2a can be controlled by the combination of a suitable organocatalyst and an acid anhydride.