Continuous-Flow Synthesis of Cationic Lipid SST-01 via Safe and Scalable Aerobic Oxidation and Reductive Amination

被引：10

作者：

Fujiwara, Katsuaki ^{[2
]}

Ishitani, Haruro ^{[1
]}

Kobayashi, Shu ^{[1
,3
]}

机构：

[1] Univ Tokyo, Grad Sch Sci, Green & Sustainable Chem Social Cooperat Lab, Bunkyo Ku, Tokyo 1130033, Japan

[2] Kyowa Kirin Co Ltd, Fuji Res Pk, Res Funct Unit, R&D Div, Shizuoka 4118731, Japan

[3] Univ Tokyo, Sch Sci, Dept Chem, Bunkyo Ku, Tokyo 1130033, Japan

来源：

ORGANIC PROCESS RESEARCH & DEVELOPMENT | 2020年 / 24卷 / 10期

关键词：

continuous-flow chemistry; catalytic oxidation; reductive amination; cationic lipid; lipid nanoparticle; ALCOHOLS; TOOL;

D O I：

10.1021/acs.oprd.0c00084

中图分类号：

O69 [应用化学];

学科分类号：

081704 ;

摘要：

The synthesis of the cationic lipid SST-01, a key component of Kyowa Kirin's siRNA-lipid nanoparticles, through a two-step homogeneous continuous-flow process is described. Safe and scalable aerobic oxidation with a catalytic CuI/TEMPO system and diluted oxygen (5% O-2 in N-2) was utilized in the first step to provide a lipid aldehyde. Subsequent reductive amination of the first-step eluent with methylamine using tetramethylammonium triacetoxyborohydride provided the target SST-01 in an overall yield of 95%.

引用

页码：1988 / 1995

页数：8

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