Continuous-Flow Synthesis of Cationic Lipid SST-01 via Safe and Scalable Aerobic Oxidation and Reductive Amination,Organic Process Research & Development

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Continuous-Flow Synthesis of Cationic Lipid SST-01 via Safe and Scalable Aerobic Oxidation and Reductive Amination
Organic Process Research & Development ( IF 3.1 ) Pub Date : 2020-07-22 , DOI: 10.1021/acs.oprd.0c00084
Katsuaki Fujiwara ₁ , Haruro Ishitani , Shu̅ Kobayashi

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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 Cu^I/TEMPO system and diluted oxygen (5% O₂ in N₂) 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%.

中文翻译：

通过安全且可扩展的好氧氧化和还原胺化连续流合成阳离子脂质SST-01

描述了通过两步均相连续流法合成的阳离子脂质SST-01（协和麒麟的siRNA-脂质纳米颗粒的关键成分）。安全和有催化的Cu可伸缩的有氧氧化^我/ TEMPO系统和稀释的氧（5％氧气₂的N ₂）被利用在第一步骤中，以提供脂质醛。随后，使用四乙酰基三乙酰氧基硼氢化铵用甲胺对第一步洗脱液进行还原胺化，可提供目标SST-01，总产率为95％。

更新日期：2020-07-22

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