Scale-Up Synthesis of Swainsonine: A Potent α-Mannosidase II Inhibitor

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• 作者：Pradeep K. Sharma ; Rajan N. Shah ; Jeremy P. Carver
• 刊名：Organic Process Research & Development
• 出版年：2008
• 出版时间：September 19, 2008
• 年：2008
• 卷：12
• 期：5
• 页码：831-836
• 全文大小：160K
• 年卷期：v.12,no.5(September 19, 2008)
• ISSN：1520-586X

文摘

The large-scale synthesis of Swainsonine 1, a potent α-mannosidase II inhibitor, has been achieved with several improvements. The key modifications were (a) performing the Wittig olefination under mild conditions and isolation of the product 4 with modified workup conditions, (b) introduction of the azido group on a large scale under Mitsunobu conditions to produce 12, (c) performing the 1, 3-dipolar cycloaddition of an unactivated azide 12 to afford the imino carboxylic ester 7, (d) formation of amide 10 from 7 under mild acidic conditions, and (e) isolation of the final compound 1 as a stable hydrochloride salt. In addition, synthesis of 11 was accomplished from 12 by telescoping the four steps.