Scale-Up Syntheses of Two Naturally Occurring Procyanidins: (-)-Epicatechin-(4,8)-(+)-catechin and (-)-Epicatechin-3-
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- 作者：Pradeep K. Sharma ; Alexander Kolchinski ; Hé ; lè ; ne A. Shea ; Jayesh J. Nair ; Yanni Gou ; Leo J. Romanczyk ; Jr. ; Harold H. Schmitz
- 刊名：Organic Process Research & Development
- 出版年：2007
- 出版时间：May 2007
- 年：2007
- 卷：11
- 期：3
- 页码：422 - 430
- 全文大小：140K
- 年卷期：v.11,no.3(May 2007)
- ISSN：1520-586X
文摘
A scaleable process for the synthesis of two naturally occurringprocyanidins, namely (-)-epicatechin-(4
,8)-(+)-catechin (1)and (-)-epicatechin-3-O-galloyl-(4,8)-(-)-epicatechin-3-O-gallate (2), is described. The key steps were highlighted byimprovements for the benzylation of (+)-catechin (3), stereoselective reduction of the C-3 keto group of (2R)-5,7,3',4'-tetrakis(benzyloxy)flavan-3-one (10), and coupling between4-hydroxyethoxy-5,7,3',4'-tetra-O-benzyl-(-)-epicatechin (11)and 5,7,3',4'-tetra-O-benzyl-(+)-catechin (4) or 5,7,3',4'-tetra-O-benzyl-(-)-epicatechin (6), respectively. The debenzylationperformed in a biphasic system resulted in an improved yieldand purity of the target compounds. The chemistry was scaled-up to produce multigram quantities of the title compounds (1and 2) for various in vitro, ex vivo, and in vivo studies.Moreover, the scale-up process provided a detailed descriptionfor the preparation of multihundred to kilogram scale quantitiesof intermediates used in the synthesis of these two titledprocyanidins.
,8)-(+)-catechin (1)and (-)-epicatechin-3-O-galloyl-(4,8)-(-)-epicatechin-3-O-gallate (2), is described. The key steps were highlighted byimprovements for the benzylation of (+)-catechin (3), stereoselective reduction of the C-3 keto group of (2R)-5,7,3',4'-tetrakis(benzyloxy)flavan-3-one (10), and coupling between4-hydroxyethoxy-5,7,3',4'-tetra-O-benzyl-(-)-epicatechin (11)and 5,7,3',4'-tetra-O-benzyl-(+)-catechin (4) or 5,7,3',4'-tetra-O-benzyl-(-)-epicatechin (6), respectively. The debenzylationperformed in a biphasic system resulted in an improved yieldand purity of the target compounds. The chemistry was scaled-up to produce multigram quantities of the title compounds (1and 2) for various in vitro, ex vivo, and in vivo studies.Moreover, the scale-up process provided a detailed descriptionfor the preparation of multihundred to kilogram scale quantitiesof intermediates used in the synthesis of these two titledprocyanidins.