Total Syntheses of the Phytotoxic Lactones Herbarumin I and II and a Synthesis-Based Solution of the Pinolidoxin Puzzle

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• 作者：Alois Fü ; rstner ; Karin Radkowski ; Conny Wirtz ; Richard Goddard ; Christian W. Lehmann ; and Richard Mynott
• 刊名：Journal of the American Chemical Society
• 出版年：2002
• 出版时间：June 19, 2002
• 年：2002
• 卷：124
• 期：24
• 页码：7061 - 7069
• 全文大小：182K
• 年卷期：v.124,no.24(June 19, 2002)
• ISSN：1520-5126

文摘

A concise approach to a family of potent herbicidal 10-membered lactones is described on thebasis of ring-closing metathesis (RCM) as the key step for the formation of the medium-sized ring. Thisincludes the first total syntheses of herbarumin I (1) and II (2) as well as the synthesis of several possiblemacrolides of the pinolidoxin series. A comparison of their spectral and analytical data with those of thenatural product allowed us to establish the stereostructure of pinolidoxin, a potent inhibitor of inducedphenylalanine ammonia lyase (PAL) activity, as shown in 46. This finding, however, makes clear that aprevious study dealing with the relative and absolute stereochemistry of this phytotoxic agent cannot becorrect. An important aspect from the preparative point of view is the fact that the stereochemical outcomeof the RCM reaction can be controlled by the choice of the catalyst. Thus, use of the ruthenium indenylidenecomplex 16 always leads to the corresponding (E)-alkenes, whereas the second generation catalyst 17bearing an N-heterocyclic carbene ligand affords the isomeric (Z)-olefin with good selectivity. This courseis deemed to reflect kinetic versus thermodynamic control of the cyclization reaction and therefore haspotentially broader ramifications for the synthesis of medium-sized rings in general. A further noteworthydesign feature is the fact that D-ribose is used as a convenient starting material for the preparation of bothenantiomers of the key building block 14 by means of a "head-to-tail" interconversion strategy.