CAS: 21394-81-0; H-D-Asp(Ome)-Oh

主要参考文献

参考标题:Design And Preparation Of Serine-Threonine Protein Phosphatase Inhibitors Based Upon The Nodularin And Microcystin Toxin Structures: Part 2.1 Synthesis Of A Functionalised Nodularin Macrocycle And A Stripped-Down Microcystin Macrocycle
作者:Antony B. Maude,Amit P. Mehrotra,David Gani
摘要:Nodularins And Microcystins Are Complex Natural Isopeptidic Hepatotoxins That Serve As Subnanomolar Inhibitors Of The Eukaryotic Serine–threonine Protein Phosphatases, Pp1 And Pp2A. In Part 1 (A. P. Mehrotra, K. L. Webster And D. Gani, J. Chem. Soc., Perkin Trans. 1, 1997, Preceding Paper) Each Of The Key Structural Or Potentially Reactive Motifs Within Each Macrocycle Type Was Assessed As A Contributor Towards Phosphatase Inhibitory Efficacy And A Stripped-Down Nodularin-Type Macrocycle Was Identified As A Suitable Precursor To Potentially Active Synthetic Inhibitors. Subsequently, Synthetic Routes To The 19-Membered Nodularin Macrocyclic System Were Developed, Using Solution-Phase Chemistry, Which Demonstrated That Only Certain Cyclisation Protocols Were Viable. Here We Describe An Extension Of This Chemistry To Provide A 19-Membered Nodularin Macrocycle, Cyclo-[(3R)-3-Hydroxymethyl-î²-Ala-( R)-Glu-î+/--Ome-î³-Sar-(R)-Asp- î+/--Ome-î²-(S)-Phe-], Appropriately Functionalised With A Hydroxymethyl Group For The Incorporation Of Lipophilic Side-Chains. We Also Demonstrate That The 25-Membered Microcystin Macrocycle, Cyclo-[î²-Ala-(R)-Glu-î+/-- Ome-î³-Sar-(R)-Ala-(S)-Leu-( R)-Asp-î+/--Ome-î²-(S)- Phe-], Can Be Prepared In Good Yield Using Similar Protocols In Which Macrocyclisation Is Effected Through The Reaction Of The Amino Group Of The (2S)-Phenylalanine Residue With The î²-Pentafluorophenyl Ester Of The (2R)-Aspartic Acid Residue.

合成参考文献

合成方法参考DOI号:10.1021/jo00129a066