Synthesis of pacidamycin analogues via an Ugi-multicomponent reaction
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- 作者：Kazuya Okamoto ; Masahiro Sakagami ; Fei Feng ; Fumiyo Takahashi ; Kouichi Uotani ; Hiroko Togame ; Hiroshi Takemoto ; Satoshi Ichikawa ; Akira Matsuda
- 关键词：DABA ; ¦Á ; ¦Â-diaminobutylic acid ; HATU ; 2-(1H-7-azabenzotriazol-1-yl)-1 ; 1 ; 3 ; 3-tetramethyluronium hexafluorophosphate ; MraY ; phospho-MurNAc-pentapeptide transferase ; NMM ; N-methylmorpholine ; SAR ; structure&ndash ; activity relationship ; U-4CR ; Ugi-four compon
- 刊名：Bioorganic and Medicinal Chemistry Letters
- 出版年：2012
- 出版时间：15 July, 2012
- 年：2012
- 卷：22
- 期：14
- 页码：4810-4815
- 全文大小：960 K
文摘
The second-generation synthesis of 3¡ä-hydroxypacidamycin D (2) has been accomplished via an Ugi-four component reaction at a late stage of the synthesis. This approach provided ready access to a range of analogues including diastereomers of the diaminobutylic acid residue and hybrid-type analogues of mureidomycins. Biological evaluations of these analogues indicated that the stereochemistry at the diaminobutylic acid residue has a crucial impact on both the MraY biochemical inhibition and whole-cell antibacterial activity.