Mannopeptimycins是一種醣肽分子的抗生素，對於抗藥性金黃色葡萄球菌(methicillin-resistant Staphylococcus aureus, MRSA) 和抗萬古黴素腸球菌 (vancomycin-resistant Enterococcus faecium, VRE)皆具有良好的抑制活性(MIC: 4-128 μg/mL)。可能藉由與Lipid II受質結合來抑制細胞壁生合成。由於此醣肽分子的全合成尚未發表，並且在先前片段合成的設計仍有修飾的空間，特別在兩個罕見的胺基酸：(2R, 3S, 4S)-hydroxyenduracididine和(2S, 3S, 4S)-hydroxyenduracididine的合成。因此本篇論文著重在這兩個具有三個連續的立體化學罕見胺基酸之合成設計：第一個罕見胺基酸(2R, 3S, 4S)-hydroxyenduracididine，利用對掌性內酯10為起始物，經由12個反應步驟可有效率得到目標分子，並且有良好的產率(7.2%)。第二個罕見胺基酸(2S, 3S, 4S)-hydroxyenduracididine，僅在二號碳位置的立體化學不同，可利用對掌性內酯11，藉由加入對甲苯磺酸吡啶鹽(pyridinium p-toluenesulfonate, PPTS)使其產生熱力學穩定的產物，改變二號碳位置的立體化學，再經由12個反應步驟得到目標分子，總產率3.2%。
在合成設計上，第一種合成設計，內酯藉由氫氧化鋰開環，再經過一系列的化學轉換形成具有多種官能基保護的亞芐基 (benzylidene)中間產物，但在亞芐基之選擇性開環較不順利，因此採用第二種合成設計，內酯藉由還原形成雙羥基產物，再經由一系列的化學轉換形成亞芐基中間產物，幸運地可利用TiCl4/NaCNBH3進行選擇性開環。另一個mannopeptimycin之片段─醣肽分子，利用D-甘露糖(D-mannose)為起始物，經由10步驟得到雙醣分子，並使其形成好的醣予體(donor)，在BF3•OEt2催化下與Fmoc-D-tyrosine之羥基進行醣基化得到醣肽分子。

In this research, we aim at synthetic design of mannopeptimycin fragment including two unusual amino acids with three continuous stereocenters: (2R, 3S, 4S)-hydroxyenduracididine, (2S, 3S, 4S)-hydroxyenduracididine and D-tyrosine-linked glycan.
The first unusual amino acid, (2R, 3S, 4S)-hydroxyenduracididine, has been achieved in twelve steps from the known chiral lactone 10. The efficiency of the synthesis is demonstrated by the high overall yield of 7.2%. The other unusual amino acid, (2S, 3S, 4S)-hydroxyenduracididine, an epimer of the first one, has been synthesized in twelve steps from the chiral lactone 25 with overall yield of 3.2%. The chiral lactone 25, a thermodynamic product was prepared by adding pyridinium p-toluenesulfonate from lactone 11.
The key transformation of the synthetic route is selective benzylidene ring opening. Fortunately, the selective ring opening of benzylidene was obtained by using TiCl4/NaCNBH3.
The design of the other mannopeptimycin fragment, D-tyrosine-linked glycan, by preparing the disaccharide in ten steps from D-mannose. BF3•OEt2-catalyzed glycosylation was achieved with Fmoc-D-tyrosine to afford the D-tyrosine-linked glycan.

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