2',3'-O-bis(tert-butyldimethylsilyl)-3-N-(p-methoxybenzyl)uridine-5'-aldehyde | 137233-53-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 2',3'-O-bis(tert-butyldimethylsilyl)-3-N-(p-methoxybenzyl)uridine-5'-aldehyde
• 英文别名: 2',3'-bis(O-tert-butyldimethylsilyl)-3-(p-methoxybenzyl)uridine-5'-aldehyde；(2S,3R,4R,5R)-3,4-bis[[tert-butyl(dimethyl)silyl]oxy]-5-[3-[(4-methoxyphenyl)methyl]-2,4-dioxopyrimidin-1-yl]oxolane-2-carbaldehyde
• CAS: 137233-53-5
• 化学式: C₂₉H₄₆N₂O₇Si₂
• 分子量: 590.864
• InChiKey: KMNKAQHANLADAE-VNSJUHMKSA-N

物化性质

• 沸点：
  600.9±65.0 °C(Predicted)
• 密度：
  1.13±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  4.94
• 重原子数：
  40
• 可旋转键数：
  11
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.62
• 拓扑面积：
  94.6
• 氢给体数：
  0
• 氢受体数：
  7

反应信息

• 作为反应物：
  描述：

  2',3'-O-bis(tert-butyldimethylsilyl)-3-N-(p-methoxybenzyl)uridine-5'-aldehyde 在 吡啶 、 盐酸 、 potassium fluoride 、 ammonium cerium(IV) nitrate 、 三乙基硼 、 三正丁基氢锡 作用下， 以 甲苯 为溶剂， 反应 22.67h， 生成 2-amino-11-(2,4-dioxo-3,4-dihydro-2H-pyrimidin-1-yl)-11β-L-allo-D-galacto-2,6,11-trideoxy-undecodiald-11,8-ose
  参考文献：
  名称：

  Synthetic Studies of the Tunicamycin Antibiotics. Preparation of (+)-Tunicaminyluracil, (+)-Tunicamycin-V, and 5'-epi-Tunicamycin-V

  摘要：

  A concise synthetic route to the tunicamycin antibiotics is described, illustrated by the preparation of (+)-tunicamycin-V (1-V). Key features of the synthesis include (1) the development and application of a silicon-mediated reductive coupling of aldehydes and allylic alcohols to construct the undecose core of the natural product and (2) the development of an efficient procedure for the synthesis of the trehalose glycosidic bond within the antibiotic. These innovations allow for the coupling of a uridine-derived aldehyde fragment with a performed trehalose-linked disaccharide allylic alcohol to form the carbohydrate core (1) of the natural product in a highly covergent manner. The resultant amino polyol is a versatile intermediate for the synthesis of any of the homologous tunicamycin antibiotics.

  DOI：

  10.1021/ja00090a018
• 作为产物：
  描述：

  尿嘧啶核苷 在 吡啶 、 咪唑 、 草酰氯 、 sodium hydride 、 二甲基亚砜 、 三乙胺 、 苯磺酸 作用下， 以 氯仿 、 N,N-二甲基甲酰胺 为溶剂， 反应 30.83h， 生成 2',3'-O-bis(tert-butyldimethylsilyl)-3-N-(p-methoxybenzyl)uridine-5'-aldehyde
  参考文献：
  名称：

  Synthetic Studies of the Tunicamycin Antibiotics. Preparation of (+)-Tunicaminyluracil, (+)-Tunicamycin-V, and 5'-epi-Tunicamycin-V

  摘要：

  A concise synthetic route to the tunicamycin antibiotics is described, illustrated by the preparation of (+)-tunicamycin-V (1-V). Key features of the synthesis include (1) the development and application of a silicon-mediated reductive coupling of aldehydes and allylic alcohols to construct the undecose core of the natural product and (2) the development of an efficient procedure for the synthesis of the trehalose glycosidic bond within the antibiotic. These innovations allow for the coupling of a uridine-derived aldehyde fragment with a performed trehalose-linked disaccharide allylic alcohol to form the carbohydrate core (1) of the natural product in a highly covergent manner. The resultant amino polyol is a versatile intermediate for the synthesis of any of the homologous tunicamycin antibiotics.

  DOI：

  10.1021/ja00090a018

文献信息

• Stereoselective Synthesis of Uridine-Derived Nucleosyl Amino Acids
  作者：Anatol P. Spork、Daniel Wiegmann、Markus Granitzka、Dietmar Stalke、Christian Ducho

  DOI：10.1021/jo201935w

  日期：2011.12.16

  nucleosyl amino acids (NAAs) represent simplified analogues of the core structure of muraymycin nucleoside antibiotics, making them useful synthetic building blocks for structure–activity relationship (SAR) studies. The key step of the developed synthetic route was the efficient and highly diastereoselective asymmetric hydrogenation of didehydro amino acid precursors toward protected NAAs. It was anticipated

  构想并合成了5'-脱氧尿苷和甘氨酸的新型杂合结构。此类核苷氨基酸（NAA）代表穆来霉素核苷抗生素核心结构的简化类似物，使其成为结构与活性关系（SAR）研究的有用合成构件。已开发的合成路线的关键步骤是将二脱氢氨基酸前体高效且高度非对映选择性地不对称氢化成受保护的NAA。预期通过该途径合成未保护的穆雷霉素衍生物将需要在尿嘧啶碱基的N-3处具有合适的中间保护基。在最初尝试使用PMB-和BOM-N-3保护后，这两个步骤都导致了脱保护步骤的问题，然后构想出N-3无保护基团的路线。尽管尿嘧啶-3-NH具有明显的酸性，但该途径与涉及N-3保护的初始策略一样有效，立体选择性也相同。所获得的NAA构件被用于合成截短的5'-脱氧村霉素类似物。
• Improved Convergent Synthesis of 5′-epi-Analogues of Muraymycin Nucleoside Antibiotics
  作者：Christian Ducho、Anatol Spork、Stefan Koppermann

  DOI：10.1055/s-0029-1217742

  日期：2009.9

  Nucleoside antibiotics represent a promising class of natural products for the development of novel antibacterial agents, with particular respect to structurally simplified analogues maintaining biological activity. There are established truncated 5'-epi-derivatives of muraymycin nucleoside antibiotics with reported antibacterial properties, but the lengthy preparation of such compounds is a major

  核苷类抗生素代表了一类有前途的天然产物，可用于开发新型抗菌剂，特别是在结构简化的类似物保持生物活性方面。已经建立了具有抗菌特性的 muraymycin 核苷抗生素的截短 5'-epi-衍生物，但此类化合物的冗长制备是更详细的构效关系 (SAR) 研究的主要障碍。本文报道了基于先前报道的使用硫叶立德化学方法对截短的 5'-epi-muraymycins 进行简明、改进的合成。这种策略的高度收敛性将允许有效合成新型 muraymycin 类似物以进行彻底的 SAR 研究。
• Novel 5′-deoxy nucleosyl amino acid scaffolds for the synthesis of muraymycin analogues
  作者：Anatol P. Spork、Christian Ducho

  DOI：10.1039/c003092a

  日期：——

  Naturally occurring nucleoside antibiotics such as muraymycins represent promising lead structures for the development of novel antibacterial agents. A concise synthesis of 5′-deoxy muraymycin derivatives has been developed. The key step was the highly stereoselective asymmetric hydrogenation of suitable didehydro amino acid precursors, providing unique nucleosyl amino acid structures.

  天然存在的核苷类抗生素（如穆拉霉素）是开发新型抗菌剂的有前景的潜在结构。我们已经开发出5-脱氧穆拉霉素衍生物的简明合成方法。关键步骤是对合适的二脱氢氨基酸前体进行高度立体选择性不对称氢化，从而获得独特的核苷类氨基酸结构。
• Silicon-mediated reductive coupling of aldehydes and allylic alcohols. A stereoselective synthesis of tunicaminyluracil
  作者：Andrew G. Myers、David Y. Gin、Katherine L. Widdowson

  DOI：10.1021/ja00025a036

  日期：1991.12
• Muraymycins, novel peptidoglycan biosynthesis inhibitors: synthesis and SAR of their analogues
  作者：Ayako Yamashita、Emily Norton、Peter J Petersen、Beth A Rasmussen、Guy Singh、Youjin Yang、Tarek S Mansour、Douglas M Ho

  DOI：10.1016/s0960-894x(03)00671-1

  日期：2003.10

  A Series Of Muraymycin analogues was synthesized. These analogues showed excellent antimicrobial activity against grain-positive organisins. These analogues also showed excellent inhibitory activity against the target peptidoglycan biosynthesis enzyme MraY, the cell membrane associated transglycosylase responsible for the formation of Lipid II. (C) 2003 Elsevier Ltd. All rights reserved.