phenyl 4-O-acetyl-3-azido-1-thio-2,3,6-trideoxy-α-L-lyxo-hexopyranoside | 863503-05-3

• 分子结构分类: 有机化合物 - 有机硫化合物 - 硫醚类
• 英文名称: phenyl 4-O-acetyl-3-azido-1-thio-2,3,6-trideoxy-α-L-lyxo-hexopyranoside
• 英文别名: thiophenyl 4-O-acetyl-3-azido-2,3,6-trideoxy-α-L-lyxo-hexopyranoside；(2S,3S,4S,6S)-4-Azido-2-methyl-6-(phenylthio)tetrahydro-2H-pyran-3-yl acetate；[(2S,3S,4S,6S)-4-azido-2-methyl-6-phenylsulfanyloxan-3-yl] acetate
• CAS: 863503-05-3
• 化学式: C₁₄H₁₇N₃O₃S
• 分子量: 307.373
• InChiKey: NMLSBVHAEGMGJS-NZPIUUIZSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  3.9
• 重原子数：
  21
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  75.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  phenyl 4-O-acetyl-3-azido-1-thio-2,3,6-trideoxy-α-L-lyxo-hexopyranoside 在 sodium hydroxide 、 4 A molecular sieve 、 2,4,6-三叔丁基嘧啶 作用下， 以 四氢呋喃 、 二氯甲烷 为溶剂， 反应 5.0h， 生成 7-[3-amino-4-O-(3-azido-2,3,6-trideoxy-α-L-lyxo-hexopyranosyl)-2,3,6-trideoxy-α-L-lyxo-hexopyranosyl]daunorubicinone
  参考文献：
  名称：

  Syntheses and Biological Activities of Disaccharide Daunorubicins

  摘要：

  Carbohydrate moiety is found in many anticancer nature products. To explore the carbohydrate moiety of daunorubicin in enhancing anticancer efficacy, several daunorubicin derivatives bearing disaccharide (1-8) have been synthesized. Their cytotoxicities were tested in leukemia K562 and colon cancer SW620 cells. Topoisomerase II (topo II) poisoning was performed with the in vivo complex of topoisomerase bioassay. In both cell lines, compounds with various terminal 2,6-dideoxy sugars (compounds 1, 3, 5, and 8) showed 30- to 60-fold higher anticancer activity than compounds with 2-deoxy- or 6-deoxy sugar (compounds 6 and 7). Compounds with an alpha-linkage between two sugar units (compound 3) showed 35-fold higher anticancer activity than compounds with a beta-linkage (compound 4). In addition, the anticancer activities of these compounds correlated with their ability to target topo II mediated genomic DNA damage in vivo. Compounds 1 and 3 with 2,6-dideoxy sugars produced more covalent topo-DNA complex than compounds with 2-deoxy sugar (6) and 6-deoxy sugar (7). Compounds with an alpha-configuration of terminal 2,6-dideoxy sugar (compounds 1 and 3) showed higher topo II poisoning than their counterparts with the beta-configuration (compounds 2 and 4). These results indicate that sugar moieties in daunorubicin play a significant role in its anticancer activity and topo II inhibition. The second sugar of disaccharide daunorubicin should possess 2,6-dideoxy with alpha-linkage to the first sugar to exhibit better anticancer activity.

  DOI：

  10.1021/jm050144u
• 作为产物：
  描述：

  (2S,3R,4S)-4-Azido-2-methyl-6-phenylsulfanyl-tetrahydro-pyran-3-ol 在 吡啶 、 18-冠醚-6 作用下， 以 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 3.0h， 生成 phenyl 4-O-acetyl-3-azido-1-thio-2,3,6-trideoxy-α-L-lyxo-hexopyranoside
  参考文献：
  名称：

  A Practical Method for the Stereoselective Generation of β-2-Deoxy Glycosyl Phosphates

  摘要：

  beta-2-Deoxy sugar nucleotides are substrates used by a variety of glycosyltransferases (Gtfs). We have developed a chemical route to synthesize beta-2-deoxy sugar phosphates that starts from a-glycosyl chlorides. Our approach reliably provides access to a range of NDP beta-2-deoxy sugars essential for studying glycosyltransferases involved in the synthesis of biologically active natural products.

  DOI：

  10.1021/ol049187f

文献信息

• Syntheses and biological activity of bisdaunorubicins
  作者：Guisheng Zhang、Lanyan Fang、Lizhi Zhu、Duxin Sun、Peng George Wang

  DOI：10.1016/j.bmc.2005.08.014

  日期：2006.1

  To study the length and flexibility of the linkers between two monomers of bisdaunorubicins for their activity against cancer cells, seven bisdaunorubicins were rationally designed and synthesized through click chemistry. Their cytotoxicity was tested in leukemia cells with MTS assay. The results showed that the compounds with short linkers exhibited higher activity than the compounds with long linkers, while the flexibility of the linker also contributed to their activity. These results indicated that the length and flexibility of the linkers between two monomers in bisdaunorubicins are very critical to maintain their activity against cancer cells. (c) 2005 Elsevier Ltd. All rights reserved.
• EP1147129A4
  申请人：——

  公开号：EP1147129A4

  公开（公告）日：2003-01-15
• SACCHARIDES LINKED TO COMPOUNDS THAT BIND CELL-SURFACE PEPTIDES OR PROTEINS
  申请人：Princeton University

  公开号：EP1147129A1

  公开（公告）日：2001-10-24
• [EN] SACCHARIDES LINKED TO COMPOUNDS THAT BIND CELL-SURFACE PEPTIDES OR PROTEINS<br/>[FR] SACCHARIDES PORTES PAR DES COMPOSES SE LIANT A DES PROTEINES OU DES PEPTIDES CELLULAIRES DE SURFACE
  申请人：UNIV PRINCETON

  公开号：WO2000042067A1

  公开（公告）日：2000-07-20

  A compound which comprises: (i) a saccharide compound having transglycosylase inhibitory activity; and (ii) a second compound that is capable of binding a protein or enzyme involved in cell wall biosynthesis, a precursor used in cell wall biosynthesis, the cell wall surface, or combinations thereof. The saccharide compound is linked directly or through a difunctional linker, to the non-saccharide compound; provided that: when the non-saccharide compound is a hexapeptide or a heptapeptide and the saccharide compound does not contain a phosphate or phosphonate ester, then the saccharide compound is not linked directly to the non-saccharide compound through a glycosidic linkage. The non-saccharide compound includes both 'natural' (aglycones that are typically associated with a carbohydrate moiety) and 'unnatural' (substances that are not typically associated with carbohydrate moiety) aglycones. Unnatural aglycones can be selected, for example, from peptide-binding dyes.