1,2:5,6-di-O-isopropylidene-3-deoxy-3-fluoro-α-D-galactofuranose | 22435-76-3

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1,2:5,6-di-O-isopropylidene-3-deoxy-3-fluoro-α-D-galactofuranose
• 英文别名: 1,2;5,6-di-O-isopropylidene-3-deoxy-3-fluoro-α-D-galactofuranose；3-deoxy-3-fluoro-1,2:5,6-di-O-isopropylidene-α-D-galactofuranose；1,2:5,6-diisopropyl-3-deoxy-3-fluoro-α-D-galactose；3-fluoro-O¹,O²;O⁵,O⁶-diisopropylidene-α-D-3-deoxy-galactofuranose；(3aR,5S,6S,6aS)-5-[(4R)-2,2-dimethyl-1,3-dioxolan-4-yl]-6-fluoro-2,2-dimethyl-3a,5,6,6a-tetrahydrofuro[2,3-d][1,3]dioxole
• CAS: 22435-76-3
• 化学式: C₁₂H₁₉FO₅
• 分子量: 262.278
• InChiKey: VELRGKXNSJVRMO-SOYHJAILSA-N

物化性质

• 沸点：
  290.3±40.0 °C(Predicted)
• 密度：
  1.24±0.1 g/cm3(Predicted)
• 溶解度：
  可溶于丙酮;氯仿；二氯甲烷；乙酸乙酯

计算性质

• 辛醇/水分配系数(LogP)：
  1
• 重原子数：
  18
• 可旋转键数：
  1
• 环数：
  3.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  46.2
• 氢给体数：
  0
• 氢受体数：
  6

反应信息

• 作为反应物：
  描述：

  1,2:5,6-di-O-isopropylidene-3-deoxy-3-fluoro-α-D-galactofuranose 在 吡啶 、 三甲基溴硅烷 、 三乙胺 作用下， 以 二氯甲烷 、 甲苯 为溶剂， 反应 28.42h， 生成 dibenzyl (2,5,6-tri-O-acetyl-3-deoxy-3-fluoro-α-D-galactofuranosyl)phosphate
  参考文献：
  名称：

  Mechanistic Investigation of UDP-Galactopyranose Mutase from Escherichia coli Using 2- and 3-Fluorinated UDP-Galactofuranose as Probes

  摘要：

  The galactofuranose moiety found in many surface constituents of microorganisms is derived from UDP-D-galactopyranose (UDP-Galp) via a unique ring contraction reaction catalyzed by UDP-Galp mutase. This enzyme, which has been isolated from several bacterial sources, is a flavoprotein. To study this catalysis, the cloned Escherichia coli mutase was purified and two fluorinated analogues, UDP-[2-F]Galf(9) and UDP-[3-F]Galf(10), were chemically synthesized. These two compounds were found to be substrates for the reduced UDP-Galp mutase with the K-m values determined to be 65 and 861 muM for 9 and 10, respectively, and the corresponding k(cat) values estimated to be 0.033 and 5.7 s(-1). Since the fluorine substituent is redox inert, a mechanism initiated by the oxidation of 2-OH or 3-OH on the galactose moiety can thus be firmly ruled out. Furthermore, both 9 and 10 are poorer substrates than UDP-Galf, and the rate reduction for 9 is especially significant. This finding may be ascribed to the inductive effect of the 2-F substituent that is immediately adjacent to the anomeric center, and is consistent with a mechanism involving formation of oxocarbenium intermediates or transition states during turnover. Interestingly, under nonreducing conditions, compounds 9 and 10 are not substrates, but instead are inhibitors for the mutase. The inactivation by 10 is time-dependent, active-site-directed. and irreversible with a K-I of 270 muM and a k(inact) of 0.19 min(-1). Since the K-I value is similar to K-m, the observed inactivation is unlikely a result of tight binding. To our surprise, the inactivated enzyme could be regenerated in the presence of dithionite, and the reduced enzyme is resistant to inactivation by these fluorinated analogues. It is possible that reduction of the enzyme-bound FAD may induce a conformational change that facilitates the breakdown of the putative covalent enzyme-inhibitor adduct to reactivate the enzyme. It is also conceivable that the reduced flavin bears a higher electron density at N-1, which may play a role in preventing the formation of the covalent adduct or facilitating its breakdown by charge stabilization of the oxocarbenium intermediates/transition states. Clearly, this study has led to the identification of a potent inactivator (10) for this enzyme, and study of its inactivation has also shed light on the possible mechanism of this mutase.

  DOI：

  10.1021/ja010473l
• 作为产物：
  描述：

  (3aR,6aR)-5-[(4R)-2,2-二甲基-1,3-二氧戊环-4-基]-2,2-二甲基-3A,6A-二氢呋喃并[2,3-d][1,3]二氧杂环戊烯-6-基乙酸酯 在 4-二甲氨基吡啶 、 二乙胺基三氟化硫 、 palladium on activated charcoal 、 氢气 、 sodium methylate 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 171.0h， 生成 1,2:5,6-di-O-isopropylidene-3-deoxy-3-fluoro-α-D-galactofuranose
  参考文献：
  名称：

  Synthesis of a MUC1-glycopeptide–BSA conjugate vaccine bearing the 3′-deoxy-3′-fluoro-Thomsen–Friedenreich antigen

  摘要：

  一种新型的MUC1糖肽–BSA conjugate疫苗被制备，其中在Thr6位点具有特别氟化的Thomsen–Friedenreich抗原侧链。初步免疫学实验显示抗MUC1小鼠抗体对肿瘤相关糖肽抗原类似物的特异性结合。

  DOI：

  10.1039/c1cc13184b

文献信息

• PROCESS FOR PREPARING SUBSTITUTED 1-O-ACYL-2-DEOXY-2-FLUORO-4-THIO-BETA-D-ARABINOFURANOSES
  申请人：Voigtländer David

  公开号：US20110152542A1

  公开（公告）日：2011-06-23

  The present invention relates to a process for preparing 1-O-acyl-2-deoxy-2-fluoro-4-thio-β-D-arabinofuranoses having formula I and intermediates thereof: wherein R 1 represents —C(O)—C 1 -C 6 -alkyl or —C(O)-aryl; and R 2 represents C 1 -C 6 -alkyl, C 1 -C 4 -perfluoroalkyl or aryl.

  本发明涉及一种制备具有式I的1-O-酰基-2-去氧-2-氟-4-硫-β-D-阿拉比呋喃糖的方法和中间体：其中R1代表—C（O）—C1-C6-烷基或—C（O）-芳基；R2代表C1-C6-烷基，C1-C4-全氟烷基或芳基。
• Synthesis and evaluation of 3″- and 4″-deoxy and -fluoro analogs of the immunostimulatory glycolipid, KRN7000
  作者：Ravinder Raju、Bernard F. Castillo、Stewart K. Richardson、Meena Thakur、Ryan Severins、Mitchell Kronenberg、Amy R. Howell

  DOI：10.1016/j.bmcl.2009.06.005

  日期：2009.8

  Four 3 ''- and 4 ''-deoxy and -fluorogalactosyl ceramides were synthesized, and their ability to stimulate iNKT cells, based on levels of IL-2 production, was assessed in three NKT cell receptor hybridomas. In two of the hybridomas, 1.2 and 2H4, all of the analogs were immunostimulatory, while in the 1.4 hybridoma only the 4 ''-fluoro analog led to the production of significant levels of IL-2. (C) 2009 Elsevier Ltd. All rights reserved.
• Synthesis of Fluorinated Mucin Core 2 Branched Oligosaccharides with the Potential of Novel Substrates and Enzyme Inhibitors for Glycosyltransferases and Sulfotransferases
  作者：Jie Xia、Jun Xue、Robert D. Locke、E. V. Chandrasekaran、T. Srikrishnan、Khushi L. Matta

  DOI：10.1021/jo052626j

  日期：2006.5.1

  Syntheses of fluorinated mucin core 2 tri- and tetrasaccharides modified at the C-3 or C-4 position of the pertinent galactose residue are reported. These compounds were used for the study of sialyltransferases and 3-O-sulfotransferases involved in the biosynthesis of O-glycans. Our acceptor substrate specificity studies on three cloned sialyltransferases (Sia-Ts) revealed that a 3- or 4-fluoro substituent in, beta 1,4Gal resulted in poor acceptors for alpha 2,6(N)Sia-T and alpha 2,3(N)Sia-T, whereas 4-fluoro-Gal,beta 1,3GalNAc alpha was a good acceptor for alpha 2,3(O)Sia-T. Uniquely, 4-F-Gal,beta 1,4GlcNAc,beta 1,6(Gal,beta 1,3)GalNAc alpha-OBn was an inhibitor of alpha 2,6(N)Sia-T activity but not alpha 2,3(N)Sia-T activity. Further we found that the activities of only Gal 3-O-sulfotransferases and not sialyltransferases were adversely affected by a C-3 fluoro substituent at the other Gal terminal of mucin core 2. The strategy of building branched mucin core 2 structures by three glycosidation sequence coupling three classes of glycosyl donors with the reactivity-matching acceptors proved to be successful in syntheses of modified mucin-type core structures of O-glycan. The relative poor yields of the glycosylations using fluorinated galactosyl donors indicated that the fluorine modification dramatically decreased the donor reactivity due to electron-withdrawing effect.
• Synthesis of methyl 3-deoxy-3-fluoro-β-d-galactopyranoside
  作者：Pavol Kováč、Cornelis P.J. Glaudemans

  DOI：10.1016/0008-6215(83)88488-2

  日期：1983.11
• 3-Deoxy-3-fluoro-d-galactose
  作者：J.S. Brimacombe、A.B. Foster、R. Hems、L.D. Hall

  DOI：10.1016/s0008-6215(00)80161-5

  日期：1968.10