1,3(R):4,6(R)-bis-O-(4-methoxybenzylidene)-D-mannitol | 201536-29-0

• 分子结构分类: 有机化合物 - 苯类化合物 - 苯酚醚
• 英文名称: 1,3(R):4,6(R)-bis-O-(4-methoxybenzylidene)-D-mannitol
• 英文别名: 1,3:4,6-di-O,O-(4-methoxybenzylidene)-D-mannitol；1,3:4,6-bis-O-(4-methoxybenzylidene)-D-mannitol；1,3:4,6-di-O-(p-methoxy)benzylidene-D-mannitol；(4R,4'R,5R,5'R)-2,2'-bis(4-Methoxyphenyl)-[4,4'-bi(1,3-dioxane)]-5,5'-diol；(4R,5R)-4-[(4R,5R)-5-hydroxy-2-(4-methoxyphenyl)-1,3-dioxan-4-yl]-2-(4-methoxyphenyl)-1,3-dioxan-5-ol
• CAS: 201536-29-0
• 化学式: C₂₂H₂₆O₈
• 分子量: 418.444
• InChiKey: NWPMHCHSJLRWII-ZHEILYIOSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  30
• 可旋转键数：
  5
• 环数：
  4.0
• sp3杂化的碳原子比例：
  0.45
• 拓扑面积：
  95.8
• 氢给体数：
  2
• 氢受体数：
  8

反应信息

• 作为反应物：
  描述：

  1,3(R):4,6(R)-bis-O-(4-methoxybenzylidene)-D-mannitol 在 20percent Pd(OH₂) on C lithium aluminium tetrahydride 、 三氯化铝 、 氢气 、 sodium hydride 、 三乙胺 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 为溶剂， 反应 24.0h， 生成 (2S,3R,4R,5S)-3,4-Bis-benzyloxy-2,5-bis-(4-methoxy-benzyloxymethyl)-pyrrolidine-1-carboxylic acid tert-butyl ester
  参考文献：
  名称：

  Studies on Novel Peptidomimetics Having Bi-directional Dispositions of Hydroxylated d-Pro-Gly Motifs Anchored on a C₂-Symmetric Iminosugar-Based Foundation

  摘要：

  A rigid pyrrolidine based scaffold comprising of 2,5-dideoxy-2,5-imino-D-idaric acid (1) is developed. Attachment of peptide strands to the carboxylic groups at both ends of this novel template led to the peptidomimetics 2 and 3. Conformational analysis by NMR studies revealed that compounds 2b, 3b and 2c, 3c take interesting turn structures (C-2 symmetric for 2c and 3c) in DMSO-d(6) consisting of identical intramolecular hydrogen bonds at two ends between LeuNH --> sugar-OH as depicted in structure A, whereas 2a and 3a display structures with regular beta-turns with hydrogen bonds between LeuNH --> Boc-C=O in one-half of their molecular frameworks (structure B), characteristic of the turn structures commonly observed in "D-Pro-Gly"-containing peptides. These results suggest that a cis hydroxyl group at the 3-position of the proline residue favors a pseudo,beta-turn-like nine-membered ring structure in hydroxyproline-containing peptides involving an intramolecular hydrogen bond between the hydroxyl and the i + 2 backbone amide.

  DOI：

  10.1021/jo010937y
• 作为产物：
  描述：

  甘露醇 、 4-甲氧基苯甲醛 在 硫酸 、 原甲酸三甲酯 作用下， 以 N,N-二甲基甲酰胺 为溶剂， 反应 2.0h， 以33%的产率得到1,3(R):4,6(R)-bis-O-(4-methoxybenzylidene)-D-mannitol
  参考文献：
  名称：

  Synthesis and Biological Evaluation of Radioiodinated Phospholipid Ether Stereoisomers

  摘要：

  Radioiodinated phospholipid ethers have shown the remarkable ability to selectively accumulate in a variety of animal tumors as well as in human tumor xenografts. It has been suggested that this tumor avidity may arise as a consequence of metabolic differences between tumor and corresponding normal tissue. One such compound, 1-O-[12-(m-iodophenyl)dodecyl]-2-O-methyl-rac-glycero- 3-phosphocholine (NM-294), contains a chiral center at the sn-2 position. The unnatural S- and natural R-enantiomers (4 and 5, respectively) of NM-294 were synthesized in order to provide further information on the mechanism(s) responsible for the tumor avidity of phospholipid ethers. In vitro cytotoxicity studies demonstrated a lack of stereospecificity. Biodistribution studies in rats bearing the Walker 256 tumor demonstrated the S- and R-isomers to have similar tissue uptake at 24 and 48 h after administration. Tumor-to-blood ratios at 24 h were 11.1 and 11.0 for the S- and R-isomers, respectively. In addition, gamma-camera scintigrams of tumor-bearing rats at various time points after iv administration of the S- and R-isomers did not show any qualitative differences in the distribution of radioactivity. Prior studies have shown that rac-NM-294 was not a substrate for phosphatidylcholine specific phospholipase C, but was a substrate for two forms of phospholipase D (PLD). Therefore, metabolism studies with 4 and 5 with various forms of PLD were performed. PLD from cabbage demonstrated a degree of stereoselectivity. In the presence of 1% ethanol, the R-isomer was metabolized to the greatest extent, followed by rac-NM-294 and the S-isomer. PLD isolated from Streptomyces chromofuscus failed to demonstrate any stereoselectivity. The results suggest that the mechanism(s) of retention of these compounds in tumors may not involve a highly stereoselective component.

  DOI：

  10.1021/jm00016a019

文献信息

• [EN] METHODS AND COMPOUNDS FOR IDENTIFYING GLYCOSYLTRANSFERASE INHIBITORS<br/>[FR] PROCÉDÉS ET COMPOSÉS POUR L'IDENTIFICATION D'INHIBITEURS DE GLYCOSYLTRANSFÉRASE
  申请人：HARVARD COLLEGE

  公开号：WO2013151697A1

  公开（公告）日：2013-10-10

  The present invention provides moenomycin-based probe compounds of Formula (I) for use in screening inhibitors of bacterial glycosyltransferases. The present invention also provides bacterial glycosyltransferase screening assays using compounds of Formula (I).

  本发明提供了用于筛选细菌糖基转移酶抑制剂的以莫诺霉素为基础的探针化合物的公式(I)。本发明还提供了使用公式(I)化合物进行细菌糖基转移酶筛选的检测方法。
• Tuning the Moenomycin Pharmacophore To Enable Discovery of Bacterial Cell Wall Synthesis Inhibitors
  作者：Christian M. Gampe、Hirokazu Tsukamoto、Emma H. Doud、Suzanne Walker、Daniel Kahne

  DOI：10.1021/ja4000933

  日期：2013.3.13

  New antibiotic drugs need to be identified to address rapidly developing resistance of bacterial pathogens to common antibiotics. The natural antibiotic moenomycin A is the prototype for compounds that bind to bacterial peptidoglycan glycosyltransferases (PGTs) and inhibit cell wall biosynthesis, but it cannot be used as a drug. Here we report the chemoenzymatic synthesis of a fluorescently labeled

  需要确定新的抗生素药物以解决细菌病原体对常见抗生素的快速发展的耐药性。天然抗生素莫诺霉素 A 是与细菌肽聚糖糖基转移酶 (PGT) 结合并抑制细胞壁生物合成的化合物的原型，但它不能用作药物。在这里，我们报告了基于最小药效团的荧光标记的、截短的 moenomycin 类似物的化学酶促合成。与莫诺霉素相比，该探针具有优化的酶结合特性，旨在鉴定与 PGT 活性位点中的保守特征结合的低微摩尔抑制剂。我们展示了它在使用来自金黄色葡萄球菌、粪肠球菌和大肠杆菌的 PGT 的置换测定中的用途。针对金黄色葡萄球菌 SgtB 筛选了 110,000 种化合物，我们确定了一种非碳水化合物类化合物，它与所有测试的 PGT 结合。我们还表明，该化合物通过几种不同的 PGT 抑制体外肽聚糖链的形成。因此，该测定能够识别靶向 PGT 活性位点的小分子，并可能为开发新抗生素提供先导化合物。
• [EN] CHEMOENZYMATIC METHODS FOR SYNTHESIZING MOENOMYCIN ANALOGS<br/>[FR] PROCÉDÉS CHIMIO-ENZYMATIQUES POUR SYNTHÉTISER DES ANALOGUES DE LA MOÉNOMYCINE
  申请人：HARVARD COLLEGE

  公开号：WO2013152279A1

  公开（公告）日：2013-10-10

  The present invention provides methods of synthesizing moenomycin analogs of Formula (I). The present invention also provides compositions comprising a compound of Formula (I) and kits for synthesizing compounds of Formula (I).

  本发明提供了合成式(I)的莫诺霉素类似物的方法。本发明还提供了包含式(I)化合物的组合物和用于合成式(I)化合物的试剂盒。
• [DE] CHIRALE DOTIERSTOFFE FÜR FLÜSSIGKRISTALLINE MEDIEN<br/>[EN] CHIRAL DOPING AGENTS FOR LIQUID CRYSTALLINE MEDIA<br/>[FR] AGENTS DE DOPAGE CHIRAUX POUR SUBSTANCES A CRISTAUX LIQUIDES
  申请人：BASF AKTIENGESELLSCHAFT

  公开号：WO1997049694A1

  公开（公告）日：1997-12-31

  (DE) Die Erfindung betrifft Verbindungen der allgemeinen Formel (I), in der die Reste X unabhängig voneinander Bor, CH2 oder (a), B Wasserstoff, C1- bis C8-Alkyl, Phenyl, Biphenylyl oder ein Rest der Formel (II), A und A1 Spacer, n 0, 1, 2 oder 3, m = 1 oder für X = CH2 Null, M und M1 gegebenenfalls durch Fluor, Chlor, Brom, Cyan, Hydroxy oder Nitro substituierte ein- oder mehrkernige aliphatische, aromatische, heteroaliphatische oder heteroaromatische Ringsysteme, die Reste Y unabhängig voneinander eine direkte Bindung, O, S, COO, OCO, OCOO, CON(R) oder N(R)CO, Z und Z1 polymerisierbare Gruppen oder Wasserstoff, R Wasserstoff oder C1- bis C4-Alkyl und R1 und R2 Wasserstoff, gegebenenfalls durch O, COO, OCO, OCOO oder N(R) unterbrochenes C1- bis C30-Alkyl, C2- bis C30-Alkenyl, C1- bis C30-Alkanoyl oder C3- bis C30-Alkenoyl oder ein Rest der Formel (III) sind, wobei T eine direkte Bindung, CO, CH2, CH=CH-CO, CH2CH2CO oder SO2 ist und A, M, Y, Z, n und m die angegebene Bedeutung haben. Die erfindungsgemäßen Verbindungen eignen sich z.B. als chirale Dotierstoffe für elektrooptische Anzeigeelemente oder für nematische oder cholesterische Flüssigkristalle zur Erzeugung farbig reflektierender Schichten oder zur Herstellung von flüssigkristallin cholesterisch geordneten Pigmenten.(EN) The invention relates to compounds of general formula (I) in which the radicals: X is mutually independently boron; CH2 or (a), B is hydrogen, C1 to C8 alkyl, phenyl, biphenylyl or a radical of formula (II); A and A1 are spacers; n is 0, 1, 2 or 3; m is 1 of zero for X = CH2; M and M1 are possibly fluorine-, chlorine-, bromine-, cyano-, hydroxy- or nitro-substituted single or multi-nuclear aliphatic, aromatic, heteroaliphatic or heteroaromatic ring systems, the radicals Y are mutually independently a direct bond O, S, COO, OCO, OCOO, CON(R) or N(R)CO; Z and Z1 are polymerisable groups or hydrogen; R is hydrogen or C1 to C4 alkyl and R1 and R2 are hydrogen; possibly O, COO, OCO, OCOO or N(R)-interrupted C1 to C30 alkyl, C2 to C30 alkenyl, C1 to C30 alkanoyl or C3 to C30 alkenoyl or a radical of formula (III) where T is a direct compound, CO, CH2, CH=CH-CO, CH2CH2CO or SO2 and A, M, Y, Z, n and m have the meanings given. The compounds of the invention are suitable as e.g. chiral doping agents for electro-optical display components or for nematic or cholesteric liquid crystals for the generation of coloured reflecting coatings of the production of liquid crystalline cholesterically ordered pigments.(FR) L'invention concerne des composés de la formule générale (I) dans laquelle les restes X désignent indépendamment les uns des autres bore, CH2 ou (a); B désigne hydrogène, alkyle C1-C8, phényle, biphénylyle ou un reste de la formule (II); A et A1 désignent des écarteurs; n vaut 0, 1, 2 ou 3; m vaut 1 ou si X = CH2, zéro; M et M1 désignent des combinaisons cycliques aliphatiques, aromatiques, hétéroaliphatiques ou hétéroaromatiques à un ou plusieurs noyaux, éventuellement substitués par fluor, chlore, brome, cynogène, hydroxy ou nitro, les restes Y désignant indépendamment les uns des autres une liaison directe O, S, COO, OCO, OCOO, CON(R) ou N(R)CO; Z et Z1 désignent des groupes polymérisables ou hydrogène; R désigne hydrogène ou alkyle C1-C4 et R1 et R2 désigne hydrogène, alkyle C1-C30 éventuellement interrompu par O, COO, OCOO ou N(R), alcényle C2-C30, alcanoyle C1-C30 ou alcénoyle C3-C30 ou un reste de la formule (III), T désignant une liaison directe, CO, CH2, CH=CH-CO, CH2CH2CO ou SO2 et A, M, Y, Z, n et m ayant la notation mentionnée. Ces composés s'utilisent par ex., comme agents de dopage chiraux pour des éléments d'affichage électro-optiques ou des cristaux liquides nématiques ou cholestériques pour produire des couches réfléchissantes colorées ou des pigments ordonnés de manière cholestérique à cristaux liquides.

  Der Erfindung càufen Stellenbigkeiten der al pillischen Formel (I), in der die R\" dx unter Aleppo-\a von einander abh\"ngige Bor, CH2 oder (a), B Wasserstoff, C1- bis C8-\ Rohst\"cke, Ph:\" nyl, Biph\" nyllyl oder eine Formel (II) A und Alten ilyen N\"rn und m 0, 1, 2 oder 3, n 3 1 oder f\" r X = CH2 Null, M und M1 mgB recyclen substituierter Einkorn-\a, C1- bis C8-Rohst\"cke, Ph folkstand, Biph\" nyllyl oder eine Formel (III) Y und Y1 polymetrisierbare Gruppen oder Wasserstoff R Wasserstoff oder C1- bis C4-\ Rohst\"cke und R1 und R2 Wasserstoff, mgB reciprocal-O, CO, OCO, OCOO oder N(R)-zerbrochene C1- bis". SO-\ Rohst\"cke, C2- bis C30-\ Alkenyl, C1- bis C30-\ Alkanoyl oder C3- bis C30-\ Alkenoyl oder eine Formel (IV) sind, wobei T eine direkte Bindung, CO, CH2, CH=CH-CO, CH2CH2CO oder SO2 ist und A, M, Y, Z, n und m die nacheinander gegebenen Befruchtung haben. Die erfindungsacam Pigmente dienen z.B. als chiralische Doping-Mittel f\" r elektrooptische Anzeigen\" rmente oder f\" r N:Dermat anistotale oder chootechnische Fl\" ssigzekrystallien zur Vermehrung farbrectif~r refundierter Schichten oder zur Herstellung von fl\" ssigzekrystallin chootechnisier~r Pigm.\ Die阉 WATCHEN eignen sich f\" r \ Z.B. \ chilarity-doped compound for electro-optical display elements, or for nematic or cholesteric liquid crystals to produce colored reflecting coatings or ordered cholesterically liquid crystal pigments.
• Synthesis of enantiomerically pure ether lipid analogues from d-mannitol
  作者：Anatoly N. Pinchuk、Boris I. Mitsner、Vitaly I. Shvets

  DOI：10.1016/0009-3084(93)90082-e

  日期：1993.4

  A new scheme for synthesis of enantiomerically pure ether lipid analogues 3-O-octadecyl-2-O-methyl-sn-glycero-phosphocholine (D-ET-18-OCH3), 1-O-octadecyl-2-O-methyl-sn-glycero-phosphocholine (L-ET-18-OCH3) and their oleyl analogues is described. The key steps are regioselective reductive cleavage of 2,5-di-O-methyl-1,3:4,6-bis-O-(40-methoxybenzylidene)-D-mannitol (I) either with NaBH3CN-Me3SiCl (Br) giving 2,5-di-O-methyl-3,4-bis-O-(4-methoxybenzyl)-D-mannitol (II) or with NaBH3CN-CF3COOH to afford 2,5-di-O-methyl-1,6-bis-O-(4-methoxybenzyl)-D-mannitol (III). Compounds (II) and (III) are chiral precursors for synthesis of ether phospholipids of L- and D-series, respectively. The procedure described proved to be applicable to the preparation of ether lipids having also the unsaturated alkyl chains. The enantiomeric excess of obtained 1- and/or 3-alkyl-2-O-methyl-sn-glycerols was about 98%, as confirmed by H-1-NMR using chiral shift reagent, Eu(hfc)3. This synthetic strategy makes possible the preparation of the enantiomers of 1- and/or 3-O-alkyl-2-O-methyl-sn-glycerophosphocholines in good yield and high optical purity from the same starting material, 2,5-di-O-methyl-1,3:4,6-bis-O-(4-methoxybenzylidene)-D-mannitol (1), without the use of additional protective groups.