苯基-alpha-O-苄基-1-硫代-alpha-L-吡喃鼠李糖苷 | 849938-16-5

• 分子结构分类: 有机化合物 - 有机氧化合物
• 中文名称: 苯基-alpha-O-苄基-1-硫代-alpha-L-吡喃鼠李糖苷
• 中文别名: 苯基-α-O-苄基-1-硫代-α-L-鼠李吡喃糖苷
• 英文名称: phenyl 2-O-benzyl-1-thio-α-L-rhamnopyranoside
• 英文别名: S-phenyl 2-O-benzyl-α-L-thiorhamnopyranoside；phenyl 2-0-benzyl-1-thio-α-L-rhamnopyranoside；(2S,3R,4R,5R,6S)-2-methyl-5-phenylmethoxy-6-phenylsulfanyloxane-3,4-diol
• CAS: 849938-16-5
• 化学式: C₁₉H₂₂O₄S
• 分子量: 346.447
• InChiKey: DXFZSIVVKMWYFP-QZCFVMSDSA-N

物化性质

• 熔点：
  92-94?C
• 溶解度：
  可溶于二氯甲烷、乙酸乙酯、甲醇

计算性质

• 辛醇/水分配系数(LogP)：
  2.8
• 重原子数：
  24
• 可旋转键数：
  5
• 环数：
  3.0
• sp3杂化的碳原子比例：
  0.37
• 拓扑面积：
  84.2
• 氢给体数：
  2
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  苯基-alpha-O-苄基-1-硫代-alpha-L-吡喃鼠李糖苷 在 palladium dihydroxide 4-二甲氨基吡啶 、 氢气 、 溴 、 三乙胺 、 silver(l) oxide 作用下， 以 四氢呋喃 、 甲醇 、 二氯甲烷 为溶剂， 反应 6.0h， 生成 3'',4''-二-O-乙酰基阿福豆苷
  参考文献：
  名称：

  Synthesis of a Potent and Selective Inhibitor of p90 Rsk

  摘要：

  The synthesis of the naturally occurring kaempferol glycoside SL0101 has been accomplished, as has its biochemical evaluation. SL0101 exhibits selective and potent p90 Rsk inhibitory activity at nanomolar concentrations without inhibiting the function of upstream kinases such as MEK, Raf, or PKC. The synthesis verified the structural assignment of the natural product and has provided access to material sufficient for detailed biological evaluation.

  DOI：

  10.1021/ol0500463
• 作为产物：
  描述：

  phenyl 2,3-O-isopropylidene-1-thio-α-L-rhamnopyranoside 在 sodium hydride 、 溶剂黄146 、 2,3-二氯-5,6-二氰基-1,4-苯醌 作用下， 以 1,4-二氧六环 、 二氯甲烷 、 水 、 N,N-二甲基甲酰胺 为溶剂， 反应 17.5h， 生成 苯基-alpha-O-苄基-1-硫代-alpha-L-吡喃鼠李糖苷
  参考文献：
  名称：

  Facile Oxidative Cleavage of 4-O-Benzyl Ethers with Dichlorodicyanoquinone in Rhamno- and Mannopyranosides

  摘要：

  On exposure to dichlorodicyanoquinone in wet dichloromethane at room temperature, equatorial 4-O-benzyl ethers are removed with moderate selectivity in the presence of other benzyl ethers in glycopyranosides and glycothiopyranosides.

  DOI：

  10.1021/jo062411p

文献信息

• Stereoselective synthesis of β-rhamnopyranosides via gold(<scp>i</scp>)-catalyzed glycosylation with 2-alkynyl-4-nitro-benzoate donors
  作者：Yugen Zhu、Zhengnan Shen、Wei Li、Biao Yu

  DOI：10.1039/c5ob02551f

  日期：——

  An effective β-rhamnosylation protocol has been developed by using α-rhamnopyranosyl ortho-hexynyl-para-nitro-benzoates as donors and Ph₃PAuBArF4 as a catalyst.

  已开发出一种有效的β-葡萄糖苷化协议，该协议使用α-葡萄糖苷基-邻-己炔基-对-硝基苯甲酸酯作为供体，Ph3PAuBArF4作为催化剂。
• RHAMNOSE SUBSTITUENTS OF SL0101 AND THERAPEUTIC USES THEREOF
  申请人：Smith Jeffrey A.

  公开号：US20100016245A1

  公开（公告）日：2010-01-21

  The present invention provides compositions and methods useful for preparing and using analogs, derivatives, and modifications of kaempferols that have anti-neoplastic activity. More specifically, the compounds are analogs, derivatives, and modifications of SLO1O1. The invention further provides compounds that are inhibitors of rsk activity. The invention further provides compounds that selectively inhibit excessive rsk activity in cancers. The present invention further provides methods for treating cancer using compounds of the invention.

  本发明提供了用于制备和使用具有抗肿瘤活性的山柰酚的类似物、衍生物和修饰物的组合物和方法。更具体地说，这些化合物是SLO1O1的类似物、衍生物和修饰物。本发明还提供了抑制rsk活性的化合物。本发明还提供了在癌症中选择性抑制过度rsk活性的化合物。本发明还提供了使用本发明中的化合物治疗癌症的方法。
• Synthesis of Inhibitors of P90Rsk
  申请人：Hecht Sidney M.

  公开号：US20080269144A1

  公开（公告）日：2008-10-30

  The synthesis of the naturally occurring kaempferol glycoside SLO1O1-1, as well as analogs thereof, has been accomplished, as has its biochemical evaluation. SLO1O1-1 exhibits selective and potent p90 Rsk inhibitory activity at nanomolar concentrations without inhibiting the function of upstream kinases such as MEK, Raf, or PKC. The synthetic scheme of the invention verified the structural assignment of the natural SLO1O1-1 product and has provided access to material sufficient for detailed biological evaluation.

  自然存在的山柰酚苷SLO1O1-1及其类似物的合成已经完成，并对其进行了生化评估。SLO1O1-1在纳摩尔浓度下表现出选择性和强效的p90 Rsk抑制活性，而不抑制MEK、Raf或PKC等上游激酶的功能。本发明的合成方案验证了天然SLO1O1-1产物的结构分配，并提供了足够详细的生物评估材料。
• Rhamnose substituents of SL0101 and therapeutic uses thereof
  申请人：Smith Jeffrey A.

  公开号：US08426568B2

  公开（公告）日：2013-04-23

  The present invention provides compositions and methods useful for preparing and using analogs, derivatives, and modifications of kaempferols that have anti-neoplastic activity. More specifically, the compounds are analogs, derivatives, and modifications of SLO1O1. The invention further provides compounds that are inhibitors of rsk activity. The invention further provides compounds that selectively inhibit excessive rsk activity in cancers. The present invention further provides methods for treating cancer using compounds of the invention.

  本发明提供了用于制备和使用具有抗肿瘤活性的山柰酚类似物、衍生物和修饰物的组合物和方法。更具体地说，这些化合物是SLO1O1的类似物、衍生物和修饰物。本发明还提供了抑制rsk活性的化合物。本发明还提供了在癌症中选择性抑制过度rsk活性的化合物。本发明还提供了使用本发明的化合物治疗癌症的方法。
• Influence of rhamnose substituents on the potency of SL0101, an inhibitor of the Ser/Thr kinase, RSK
  作者：Jeffrey A. Smith、David J. Maloney、David E. Clark、Yaming Xu、Sidney M. Hecht、Deborah A. Lannigan

  DOI：10.1016/j.bmc.2006.05.009

  日期：2006.9

  We have previously reported the isolation of kaempferol 3-O-(3'',4"-di-O-acetyl-alpha-L-rhamnopyrano side) from Forsteronia refracta [Xu, Y.-M.; Smith, J. A.; Lannigan, D. A.; Hecht, S. M. Biorg. Med. Chem. 2006,14, 3974-3977.]. This flavonoid glycoside, termed SL0101, is a specific inhibitor of p90 ribosomal S6 kinase (RSK) with a dissociation constant of 1 mu M. In intact cells, however, the EC50 for inhibition of RSK activity is 50 mu M, which suggests that the efficacy of SL0101 could be limited by cellular uptake. Therefore, we investigated the possibility of developing a more potent RSK inhibitor by synthesizing SL0101 analogs with increased hydrophobic character. The total syntheses of kaempferol 3-O-(3",4"-di-O-butyryl-alpha-L-rhamnopyranoside) (Bu-SL0101) and kaempferol 3-O-(2",3",4"-tri-O-acetyl-alpha-L-rhamnopyranoside) (3Ac-SL0101) were performed. The IC50 for inhibition of RSK activity in in vitro kinase assays for the analogs was similar to that obtained for SL0101. 3Ac-SL0101 demonstrated the same remarkable specificity for inhibiting RSK activity in intact cells as SL0101; however, Bu-SL0101 was not completely specific. 3Ac-SL0101 was similar to 2-fold more potent at inhibiting MCF-7 cell proliferation compared to SL0101 and preferentially decreased MCF-7 cell growth, as compared to the growth of the normal human breast line, MCF-10A. Thus the discovery of 3Ac-SL0101 as a more potent RSK-specific inhibitor than SL0101 should facilitate the development of RSK inhibitors as anti-cancer chemotherapeutic agents. (c) 2006 Elsevier Ltd. All rights reserved.