1,2-O-isopropylidene-5-O-(tert-butyldimethylsilyl)-3-C-ethynyl-α-D-ribofuranose | 180300-93-0

• 分子结构分类: 有机化合物 - 有机氧化合物
• 英文名称: 1,2-O-isopropylidene-5-O-(tert-butyldimethylsilyl)-3-C-ethynyl-α-D-ribofuranose
• 英文别名: (3aR,5R,6R,6aR)-5-(((tert-butyldimethylsilyl)oxy)methyl)-6-ethynyl-2,2-dimethyltetrahydrofuro[2,3-d][1,3]dioxol-6-ol；5-O-tert-butyldimethylsilyl-3-C-ethynyl-1,2-O-isopropylidene-α-D-ribofuranose；(3aR,5R,6R,6aR)-5-[[tert-butyl(dimethyl)silyl]oxymethyl]-6-ethynyl-2,2-dimethyl-5,6a-dihydro-3aH-furo[2,3-d][1,3]dioxol-6-ol
• CAS: 180300-93-0
• 化学式: C₁₆H₂₈O₅Si
• 分子量: 328.481
• InChiKey: LHIPAUKVLOBXMC-OQMKEHIESA-N

计算性质

• 辛醇/水分配系数(LogP)：
  2.25
• 重原子数：
  22
• 可旋转键数：
  5
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  57.2
• 氢给体数：
  1
• 氢受体数：
  5

反应信息

• 作为反应物：
  描述：

  1,2-O-isopropylidene-5-O-(tert-butyldimethylsilyl)-3-C-ethynyl-α-D-ribofuranose 在 甲醇 、 4-二甲氨基吡啶 、 N,O-双三甲硅基乙酰胺 、 三氟甲磺酸三甲基硅酯 、 四丁基氟化铵 、 水 、 sodium methylate 、 sodium hydride 、 溶剂黄146 、 三乙胺 作用下， 以 四氢呋喃 、 二氯甲烷 、 乙腈 为溶剂， 反应 22.33h， 生成 1-[3-C-ethynyl-3-O-(2-propynyl)-β-D-ribo-pentofuranosyl]uracil
  参考文献：
  名称：

  目标兼具灵活性：合成C（3 '）-螺旋型核苷

  摘要：

  我们报告了一个简单的策略，用于合成以（2 + 2 + 2）-环三聚为关键反应的C（3'）-螺二氢异苯并呋喃核苷的集合。环三聚反应容易与具有二炔单元的未保护的核苷一起进行。当二炔的两个炔都是末端时，区域选择性差。然而，当末端炔烃之一被另外取代时，环三聚是高度非对映选择性的。由于关键的双环环化是最后一步，因此该策略在炔烃方面提供了灵活性，因此适合合成聚焦的小分子文库。

  DOI：

  10.1016/j.tetlet.2011.06.100
• 作为产物：
  描述：

  乙烯 、 5-O-(tert-butyldimethylsilyl)-1,2-O-isopropylidene-α-D-erythro-pentofuranos-3-ulose 在 正丁基氯化镁 作用下， 以 四氢呋喃 为溶剂， 反应 0.75h， 以84%的产率得到1,2-O-isopropylidene-5-O-(tert-butyldimethylsilyl)-3-C-ethynyl-α-D-ribofuranose
  参考文献：
  名称：

  The influence of electronic factors on palladium-mediated cycloisomerization: a systematic investigation of competitive 5-exo-dig versus 6-endo-dig cyclizations of sugar alkynols

  摘要：

  Pd-mediated cycloisomerization of 3-C-alkynyl-allo- and ribofuranose derivatives was investigated in detail to understand the influence of electronic factors on the regioselectivity in ring closure reaction. The reactions in general are influenced by the electronic nature of the substituent on the alkyne unit. A preference for endo-dig cyclization over exo-dig is noted, if the alkynyl substituent is not sufficiently electron withdrawing, (c) 2007 Elsevier Ltd. All rights reserved.

  DOI：

  10.1016/j.tet.2007.10.072

文献信息

• 3'-substituted nucleoside derivatives
  申请人：Matsuda; Akira

  公开号：US05763418A1

  公开（公告）日：1998-06-09

  The invention relates to a 3'-substituted nucleoside derivative represented by the following general formula (1): ##STR1## wherein B means a nucleic acid base which may have a substituent, Z represents a lower alkynyl or lower alkenyl group which may be substituted by a group represented by the formula: ##STR2## in which R.sup.a, R.sup.b and R.sup.c are individually a lower alkyl group or a phenyl group, or an oxiranyl group which may have at least one lower alkyl group, R.sup.1 and R.sup.2 individually represent H or an ester-forming residue capable of easily leaving in a living body, and R.sup.3 is H, a mono- or polyphosphoric acid residue, or an ester-forming residue capable of easily leaving in a living body, with the proviso that the sugar moiety is ribose, or a pharmaceutically acceptable salt thereof. The 3'-substituted nucleoside derivative according to the invention has an excellent antitumor activity and is hence useful for treatment for and prevention of cancers.

  该发明涉及一种由下述一般式(1)表示的3'-取代核苷衍生物：##STR1##其中B表示可能有取代基的核酸碱基，Z代表可能被下述式表示的基团取代的低炔基或低烯基基团：##STR2##其中R.sup.a、R.sup.b和R.sup.c分别为低烷基基团或苯基团，或者可能具有至少一个低烷基基团的环氧丙基基团，R.sup.1和R.sup.2分别表示H或者在活体中容易脱离的酯基残基，R.sup.3为H、单磷酸或多磷酸残基，或者在活体中容易脱离的酯基残基，但糖基是核糖，或其药用可接受盐。根据该发明的3'-取代核苷衍生物具有优异的抗肿瘤活性，因此对于癌症的治疗和预防非常有用。
• Discovery of a Series of Potent, Selective, and Orally Bioavailable Nucleoside Inhibitors of CD73 That Demonstrates <i>In Vivo</i> Antitumor Activity
  作者：Jim Li、Lijing Chen、Roland J. Billedeau、Timothy F. Stanton、John T. P. Chiang、Clarissa C. Lee、Weiqun Li、Susanne Steggerda、Ethan Emberley、Matthew Gross、Deepthi Bhupathi、Xiaoying Che、Jason Chen、Rosalyn Dang、Tony Huang、Yong Ma、Andrew MacKinnon、Amani Makkouk、Gisele Marguier、Silinda Neou、Natalija Sotirovska、Sandra Spurlock、Jing Zhang、Winter Zhang、Michael van Zandt、Lin Yuan、Jennifer Savoy、Francesco Parlati、Eric B. Sjogren

  DOI：10.1021/acs.jmedchem.2c01287

  日期：2023.1.12

  into highly immunosuppressive adenosine that plays a critical role in tumor progression. Herein, we report our efforts in developing orally bioavailable and highly potent small-molecule CD73 inhibitors from the reported hit molecule 2 to lead molecule 20 and then finally to compound 49. Compound 49 was able to reverse AMP-mediated suppression of CD8+ T cells and completely inhibited CD73 activity in

  CD73（ecto-5'-核苷酸酶）已成为许多癌症的癌症免疫治疗的有吸引力的靶标。CD73 催化单磷酸腺苷 (AMP) 水解为高度免疫抑制的腺苷，腺苷在肿瘤进展中起着关键作用。在此，我们报告了我们在开发口服生物利用度和高效小分子 CD73 抑制剂方面所做的努力，从报道的命中分子2到先导分子20，然后最终到化合物49。化合物49能够逆转 AMP 介导的 CD8 + T 细胞抑制，并完全抑制各种癌症患者血清样本中的 CD73 活性。在临床前体内研究中，口服给药49显示出与疗效相关的稳健的剂量依赖性药代动力学/药效学 (PK/PD) 关系。化合物49还证明了预期的免疫介导的抗肿瘤作用机制，并且在口服给药后不仅作为单一药物有效，而且在小鼠肿瘤模型中与化疗药物或检查点抑制剂联合使用也有效。
• The isochroman- and 1,3-dihydroisobenzofuran-annulation on carbohydrate templates via [2+2+2]-cyclotrimerization and synthesis of some tricyclic nucleosides
  作者：Sharad B. Suryawanshi、Mangesh P. Dushing、Rajesh G. Gonnade、C.V. Ramana

  DOI：10.1016/j.tet.2010.06.011

  日期：2010.8

  The synthesis of enantiopure tricyclic systems comprising isochroman or dihydroisobenzofuran units integrated with sugar templates has been documented. The alkyne cylotrimerization reaction has been employed with easily accessible sugar diynes for the key bicyclic ring construction and thus a provision to alter the functional groups on the newly formed aromatic rings. By selecting two representative trimerization products, we have synthesized the tricyclic nucleosides by simple synthetic manipulations. (c) 2010 Elsevier Ltd. All rights reserved.
• Target cum flexibility: synthesis of C(3′)-spiroannulated nucleosides
  作者：Mangesh P. Dushing、C.V. Ramana

  DOI：10.1016/j.tetlet.2011.06.100

  日期：2011.9

  report a simple strategy for the synthesis of a collection of C(3′)-spirodihydroisobenzo-furannulated nucleosides featuring a [2+2+2]-cyclotrimerization as the key reaction. The cyclotrimerization reactions are facile with the unprotected nucleosides having a diyne unit. When both alkynes of the diyne are terminal, the regioselectivity is poor. However, when one of the terminal alkynes is additionally

  我们报告了一个简单的策略，用于合成以（2 + 2 + 2）-环三聚为关键反应的C（3'）-螺二氢异苯并呋喃核苷的集合。环三聚反应容易与具有二炔单元的未保护的核苷一起进行。当二炔的两个炔都是末端时，区域选择性差。然而，当末端炔烃之一被另外取代时，环三聚是高度非对映选择性的。由于关键的双环环化是最后一步，因此该策略在炔烃方面提供了灵活性，因此适合合成聚焦的小分子文库。
• The influence of electronic factors on palladium-mediated cycloisomerization: a systematic investigation of competitive 5-exo-dig versus 6-endo-dig cyclizations of sugar alkynols
  作者：C.V. Ramana、Rosy Mallik、Rajesh G. Gonnade

  DOI：10.1016/j.tet.2007.10.072

  日期：2008.1

  Pd-mediated cycloisomerization of 3-C-alkynyl-allo- and ribofuranose derivatives was investigated in detail to understand the influence of electronic factors on the regioselectivity in ring closure reaction. The reactions in general are influenced by the electronic nature of the substituent on the alkyne unit. A preference for endo-dig cyclization over exo-dig is noted, if the alkynyl substituent is not sufficiently electron withdrawing, (c) 2007 Elsevier Ltd. All rights reserved.