1,4-anhydro-2-deoxy-3,5-O-(1,1,3,3-tetraisopropyldisiloxan-1,3-diyl)-4-thio-D-erythro-pent-1-enitol | 209048-61-3

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 二氢噻吩类
• 英文名称: 1,4-anhydro-2-deoxy-3,5-O-(1,1,3,3-tetraisopropyldisiloxan-1,3-diyl)-4-thio-D-erythro-pent-1-enitol
• 英文别名: 3,5-O-(tetraisopropyldisiloxane-1,3-diyl)-4-thiofuranoid glycal；(6aR,9aS)-2,2,4,4-tetraisopropyl-6a,9a-dihydro-6H-thieno[3,2-f][1,3,5,2,4]trioxadisilocin；(6aR,9aS)-2,2,4,4-Tetraisopropyl-6a,9a-dihydro-6H-thieno[3,2-f][1,3,5,2,4]trioxadisilocine；(6aR,9aS)-2,2,4,4-tetra(propan-2-yl)-6a,9a-dihydro-6H-thieno[3,2-f][1,3,5,2,4]trioxadisilocine
• CAS: 209048-61-3
• 化学式: C₁₇H₃₄O₃SSi₂
• 分子量: 374.692
• InChiKey: HCGUNOJLTMLCCM-DLBZAZTESA-N

物化性质

• 沸点：
  367.5±42.0 °C(Predicted)
• 密度：
  1.00±0.1 g/cm3(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  5.57
• 重原子数：
  23
• 可旋转键数：
  4
• 环数：
  2.0
• sp3杂化的碳原子比例：
  0.88
• 拓扑面积：
  53
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  1,4-anhydro-2-deoxy-3,5-O-(1,1,3,3-tetraisopropyldisiloxan-1,3-diyl)-4-thio-D-erythro-pent-1-enitol 在 钯 4-二甲氨基吡啶 、 三乙基硼 、 敌草腈 、 2,2,6,6-tetramethylpiperidinyl-lithium 、 四丁基氟化铵 、 氨 、 氢气 、 氧气 、 三正丁基氢锡 、 sodium methylate 、 sodium 、 sodium carbonate 、 N,N-二异丙基乙胺 、 4,4'-二氨基二苯乙烯-2,2'-二磺酸 、 lithium diisopropyl amide 作用下， 以 四氢呋喃 、 甲醇 、 乙醚 、 二氯甲烷 、 N,N-二甲基甲酰胺 、 甲苯 、 乙腈 为溶剂， 反应 11.67h， 生成 1-[2-deoxy-3,5-bis-O-(t-butyldimethylsilyl)-2-fluoromethyl-4-thio-β-D-arabinofuranosyl]thymine
  参考文献：
  名称：

  新的立体选择性进入4-硫呋喃类化合物糖基的2'-β-碳取代的2'-脱氧-4'-硫代核苷。

  摘要：

  已通过PhSeCl介导的亲电糖基化反应合成了2'-β-甲基-和2'-β-羟甲基-2'-脱氧-4'-硫代核苷，使用在C2-位具有碳取代基的4-硫代呋喃类糖作为糖基供体。这些糖的制备是通过用LTMP对1-氯-4-硫代呋喃呋喃基糖进行C2锂化反应，然后将Birch还原成氯原子来进行的。[反应：看文字]

  DOI：

  10.1021/ol040035u
• 作为产物：
  描述：

  1-O-acetyl-2-deoxy-3,5-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl)-4-thio-D-erythro-pentofuranose 在 氨 、 三乙胺 作用下， 以 甲醇 、 二氯甲烷 为溶剂， 反应 4.0h， 生成 1,4-anhydro-2-deoxy-3,5-O-(1,1,3,3-tetraisopropyldisiloxan-1,3-diyl)-4-thio-D-erythro-pent-1-enitol
  参考文献：
  名称：

  立体选择性合成4'-硫代核苷的β-异头物，基于对4-硫呋喃类化合物糖基的亲电糖基化。

  摘要：

  制备了具有不同3,5-O-甲硅烷基保护基的三种类型的4-硫呋喃基糖，并对其亲电性进行了研究。3,5-双-O-（叔丁基二甲基甲硅烷基）-4-硫呋喃类化合物糖基（5）是通过将2-脱氧-4-硫代-D-赤型戊呋喃糖（4）进行甲磺酸化并随后进行碱促进的消除反应而获得的，热消除亚砜衍生物适用于制备3,5-O-（四异丙基二硅氧烷-1,3-二基）（9）和3,5-O-（二叔丁基亚甲硅烷基）（11）4-硫代缩醛。通过使用尿嘧啶，胸腺嘧啶，胞嘧啶和N（6）-苯甲酰腺嘌呤的甲硅烷基化衍生物，在PhSeCl或NIS存在下，进行这些4-硫代糖基的糖基化反应。在这三种4-硫代糖中，有11种是出色的糖基供体，

  DOI：

  10.1021/jo020037x

文献信息

• Synthesis of 4′-substituted 2′-deoxy-4′-thiocytidines and its evaluation for antineoplastic and antiviral activities
  作者：Kazuhiro Haraguchi、Hiroki Kumamoto、Kiju Konno、Hideki Yagi、Yutaka Tatano、Yuki Odanaka、Satoko Shimbara Matsubayashi、Robert Snoeck、Graciela Andrei

  DOI：10.1016/j.tet.2019.06.044

  日期：2019.8

  glycosidation utilizing 36 and 43 for the synthesis of 37 and 44. Introduction of the azido group was carried out by nucleophilic substitution in the 4′-benzoyloxy derivative 22a. On the other hand, 9 and 10 were synthesized by way of the chemical manipulation of the hydroxymethyl group at the 4′-position of 46. Evaluation of the antineoplastic activity of 2 and 7–10 against human B-cell (CCRF-SB) and

  4′-叠氮基-（7），4′- C-氟甲基-（8 ），4′- C-乙炔基-（9）和4′- C-氰基-（10）2′-脱氧-4′-硫胞苷具有已合成。在这项研究中，发现利用路易斯酸促进的Vorbrüggen型糖苷化反应中利用12分离的4'-硫尿嘧啶核苷13的产率要高于甲硅烷基化尿嘧啶和11之间的亲电糖苷化反应的产率。这一改进的结果促使我们用36和43进行糖苷化以合成37和44。叠氮基的引入是通过在4'-苯甲酰氧基衍生物22a中的亲核取代进行的。另一方面，通过化学操作46的4'-位上的羟甲基合成了9和10。 对2和7-10对人B细胞（CCRF-SB）和T细胞白血病（Molt-4）细胞的抗肿瘤活性的评估表明，4'-叠氮基（7）和4'- C-氟甲基-（8）衍生物表现出细胞毒性活性，而在4'- C-乙炔基-（9）和4'- C-氰基-（10）衍生物以及母体化合物2中未观察到细胞毒性。具有对VZV和HSV-1
• Stereoselective entry to 1′-C-branched 4′-thionucleosides from 4-thiofuranoid glycal: synthesis of 4′-thioangustmycin C
  作者：Kazuhiro Haraguchi、Haruhiko Takahashi、Hiromichi Tanaka

  DOI：10.1016/s0040-4039(02)01131-0

  日期：2002.8

  1′-C-carbon-substituted 4′-thionucleosides has been developed. The present method consists of the following steps: (1) preparation of the 1-C-carbon-substituted 4-thiofuranoid glycals based on lithiation, and (2) NIS- or PhSeCl-initiated stereoselective glycosidation to these 1-substituted glycals. This synthetic sequence enabled us to synthesize the 4′-thio analogue of antitumor antibiotic angustmycin

  已经开发了用于合成新型1' - C-碳取代的4'-硫代核苷的立体选择性合成方法。本方法包括以下步骤：（1）基于锂化制备1 - C-碳取代的4-硫呋喃类糖，和（2）NIS-或PhSeCl引发的对这些1-取代的糖的立体选择性糖苷化。该合成序列使我们能够合成抗肿瘤抗生素阿古霉素C的4'-硫代类似物。
• Electrophilic addition to 4-thio furanoid glycal: a highly stereoselective entry to 2′-deoxy-4′-thio pyrimidine nucleosides
  作者：Kazuhiro Haraguchi、Ayako Nishikawa、Eiko Sasakura、Hiromichi Tanaka、Kazuo T. Nakamura、Tadashi Miyasaka

  DOI：10.1016/s0040-4039(98)00543-7

  日期：1998.5

  4-Thio furanoid glycals with different types of O-silyl protection have been prepared from benzyl 3,5-di-O-benzyl-2-deoxy-1,4-dithio-D-erythro-pentofuranoside. Face-selectivity for PhSeCl- or N-iodosuccimide-initiated addition of a pyrimidine base to the thioglycal was found to be controlled by O-silyl protecting groups. Using the thioglycal protected with a 3,5-O-di-t-butylsilyl group, a highly stereoselective synthesis of beta-2'-deoxy-4'-thio pyrimidine nucleosides has been accomplished. (C) 1998 Elsevier Science Ltd. All rights reserved.
• Synthesis and Anti-HIV Activity of 4′-Substituted 4′-Thiothymidines: A New Entry Based on Nucleophilic Substitution of the 4′-Acetoxy Group
  作者：Kazuhiro Haraguchi、Hisashi Shimada、Hiromichi Tanaka、Takayuki Hamasaki、Masanori Baba、Elizabeth A. Gullen、Ginger E. Dutschman、Yung-Chi Cheng

  DOI：10.1021/jm070824s

  日期：2008.3.1

  Diacetoxylation of 1-(2,5-dideoxy-beta-L-glycero-pent-4-eno-4-thiofuranosyl)thymine (13) with Pb(OAc)(4) allowed introduction of an acetoxy leaving group to the 4 '-position. Nucleophilic substitution of the resulting 4 '-acetoxy derivative (14) with silicon reagents enabled us to prepare the 4 '-phenylthio (17a), 4 '-azido (18a), 4 '-methoxy (20a), and 4 '-allyl (21a) analogues of 4 '-thiothymidine. 4 '-Cyano (25a) and 4 '-ethynyl (31) nucleosides were also synthesized from 3 ',5 '-bis-O-TBDMS derivative (24). Among novel 4 '-substituted 4 '-thiothymidines, the 4 '-azido (33), 4 '-cyano (36), and 4 '-ethynyl (37) derivatives were found to show potent inhibitory activity against HIV-1 and HIV-2. It is noteworthy that 36 and 37 were also inhibitory against replication of HIV variant resistant to 3TC (HIV-1(M184V)), being as potent as against HIV-1(IIIB).
• Synthesis and antiviral activities of 1′-carbon-substituted 4′-thiothymidines
  作者：Kazuhiro Haraguchi、Haruhiko Takahashi、Hiromichi Tanaka、Hiroyuki Hayakawa、Noriyuki Ashida、Takao Nitanda、Masanori Baba

  DOI：10.1016/j.bmc.2004.07.057

  日期：2004.10

  4-Thiofuranoid glycals substituted at the 1-position with methyl (5), (t-butyldimethylsilyloxy)methyl (7), and acetoxymethyl (8) groups were prepared from the 3,5-O-(1,1,3,3-tetraisopropyldisiloxane-1,3-diyl) (TIPDS)-4-thiofuranoid glycal (3) by way of LDA-lithiation. N-Iodosuccimide-initiated electrophilic glycosidation between silylated thymine and these 1-carbon-substituted 4-thioglycals gave the respective beta-anomers (9, 10, and 13) stereo selectively. Tin radical-mediated removal of the T-iodine atom from these products provided the corresponding 1'-branched 4'-thiothymidine derivatives (11, 12, and 14) in good yields. The 1'-hydroxymethyl derivative (15) served as a precursor for the preparation of the formyl (16), cyanoethenyl (17), and cyano (19) derivatives. Among the deprotected 1'-branched 4'-thiothymidines (20-25), the 1'-methyl analogue 20 showed the most potent anti-HSV-1 activity, but it was much less active than the parent compound 4'-thiothymidine. (C) 2004 Elsevier Ltd. All rights reserved.