2-chloro-4,4-pentamethylene-1,3,2-oxathiaphospholane | 198637-74-0

• 分子结构分类: 有机化合物 - 有机磷化合物 - 有机硫代磷化合物
• 英文名称: 2-chloro-4,4-pentamethylene-1,3,2-oxathiaphospholane
• 英文别名: 2-chloro-3-oxa-1-thia-2-phosphaspiro[4.5]decane
• CAS: 198637-74-0
• 化学式: C₇H₁₂ClOPS
• 分子量: 210.664
• InChiKey: SXNNCIITGICZJF-UHFFFAOYSA-N

物化性质

• 沸点：
  274.9±23.0 °C(Predicted)

计算性质

• 辛醇/水分配系数(LogP)：
  2.6
• 重原子数：
  11
• 可旋转键数：
  0
• 环数：
  2.0
• sp3杂化的碳原子比例：
  1.0
• 拓扑面积：
  34.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  2-chloro-4,4-pentamethylene-1,3,2-oxathiaphospholane 在 sulfur 、 N,N-二异丙基乙胺 作用下， 以 乙腈 为溶剂， 反应 12.08h， 生成 5’-O-DMT-N²-isobutyryl-2’-deoxyguanosine-3’-O-(2-thio-4,4-pentamethylene-1,3,2-oxathiaphospholane)
  参考文献：
  名称：

  Deoxyribonucleoside 3‘-O-(2-Thio- and 2-Oxo-“spiro”-4,4-pentamethylene-1,3,2-oxathiaphospholane)s:  Monomers for Stereocontrolled Synthesis of Oligo(deoxyribonucleoside phosphorothioate)s and Chimeric PS/PO Oligonucleotides

  摘要：

  New monomers, 5'-O-DMT-deoxyribonucleoside 3'-O-(2-thio-"spiro"-4,4-pentamethylene-1,3,2-oxathiaphospholane)s, were prepared and used for the stereocontrolled synthesis of PS-Oligos via the oxathiaphospholane approach. These monomers and their Zero analogues were used for the synthesis of "chimeric" constructs (PS/PO-Oligos) possessing phosphate and P-stereodefined phosphorothioate internucleotide linkages. The yield of a single coupling step is approximately 92-95%, and resulting oligomers are free of nucleobase- and sugar-phosphorothioate backbone modifications. Thermal dissociation studies showed that for heteroduplexes formed by [R-P]-, [S-P]-, or [mix]-PS/PO-T-10 with dA(12), dA(30), Or poly(dA), for each template, the melting temperatures, as well as free Gibbs' energies of dissociation process, are virtually equal. Stereochemical evidence derived from crystallographic analysis of one of the oxathiaphospholane monomers strongly supports the participation of pentacoordinate intermediates in the mechanism of the oxathiaphospholane ring-opening condensation.

  DOI：

  10.1021/ja973801j
• 作为产物：
  描述：

  1-mercapto-1,1-pentamethylenethan-2-ol 在 吡啶 、 三氯化磷 作用下， 以 苯 为溶剂， 反应 0.5h， 以76%的产率得到2-chloro-4,4-pentamethylene-1,3,2-oxathiaphospholane
  参考文献：
  名称：

  Deoxyribonucleoside 3‘-O-(2-Thio- and 2-Oxo-“spiro”-4,4-pentamethylene-1,3,2-oxathiaphospholane)s:  Monomers for Stereocontrolled Synthesis of Oligo(deoxyribonucleoside phosphorothioate)s and Chimeric PS/PO Oligonucleotides

  摘要：

  New monomers, 5'-O-DMT-deoxyribonucleoside 3'-O-(2-thio-"spiro"-4,4-pentamethylene-1,3,2-oxathiaphospholane)s, were prepared and used for the stereocontrolled synthesis of PS-Oligos via the oxathiaphospholane approach. These monomers and their Zero analogues were used for the synthesis of "chimeric" constructs (PS/PO-Oligos) possessing phosphate and P-stereodefined phosphorothioate internucleotide linkages. The yield of a single coupling step is approximately 92-95%, and resulting oligomers are free of nucleobase- and sugar-phosphorothioate backbone modifications. Thermal dissociation studies showed that for heteroduplexes formed by [R-P]-, [S-P]-, or [mix]-PS/PO-T-10 with dA(12), dA(30), Or poly(dA), for each template, the melting temperatures, as well as free Gibbs' energies of dissociation process, are virtually equal. Stereochemical evidence derived from crystallographic analysis of one of the oxathiaphospholane monomers strongly supports the participation of pentacoordinate intermediates in the mechanism of the oxathiaphospholane ring-opening condensation.

  DOI：

  10.1021/ja973801j

文献信息

• Diastereomerically pure nucleoside-5′-O-(2-thio-4,4-pentamethylene-1,3,2-oxathiaphospholane)s-Substrates for synthesis of P-chiral derivatives of nucleoside-5′-O-phosphorothioates
  作者：Agnieszka Tomaszewska、Piotr Guga、Wojciech J. Stec

  DOI：10.1002/chir.20905

  日期：2011.3

  A method for stereocontrolled chemical synthesis of P‐substituted nucleoside 5′‐O‐phosphorothioates has been elaborated. Selected 3′‐O‐acylated deoxyribonucleoside‐ and 2′,3′‐O,O‐diacylated ribonucleoside‐5′‐O‐(2‐thio‐4,4‐pentamethylene‐1,3,2‐oxathiaphospholane)s were chromatographically separated into P‐diastereomers. Their reaction with anions of phosphorus‐containing acids was highly stereoselective

  拟定了一种立体控制化学合成P-取代核苷5'- O-硫代磷酸酯的方法。选择3' ø -acylated deoxyribonucleoside-和2'，3'- O，O- -diacylated核糖核苷-5'- Ö - （2-硫代-4,4-五亚甲基-1,3,2-oxathiaphospholane）类是色谱法分为P-非对映异构体。它们与含磷酸阴离子的反应具有很高的立体选择性（≥90％），并以令人满意的产率提供了相应的P-手性α-硫代二磷酸及其膦酸酯类似物。手性，2011年。©2010 Wiley-Liss，Inc.。
• <i>P</i>-Stereodefined phosphorothioate analogs of glycol nucleic acids—synthesis and structural properties
  作者：Agnieszka Tomaszewska-Antczak、Katarzyna Jastrzębska、Anna Maciaszek、Barbara Mikołajczyk、Piotr Guga

  DOI：10.1039/c8ra05568h

  日期：——

  (OTP-GN′) containing a second stereogenic center at the phosphorus atom. These monomers were chromatographically separated into P-diastereoisomers, which were further used for the synthesis of P-stereodefined “dinucleoside” phosphorothioates GNPST (GN = GA, GC, GG, GT). The absolute configuration at the phosphorus atom for all eight GNPST was established enzymatically and verified chemically, and correlated

  对映体纯、受保护的 GNA 型无环核苷（乙二醇核酸）( G N')，从 ( R )-(+)- 和 ( S )-(−)-缩水甘油和四个典型 DNA 核碱基 (Ade、 Cyt、Gua 和 Thy）被转化为 3'- O -DMT 保护的 2-硫代-4,4-五亚甲基-1,3,2-氧杂硫磷烷衍生物 (OTP- G N')，其在磷原子。这些单体通过色谱分离成P-非对映异构体，进一步用于合成P-立体定义的“二核苷”硫代磷酸酯G N PS T ( G N = G A, G C, G G, G T)。所有八个G N PS T 的磷原子的绝对构型均通过酶法建立并经过化学验证，并与 OTP- G N' 单体在硅胶上的色谱迁移率相关。 G N PS单元（源自 ( R )-(+)-缩水甘油）被引入自互补 PS-(DNA/GNA) 八聚体中，该八聚体具有预选的 P 原子绝对构型。 热解离实验表明，双链体的热力学稳定
• Homopurine <i>R</i>_P-stereodefined phosphorothioate analogs of DNA with hampered Watson–Crick base pairings form Hoogsteen paired parallel duplexes with (2′-OMe)-RNAs
  作者：Anna Maciaszek、Katarzyna Jastrzębska、Piotr Guga

  DOI：10.1039/c8ob03112f

  日期：——

  phosphorothioate oligomers ((RP-PS)-DN(NX)A) with hampered Watson-Crick base pairings. It was found that the m6dA units slightly reduce the thermodynamic stability of antiparallel duplexes formed with RNA and (2'-OMe)-RNA matrices, whereas m,m2dG units prevent their formation. The m6dA units stabilize (by up to 4.5 °C per modified unit) the parallel duplexes formed by (RP-PS)-DN(NX)A with Hoogsteen-paired (2'-OMe)-RNA

  5'-O-DMT-N6-甲基-脱氧腺苷和5'-O-DMT-N2，N2-合成了二甲基-O6-二苯基氨基甲酰基-脱氧鸟苷（OTP-NY，NY = DMT-m6dA或DMT-m，m2dGDPC），拆分为纯P-非对映异构体，并用于P-立体控制合成的2'，3,5，-硫代磷酸核苷NXPST（NX = m6dA或m，m2dG），其中立体生成的磷原子的绝对构型通过酶法建立。非对映体纯OTP-NY和标准OTP-N（N = DMT-dABz或DMT-dGBz，DPC）用于合成受阻的RP-立体定义的硫代磷酸酯低聚物（（RP-PS）-DN（NX）A）沃森克里克碱基配对。发现m6dA单元会稍微降低与RNA和（2' -OMe）-RNA矩阵，而m，m2dG单位阻止其形成。与类似的参考双链体相比，m6dA单元可稳定（每个修饰单元最高4.5°C）由（RP-PS）-DN（NX）A与Hoogsteen配对（2'-OMe）-RN
• Thermal stability and conformation of antiparallel duplexes formed by P-stereodefined phosphorothioate DNA/LNA chimeric oligomers with DNA and RNA matrices
  作者：Katarzyna Jastrzębska、Anna Maciaszek、Rafał Dolot、Grzegorz Bujacz、Piotr Guga

  DOI：10.1039/c5ob01474c

  日期：——

  phosphorothioate oligomers the biggest enhancement in thermal stability of Watson–Crick paired duplexes was found for [SP-PS]-(DNA/LNA)/RNA duplexes (on average 8.2 °C per LNA nucleotide), followed by [RP-PS]-(DNA/LNA)/RNA (6.3 °C), [RP-PS]-(DNA/LNA)/DNA (3.8 °C) and [SP-PS]-(DNA/LNA)/DNA (2.4 °C per LNA nucleotide). However, detailed analysis of the thermal dissociation data showed that the thermal stability

  3'- ø - （2-硫代-4,4-五亚甲基-1,3,2-oxathiaphospholane）LNA型核苷（LNA-的OTP的衍生物，图2a-d ; B'=祢，阿德的Bz，细胞色素的Bz，分别合成了Gua dmf并分离为纯P-非对映异构体。X射线分析允许在去三苯甲基化的，快速洗脱的非对映异构体2a中分配磷原子的绝对构型。非对映异构纯LNA-OTP单体用于固相合成包含2-3个LNA单元的P-立体定义的嵌合PS-（DNA / LNA）11-聚体。正式地，在硫代磷酸酯低聚物中，发现沃森-克里克配对双链体的热稳定性最大[ S P-PS]-（DNA / LNA）/ RNA双链体（每个LNA核苷酸平均8.2°C），然后是[ R P -PS]-（DNA / LNA）/ RNA（6.3°C），[ R P -PS ]-（DNA / LNA）/ DNA（3.8°C）和[ S P -PS]-（DNA / LNA）/
• TAU-TARGETING OLIGONUCLEOTIDE GAPMERS
  申请人：Eisai R&D Management Co., Ltd.

  公开号：US20220195437A1

  公开（公告）日：2022-06-23

  Antisense oligonucleotides are provided. These antisense oligonucleotides are useful in the preparation of gapmers for inhibition of Tau mRNA transcription. Inhibition of Tau mRNA transcription may result in decrease of amounts of Tau protein in a subject, allowing treatment of diseases and disorders related to expression of Tau, including Alzheimer's disease and primary tauopathies.

  提供了反义寡核苷酸。这些反义寡核苷酸在制备gapmers以抑制Tau mRNA转录方面非常有用。抑制Tau mRNA转录可能导致受试者Tau蛋白质量的降低，从而治疗与Tau表达有关的疾病和疾病，包括阿尔茨海默病和原发性Tau病。