(2R,5S)-2-chloro-3,1-oxaza-2-phosphabicyclo[3.3.0]octane | 215190-93-5

• 分子结构分类: 有机化合物 - 有机杂环化合物 - 吡咯烷类
• 英文名称: (2R,5S)-2-chloro-3,1-oxaza-2-phosphabicyclo[3.3.0]octane
• 英文别名: (3aS)-1-chlorotetrahydro-1H,3H-pyrrolo[1,2-c][1,3,2]oxazaphosphole；(3aS)-1-chloro-3a,4,5,6-tetrahydro-3H-pyrrolo[1,2-c][1,3,2]oxazaphosphole
• CAS: 215190-93-5
• 化学式: C₅H₉ClNOP
• 分子量: 165.559
• InChiKey: BGBQOIIZKBFXKF-GXRJOMEUSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.3
• 重原子数：
  9
• 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：
  12.5
• 氢给体数：
  0
• 氢受体数：
  2

反应信息

• 作为反应物：
  描述：

  (2R,5S)-2-chloro-3,1-oxaza-2-phosphabicyclo[3.3.0]octane 在 N,N-二异丙基乙胺 作用下， 以 二氯甲烷 为溶剂， 生成 5'-O-胸苷酰 3'-O-(2'-脱氧腺苷)硫代磷酸酯
  参考文献：
  名称：

  Stereo-enriched phosphorothioate oligodeoxynucleotides: synthesis, biophysical and biological properties

  摘要：

  Stereo-enriched [Rp] and [Sp]-phosphorothioate oligodeoxynucleotides are synthesized using oxazaphospholidine derivatized monomers. Three different designs of phosphorothioate oligodeoxynucleotides (PS-oligos), (i) stereo-enriched all-[Rp] or all-[Sp] PS-linkages, (ii) stereo-random mixture of PS-linkages, and (iii) segments containing certain number of stereo-enriched [Rp] and [Sp] PS-linkages ([Sp-Rp-Sp] or [Rp-Sp-Rp]), have been studied. Thermal melting studies of these PS-oligos with RNA complementary strands showed that the binding affinities are in the order [Rp] > [Sp-Rp-Sp] = [Rp-Sp-Rp] > stereo-random > [Sp]. Circular dichroism (CD) studies suggest that the stereochemistry of the PS-oligo does not affect the global conformation of the duplex. The in vitro nuclease stability of these PS-oligos is in the order [Sp] > [Sp-Rp-Sp], stereo-random > [Rp]. The RNase H activation is in the order [Rp] > stereo-random > [Rp-Sp-Rp] > [Sp] > [Sp-Rp-Sp]. Studies in a cancer cell Line of PS-oligos targeted to MDM2 mRNA showed that all oligos had similar biological activity under the experimental conditions employed. Protein- and enzyme-binding studies showed insignificant stereo-dependent binding to proteins. The [Sp] and [Sp-Rp-Sp] chimeric and stereo-random PS-oligos that contained a CpG motif showed higher cell proliferation than [Rp] PS-oligo of the same sequence. (C) 2000 Elsevier Science Ltd. All rights reserved.

  DOI：

  10.1016/s0968-0896(99)00275-8
• 作为产物：
  描述：

  L-脯氨醇 在 三乙胺 、 三氯化磷 作用下， 以 苯 为溶剂， 以82%的产率得到(2R,5S)-2-chloro-3,1-oxaza-2-phosphabicyclo[3.3.0]octane
  参考文献：
  名称：

  用于 Pd 催化不对称烯丙基化的新型高效 P-手性二茂铁亚氨基二氨基亚磷酸酯配体

  摘要：

  通过用衍生自 (S)-2-苯胺基甲基吡咯烷或 (S)-脯氨醇的氯亚磷酸酯处理基于二茂铁的亚氨基醇，合成了新型 P*-手性 P，N-二齿配体。金属螯合物与配体 – [Rh(CO)(PN)Cl] 和 [Pd(PN)(allyl)]+X– (X– = BF4–, Cl–, I–, CH12B11–) – 获得并所有新化合物均通过 1H、13C、31P NMR、IR、MS（EI、CI、FAB、ESI 和等离子体解吸技术）和 X 射线分析（亚氨基醇 2d 和复合物 7）进行了全面表征。在 Pd 催化的乙酸 1,3-二苯基烯丙酯与丙二酸二甲酯和对甲苯亚磺酸酯的烯丙基取代中，P*-手性二酰胺基亚磷酸酯产生高达 97% 的 ee。(© Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2005)

  DOI：

  10.1002/ejoc.200400780

文献信息

• Solid-Phase Synthesis of Stereoregular Oligodeoxyribonucleoside Phosphorothioates Using Bicyclic Oxazaphospholidine Derivatives as Monomer Units
  作者：Natsuhisa Oka、Mika Yamamoto、Terutoshi Sato、Takeshi Wada

  DOI：10.1021/ja805780u

  日期：2008.11.26

  Nucleoside 3'-O-bicylic oxazaphospholidine derivatives were designed as monomer units for a solid-phase synthesis of stereoregular oligodeoxyribonucleoside phosphorothioates (PS-ODNs). The trans-isomers of appropriately designed nucleoside 3'-O-bicyclic oxazaphospholidine derivatives were generated exclusively by the reaction between the 3'-OH of the corresponding protected nucleosides and 2-chloro-1

  核苷 3'-O-双环 oxazaphospholidine 衍生物被设计为单体单元，用于固相合成有规立构寡脱氧核糖核苷硫代磷酸酯 (PS-ODNs)。适当设计的核苷 3'-O-双环 oxazaphospholidine 衍生物的反式异构体仅通过相应受保护核苷的 3'-OH 与 2-氯-1,3,2-oxazaphospholidine 衍生物之间的反应生成。得到的反式-氧氮杂磷脂异构体在构型上是稳定的，在固体载体上缩合过程中，在酸性活化剂存在下差向异构化不会损害它们的非对映纯度。因此，通过使用氧氮杂磷脂单体和酸性活化剂形成 (Rp)- 和 (Sp)-硫代磷酸酯核苷酸间键的过程中，非对映纯度没有任何损失（非对映选择性 > 或 = 99:1）。此外，从头分子轨道计算表明，氧氮杂磷脂衍生物的差向异构化最有可能通过 N-质子化加速的边缘反转过程进行。计算不仅合理化了本研究中观察到的环结构与 oxazaphospholidines
• Solid-phase stereoselective synthesis of oligonucleoside phosphorothioates: The nucleoside bicyclic oxazaphospholidines as novel synthons
  作者：Radhakrishnan P Iyer、Mao-Jun Guo、Dong Yu、Sudhir Agrawal

  DOI：10.1016/s0040-4039(98)00380-3

  日期：1998.4

  The nucleoside bicylic oxazaphospholidine derived from L-, or D-prolinol is a novel synthon with potential for solid-phase stereoselective synthesis of oligonucleoside phosphorothioates.

  衍生自L-或D-脯氨醇的核苷二环氧杂氮杂膦烷是一种新型合成子，具有固相立体选择性合成寡核苷硫代磷酸酯的潜力。
• OPTICALLY ACTIVE SEGMENT FOR STEREOCONTROLLED OLIGONUCLEOTIDE SYNTHESIS, PRODUCTION METHOD FOR SAME, AND STEREOCONTROLLED OLIGONUCLEOTIDE SYNTHESIS METHOD USING SAME
  申请人：Natias Inc.

  公开号：EP3778616A1

  公开（公告）日：2021-02-17

  An optically active segment for use in synthesis of a stereocontrolled oligonucleotide represented by the following formula (I), a method for producing the same, and a method for synthesizing a stereocontrolled oligonucleotide therefrom are provided. In formula, B is a protected/unprotected nucleoside base; R1 is substituted/unsubstituted aliphatic group; R2, R3 is a DMTr group or -P(R11)(NR12)2; R11 is OCH2CH2CN, SCH2CH2CN, etc.; R12 is a substituted/unsubstituted aliphatic group or aromatic group; X is H, an alkyl, O-alkyl, etc.; Y is H, NHR13, a halogen, etc., or a hydroxyl group protected with an acyl, ether, or silyl, or forms an X-Y bond with X; and n is an integer of 0 or more and 4 or less.

  本发明提供了一种用于合成下式（I）所代表的立体可控寡核苷酸的光学活性片段、生产该片段的方法以及用其合成立体可控寡核苷酸的方法。式中，B 是受保护/未受保护的核苷酸碱基；R1 是取代/未取代的脂肪族基团；R2、R3 是 DMTr 基团或 -P(R11)(NR12)2；R11 是 OCH2CH2CN、SCH2CH2CN 等；R12 是取代/未取代的脂肪族基团或芳香族基团；X 是 H、烷基、O-烷基等；Y 是 H、NHR13、卤素等、或用酰基、醚或硅烷基保护的羟基，或与 X 形成 X-Y 键；n 为 0 或 0 以上 4 或 4 以下的整数。
• Synthesis of phosphorylated sulfoximines and sulfinamides and their application as ligands in asymmetric metal catalysis
  作者：Eduard B. Benetskiy、Carsten Bolm

  DOI：10.1016/j.tetasy.2011.02.005

  日期：2011.2

  Starting from inexpensive materials and following simple protocols various N-phosphorylated sulfoximines and sulfinamides have been synthesized. The newly prepared compounds were then applied as chiral ligands in asymmetric transition metal catalysis. Phosphorus triamide-type ligands derived from (S)-glutamic acid were found to be the most efficient stereoselectors in enantioselective palladium-catalyzed allylic substitutions (up to 97% ee). On the other hand, diamidophosphite-type structures stemming from (S)-proline were the best ligands in rhodium-catalyzed hydrogenation reactions (up to 84% ee). (C) 2011 Elsevier Ltd. All rights reserved.
• Solid-phase stereoselective synthesis of 2′-O-methyl-oligoribonucleoside phosphorothioates using nucleoside bicyclic oxazaphospholidines
  作者：MaoJun Guo、Dong Yu、Radhakrishnan P. Iyer、Sudhir Agrawal

  DOI：10.1016/s0960-894x(98)00450-8

  日期：1998.9

  The use of 2'-OMe-ribonucleoside bicyclic oxazaphospholidines derived from (R)- or (S)-2-pyrrolidinemethanol has enabled the stereoselective synthesis of (R-p)-, and (S-p)-2'-O-methyloligoribonucleoside phosphorothioates. Interestingly, higher stereoselectivity (96-98%) was observed in the synthesis of (S-p)-2'-O-methyl-oligoribonucleoside phosphorothioates compared to that in the case of(S,)oligodeoxyribonucleoside phosphorothioates (90%). (C) 1998 Published by Elsevier Science Ltd. All rights reserved.