diethyl benzyloxymethylphosphonate | 89268-01-9

• 分子结构分类: 有机化合物 - 有机酸及其衍生物 - 有机膦酸及其衍生物
• 英文名称: diethyl benzyloxymethylphosphonate
• 英文别名: Phosphonic acid, [(phenylmethoxy)methyl]-, diethyl ester；diethoxyphosphorylmethoxymethylbenzene
• CAS: 89268-01-9
• 化学式: C₁₂H₁₉O₄P
• 分子量: 258.254
• InChiKey: RSWAARAHUXRVGB-UHFFFAOYSA-N

计算性质

• 辛醇/水分配系数(LogP)：
  1.6
• 重原子数：
  17
• 可旋转键数：
  8
• 环数：
  1.0
• sp3杂化的碳原子比例：
  0.5
• 拓扑面积：
  44.8
• 氢给体数：
  0
• 氢受体数：
  4

反应信息

• 作为反应物：
  描述：

  diethyl benzyloxymethylphosphonate 在 氢氧化钾 作用下， 以 乙醇 为溶剂， 反应 2.5h， 以3.5 g的产率得到ethyl hydrogen benzyloxymethylphosphonate
  参考文献：
  名称：

  α-Functionalized Phosphonylphosphinates:  Synthesis and Evaluation as Transcarbamoylase Inhibitors

  摘要：

  Diverse alpha-methyl-substituted phosphonylphosphinates (P-C-P-C-X) are accessible from a protected, pentafluorophenylsulfonated phosphonylphosphinate via nucleophilic displacement. The utility of this route is demonstrated with several nitrogen nucleophiles. The resulting amine and amino acid phosphonylphosphinate derivatives were evaluated as inhibitors of Streptococcus faecalis ornithine transcarbamoylase (OTC). Compared with the structurally related phosphonoacetyl-L-ornithine (L-PALO), a known inhibitor of OTCs from various sources, the phosphonylphosphinates are surprisingly poor inhibitors, binding several orders of magnitude less tightly to the enzyme. These results suggest that the tetrahedral intermediate formed in the normal transcarbamoylase reaction is poorly mimicked by a tetrahedral and anionic phosphonate, either because of directly unfavorable interactions with a hydrogen-bond acceptor within the active site or because transition-state analogues are unable to induce the protein conformation changes that normally accompany reaction.

  DOI：

  10.1021/jm991008q
• 作为产物：
  描述：

  苯甲醇 在 盐酸 、 乙醚 作用下， 生成 diethyl benzyloxymethylphosphonate
  参考文献：
  名称：

  Abramow; Ssergejewa; Tschelpanowa, Zhurnal Obshchei Khimii, 1944, vol. 14, p. 1030,1033, 1035

  摘要：

  DOI：

文献信息

• Diastereoselective Synthesis of 2-Amino-4-phosphonobutanoic Acids by Conjugate Addition of Lithiated Schöllkopf's Bislactim Ethers to Vinylphosphonates
  作者：María Ruiz、M. Carmen Fernández、Aniana Díaz、José M. Quintela、Vicente Ojea

  DOI：10.1021/jo034707q

  日期：2003.10.1

  Conjugate additions of lithiated bislactim ethers derived from cyclo-[Gly-Val] and cyclo-[Ala-Val] to alpha-, beta-, or alpha,beta-substituted vinylphosphonates allow direct and stereoselective access to a variety of 3- or 4-monosubstituted and 2,3-, 2,4-, or 3,4-disubstituted 2-amino-4-phosphonobutanoic acids (AP4 derivatives) in enantiomerically pure form. The relative stereochemistry was assigned

  将衍生自环-[Gly-Val]和环-[Ala-Val]的锂化双lactimin醚与α-，β-或α，β-取代的乙烯基膦酸酯共轭加成可直接和立体选择性地获得各种3-或4对映体纯形式的-单取代和2,3-，2,4-或3,4-二取代的2-氨基-4-膦酰基丁酸（AP4衍生物）。通过X-射线衍射分析或1，2-氧杂磷杂环丁烷衍生物的NMR研究确定相对立体化学。调用竞争性的八元“紧凑”和“松弛”过渡态结构以合理化共轭添加物的立体化学结果。
• [EN] NEW ANTIBACTERIAL COMPOUNDS AND BIOLOGICAL APPLICATIONS THEREOF<br/>[FR] NOUVEAUX COMPOSÉS ANTIBACTÉRIENS ET LEURS APPLICATIONS BIOLOGIQUES
  申请人：BIODIM LAB

  公开号：WO2014067904A1

  公开（公告）日：2014-05-08

  The invention relates to compounds of formulae (Ia), (Ib) or (Ic) wherein, - A1 and A2, identical or different, are H, (C1-C6) alkyl, (C1-C6) fluoroalkyl, (C2-C6) alkenyl, (C2-C6) alkynyl, (C1-C6) alkyl-ORa, (C1-C6) alkyl-SRa, (C1-C6) alkyl-NRaRb, ORa, SRa, NRaRb, or CORa; - A3 is H, OH or form a carbonyl with A4; - A4 is H, OH or form a carbonyl with A3; - A5 is H, CRaRbOH, F, OH or forms a double bond with X in the case where X is CH; - A6 is H or F; - X is CH2, CHF, CF2, CHOH, O, S, NRa or a simple bond, or X is CH in the case where A5 forms with X a double bond; - Y is P(O) (ORa) (ORb) or P (O) (ORa) (NRaRb); - V is O or S; - A7 is H, (C1-C6) alkyl, (C1-C6) fluoroalkyl, (C2-C6) alkenyl, (C2-C6) alkynyl or (C1-C6) alkyl-ORa; - A8 is OH or H, - Ra and Rb, identical or different, are H, (C1-C6) alkyl, (C1-C6) fluoroalkyl, (C1-C6) alkyl-OH or (C1-C6) alkyl-O- (C1- C6) alkyl; and their addition salts thereof with acids and bases, their preparation and their use in the antibacterial prevention and therapy, used alone or in association with antibacterials, antivirulence agents or drugs reinforcing the host innate immunity.

  该发明涉及以下式(Ia)、(Ib)或(Ic)的化合物，其中，- A1和A2，相同或不同，为H、(C1-C6)烷基、(C1-C6)氟烷基、(C2-C6)烯基、(C2-C6)炔基、(C1-C6)烷基-ORa、(C1-C6)烷基-SRa、(C1-C6)烷基-NRaRb、ORa、SRa、NRaRb或CORa；- A3为H、OH或与A4形成羰基；- A4为H、OH或与A3形成羰基；- A5为H、CRaRbOH、F、OH或与X形成双键，其中X为CH时；- A6为H或F；- X为CH2、CHF、CF2、CHOH、O、S、NRa或简单键，或当A5与X形成双键时X为CH；- Y为P(O)(ORa)(ORb)或P(O)(ORa)(NRaRb)；- V为O或S；- A7为H、(C1-C6)烷基、(C1-C6)氟烷基、(C2-C6)烯基、(C2-C6)炔基或(C1-C6)烷基-ORa；- A8为OH或H；- Ra和Rb，相同或不同，为H、(C1-C6)烷基、(C1-C6)氟烷基、(C1-C6)烷基-OH或(C1-C6)烷基-O-(C1-C6)烷基；以及它们与酸和碱的加成盐，它们的制备以及它们在抗菌预防和治疗中的用途，单独使用或与抗菌剂、抗毒力剂或增强宿主先天免疫力的药物结合使用。
• A convenient one-pot synthesis of polyenic enol ethers
  作者：Yen Vo-Quang、Denis Carniato、Liliane Vo-Quang、Fran�ois Le Goffic

  DOI：10.1039/c39830001505

  日期：——

  Diethyl alkoxymethylphosphonates react with unsaturated aldehydes to give polyenic enol ethers with a good stereoselectivity.

  烷氧基甲基膦酸二乙酯与不饱和醛反应，得到具有良好立体选择性的多烯醇。
• Synthesis of Rovafovir Etalafenamide (Part III): Evolution of the Synthetic Process to the Phosphonamidate Fragment
  作者：Andrea Ambrosi、Dustin A. Bringley、Selcuk Calimsiz、Jeffrey A. O. Garber、Huy Huynh、Sankar Mohan、Keshab Sarma、Jinyu Shen、Jonah Curl、Bernard Kwong、Olga Lapina、Edmund Leung、Lennie Lin、Andrew Martins、Teague McGinitie、Jaspal Phull、Ben Roberts、Mary Rosario、Bing Shi、Eric A. Standley、Li Wang、Xueqing Wang、Guojun Yu

  DOI：10.1021/acs.oprd.0c00428

  日期：2021.5.21

  Phosphonamidate 1 is a key fragment in the assembly of rovafovir etalafenamide, a novel nucleotide reverse transcriptase inhibitor under development at Gilead Sciences for the treatment of HIV infection. An early manufacturing route, relying on simulated moving bed (SMB) chromatography for the separation of phosphorus diastereomers, was executed on scale to produce multiple batches of 1. However, developing

  膦酰氨基甲酸酯1是rovafovir etalafenamide组装过程中的关键片段，该药物是Gilead Sciences研发的用于治疗HIV感染的新型核苷酸逆转录酶抑制剂。依靠模拟移动床（SMB）色谱法分离磷非对映异构体的早期生产路线可大规模生产1批。但是，考虑到与SMB相关的高生产成本，长交货期和高工艺质量强度（PMI），开发替代合成条件变得合乎需要。本文描述了几种改善这些因素的策略，包括差向异构化和不需要的（R）-磷非对映异构体，设计立体选择性方法以在磷处建立所需的（S）-构型，并鉴定条件或衍生物以允许选择性结晶。最终，开发了第二代至1的途径并进行了规模论证。新路线通过选择性结晶实现了磷非对映异构体的分离，不需要SMB，并提供了更低的PMI，成本和交货时间。
• [EN] ELECTRONIC DEVICES COMPRISING NOVEL PHOSPHONIC ACID SURFACE MODIFIERS<br/>[FR] DISPOSITIFS ÉLECTRONIQUES COMPRENANT DE NOUVEAUX MODIFICATEURS DE SURFACE À BASE D'ACIDE PHOSPHONIQUE
  申请人：GEORGIA TECH RES INST

  公开号：WO2010115854A1

  公开（公告）日：2010-10-14

  In some embodiments, the inventions described herein relate to a composition of matter comprising a molecule having the structure: wherein: independently at each occurrence, R1 is a halogen, a alkyl group, a heteroalkyl group, an aryl group, or a heteroaryl group; R2 comprises from 3 to 30 CH2- groups, n = 0-5, m = 0-5, q = 1-3, and R2 comprises at least one ether linkage

  在某些实施例中，所述发明涉及一种物质组合物，其包括具有以下结构的分子：其中：在每次出现时，R1是卤素、烷基、杂烷基、芳基或杂芳基中的任意一种；R2包括3至30个CH2-基团，n = 0-5，m = 0-5，q = 1-3，且R2至少包括一个醚键。