13716-45-5Relevant articles and documents
Structures of products of the reactions of halotriorganosilanes with triethyl phosphite and with sodium dialkyl phosphites
Bugerenko,Chernyshev,Popov
, p. 1334 - 1337 (1967)
1. The reaction of bromotriethylsilane with triethyl phosphite at high temperatures (155-180°) goes with formation mainly of silyl-substituted tervalent phosphorus derivatives, which readily combine with sulfur and undergo Arbuzov reaction with ethyl bromide. 2. In the reactions of trialkylhalosilanes with sodium diethyl phosphite the products are not quinquevalent phosphorus compounds containing the Si-P bond as was supposed earlier, but the isomeric tervalent phosphorus compounds containing the Si-O-P link. 3. The thione-thiol isomerization of Si-P was effected in presence of ethyl bromide.
A new selenium-transferring reagent - Triphenylphosphine selenide
Bollmark,Stawinski
, p. 771 - 772 (2001)
Triphenylphosphine selenide and its polymer-supported counterpart are found to be efficient selenium-transferring reagents for the conversion of H-phosphonate diesters and phosphite triesters into the corresponding phosphoroselenoate derivatives.
New Synthesis of Diethyl Trimethylsilyl Phosphite
Morgalyuk,Strelkova,Buyanovskaya,Brel
, p. 1442 - 1443 (2019)
Diethyl phosphonate rapidly reacted with hexamethyldisilazane at 20°C in the presence of 52 mol % of zinc(II) chloride to give 76% of diethyl trimethylsilyl phosphite.
Synthesis of Rovafovir Etalafenamide (Part III): Evolution of the Synthetic Process to the Phosphonamidate Fragment
Ambrosi, Andrea,Bringley, Dustin A.,Calimsiz, Selcuk,Curl, Jonah,Garber, Jeffrey A. O.,Huynh, Huy,Kwong, Bernard,Lapina, Olga,Leung, Edmund,Lin, Lennie,Martins, Andrew,McGinitie, Teague,Mohan, Sankar,Phull, Jaspal,Roberts, Ben,Rosario, Mary,Sarma, Keshab,Shen, Jinyu,Shi, Bing,Standley, Eric A.,Wang, Li,Wang, Xueqing,Yu, Guojun
supporting information, p. 1247 - 1262 (2021/05/29)
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 alternative synthetic conditions became desirable in consideration of the high production cost, long lead time, and high process mass intensity (PMI) associated with SMB. Several strategies to improve these factors are described herein, including epimerization and recycling of the undesired (R)-phosphorus diastereomer, design of stereoselective approaches to establish the desired (S)-configuration at phosphorus, and identification of conditions or derivatives to allow for selective crystallization. Ultimately, a second-generation route to 1 was developed and demonstrated on scale. The new route achieves the separation of phosphorus diastereomers by means of selective crystallization, does not require SMB, and offers lower PMI, cost, and lead time.
Steric Enforcement of cis-Epoxide Formation in the Radical C-O-Coupling Reaction by Which (S)-2-Hydroxypropylphosphonate Epoxidase (HppE) Produces Fosfomycin
Zhou, Shengbin,Pan, Juan,Davis, Katherine M.,Schaperdoth, Irene,Wang, Bo,Boal, Amie K.,Krebs, Carsten,Bollinger, J. Martin
supporting information, p. 20397 - 20406 (2019/12/27)
(S)-2-Hydroxypropylphosphonate [(S)-2-HPP, 1] epoxidase (HppE) reduces H2O2 at its nonheme-iron cofactor to install the oxirane "warhead" of the antibiotic fosfomycin. The net replacement of the C1 pro-R hydrogen of 1 by its C2 oxygen, with inversion of configuration at C1, yields the cis-epoxide of the drug [(1R,2S)-epoxypropylphosphonic acid (cis-Fos, 2)]. Here we show that HppE achieves ~95% selectivity for C1 inversion and cis-epoxide formation via steric guidance of a radical-coupling mechanism. Published structures of the HppE·FeII·1 and HppE·ZnII·2 complexes reveal distinct pockets for C3 of the substrate and product and identify four hydrophobic residues - Leu120, Leu144, Phe182, and Leu193 - close to C3 in one of the complexes. Replacement of Leu193 in the substrate C3 pocket with the bulkier Phe enhances stereoselectivity (cis:trans ~99:1), whereas the Leu120Phe substitution in the product C3 pocket diminishes it (~82:18). Retention of C1 configuration and trans-epoxide formation become predominant with the bulk-reducing Phe182Ala substitution in the substrate C3 pocket (~13:87), trifluorination of C3 (~23:77), or both (~1:99). The effect of C3 trifluorination is counteracted by the more constrained substrate C3 pockets in the Leu193Phe (~56:44) and Leu144Phe/Leu193Phe (~90:10) variants. The ability of HppE to epoxidize substrate analogues bearing halogens at C3, C1, or both is inconsistent with a published hypothesis of polar cyclization via a C1 carbocation. Rather, specific enzyme-substrate contacts drive inversion of the C1 radical - as proposed in a recent computational study - to direct formation of the more potently antibacterial cis-epoxide by radicaloid C-O coupling.