3491-28-9Relevant academic research and scientific papers
Compact reaction-module on a pad for scalable flow-production of organophosphates as drug scaffolds
Kang, In Seok,Kim, Dong-Pyo,Ramanjaneyulu, Bandaru T.,Vidyacharan, Shinde,Yang, Yu Dong,Yim, Se Jun
, p. 973 - 978 (2020/03/13)
Continuous pharmaceutical manufacturing receives intense attention as an alternative way to meet flexible market needs with the assurance of higher safety and quality control. Here, we report a compact reaction-module on a pad (CRP, 170 × 170 × 1.2 mm) for scale-up production of drug precursors in a continuous-flow. The CRP system was devised by stacking 9 films of the patterned polyimide to integrate micro-flow circuits, combining the functions of the even distribution of feeds, being completely mixed in less than a few milliseconds. A methodology of using a highly reactive species for the single-step synthesis of α-phosphonyloxy ketone, a drug scaffold, required the synthesis time of a few seconds in microfluidics. The fast reaction in the single CRP was capable of producing 19.2 g h-1 drug precursor, which indicates a solid step toward kilogram-scale pharmaceutical manufacturing in small footage.
Fast-Synthesis of α-Phosphonyloxy Ketones as Drug Scaffolds in a Capillary Microreactor
Ramanjaneyulu, Bandaru T.,Vidyacharan, Shinde,Yim, Se Jun,Kim, Dong-Pyo
supporting information, p. 7730 - 7734 (2019/12/24)
A simple, room temperature approach for the fast single-step synthesis of α-phosphonyloxy ketone, a drug scaffold, has been developed which involves highly reactive species i.e., 1,2-dicarbonyls that readily react with trialkyl phosphites and formic acids in batch as well as in continuous-flow with the flow rate of 3 ml/min (tR = ～4 s). The present approach reduced the synthesis time from hours to minutes in batch, which was further lowered to a few seconds precisely controlled by single capillary microfluidics. A wide range of 1,2-dicarbonyl derivatives were smoothly transformed to their corresponding α-phosphonyloxy ketones in moderate to good yields (50–82 %) under optimized flow-reaction conditions. Further, the α-phosphonyloxy ketones produced can be utilized in batch process to form benzoin, oxazole core, and α,α′-diarylated carbonyl compounds in 82 %, 50 %, and 54 % yields, respectively, which are alternative key precursors/scaffolds of natural products and active pharmaceutical ingredients (APIs).
I2O5/DBU mediated direct α-phosphoryloxylation of ketones with H-phosphonates leading to α-hydroxyketone phosphates
Liu, Chunli,Wei, Wei,Yang, Daoshan,Zheng, Yuanyuan,Bi, Yanshuai,Chen, Min,Wang, Hua
, p. 6901 - 6906 (2015/08/24)
A simple and convenient procedure has been developed for the construction of α-hydroxyketone phosphates via I2O5/DBU mediated direct α-phosphoryloxylation of ketones with H-phosphonates. This new reaction proceeds through three steps involving α-iodination of ketones, oxidation of H-phosphonates, and nucleophilic substitution of α-iodo ketones to access a series of α-hydroxyketone phosphates of biological importance.
Pd-catalyzed carbonylative access to aroyl phosphonates from (hetero)aryl bromides
Lian, Zhong,Yin, Hongfei,Friis, Stig D.,Skrydstrup, Troels
, p. 7831 - 7834 (2015/05/13)
The first transition-metal catalysed carbonylation with a phosphorus nucleophile is presented. This transformation provides efficient and mild access to aroylphosphonates under mild conditions, thus ensuring a broad substrate scope. The utility of aroylph
Cyanide-catalyzed additions of acyl phosphonates to aldehydes: A new acyl donor for benzoin-type reactions
Bausch, Cory C.,Johnson, Jeffrey S.
, p. 1207 - 1211 (2007/10/03)
Acyl phosphonates have been utilized as new acyl donors for cyanide-catalyzed benzoin-type reactions. Cyanation of acyl phosphonates, followed by a [1,2]-phosphoryl migration generates the active acyl anion intermediate. The presumed (cyano)phosphate anion reacts with a variety of aryl aldehydes to yield phosphate ester-protected, unsymmetrical benzoins in good to excellent yields. The unsymmetrical benzoin product can be obtained after deprotection of the phosphate ester with an aqueous amine solution.
Enhanced chromatographic resolution of alcohol enantiomers as phosphate or phosphonate derivatives
Leblanc, Yves,Dufresne, Claude,Carson, Rebekah,Morency, Louis,Welch, Christopher J
, p. 3063 - 3066 (2007/10/03)
Phosphate and phosphonate derivatives of chiral alcohols show enhanced resolution by HPLC using a chiral support. Labile derivatives were also prepared that allow separation and recovery of the corresponding alcohol after basic hydrolysis.
Lanthanoid-metal-mediated reaction of acylphosphonates: evidence for the formation of an acyllanthanoid complex
Taniguchi, Yuki,Fujii, Nobuto,Takaki, Ken,Fujiwara, Yuzo
, p. 173 - 180 (2007/10/02)
The reactions of diethyl acylphosphonates (1a-e) with Yb and Sm were examined.Reactivities of Yb to 1a-e are different from those of Li and Na.Typically, ethyl benzoylphosphonate (1a) reacts with Yb metal in tetrahydrofuran-hexamethylphosphoramide to afford diethyl 1,2-diphenyl-2-oxoethyl phosphate (2a) and diethyl 1-(diethyl-phosphoryloxy)-1-phenylmethylphosphonate (3a) The formations of 2a and 3a were explained best by the formation of acylytterbium complexes.Keywords: Ytterbium; Samarium; Acylphosphonate; Phosphorus
Photochemistry of phosphate esters: α-keto phosphates as a photoprotecting group for caged phosphate
Givens, Richard S.,Athey, Phillip S.,Matuszewski, Bogdan,Kueper III, L. William,Xue, Jie-You,Fister, Thomas
, p. 6001 - 6012 (2007/10/02)
Irradiation of two families of α-keto phosphates yielded rearrangement products and deprotected phosphates as the major products. For both sets of reactants, the triplet excited state of the ketone reacted with quantum efficiencies that ranged from 0.10 to 0.38. Desyl phosphates yielded 2-phenylbenzo[6]furan independent of the nature of the solvent whereas phosphate esters of α-hydroxy-p-methoxyacetophenone rearranged to esters of p-methoxyphenylacetic acid. In all cases, the phosphate group with the remaining ligands intact was released in nearly quantitative yield. The desyl group was further developed as a cage ligand for cAMP. Upon photolysis, the desyl caged ester of cAMP (13) quantitatively released the nucleotide with a quantum efficiency of 0.33 ± 0.01 and a unimolecular rate constant of 7.1 × 108s-1. Additional synthetic, product, and mechanistic studies are reported for the two series of α-keto phosphates.
New Photochemically Labile Protecting Group for Phosphates
Furuta, Toshiaki,Torigai, Hiromi,Osawa, Tomoko,Iwamura, Michiko
, p. 1179 - 1182 (2007/10/02)
New photochemically labile phosphate protecting group was developed.These phosphate esters have high molar extinction coefficient (ε340=34500 dm3 mol-1cm-1) and rapidly release parent phosphates upon irradiation (>300 nm) with high quantum efficiency for disappearance (φdis=0.22 at 340 nm).
Silyl Phosphites. 16. Mechanism of the Perkow Reaction and the Kukhtin-Ramirez Reaction. Elucidation by means of a New Type of Phosphoryl Rearrangements Utilizing Silyl Phosphites
Sekine, Mitsuo,Nakajima, Masashi,Hata, Tsujiaki
, p. 4030 - 4034 (2007/10/02)
Reactions of α-lithiated diethyl α-benzylphosphonate (4) with benzoyl chloride and chloroiodomethane afforded benzoylated and chloromethylated products (1 and 2) corresponding to the 1:1 carbonyl adducts of diethyl trimethylsilyl phosphite with benzil and phenacyl chloride which were not obtained by the reactions between the phosphite and benzil or phenacyl chloride.Pyrolysis of 1 and 2 afforded 1,3,2-dioxaphosphole (6) and enol phosphate (8).On the other hand, treatment of 1 and 2 with tetrabutylammonium fluoride afforded benzoin phosphate (7)and 1,2-epoxy phosphonate (14), respectively, as the main products.These results are also discussed in connection with the mechanism of the Perkow reaction and the Kukhtin-Ramirez reaction.
