113680-16-3Relevant academic research and scientific papers
Photophysics and photodeprotection reactions of p -methoxyphenacyl phototriggers: An ultrafast and nanosecond time-resolved spectroscopic and density functional theory study
An, Hui-Ying,Kwok, Wai Ming,Ma, Chensheng,Guan, Xiangguo,Kan, Jovi Tze Wai,Toy, Patrick H.,Phillips, David Lee
, p. 5837 - 5851 (2010)
Time-resolved spectroscopic experiments were performed to investigate the kinetics and mechanisms of the photodeprotection reactions for p-methoxyphenacyl (pMP) compounds, p-methoxyphenacyl diethyl phosphate (MPEP) and diphenyl phosphate (MPPP). The experimental results reveal that compared to the previous reports for the counterpart p-hydroxyphenacyl (pHP) phosphates, the 3nπ/ππ* mixed character triplet of pMP acts as a reactive precursor that leads to the subsequent solvent and leaving group dependent chemical reactions and further affects the formation of photoproducts. The MPPP triplet in H2O/CH3CN and in fluorinated alcohols shows a rapid heterolytic cleavage (τ ≈ 5.4 ns) that results in deprotection and formation of a solvolytic rearrangement product, whereas the MPPP triplet in CH3CN and the MPEP triplet in CH3CN and H2O/CH3CN and fluorinated alcohols decay on a much longer time scale (τ ≈ 100 ns) with little observation of the rearrangement product. The density functional theory (DFT) calculations reveal a substantial solvation effect that is connected with the methoxy versus hydroxyl substitution in accounting for the different deprotection reactivity of pMP and pHP compounds. The results reported here provide new insight in elucidating the solvent and leaving group dependent dual reactivity of pMP compounds on the formation of the rearrangement versus reductive photoproduct.
Aroyl group driven [1,2] phosphonate-phosphate/phosphine oxide-phosphinate rearrangement
Khan, Shahnawaz,Battula, Satyanarayana,Ahmed, Qazi Naveed
, p. 4273 - 4279 (2016)
Aroyl group driven phosphonate-phosphate rearrangement in dialkyl/aryl(α-hydroxy-β-oxo-β-arylethyl)phosphonates having α-proton under basic conditions is presented and extended to a novel one-pot direct coupling method between 2-oxoaldehydes (2OA) and H-p
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).
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.
