136850-48-1Relevant academic research and scientific papers
Studies on synthesis and biological activity of oxidative aglafolin derivatives
Wang, Xianyou,Xie, Zhuoqun,Fu, Bin,Li, Nan,Wang, Mingan,Ma, Yongqiang,Du, Fengpei,Xu, Yanjun,Qin, Zhaohai
, p. 1430 - 1434 (2015)
The synthesis of the key intermediate of rocaglamide, oxidative aglafolin, was studied, and its diastereoisomers were obtained. The amination of oxidative aglafolin was also investigated, affording amino derivatives. The preliminary bioassay results indic
A biomimetic approach to the rocaglamides employing photogeneration of oxidopyryliums derived from 3-hydroxyflavones
Gerard, Baudouin,Jones II, Guilford,Porco Jr., John A.
, p. 13620 - 13621 (2004)
A unified biomimetic approach to the aglain-forbaglin-rocaglamide classes of natural products is reported. The approach involves photogeneration of oxidopyryliums via excited-state intramolecular proton transfer (ESIPT) of 3-hydroxyflavones followed by [3
COMPOSITIONS AND METHODS FOR INHIBITING VIRAL INFECTION
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Paragraph 0507-0508, (2020/05/06)
Described herein are compounds, agents, compositions, and methods related to the treatment of a viral infection (e.g., Hepatitis C viral infection). In particular, the compounds, agents, compositions, and methods described herein inhibit viral entry into a target cell.
Intercepted Retro-Nazarov Reaction: Syntheses of Amidino-Rocaglate Derivatives and Their Biological Evaluation as eIF4A Inhibitors
Zhang, Wenhan,Chu, Jennifer,Cyr, Andrew M.,Yueh, Han,Brown, Lauren E.,Wang, Tony T.,Pelletier, Jerry,Porco, John A.
, p. 12891 - 12900 (2019/09/09)
Rocaglates are a family of natural products isolated from the genus Aglaia which possess a highly substituted cyclopenta[b]benzofuran skeleton and inhibit cap-dependent protein synthesis. Rocaglates are attractive compounds due to their potential for inhibiting tumor cell maintenance in vivo by specifically targeting eukaryotic initiation factor 4A (eIF4A) and interfering with recruitment of ribosomes to mRNA. In this paper, we describe an intercepted retro-Nazarov reaction utilizing intramolecular tosyl migration to generate a reactive oxyallyl cation on the rocaglate skeleton. Trapping of the oxyallyl cation with a diverse range of nucleophiles has been used to generate over 50 novel amidino-rocaglate (ADR) and amino-rocaglate derivatives. Subsequently, these derivatives were evaluated for their ability to inhibit cap-dependent protein synthesis where they were found to outperform previous lead compounds including the rocaglate hydroxamate CR-1-31-B.
Chemical Synthesis Enables Structural Reengineering of Aglaroxin C Leading to Inhibition Bias for Hepatitis C Viral Infection
Zhang, Wenhan,Liu, Shufeng,Maiga, Rayelle I.,Pelletier, Jerry,Brown, Lauren E.,Wang, Tony T.,Porco, John A.
, p. 1312 - 1323 (2019/01/21)
As a unique rocaglate (flavagline) natural product, aglaroxin C displays intriguing biological activity by inhibiting hepatitis C viral entry. To further elucidate structure-activity relationships and diversify the pyrimidinone scaffold, we report a concise synthesis of aglaroxin C utilizing a highly regioselective pyrimidinone condensation. We have prepared more than 40 aglaroxin C analogues utilizing various amidine condensation partners. Through biological evaluation of analogues, we have discovered two lead compounds, CMLD012043 and CMLD012044, which show preferential bias for the inhibition of hepatitis C viral entry vs translation inhibition. Overall, the study demonstrates the power of chemical synthesis to produce natural product variants with both target inhibition bias and improved therapeutic indexes.
Formal synthesis of (±)-methyl rocaglate using an unprecedented acetyl bromide mediated Nazarov reaction
Magnus, Philip,Freund, Wesley A.,Moorhead, Eric J.,Rainey, Trevor
, p. 6140 - 6142 (2012/05/07)
To date the prototype Nazarov cyclization of a cross-conjugated pentadienone to the core structure of the rocaglate natural products has not been successful (9 into 12). It has been found that this conversion can be achieved by the use of acetylbromide in excellent yield and results in a strategically very direct route to these antitumor agents.
Nazarov cyclization initiated by peracid oxidation: The total synthesis of (±)-rocaglamide
Malona, John A.,Cariou, Kevin,Frontier, Alison J.
supporting information; experimental part, p. 7560 - 7561 (2009/10/17)
(Chemical Equation Presented) The total syntheses of aglafolin, rocagloic acid, and rocaglamide using Nazarov cyclization are described. Generation of the necessary oxyallyl cation intermediate was accomplished via peracid oxidation of an allenol ether to generate an unusual oxycarbeniumion species that undergoes cyclization. The synthesis is efficient, hig hly diastereoselective, and strategically distinct from previous syntheses of rocaglamide.
Synthesis of the Novel Anti-leukaemic Tetrahydrocyclopentabenzofuran, Rocaglamide and Related Synthetic Studies
Davey, Andrew E.,Schaeffer, Marcel J.,Taylor, Richard J. K.
, p. 2657 - 2666 (2007/10/02)
Two approaches to the rocaglamide tricyclic skeleton are described.The first, which employs an unusual dithianyl anion to carbonyl addition reaction, provides access to α-phenyl rocaglamide analogues.The second route involves an intramolecular keto aldehyde pinacolic coupling in the key step and can be used for the preparation of a whole range of rocaglamide analogues possessing both α- and β-phenyl substituents.A total synthesis of rocaglamide, in racemic form, is described using this second approach.The synthetic route commences with phloroglucinol, an inexpensive and readily-available starting material, and takes only 8/9 steps giving an overall yield > 6percent.The synthesis of 1-epi-rocaglamide 29b is also described.
