- Traceless solid-phase α-hydroxytropolone synthesis
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α-Hydroxytropolones are established inhibitors of several therapeutically relevant binuclear metalloenzymes, and thus lead drug targets for various human diseases. We have leveraged a recently-disclosed three-component oxidopyrylium cycloaddition in the first solid-phase synthesis of α-hydroxytropolones. We also showed that, while minor impurities exist after cleavage and aqueous wash, the semi-crude products display activity in HIV RT-associated RNaseH enzymatic and cell-based assays consistent with pure molecules made in solution phase. These proof-of-principle studies demonstrate the feasibility of solid-phase α-hydroxytropolone synthesis and its potential to serve as a powerful platform for α-hydroxytropolone-based drug discovery and development.
- D'Erasmo, Michael P.,Masaoka, Takashi,Wilson, Jennifer A.,Hunte, Errol M.,Beutler, John A.,Le Grice, Stuart F. J.,Murelli, Ryan P.
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supporting information
p. 1789 - 1792
(2016/09/23)
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- Alkali-free, solvent-free conditions through the Feist - Benary reaction process for preparing substituted furyl method (by machine translation)
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The present invention provides a process for preparing multi-substituted furyl method, namely in alkali-free, under solvent-free conditions, α - halo with β - dicarbonyl compounds react multi-substituted furyl compound. The invention of the multi-substitu
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Paragraph 0049; 0050; 0051
(2017/02/09)
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- Triflic acid-mediated rearrangements of 3-methoxy-8-oxabicyclo[3.2.1]octa- 3,6-dien-2-ones: Synthesis of methoxytropolones and furans
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Methoxytropolones are useful scaffolds for therapeutic development because of their known biological activity and established value in the synthesis of α-hydroxytropolones. Upon treatment with triflic acid, a series of 3-methoxy-8-oxabicyclo[3.2.1]octa-3,6-dien-2-ones rearrange rapidly and cleanly to form methoxytropolones. Interestingly, bicycles that are derived from dimethyl acetylenedicarboxylate (R2 = R3 = CO 2Me) instead form furans as the major product.
- Williams, Yvonne D.,Meck, Christine,Mohd, Noushad,Murelli, Ryan P.
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p. 11707 - 11713
(2014/01/06)
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- A mild, convenient and efficient single-step method for the synthesis of polysubstituted furans via ammonium ylide routes
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A new and convenient cyclization method for the synthesis of polysubstituted furans in a single-step via ammonium ylide routes was reported. In this process, dimethyl acetylenedicarboxylate reacted with ammonium ylide to produce polysubstituted furan in the presence of anhydrous K2CO 3 at room temperature. It is very economical, environmentally friendly and very easy to carry out. Georg Thieme Verlag Stuttgart.
- Fan, Mingjin,Guo, Lina,Liu, Xueyuan,Liu, Weimin,Liang, Yongmin
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p. 391 - 396
(2007/10/03)
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- Studies Dealing with the Excited-State Behavior of Substituted 8-Oxabicyclooct-6-en-2-ones
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A series of 8-oxabicyclooct-6-en-2-ones was prepared by the rhodium(II)-catalyzed cyclization-cycloaddition reaction of α-diazopentanedione with various alkynes.The photochemical behavior of these oxabicyclic enones was investigated.Both direct and sensitized photolysis cleanly results in a 1,3-acyl shift.A slower, secondary photoprocess involving intramolecular hydrogen atom transfer and intramolecular cycloaddition of the resulting ketene was also uncovered.The photobehavior of the closely related 9-oxabenzocycloheptene system was also examined.The initially formed 1,3-sigmatropic rearranged product was found to undergo a novel 1,4-methoxyl migration on extended photolysis.The photochemistry of the homologous 7-oxabicyclohepten-2-one was studied.The results obtained can be interpreted in terms of an initial Norrish type I cleavage.The resulting diradical either couples to give the 1,3-acyl shift product or undergoes bond fragmentation, giving products derived from a stepwise retro-Diels-Alder reaction.
- Padwa, Albert,Zhi, Lin,Fryxell, Glen E.
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p. 1077 - 1083
(2007/10/02)
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