- Fungal Dioxygenase AsqJ Is Promiscuous and Bimodal: Substrate-Directed Formation of Quinolones versus Quinazolinones
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Previous studies showed that the FeII/α-ketoglutarate dependent dioxygenase AsqJ induces a skeletal rearrangement in viridicatin biosynthesis in Aspergillus nidulans, generating a quinolone scaffold from benzo[1,4]diazepine-2,5-dione substrates. We report that AsqJ catalyzes an additional, entirely different reaction, simply by a change in substituent in the benzodiazepinedione substrate. This new mechanism is established by substrate screening, application of functional probes, and computational analysis. AsqJ excises H2CO from the heterocyclic ring structure of suitable benzo[1,4]diazepine-2,5-dione substrates to generate quinazolinones. This novel AsqJ catalysis pathway is governed by a single substituent within the complex substrate. This unique substrate-directed reactivity of AsqJ enables the targeted biocatalytic generation of either quinolones or quinazolinones, two alkaloid frameworks of exceptional biomedical relevance.
- Einsiedler, Manuel,Jamieson, Cooper S.,Maskeri, Mark A.,Houk, Kendall N.,Gulder, Tobias A. M.
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supporting information
p. 8297 - 8302
(2021/03/01)
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- MgI2-Mediated Chemoselective Cleavage of Protecting Groups: An Alternative to Conventional Deprotection Methodologies
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The scope of MgI2 as a valuable tool for quantitative and mild chemoselective cleavage of protecting groups is described here. This novel synthetic approach expands the use of protecting groups, widens the concept of orthogonality in synthetic processes, and offers a facile opportunity to release compounds from solid supports. Amazing MgI2: Protecting groups have had a tremendous positive impact on the art of biomolecule synthesis. In a context in which the use of attractive protecting groups is often limited by harsh deprotection conditions and low chemoselective flexibility, MgI2 offers, by the execution of a very simple protocol, a fresh vision with extensive perspectives.
- Berthet, Mathéo,Davanier, Florian,Dujardin, Gilles,Martinez, Jean,Parrot, Isabelle
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supporting information
p. 11014 - 11016
(2015/11/10)
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- Direct synthesis of Fmoc-protected amino acids using organozinc chemistry: Application to polymethoxylated phenylalanines and 4-oxoamino acids
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The newN-Fmoc 3-iodoalaninetert-butyl ester derived organozinc reagent1, obtained in 7 steps from optically pure 3-serine, was coupled to a range of electrophiles under palladium catalysis to give substituted phenylalanines and 4-oxoamino acids in variabl
- Deboves,Montalbetti,Jackson
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p. 1876 - 1884
(2007/10/03)
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- 2'-Deoxypuromycin: Synthesis and antiviral evaluation
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A new synthesis of 2'-deoxypuromycin (18) as well as its α-anomer 17 is described. Reaction of 1,5-di-O-acetyl-2,3-dideoxy-3-phthalimido-β-D-erythro-pentofuranose (3) with silylated 6-dimethylaminopurine using trimethylsilyl trifluoromethanesulfonate as catalyst afforded the α and β nucleosides 7 and 12 in 15 and 25% yield, respectively. After deblocking of both amino and hydroxy groups with methylamine in ethanol, the nucleosides were condensed with Fmoc-4-O-methyl-L-tyrosine and subsequently deprotected to give the target compounds 17 and 18. Compound 3 is converted into its glycosyl bromide 4 in quantitative yield on treatment with trimethylsilyl bromide, and reacted with the sodium salt of 6-dimethylaminopurine to give the corresponding protected N-7 and N-9 α glycosyl nucleosides 7 and 8 in 34 and 39% yield, respectively. The 2'-deoxypuromycin is inactive against HIV-1 in MT-4 cells.
- Motawia,Meldal,Sofan,Stein,Pedersen,Nielsen
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p. 265 - 270
(2007/10/02)
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- Site-specific incorporation of non-natural residues into peptides: Effect of residue structure on suppression and translation efficiencies
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A systematic survey of the structural requirements for biosynthetic incorporation of non-natural residues into a polypeptide is presented. Relative translation efficiencies for a series of 12 semi-synthetic acylated suppressor tRNAs ranged from 0 to 91% depending on the structure of the residue incorporated.
- Bain,Wacker, Dean A.,Kuo, Eric E.,Chamberlin, A. Richard
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p. 2389 - 2400
(2007/10/02)
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