775-06-4Relevant articles and documents
Oxidative cyclization of N-methyl-dopa by a fungal flavoenzyme of the amine oxidase family
Lahham, Majd,Pavkov-Keller, Tea,Fuchs, Michael,Niederhauser, Johannes,Chalhoub, Gabriel,Daniel, Bastian,Kroutil, Wolfgang,Gruber, Karl,Macheroux, Peter
, p. 17021 - 17032 (2018/11/21)
Flavin-dependent enzymes catalyze many oxidations, including formation of ring structures in natural products. The gene cluster for biosynthesis of fumisoquins, secondary metabolites structurally related to isoquinolines, in the filamentous fungus Aspergillus fumigatus harbors a gene that encodes a flavoprotein of the amine oxidase family, termed fsqB (fumisoquin biosynthesis gene B). This enzyme catalyzes an oxidative ring closure reaction that leads to the formation of isoquinoline products. This reaction is reminiscent of the oxidative cyclization reported for berberine bridge enzyme and tetrahydrocannabinol synthase. Despite these similarities, amine oxidases and berberine bridge enzyme–like enzymes possess distinct structural properties, prompting us to investigate the structure–function relationships of FsqB. Here, we report the recombinant production and purification of FsqB, elucidation of its crystal structure, and kinetic analysis employing five putative substrates. The crystal structure at 2.6 ? resolution revealed that FsqB is a member of the amine oxidase family with a covalently bound FAD cofactor. N-methyl-dopa was the best substrate for FsqB and was completely converted to the cyclic isoquinoline product. The absence of the meta-hydroxyl group, as e.g. in L-Nmethyl-tyrosine, resulted in a 25-fold lower rate of reduction and the formation of the demethylated product L-tyrosine, instead of a cyclic product. Surprisingly, FsqB did not accept the D-stereoisomer of N-methyltyrosine, in contrast to N-methyl-dopa, for which both stereoisomers were oxidized with similar rates. On the basis of the crystal structure and docking calculations, we postulate a substrate-dependent population of distinct binding modes that rationalizes stereospecific oxidation in the FsqB active site.
Deracemization of racemic amino acids using (R)- and (S)-alanine racemase chiral analogues as chiral converters
Paik, Man-Jeong,Jeon, So Hee,Kang, Jong Seong,Kim, Kwan Mook,Lee, Wonjae
, p. 2186 - 2188 (2014/12/10)
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FLUORINE RADIOLABELLING PROCESS
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Page/Page column 100, (2012/02/01)
The invention relates to a process for producing a process for producing an 18F-labelled compound, the process comprising treating a compound of formula (I): wherein EDG is an electron-donating group selected from -OH, -OR4, -NHR5 and -NR55R5; R1, R2, X1 and X2 are as defined herein; and R3 is selected from H, X3 and X4, wherein X3 is a monodentate cleavable surrogate group, and X4 is a bidentate cleavable surrogate group which is bonded (a) to said X or X and (b) to the ring carbon atom para to EDG; with [18F]fluoride in the presence of an oxidant, thereby producing, when R3 in the compound of formula (I) is H, an 18F-labelled compound of formula (II), wherein EDG is as defined above and R1, R2, X1 and X2 are as defined herein; or thereby producing, when R3 in the compound of formula (I) is said monodentate cleavable surrogate group X4, a compound of formula (Ilc), wherein EDG' is O, NR5, -NR55R5 or [OR4]+, and wherein R4, R5, R55, R1, R2, X1, X2 and X3 are as defined herein; or thereby producing, when R3 in the compound of formula (I) is said bidentate cleavable surrogate group X4, a compound of formula (IIc) or a compound of formula (IId), wherein EDG' is O, NR5, -NR55R5 or [OR4]+, and wherein R4, R5, R55, R1, R2, X1, X2 and X4 are as defined herein.
