503561-02-2Relevant articles and documents
Asymmetric synthesis of a tricyclic core structure of the securinega alkaloids virosecurinine and allosecurinine
Kammler, Rainer,Polborn, Kurt,Wanner, Klaus Th.
, p. 3359 - 3368 (2003)
A concise asymmetric synthesis of tricyclic core structures of virosecurinine [(+)-1] and allosecurinine [(-)-2] is presented. An asymmetric electrophilic α-amidoalkylation reaction employing a chiral enamide gave access to enantiopure (S)-2-anisylpiperidine with the diastereoselectivity (d.s.) of 93/7. The latter was transformed into the target compounds, with the main steps involving a Birch-reduction followed by an ozonolysis of the resulting 1,4-cylohexadiene and a final spirocyclization reaction.
Combined Imine Reductase and Amine Oxidase Catalyzed Deracemization of Nitrogen Heterocycles
Heath, Rachel S.,Pontini, Marta,Hussain, Shahed,Turner, Nicholas J.
, p. 117 - 120 (2016/01/26)
A novel amine oxidase (AO)/imine reductase (IRED) system was developed for the deracemization of racemic amines. By combining (R)-6-hydroxy-d-nicotine oxidase (6-HDNO) with an (R)-IRED, a panel of racemic 2-substituted piperidines and pyrrolidines were deracemized to yield the (S)-amines in high yields and enantiomeric excess values. Other N-heterocycles were deracemized with monoamine oxidase (MAO-N) or 6-HDNO in combination with ammonia borane, which allowed comparison of the two enzyme deracemization approaches with that involving a chemical reducing agent.
An (R)-imine reductase biocatalyst for the asymmetric reduction of cyclic imines
Hussain, Shahed,Leipold, Friedemann,Man, Henry,Wells, Elizabeth,France, Scott P.,Mulholland, Keith R.,Grogan, Gideon,Turner, Nicholas J.
, p. 579 - 583 (2015/03/05)
Although the range of biocatalysts available for the synthesis of enantiomerically pure chiral amines continues to expand, few existing methods provide access to secondary amines. To address this shortcoming, we have over-expressed the gene for an (R)-imine reductase [(R)-IRED] from Streptomyces sp. GF3587 in Escherichia coli to create a recombinant whole-cell biocatalyst for the asymmetric reduction of prochiral imines. The (R)-IRED was screened against a panel of cyclic imines and two iminium ions and was shown to possess high catalytic activity and enantioselectivity. Preparative-scale synthesis of the alkaloid (R)-coniine (90 % yield; 99 % ee) from the imine precursor was performed on a gram-scale. A homology model of the enzyme active site, based on the structure of a closely related (R)-IRED from Streptomyces kanamyceticus, was constructed and used to identify potential amino acids as targets for
Structure, activity and stereoselectivity of NADPH-dependent oxidoreductases catalysing the S-selective reduction of the imine substrate 2-methylpyrroline
Man, Henry,Wells, Elizabeth,Hussain, Shahed,Leipold, Friedemann,Hart, Sam,Turkenburg, Johan P.,Turner, Nicholas J.,Grogan, Gideon
, p. 1052 - 1059 (2015/05/05)
Oxidoreductases from Streptomyces sp. GF3546 [3546-IRED], Bacillus cereus BAG3X2 (BcIRED) and Nocardiopsis halophila (NhIRED) each reduce prochiral 2-methylpyrroline (2MPN) to (S)-2-methylpyrrolidine with >95 % ee and also a number of other imine substrates with good selectivity. Structures of BcIRED and NhIRED have helped to identify conserved active site residues within this subgroup of imine reductases that have S selectivity towards 2MPN, including a tyrosine residue that has a possible role in catalysis and superimposes with an aspartate in related enzymes that display R selectivity towards the same substrate. Mutation of this tyrosine residue - Tyr169 - in 3546-IRED to Phe resulted in a mutant of negligible activity. The data together provide structural evidence for the location and significance of the Tyr residue in this group of imine reductases, and permit a comparison of the active sites of enzymes that reduce 2MPN with either R or S selectivity.
Applications of N′-alkylated derivatives of TsDPEN in the asymmetric transfer hydrogenation of C=O and C=N bonds
Martins, Jose E.D.,Contreras Redondo, Miguel A.,Wills, Martin
experimental part, p. 2258 - 2264 (2010/11/03)
Arene/Ru(II) complexes of (R,R)-N-alkyl-TsDPEN ligands are effective in the asymmetric transfer hydrogenation of ketones and imines in formic acid/triethylamine solution. The complex derived from the N′-Bn derivative of TsDPEN reduces monocyclic imines in up to 60% ee, whilst the N′-Me derivative of TsDPEN forms a more active catalyst than the non-alkylated analogue and reduces ketones in up to 97% ee.
Chiral oxime ethers in asymmetric synthesis. Part 5. Asymmetric synthesis of 2-substituted 5- to 8-membered nitrogen heterocycles by oxime addition-ring-closing metathesis
Hunt, James C. A.,Laurent, Pierre,Moody, Christopher J.
, p. 2378 - 2389 (2007/10/03)
Addition of organometallic reagents to chiral oxime ethers 1 derived from an unsaturated aldehyde, or addition of an alkene containing organometallic to chiral aldoxime ethers 2 results in highly stereoselective formation of the hydroxylamines 6. N-Allylation gives the dienes 7 which undergo ring-closing metathesis (RCM) reaction to give the 5-, 6-, and 7-membered nitrogen heterocycles 8. Likewise, the benzyl carbamates 9, also prepared by stereoselective addition to oxime ethers, were converted into dienes 10, which underwent RCM to give the 5- to 8-membered azacycles 11. The oxime addition-RCM protocol is thus a versatile method for the asymmetric synthesis of nitrogen heterocycles, further exemplified by the conversion of the unsaturated heterocycles into chiral piperidines, including the alkaloid (-)-coniine.
