52795-52-5Relevant academic research and scientific papers
Method for Preparing Unnatural Amino Acids
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Paragraph 0172; 0173; 0223; 0224, (2017/01/09)
The present invention relates to a manufacturing method of unnatural amino acids and unnatural amino acids manufactured thereby. Specifically, the present invention relates to an asymmetric synthesis method which can manufacture unnatural amino acids having significantly high optical purity, and to the unnatural amino acids manufactured thereby. A manufacturing method of unnatural amino acids represented by chemical formula 6 or chemical formula 7 comprises the steps of: synthesizing a compound represented by chemical formula 4 or chemical formula 5; manufacturing a diol compound; and manufacturing a carboxylic acid compound.COPYRIGHT KIPO 2016
Crystallographic studies on the reaction of isopenicillin N synthase with an unsaturated substrate analogue
Elkins, Jonathan M.,Rutledge, Peter J.,Burzlaff, Nicolai I.,Clifton, Ian J.,Adlington, Robert M.,Roach, Peter L.,Baldwin, Jack E.
, p. 1455 - 1460 (2007/10/03)
Isopenicillin N synthase (IPNS) catalyses conversion of the linear tripeptie δ-(L-α-aminoadipoyl)-L-cysteinyl-D-valine (ACV) to isopenicillin N (IPN), the central step in biosynthesis of the β-lactam antibiotics. The unsaturated substrate analogue δ-(L-α-aminoadipoyl)-L-cysteinyl-D-vinylglycine (ACvG) has previously been incubated with IPNS and a single product was isolated, a 2-α-hydroxymethyl isopenicillin N (HMPen), formed via a monooxygenase mode of reactivity. ACvG has now been crystallised with IPNS and the structure of the anaerobic IPNS:Fe(II):ACvG complex determined to 1.15 A resolution. Furthermore, by exposing the anaerobically grown crystals to high-pressure oxygen gas, a structure corresponding to the bicyclic product HMPen has been obtained at 1.60 A resolution. In light of these and other IPNS structures, and recent developments with related dioxygenases, the [2 + 2] cycloaddition mechanism for HMPen formation from ACvG has been revised, and a stepwise radical mechanism is proposed. This revised mechanism remains consistent with the observed stereospecificity of the transformation, but fits better with apparent constraints on the coordination geometry around the active site iron atom.
Synthesis of enantiomerically enriched β,γ-unsaturated-α-amino acids
Rose, Nicholas G.W,Blaskovich, Mark A,Wong, Alex,Lajoie, Gilles A
, p. 1497 - 1507 (2007/10/03)
A variety of enantiomerically enriched β,γ-unsaturated-α-amino acids are synthesized by olefination of a Cbz-protected serine aldehyde equivalent, readily prepared from serine. A cyclic ortho ester protecting group is employed to minimize racemization. The deprotected amino acids are obtained in good yield, ranging from 70-95% ee, with double-bond geometry determined by the type of Wittig reagent used. Isotopically labeled side chains are readily introduced by this procedure, and free γ-13C-vinylglycine was prepared in 44% yield from the protected serine aldehyde synthon.
Simple Synthesis of L- and D-Vinylglycine (2-Aminobut-3-enoic Acid) and Related Amino Acid
Hallinan, Keith O.,Crout, David H. G.,Errington, William
, p. 3537 - 3544 (2007/10/02)
A three-step synthesis of vinylglycine 1 has been developed using a readily available starting material (but-3-enenitrile 2), based on the Neber rearrangement of the corresponding N-chloroimidate, and using cheap, convenient reagents.Also described is a convenient optical resolution of the N-tert-butoxycarbonyl derivative by papain-catalysed enantioselective esterifucation in a two-phase system.From the optically active amino acid, related amino acids obtained via epoxidation, dihydroxylation and cyclopropanation have been prepared.The related β,γ-unsaturated amino acids (E)-2-aminopent-3-enoic acid 20 and (E)-2-amino-3-methylpent-3-enoic acid 22 have been synthesised using the same approach.
A General and Practical Synthesis of (R)-Phthalimido Aldehydes and D-α-Amino Acids from D-Mannitol
Mulzer, Johann,Angermann, Alfred,Schubert, Boris,Seilz, Carsten
, p. 5294 - 5299 (2007/10/02)
A short and practical synthesis of five D-α-amino acids is described from D-mannitol as the chiral educt.The key steps in the sequence are (a) the erythro-selective addition of organometals to (R)-2,3-O-isopropylideneglyceralaldehyde, (b) the Mitsunobu inversion substituting N-phthalimide for hydroxyl, and (c) acetonide hydrolysis and glycol cleavage to give the N -phthaloyl-(R)-α-aminoaldehydes 7.These are oxidized under Jones conditions to give the N-protected amino acids 8.The examples investigated (alanine, aminobutyric acid, norvaline, and allyl- and vinylglycine) demonstrate the general applicability of the method.
ASYMMETRIC SYNTHESES VIA HETEROCYCLIC INTERMEDIATES-XXII; ENANTIOSELECTIVE SYNTHESIS OF α-ALKENYL GLYCINE METHYL ESTERS AND α-ALKENYL GLYCINES (β,γ-UNSATURATED AMINO ACIDS)
Schoellkopf, Ulrich,Nozulak, Joachim,Groth, Ulrich
, p. 1409 - 1418 (2007/10/02)
Enantioselective syntheses of α-alkenyl glycines of type 10 and of type 23 are described that provide these uncommon amino acids with predictable configuration and with ee-values of >95percent.Both approaches are based on the bislactim ether method developed by Schoellkopf et al.As for 10: The lithiated bis-lactim ether 6 of cyclo(L-val-gly) is reacted with 2alkanals 2 to give the addition products 7 with de>95percent.These on acid hydrolysis afford L-valinate 8 and the methyl (2R)-2-amino-4-(dimethyl t-butyl)silyl-3-hydroxyalkanoates 9 which are convertible into the (R)-α-alkenyl glycines of type 10.The scope of this synthesis is limited by the fact that the compounds 9 are thermolabile when disubstituted at C-4.As for 23: The lithiated bis-lactim ether 6 is reacted with thioketones 14 to give the addition products 15 with de>95percent.The S-methyl compounds 16 undergo elimination to give regioselectively the olefins 18 when treated with Raney-Ni.Alternatively, the olefins 18 are obtained from the sulfonium salts 24 by dimethyl sulfide elimination, although this route is less regiospecific.The compounds 18 are cleaved by dilute hydrochloric acid, liberating L-valinate 8 and (R)-α-alkenyl glycine methyl esters 21, which on further hydrolysis yield (R)-α-alkenyl glycines 23.This synthesis is limited only by the availability of thioketones 14.
ENANTIOSELECTIVE SYNTHESIS OF NON-PROTEINOGENIC AMINO ACIDS VIA METALLATED BIS-LACTIM ETHERS OF 2,5-DIKETOPIPERAZINES
Schoellkopf, Ulrich
, p. 2085 - 2092 (2007/10/02)
Bis-lactim ethers 1 of 2,5-diketopiperazines contain a chiral inducing center, an acidic CH-bond and two sites susceptible to hydrolysis.They react with BuLi to give Li compounds of type 4, 15, 29 or 32, which possess a prochiral C atom.They readily add electrophiles (such as alkylating agents or carbonyl compounds) with unusually high diastereoface differentiation.In many cases the d.e-value (d.e. = diastereomeric excess = asymmetric induction) of the adduct exceeds 95percent.On hydrolysis the adducts are cleaved liberating the chiral auxiliary (used to build up the bis-lactim ether 1) and the target molecules, the optically active amino acid methyl esters of type 8, 19, 25 or 36.The two amino acid esters are separable either by fractional distillation or (eventually after further hydrolysis to amino acids) by chromatography.Transition state models are discussed that could explain the exceptionally high asymmetric induction and the predictability of the induced configuration.
