13510-08-2Relevant articles and documents
Chiral ligand-exchange resolution of underivatized amino acids on a dynamically modified stationary phase for RP-HPTLC
Remelli, Maurizio,Faccini, Stefania,Conato, Chiara
, p. 313 - 318 (2014)
The synthesis of Spi(τ-dec), derived from the selective alkylation of L-spinacine (4,5,6,7-tetrahydro-1H-imidazo[4,5-c]pyridine-6-carboxylic acid) at the τ-nitrogen of its heteroaromatic ring, with a linear hydrocarbon chain of 10 carbon atoms, is described here for the first time. Spi(τ-dec) was successfully employed in the past to prepare home-made chiral columns for chiral ligand-exchange high-performance liquid chromatography. In the present article a new method is described, using Spi(τ-dec) as a chiral selector in high-performance thin-layer chromatography (HPTLC): commercial hydrophobic plates were first coated with Spi(τ-dec) and then treated with copper sulfate. The performance of this new chiral stationary phase was tested against racemic mixtures of aromatic amino acids, after appropriate optimization of both the conditions of preparation of the plates and the mobile phase composition. The enantioselectivity values obtained for the studied compounds were higher than those reported in the literature for similar systems. The method employed here for the preparation of chiral HPTLC plates proved practical, efficient, and inexpensive. Chirality 26:313-318, 2014. 2014 Wiley Periodicals, Inc.
The stereocontrolled synthesis of orthogonally protected (R)-α- methyltryptophan
Goodman, Murray,Zhang, Jinfang,Gantzel, Peter,Benedetti, Ettore
, p. 9589 - 9592 (1998)
An expedient and highly stereocontrolled route to (R)-α- methyltryptophan and its orthogonally protected analogs has been developed via a four-step conversion from L-alanine in good overall yields. The stereochemistry of the products is confirmed by X-ray diffraction analysis, NMR spectroscopy and optical rotations.
Asymmetric synthesis of α-methyl-α-amino acids via diastereoselective alkylation of (1s)-(+)-3-carene derived tricyclic iminolactone
Lu, Ta-Jung,Lin, Cheng-Kun
experimental part, p. 1621 - 1633 (2011/06/17)
A novel carene-based alanine-equivalent tricyclic iminolactone 16 has been synthesized via stereoselective dihydroxylation of the double bond, IBX oxidation of the secondary alcohol, esterification of the tertiary alcohol, deprotection of the resulting ester, and subsequent cyclization from commercially available (1S)-(+)-3-carene in 79% overall yield. The iminolactone 16 demonstrated high reactivity toward alkylation with a wide range of electrophiles at room temperature under phasetransfer catalysis conditions. The alkylated products were produced with excellent diastereoselectivities (>98% de) in good isolated yields (86-94%). High yields (83-91%) of optically pure (S)-R-methyl-R-substituted-R-amino acids were obtained by basic hydrolysis of the dialkylated iminolactones with the recovery of the chiral auxiliary 15 (78-87%).
Asymmetric synthesis of α-Methyl α-Amino Acids through diastereoselective alkylation under mild reaction conditions of an iminic alanine template with a 1,2,3,6-Tetrahydro-2-Pyrazinone structure
Najera, Carmen,Abellan, Tomas,Sansano, Jose M.
, p. 2809 - 2820 (2007/10/03)
(6R)-6-Isopropyl-3-methyl-5-phenyl-1,2,3,6-tetrahydro-2-pyrazinone, obtained from (R)-valine and (S)-alanine, is highly diastereoselectively alkylated at room temperature by: a) activated alkyl halides under solid-liquid PTC conditions, b) non-activated alkyl halides with organic bases, c) electrophilic olefins employing both solid-liquid PTC conditions and organic bases, and d) allylic carbonates by means of palladium catalysis under neutral conditions. Enantiomerically pure (S)-α-methyl α-amino acids 8 are obtained by hydrolysis of the alkylated pyrazinones.
Enantiospecific alkylations of alanine
Alonso, Francisco,Davies, Stephen G.,Elend, Almut S.,Haggitt, Jane L.
, p. 257 - 264 (2007/10/03)
Reaction of ferrocenecarbaldehyde 3 with sodium (S)-alaninate followed by pivaloyl chloride generates (2S,4S)-2-ferrocenyl-3-pivaloyl-4-methyl-1,3-oxazolidin-5-one 5 (>98% de). Compound 5 undergoes stereospecific 4-alkylation with complete retention of configuration on treatment sequentially with lithium diisopropylamide and an appropriate alkyl bromide {benzyl bromide, allyl bromide, crotyl [(E)-2-enyl] bromide, α-bromo-o-xylene, cinnamyl bromide, 2-(bromomethyl)naphthalene, 1-(tert-butoxycarbonyl)-3-(bromomethyl)indole and bromoacetonitrile} to generate the corresponding (2S,4R)-2-ferrocenyl-3-pivaloyl-4-alkyl-4-methyl-1,3-oxazolidin-5-ones 7a-h. Hydrolysis of (2S,4R)-7a-h on Amberlyst-15 generates the free (R)-α-methyl-α-amino acids (R)-8a-h.
Tetrahydro-pyrrolo-[2,3-b]indole-1,2,8-tricarboxylic acid ester in the enantiospecific preparation of α-methyltryptophan: Application in the preparation of carbon-14 labeled PD 145942 and PD 154075
Ekhato, I. Victor,Huang, Yun
, p. 1019 - 1038 (2007/10/03)
[2R-(2α,3aβ,8aβ)]-2,3,3a,8a-Tetrahydro-pyrrolo[2.3-b]indole-1,2,8 -tricarboxylic acid-1,8-dibenzyl ester 2-methyl ester, its [2S-(2β,3aα,8aα)]-isomer, and the tribenzyl ester analogs were prepared. From these [2,3-b]indole-1,2,8-tricarboxylic acid esters we accomplished a simple, high yielding preparation of enantiopure α-methyltryptophan and methyl ester derivatives. Using this protocol, we inexpensively made (R)-α-[14C]methyltryptophan methyl ester, and in subsequent reactions converted it into [1-(2-hydroxy-cyclohexylcarbamoyl)-2-(1H-indol-3-yl)-1 -[14C]methylethyl]carbamic acid adamantan-2-yl ester (PD 145942) and [2-(1H-indole-3-yl)-1-[14C]methyl-1(1-phenyl-ethylcarbamoyl)-ethyl]carbamic acid benzofuran-2-yl methyl ester (PD 154075). Both of these compounds are drug candidates in preclinical study for the treatment of anxiety and emesis respectively.
Pharmacokinetics of α-methyl-L-tryptophan in rhesus monkeys and calculation of the lumped constant for estimating the rate of serotonin synthesis
Shoaf, Susan E.,Schmall, Bernard
, p. 219 - 224 (2007/10/03)
We have determined several kinetic and pharmacokinetic parameters of L- tryptophan (Trp) and α-methyl-L-tryptophan (αMTrp) in the rhesus monkey from which the lumped constant for the αMTrp method of estimating serotonin synthesis rates is calculated. αMTrp was isolated from DL-αMTrp using a chiral separation column with high performance liquid chromatography. αMTrp (50 μg/kg) was administered i.v. to four adult male rhesus monkeys and arterial blood samples were collected for a 4-hr period. Plasma concentrations, as determined by high performance liquid chromatography with electrochemical detection, were best fitted by a tri-exponential equation. Plasma protein binding of Trp and αMTrp was determined by measuring concentrations in ultrafiltrates obtained at 30°C. After a 2-hr adjusted rate infusion of αMTrp designed to establish steady-state plasma concentrations, three adult male rhesus monkeys were killed by exsanguination with perfused ice-cold saline. Brain/arterial plasma concentration ratios of Trp and αMTrp and the Michaelis-Menten parameters for tryptophan hydroxylase, EC 1.14.16.4, with Trp and αMTrp as initiating substrates, were determined for seven brain regions. The lumped constants determined for the different brain regions were not significantly different from each other and indicate, that for modeling purposes, the brain may be treated as a homogeneous area and the lumped constant given a single value, 0.18 ± 0.05.
Biocatalytic Resolution of Tertiary α-Substituted Carboxylic Acid Esters: Efficient Preparation of a Quaternary Asymmetric Carbon Center
Yee, Christopher,Blythe, Todd A.,McNabb, Thomas J.,Walts, Alan E.
, p. 3525 - 3527 (2007/10/02)
A method for resolving a variety of tertiary α-substituted carboxylic acid esters employing a previously undescribed enzyme is reported.
Enantiospecific Synthesis with Amino Acids. Part 1. Tryptophan as a Chiron for the Synthesis of α-Substituted Tryptophan Derivatives
Bourne, Gregory T.,Crich, David,Davies, John W.,Horwell, David C.
, p. 1693 - 1699 (2007/10/02)
Nα-Methoxycarbonyl-(S)-tryptophan methyl ester is cyclised with 85percent phosphoric acid to give (2S,3aR,8aS)-1,2-bis(methoxycarbonyl)-1,2,3,3a,8,8a-hexahydropyrroloindole which on reaction with toluene-p-sulphonyl chloride gives (2S,3a
