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Amino Acids: The Forum for Amino Acid, Peptide and Protein Research (v.24, #3)
Synthesis and use of N,N-di-Boc-glutamate γ-semialdehydes and related aldehydes by V. Constantinou-Kokotou; V. Magrioti (pp. 231-243).
This review article focuses on the synthesis and reactions of N,N-di-Boc glutamate and aspartate semialdehydes as well as related aldehydes. These building blocks are prepared according to various strategies from glutamic and aspartic acids and find interesting synthetic applications. In the first part, the methods for the synthesis of N,N-di-Boc-amino aldehydes are summarized. The applications of these chiral synthons for the synthesis of unnatural amino acids and other bioactive compounds are discussed in the second section.
Keywords: Keywords: Amino aldehydes; Chiral synthons; N; N-di-Boc-Glutamate semialdehydes; Wittig reaction; Unnatural amino acids
γ-Fluorinated analogues of glutamic acid and glutamine by R. Dave; B. Badet; P. Meffre (pp. 245-261).
γ-Fluorinated analogues of glutamic acid and glutamine are compounds of biological interest. Syntheses of such compounds are extensively reviewed in this article. 4-Fluoroglutamic acid was prepared as a mixture of racemic diastereomers by Michael reaction, inverse-Michael reaction or by electrophilic / nucleophilic fluorination. Optically enriched 4-fluoroglutamic acids were obtained by several resolution techniques as well as by asymmetric methodologies using the chiral pool. 4-Fluoroglutamine was prepared as a mixture of stereoisomers as well as in racemic erythro and threo forms from the corresponding 4-fluoroglutamic acids using aminolysis and conventional protection and deprotection strategies. Racemic 4,4-difluoroglutamic acid was synthesized by a nitroaldol reaction and its L-enantiomer obtained via three different asymmetric routes. Racemic 4,4-difluoroglutamic acid was converted into the corresponding 4,4-difluoroglutamine using a protection / aminolysis / deprotection sequence while N-Boc-L-4,4-difluoroglutamine was prepared directly from (R)-Garner's aldehyde using a Reformatsky reaction as the key step.
Keywords: Keywords: Glutamine; Glutamine-dependent amidotransferase; γ-Fluorinated glutamic acid; γ-Fluorinated glutamine; 4-Fluoroglutamic acid; 4-Fluoroglutamine; 4-Fluoromethotrexate; γ; γ-Difluorinated glutamic acid; γ; γ-Difluorinated glutamine; 4; 4-Difluoroglutamic acid; 4; 4-Difluoroglutamine; 4; 4-Difluoromethotrexate
Synthesis of novel acetylene-containing amino acids by M. I. Jsselstijn; J. Kaiser; F. L. van Delft; H. E. Schoemaker; F. P. J. T. Rutjes (pp. 263-266).
Novel synthetic procedures for the modification of non-proteinogenic acetylene-containing amino acids have been developed. The functionalization either proceeds via zinc/copper-mediated introduction of alkyl substituents, or via tungsten-catalyzed ring-closing alkyne metathesis reactions.
Keywords: Keywords: Organozinc reagent; Alkyne metathesis; Non-proteinogenic amino acids; Unsaturated amino acids; Acetylenic amino acids; β-Turn mimic
Asymmetric synthesis of all stereoisomers of 6-methylpipecolic acids by H. Takahata; M. Shimizu (pp. 267-272).
Asymmetric synthesis of all four stereoisomers of 6-methylpipecolic acids with high enantiomeric purity via iterative AD reaction, starting from 1,6-heptadiene, has been described.
Keywords: Keywords: Asymmetric synthesis; 6-Methypipecolic acid; Asymmetric dihydroxylation; Enantiomeric enhancement
Synthesis and transformations of a pyrazole containing α,β-didehydro-α-amino acid derivatives by L. Vraničar; F. Požgan; S. Polanc; M. Kočevar (pp. 273-280).
2H-Pyran-2-ones 1 were transformed with various hydrazines into (E)- or (Z)-α,β-didehydro-α-amino acid (DDAA) derivatives 4 (and 7) containing a highly substituted pyrazolyl moiety attached at the β-position. With heterocyclic hydrazines, the products 4 were accompanied also by decarboxylated enamines E-6. In order to separate (E/Z)-mixtures of acids, they were transformed to the corresponding methyl esters 9 and 10 by the application of diazomethane. Catalytic hydrogenation under high pressures with Pd/C as a catalyst resulted in the formation of racemic alanine derivatives 11.
Keywords: Key words: Amino acids; Dehydroamino acid derivatives; Esterification; Hydrogenation; Pyrazoles; Alanines
Synthesis of N-quinonyltaurines by S. Gorohovsky; G. Temtsin-Krayz; S. Bittner (pp. 281-287).
Both 1,4-benzoquinones and 1,4-naphthoquinones were attached to the non-proteinogenic amino acid taurine to form N-quinonyl taurine derivatives. The products were formed via the direct Michael-like addition or by substitution of a good leaving group. An attempt to bridge the two moieties via an ureido spacer resulted in the formation of a bis-quinonylamino isocyanurate derivative. Preliminary MO calculations provided internal ground-state geometries and orbital coefficients of the HOMO levels in two representing taurine conjugates.
Keywords: Keywords: Amino acids; Taurine; Quinones; Isocyanates; Isocyanurate
Synthesis of orthogonally protected (3R,4S)- and (3S,4S)-4,5-diamino-3-hydroxypentanoic acids by Z. Czajgucki; P. Sowiński; R. Andruszkiewicz (pp. 289-291).
The paper describes two methods of the synthesis of ethyl (3R,4S)- and (3S,4S)-4-[(benzyloxycarbonyl)amino]-5-[(tert-butyloxycarbonyl)amino]-3-hydroxypentanoates, useful for the syntheses of edeine analogs. Differently N-protected (S)-2,3-diaminopropanoic acid was used as a substrate in both procedures. The absolute configuration of newly generated asymmetric carbon atoms C-3 in β-hydroxy-γ,δ-diamino products was assigned by means of 1H NMR spectroscopy after their transformation into corresponding piperidin-2-ones.
Keywords: Keywords: Amino acids; Protecting groups; NMR spectroscopy
Synthesis and paralytic activities of squaryl amino acid-containing polyamine toxins by T. Shinada; Y. Nakagawa; K. Hayashi; G. Corzo; T. Nakajima; Y. Ohfune (pp. 293-301).
Eight analogs 4a-7a and 4b-7b of philanthotoxin (PhTX) from wasp venom and nephilatoxin-8 (NPTX-8) from spider venom whose tyrosine or asparagine linker is replaced by squaryl (sq) amino acid or 4-amino squaryl (4-asq) amino acid have been synthesized in an efficient manner via coupling of N-acyl squaryl amino acid intermediate 19 or 26 with the corresponding polyamine part. Preliminary bioassay using crickets revealed that the analogs substituted by glutamate-type squaryl amino acid-containing NPTX 7a and 7b showed more potent paralytic activities than that of NPTX-8.
Keywords: Keywords: Philanthotoxin; Nephilatoxin-8; Polyamine toxins; Paralytic activity -Glutamate receptors; Squaric acid; Squaryl amino acid; 4-Hydroxycyclobuten-1-one; 2; 3-dioxocyclobutene; N-Acyl squaryl amino acid; Squaryl amino acid-containing polyamine toxins; Insecticidal activity
3-Carboxy-4-phosphonocyclopentane amino acids: New metabotropic glutamate receptor ligands by A.-S. Bessis; G. Vadesne; E. Bourrat; G. Bertho; J.-P. Pin; F. C. Acher (pp. 303-310).
Two glutamic acid analogs (1SR,3RS,4RS)- and (1SR,3SR,4SR)-1-amino-4-phosphono cyclopentane-1,3-dicarboxylic acids (APCPD) have been synthesized. Pure E-(diethoxy-phosphoryl)-acrylic acid ethyl ester was obtained from ethyl propiolate, phenol and triethylphosphite. It was used as dienophile in a Diels-Alder reaction. Oxidation and cyclization afforded 3-(ethoxy-carbonyl)-4-(diethoxy-phosphoryl)-cyclopentanone. Bucherer-Bergs reaction and hydrolysis yielded APCPD-III and -IV which are inactive on mGlu1a receptor and antagonists on mGlu2 and mGlu8a receptors.
Keywords: Keywords: Cyclopentane glutamate analog; ACPT; L-AP4; Metabotropic glutamate receptors
Solution phase synthesis of the 14-residue peptaibol antibiotic trichovirin I by H. Brückner; A. Koza (pp. 311-323).
The 14-residue peptaibol antibiotic trichovirin I 4A of the structure Ac-Aib-L-Asn-L-Leu-Aib-L-Pro-L-Ala-L-Val-Aib-L-Pro-Aib-L-Leu-Aib-L-Pro-L-Leuol (Aib = α-aminoisobutyric acid, Leuol = leucinol) was synthesized by stepwise conventional solution phase synthesis using the Z/OtBu(OMe) strategy and HOBt/EDC as coupling reagents. Intermediates were fully characterized and the identity of the synthetic peptide with the component 4A of the natural, microheterogeneous peptide mixture was proven by electrospray mass spectrometry, HPLC, and bioassay.
Keywords: Keywords: Peptaibols; Peptide antibiotics; Trichovirin; Peptide synthesis; Trichoderma viride; α-Aminoisobutyric acid (Aib)
New development in the tritium labelling of peptides and proteins using solid catalytic isotopic exchange with spillover-tritium by Yu. A. Zolotarev; A. K. Dadayan; E. V. Bocharov; Yu. A. Borisov; B. V. Vaskovsky; E. M Dorokhova; N. F. Myasoedov (pp. 325-333).
The mechanism of the reaction of high temperature solid state catalytic isotope exchange (HSCIE) of hydrogen in peptides with spillover-tritium at 140–180°C was analyzed. This reaction was used for preparing [3H]enkephalins such as [3H]DALG with specific activity of 138 Ci/mmol and [3H]LENK with specific activity of 120 Ci/mmol at 180°C. The analogues of [3H]ACTG4–10 with specific activity of 80 Ci/mmol, [3H]zervamicin IIB with specific activity of 70 Ci/mmol and [3H]conotoxin G1 with specific activity 35 Ci/mmol were produced. The obtained preparations completely retained their biological activity. [3H]Peptide analysis using 3H NMR spectroscopy on a Varian UNITY-600 spectrometer at 640 MHz was carried out. The reaction ability of amino fragments in HSCIE was shown to depend both of their structures and on the availability and the mobility of the peptide chain. The reaction of HSCIE with the β-galactosidase from Termoanaerobacter ethanolicus was studied. The selected HSCIE conditions allow to prepare [3H] β-galactosidase with specific activity of 1440 Ci/mmol and completely retained its the enzymatic activity.
Keywords: Keywords: Tritium labelled; Amino acids; Peptides; Enkephalins; Spillover-hydrogen; Isotope exchange; Tritium NMR