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N-Pyrazinoyl substituted amino acids as potential antimycobacterial agents-the synthesis and biological evaluation of enantiomers
Tuberculosis is an infectious disease caused by Mycobacterium tuberculosis (Mtb), each year causing millions of deaths. In this article, we present the synthesis and biological evaluations of new potential antimycobacterial compounds containing a fragment of the first-line antitubercular drug pyrazinamide (PZA), coupled with methyl or ethyl esters of selected amino acids. The antimicrobial activity was evaluated on a variety of (myco)bacterial strains, including Mtb H37Ra, M. smegmatis, M. aurum, Staphylococcus aureus, Pseudomonas aeruginosa, and fungal strains, including Candida albicans and Aspergillus flavus. Emphasis was placed on the comparison of enantiomer activities. None of the synthesized compounds showed any significant activity against fungal strains, and their antibacterial activities were also low, the best minimum inhibitory concentration (MIC) value was 31.25 μM. However, several compounds presented high activity against Mtb. Overall, higher activity was seen in derivatives containing l-amino acids. Similarly, the activity seems tied to the more lipophilic compounds. The most active derivative contained phenylglycine moiety (PC-d/l-Pgl-Me, MIC 1.95 μg/mL). All active compounds possessed low cytotoxicity and good selectivity towards Mtb. To the best of our knowledge, this is the first study comparing the activities of the d- and l-amino acid derivatives of pyrazinamide as potential antimycobacterial compounds.
Bárta, Pavel,Dole?al, Martin,Horá?ek, Ond?ej,Jand'Ourek, Ond?ej,Janou?ek, Ji?í,Juhás, Martin,Kone?ná, Klára,Ku?era, Radim,Ku?erová, Lucie,Kubí?ek, Vladimír,Kune?, Ji?í,Paterová, Pavla,Zitko, Jan
(2020/04/09)

Exciton-Coupled Circular Dichroism Characterization of Monotopically Binding Guests in Host?Guest Complexes with a Bis(zinc porphyrin) Tweezer
A stiff-stilbene-linked bisporphyrin tweezer with inherent helicity was used for exciton-coupled circular dichroism (ECCD) characterization of a series of monotopically binding amine guest molecules. CD signals were observed for a variety of monoamines at relatively low tweezer/amine (host/guest) ratios between 1 : 10 to 1 : 70. For the amines producing the most intense CD signals, a binding stoichiometry of 1 : 2 was found. A likely explanation is the presence of guest-guest interactions in the complexes. This is supported by the correlation observed between CD signal intensity and magnitude of possible noncovalent binding between the guests, which can be divided into three groups showing no, moderate and strong response, respectively. Further support for this rationalization comes from molecular modelling.
Olsson, Sandra,Sch?fer, Clara,Blom, Magnus,Gogoll, Adolf
p. 1169 - 1178
(2019/01/04)

Method for preparing amino ether compounds
The invention belongs to the technical field of organic synthesis and relates to a method for preparing amino ether compounds. The method comprises the following steps: by taking amino alcohol as a raw material, protecting amino in the amino alcohol so as to obtain Schiff base; carrying out an etherification reaction on the hydroxyl group in the Schiff base; and finally, performing amino deprotection, thereby obtaining corresponding amino ethers. The method disclosed by the invention has high regio-selectivity, the substrates of higher than 99.9% are subjected to etherification reaction, the reaction conversion ratio of each step is higher than 99.8%, and the total yield is higher than 95%; when amino alcohol is chiral, the amino ethers with retention of configuration can be obtained; and moreover, each step of the method is a conventional operation, the process cost is low, and three wastes are few, the energy consumption is low, an environment-friendly effect is achieved, and large-scale industrial production is easily realized.
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Paragraph 0061; 0064; 0065

(2017/08/26)

STABILIZED POLYPEPTIDES AND USES THEREOF
The present invention provides inventive stabilized STAT polypeptides, pharmaceutical compositions thereof, and methods of making and using inventive stabilized STAT polypeptides.
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Sheet 21/22

(2015/04/22)

In situ deprotection and incorporation of unnatural amino acids during cell-free protein synthesis
The S30 extract from E. coli BL21 Star (DE3) used for cell-free protein synthesis removes a wide range of α-amino acid protecting groups by cleaving α-carboxyl hydrazides; methyl, benzyl, tert-butyl, and adamantyl esters; tert-butyl and adamantyl carboxamides; α-amino form-, acet-, trifluoroacet-, and benzamides and sidechain hydrazides and esters. The free amino acids are produced and incorporated into a protein under standard conditions. This approach allows the deprotection of amino acids to be carried out in situ to avoid separate processing steps. The advantages of this approach are demonstrated by the efficient incorporation of the chemically intractable (S)-4-fluoroleucine, (S)-4,5- dehydroleucine, and (2S,3R)-4-chlorovaline into a protein through the direct use of their respective precursors, namely, (S)-4-fluoroleucine hydrazide, (S)-4,5-dehydroleucine hydrazide, and (2S,3R)-4-chlorovaline methyl ester. These results also show that the fluoroand dehydroleucine and the chlorovaline are incorporated into a protein by the normal biosynthetic machinery as substitutes for leucine and isoleucine, respectively. Copyright
Arthur, Isaac N.,Hennessy, James E.,Padmakshan, Dharshana,Stigers, Dannon J.,Lesturgez, Stéphanie,Fraser, Samuel A.,Liutkus, Mantas,Otting, Gottfried,Oakeshott, John G.,Easton, Christopher J.
supporting information
p. 6824 - 6830
(2013/06/26)

Comparative studies on enantiomer resolution of α-amino acids and their esters using (18-crown-6)-tetracarboxylic acid as a chiral crown ether selector by nmr spectroscopy and high-performance liquid chromatography
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Bang, Eunjung,Jin, Jing Yu,Hong, Joon Hee,Kang, Jong Seong,Lee, Weontae,Lee, Wonjae
p. 3481 - 3484
(2013/01/15)

Asperelines A-F, peptaibols from the marine-derived fungus Trichoderma asperellum
Fermentation of the marine-derived fungus Trichoderma asperellum, collected from the sediment of the Antarctic Penguin Island, resulted in the isolation of six new peptaibols named asperelines A-F (1-6), which are characterized by an acetylated N-terminus and a C-terminus containing an uncommon prolinol residue. Structures were determined by extensive 1D and 2D NMR (1H- 1H COSY, HMQC, HMBC, NOESY) spectroscopic data analysis combined with ESIMS/MS fragmentation. The absolute configurations of the amino acid residues possessing a chiral R-carbon and of the prolinol residue were determined to be L and S, respectively, using a new method of 1H NMR spectroscopic comparison of complexes formed between the chiral reagent Ru(D 4-Por*)CO and amino acids derived from the peptaibols with those formed with reference standards.
Ren, Jinwei,Xue, Chunmei,Tian, Li,Xu, Minjuan,Chen, Jian,Deng, Zhiwei,Proksch, Peter,Lin, Wenhan
experimental part
p. 1036 - 1044
(2011/02/28)

Enantioselective benzoylation of α-amino esters using (S)-1-benzoyl-2-(α-acetoxyethyl)benzimidazole, a chiral benzimidazolide
(Chemical Equation Presented) A new chiral benzimidazolide is developed as a nonenzymatic acylating agent for enantioselective benzoylation of racemic α-amino esters. The process is highly efficient, which exhibits uniformly high enantioselectivity for α-amino esters with or without aryl substituents under mild reaction conditions. The chiral benzimidazolide is inexpensive and is easily accessible.
Karnik, Anil V.,Kamath, Suchitra S.
p. 7435 - 7438
(2008/02/11)

Diastereoselective synthesis of quaternary α-amino acids from diketopiperazine templates
Sequential enolate alkylations of (S)-N(1)-methyl-5-methoxy-6-isopropyl-3, 6-dihydropyrazin-2-one and (S)-N(1)-p-methoxybenzyl-5-methoxy-6-isopropyl-3,6- dihydropyrazin-2-one proceed with excellent levels of diastereoselectivity (>90% de) affording quaternary α-amino acids in high enantiomeric excess (>98% ee) after deprotection and hydrolysis. This journal is The Royal Society of Chemistry.
Davies, Stephen G.,Christopher Garner,Ouzman, Jaqueline V. A.,Roberts, Paul M.,Smith, Andrew D.,Snow, Emma J.,Thomson, James E.,Tamayo, Juan A.,Vickers, Richard J.
p. 2138 - 2147
(2008/03/14)

A novel naphthylmethyleneimino-type photocleavable protecting group for primary amines
A novel naphthylmethyleneimino-type protecting group for aliphatic and aromatic primary amines including α-amino acids was devised and its introduction was accomplished in good to excellent yields. This type of protecting group was found to be cleanly removed photochemically to regenerate the primary amines in good to high yields, regardless of steric and electronic properties. Georg Thieme Verlag Stuttgart.
Igarashi, Tetsutaro,Shimokawa, Masaru,Iwasaki, Miyuki,Nagata, Kensaku,Fujii, Masato,Sakurai, Tadamitsu
p. 1436 - 1440
(2008/02/13)

N-Nosyl-α-amino acids in solution phase peptide synthesis
A highly efficient and practical synthesis of peptides in solution phase has been developed. The procedure is based on the use of p-nitrobenzenesulfonyl (nosyl) group for the protection of the amino function of α-amino acids. Every step of the procedure,
Leggio, Antonella,Di Gioia, Maria Luisa,Perri, Francesca,Liguori, Angelo
p. 8164 - 8173
(2008/02/08)

Stereoselective synthesis of δ-heteroaryl substituted β-hydroxy-γ,δ-unsaturated α-amino acids
Enantiomerically pure δ-heteroaryl substituted β-hydroxy-γ,δ-unsaturated α-amino acids were stereoselectively synthesized starting from (2R)-(+)-2,5-dihydro-3,6-dimethoxy-2-isopropylpyrazine (Schoellkopf's reagent) and suitable β-heteroaryl-α,β-unsaturate
Cremonesi, Giuseppe,Croce, Piero Dalla,Fontana, Francesco,Rosa, Concetta La
p. 2637 - 2641
(2007/10/03)

Enantiodiscrimination of racemic electrophiles by diketopiperazine enolates: asymmetric synthesis of methyl 2-amino-3-aryl-butanoates and 3-methyl-aspartates
Enolates of (S)-N,N′-bis-(p-methoxybenzyl)-3-iso-propylpiperazine-2,5-dione exhibit high levels of enantiodiscrimination in alkylations with (RS)-1-aryl-1-bromoethanes and (RS)-2-bromoesters, affording substituted diketopiperazines containing two new stereogenic centres in high de. Deprotection and hydrolysis of the resultant substituted diketopiperazines provides a route to the asymmetric synthesis of homochiral methyl 2-amino-3-aryl-butanoates and 3-methyl-aspartates in high de and ee.
Bull, Steven D.,Davies, Stephen G.,Epstein, Simon W.,Garner, A. Christopher,Mujtaba, Nadeam,Roberts, Paul M.,Savory, Edward D.,Smith, Andrew D.,Tamayo, Juan A.,Watkin, David J.
p. 7911 - 7925
(2007/10/03)

P38 inhibitors and methods of use thereof
Inhibitors of p38 and methods for producing these inhibitors are provided. Also provided are pharmaceutical compositions comprising the inhibitors of the invention, methods of utilizing the inhibitors and pharmaceutical compositions comprising said inhibi
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Page/Page column 23

(2010/11/24)

Compositions and methods for selectively binding amines or amino acid enantiomers over their counter-enantiomers
Naphthyl crown ether ligand molecules containing at least two naphthyl groups that are covalently bonded to suitable solid supports and coated by hydrophobic organic solvents are disclosed. These compositions and associated methods are characterized by selectivity of desired amine or amino acid enantiomers over their counter-enantiomers and derivatives. The composition preferably has an α-value greater than or equal to 4. This allows for the separation of such enantiomers with nonchromatographic resin bed separations of three separation stages or less.
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Page column 17; 18

(2010/11/30)

Amino acid N-carboxyanhydrides: Activated peptide monomers behaving as phosphate-activating agents in aqueous solution
The hydrolysis of valine N-carboxyanhydride (NCA) in aqueous phosphate buffers was shown to proceed through nucleophilic catalysis via an aminoacyl phosphate intermediate that displays phosphorylating capabilities through a potentially prebiotic process that simulates modern biochemical metabolic pathways. Copyright
Biron, Jean-Philippe,Pascal, Robert
p. 9198 - 9199
(2007/10/03)

Kinetic resolution of amines with enantiopure 3-N,N-diacylaminoquinazolin-4(3H)-ones
The title compounds (DAQs) are chiral when the two N-acyl groups are different because of the absence of rotation around the N-N bond (a chiral axis). Enantiopure DAQs have been obtained by incorporation of a chiral centre in enantiopure form either into the substituent at the Q2-position or into one of the N-acyl groups, or into both, followed by separation of diastereoisomers. This separation is unnecessary in one case because conversion of the N-monoacylaminoquinazolinone (MAQ) into the DAQ is completely diastereoselective. Neither is separation of diastereoisomers necessary with 3-[N,N-di-(S)-2-acetoxypropanoylamino]-2-diphenylmethylquinazolin-4(3H)-one 37a: this DAQ 37a has its N-N bond rendered a chiral axis by the bias in its imide moiety wholly in favour of one exo/endo conformation. The high chemoselectivity exhibited by N,N-diacetyl- or N,N-dibenzoylaminoquinazolinones in reaction with the less hindered of two secondary amines (pyrrolidine in the presence of 1 eq. of piperidine) has a stereoselective counterpart: reaction of the above enantiopure DAQs enantioselectively with racemic amines leading to kinetic resolution. Using 1 eq. of DAQ and 2 eq. of amine, both the derivatised and unreacted amine enantiomers are recovered with high enantiomeric excess (ee) (better than 90% ee in some cases). Some of the higher ees are found in the recovered amides where non-chemoselective attack on both N-acyl groups of the DAQ has occurred: from the opposite configurations of the amine component in the two amides and from the low enantiopurity of the recovered unreacted amine, reaction of each of the N-acyl groups with complementary enantiomers of the amine is occurring (parallel kinetic resolution). Although higher ees are, in general, obtained using secondary amines, high ees are obtained in some cases using 1-phenylethylamine and, in particular, amino acid esters (valine and alanine). The sense of enantioselectivity in the reactions of these DAQs with amines is controlled by the configuration of the N-N axis: replacing the Q group in an N-(S)-2-acetoxypropanoyl-N-acetyl-bearing DAQ by phthalimide, thus eliminating the N-N chiral axis, drastically reduces the level of kinetic resolution.
Al-Sehemi, Abdullah G.,Atkinson, Robert S.,Fawcett, John
p. 257 - 274
(2007/10/03)

A convenient protocol for selective cleavage of 2-hydroxy acid amides. Application to semisynthesis of the cyclic heptapeptide aza HUN-7293.
A two-step protocol for the first chemoselective cleavage of 2-hydroxy acid amides has been developed. Mesylation of the model substrate 2-(hydroxypropionylamino)-4-methylpentanoic acid methyl ester (11) followed by treatment with N-ethylthiourea (13) all
Schreiner, Erwin P,Kern, Michael,Steck, Andrea
p. 8299 - 8304
(2007/10/03)

Direct organo-catalytic asymmetric α-amination of aldehydes - A simple approach to optically active α-amino aldehydes, α-amino alcohols, and α-amino acids
L-Proline as the catalyst: The first direct asymmetric α-amination of aldehydes using L-proline as the catalyst is presented (see scheme; Pg = protecting group). This new reaction gives easy access to optically active α-amino aldehydes, α-amino alcohols, and α-amino acids from simple and easily available starting materials and catalysts. The reactions proceed in high yields and excellent enantioselectivities with as little as 2 mol % of the catalyst.
Bogevig, Anders,Juhl, Karsten,Kumaragurubaran, Nagaswamy,Zhuang, Wei,Jorgensen, Karl Anker
p. 1790 - 1793
(2007/10/03)

Conjugate additions of organocuprates to a 3-methylene-6-isopropyldiketopiperazine acceptor for the asymmetric synthesis of homochiral α-amino acids
Addition of a range of organocuprates to (S)-N,N′-bis(p-methoxybenzyl)-3-methylene-6-isopropylpiperazine-2, 5-dione 8 affords cis-3-isopropyl-6-alkyldiketopiperazines in excellent yield and >95% de. Subsequent deprotection and hydrolysis of these cis-3-isopropyl-6-alkyldiketopiperazines affords homochiral (S)-α-amino acids in excellent yield.
Bull,Davies,Garner,O'Shea
p. 3281 - 3287
(2007/10/03)

Stereoselective synthesis of 3-heteroaromatic-substituted alanines
An asymmetric synthesis of (R)-3-heterocyclic-substituted alanines starting from (2S)-(+)-2,5-dihydro-3,6-dimethoxy-2-isopropylpyrazine (Schollkopf reagent) and heteroaromatic halogenomethyl derivatives via hydrolysis of intermediate adducts is reported.
Croce, Piero Dalla,La Rosa, Concetta,Pizzatti, Enrica
p. 2635 - 2642
(2007/10/03)

Stereoselective aldol addition of a chiral glycine enolate synthon to heteroaromatic aldehydes
The stereocontrolled addition of (2S)-(+)-2,5-dihydro-3,6-dimethoxy-2- isopropylpyrazine (1) to heterocyclic aldehydes (2) gives mainly a mixture of syn/anti isomers (3) and (4) whose steric configuration was assigned on the basis of spectroscopic data and accepted model for aldol condensation of 1. The possible conversion of adducts to threo β-substituted heteroaromatic serines is demonstrated.
Croce, Piero Dalla,Ferraccioli, Raffaella,La Rosa, Concetta,Pizzatti, Enrica
p. 1337 - 1344
(2007/10/03)

2(3H)-and 2(5H)-furanones. VIII. Preparation and α nucleophilicity of (S)-γ-isopropyl-α-methyl-β-tetramic acid
An efficient preparation of (S)-γ-isopropyl-α-methyl-β-tetramic acid has been established, and the α nucleophilicity of the acid has been also examined.
Toyooka, Naoki,Nishio, Morihiro,Shinoda, Hiroyuki,Momose, Takefumi
p. 1427 - 1431
(2007/10/03)

Efficient synthesis of differentially protected (S,S)-2,7- diaminooctanedioic acid, the dicarba analogue of cystine
Convenient preparative syntheses of differentially protected forms of (S,S)-2,7-diaminooctanedioic acid (2), suitable for application in peptide chemistry, are described. The key compound, the di-Cbz-protected phenacyl monoester 7a (Cbz = [(benzyloxy)carb
Lange, Meinolf,Fischer, Peter M.
p. 2053 - 2061
(2007/10/03)

Stereoselective synthesis of meso-2,6-diaminopimelic acid and its selectively protected derivatives
Four synthetic routes to selectively protected derivatives and isomers of meso-diaminopimelic acid (DAP) (1a), a key constituent of bacterial peptidoglycan, were investigated. N-(tert-butyloxycarbonyl)-D-allylglycine (2) and N-(benzyloxycarbonyl)-L-allylglycine (4) were esterified to ethylene glycol and cyclized via olefin metathesis to a protected derivative 7 of 2,7- diaminosuberic acid. Analogous linking of propane-1,3-diol with 2 and potential precursors of N-(benzyloxycarbonyl)-L-vinylglycine moieties, such as N-(benzyloxycarbonyl)-L-glutamate or N-(benzyloxycarbonyl)-L-methionine sulfoxide, gave 12 or 15, both of which produced the α,β-unsaturated ester 14 upon attempted generation of the vinylglycine precursor for olefin metathesis to DAP derivatives. An alternative route, based on SnCl4- catalyzed ene reaction of methyl N-(benzyloxycarbonyl)-L-allylglycinate (18) with glyoxylate esters of phenylcyclohexanol isomers as chiral auxiliaries, gave ca. 85:15 ratios of diastereomeric alcohols (19 or 20). These could be transformed to DAP derivatives in a series of steps employing azide displacement of corresponding mesylates to introduce the second nitrogen. A third method, involving reduction of pure dimethyl (6S)-2-keto-6-[N- (benzyloxycarbonyl)amino]pimelate (32) to the corresponding alcohol 33 with (S)-binaphthol-ruthenium catalyst as the key step, gives a 79:21 isomeric ratio. The fourth route employs the bis(oxazoline)-copper complex 41 as a chiral catalyst for the ene reaction of methyl (S)-4- (phenylthio)allylglycinate (39) and methyl glyoxylate to afford 42 and 94:6 isometric ratio. Nickel boride removal of sulfur and the double bond in the presence of the Cbz group gives the desired alcohol, dimethyl (2S,6S)-6-[N- (benzyloxycarbonyl)amino]-2-hydroxyheptane-1,7-dioate (33). The required selectively protected second nitrogen is introduced using Mitsunobu inversion with N-tert-butyl [[2-(trimethylsilyl)-ethyl]sulfonyl]carbomate (34) as a key step.
Gao, Yong,Lane-Bell, Patricia,Vederas, John C.
p. 2133 - 2143
(2007/10/03)

Stereoselective synthesis of α,α'-bridged bis(α-alanine) derivatives
Stereoselective syntheses of α,α'-dimethylated C2-C4 alkylene- bridged bis(glycine) methyl esters are described. The products were further converted into N-Fmoc-protected bis(amino acids).
Lange, Meinolf,Undheim, Kjell
p. 5337 - 5344
(2007/10/03)

Ruthenium(II) in ring closing metathesis for the stereoselective preparation of cyclic 1-amino-1-carboxylic acids
Stereoselective synthesis of α-amino acids where the α-carbon of the amino acid is incorporated into a five-, six- or seven-membered ring is described. The stereoselective control results from stepwise bisalkenylation of (R)-2,5-dihydro-3,6-dimethoxy-2-isopropylpyrazine. Ring closing metathesis was effected by ruthenium(II)catalysis. The spiro-cycloalkene intermediates were further transformed into 1-aminocycloalkene-1-carboxylic acid derivatives by mild acid hydrolysis.
Hammer, Kristin,Undheim, Kjell
p. 2309 - 2322
(2007/10/03)

Asymmetric synthesis of (R)-N-(t-butoxycarbonyl)-4-cyanophenylalanine methyl ester
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Pecunioso, Angelo,Papini, Damiano,Tamburini, Bruno,Tinazzi, Francesco
p. 218 - 221
(2007/10/03)

A new approach to the synthesis of piperazinomycin and bouvardin: Facile access to cycloisodityrosine via an intramolecular SNAr reaction
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Beugelmans, Rene,Bigot, Antony,Bois-Choussy, Michele,Zhu, Jieping
p. 771 - 774
(2007/10/03)

Stereospecific Synthesis of α-Deuteriated α-Amino Acids: Regiospecific Deuteriation of Chiral 3-Isopropyl-2,5-dimethoxy-3,6-dihydropyrazines
Base-catalysed deuteriation of (3R)- or (3S)-3-isopropyl-2,5-dimethoxy-3,6-dihydropyrazines in refluxing CH3O2H-2H2O gives the -isotopomer in excellent yields without disturbing the stereogenic centre at C-3.These compounds provide convenient and efficient access to a range of (R)- and (S)-α-deuteriated α-amino acids, including serine, aspartic acid, allylglycine and phenylalanine, via alkylation of the butyllithium generated C-6 anion.
Rose, Janet E.,Leeson, Paul D.,Gani, David
p. 157 - 166
(2007/10/02)

Enantioselective synthesis of isotopically labelled L-α-amino acids preparation of 13C-, 18O- and 2H-labelled L-serines and L-threonines
[3-18O]-L-serine, [3-13C]-L-serine, [3-18O]-L-threonine, [3,4-13C2]-L-threonine and [3-2H]-L-threonine are prepared from simple commercially available, isotopically enriched starting materials like H218O, [13C] paraformaldehyde, [13C2]-acetaldehyde and (1-2H]-acetaldehyde. The introduction of the side chain is based on the reaction of the anion of the bislactimether of cyclo-(D-Val-Gly) with a suitable reagent. For serine this is isotopically labelled benzylchloromethylether, whereas for threonine labelled acetaldehyde is used in combination with chlorotitaniumtris[diethylamide], introducing both stereocentres in one single step. The isotopomers of serine and threonine are obtained on the gram scale in good yields and high enantiomeric and diasteriomeric excesses. New syntheses for [18O]-benzylalcohol and isotopically enriched benzylchloromethylether are reported. Following the presented synthetic scheme these amino acids can be labelled at any position or at any combination of positions.
Karstens,Berger,Van Haren,Lugtenburg,Raap
p. 1077 - 1096
(2007/10/02)

Asymmetric total synthesis of the individual diastereoisomers of hypoglycin A
The individual diastereoisomers that constitute the unusual methylenecyclopropane containing α-amino acid hypoglycin A have been synthesised utilising the Sharpless epoxidation to permit an asymmetric methylenecyclopropane synthesis.
Baldwin, Jack E.,Adlington, Robert M.,Bebbington, David,Russell, Andrew T.
p. 12015 - 12028
(2007/10/02)

Regiospecific Deuteriation of Chiral 3-Isopropyl-2,5-dimethoxy-3,6-dihydropyrazines in the Stereospecific Synthesis of α-Deuteriated α-Amino Acids
Base-catalysed deuteriation of (3R)- or (3S)-3-isopropyl-2,5-dimethoxy-3,6-dihydropyrazine in refluxing CH3O(2)H-(2)H2O gives the isotopomer in excellent yield without disturbing the stereogenic centre at C-3, and thus providing convenient and e
Rose, Janet E.,Leeson, Paul D.,Gani, David
p. 1563 - 1566
(2007/10/02)

68. Stereoselective Synthesis of (2S,6S)-2,6-Diaminoheptanedioic Acid and of Unsymmetrical Derivatives of meso-2,6-Diaminoheptanedioic Acid
Specific inhibition of enzymes of the diaminopimelate pathway (L-lysine biosynthesis) should, in principle, lead to selective antibacterial agents or herbicides.For this purpose, enantioselective syntheses were devised for (2S,6S)-2,6-diaminoheptanedioic acid (L,L-diaminopimelate, 1), (2R,6S)-2,6-diamino-2-methylhept-3-enedioic acid (10), (2R,6S)-2,6-diaminohept-3-enedioic acid (9),(2R,6S)-2,6-diamino-4-fluorohept-3-enedioic (42),and (2S,6S)-2,6-diamino-3-chloroheptanedioic acid (5).The Schoellkopf bislactim-ether methodology was applied to control the configuration of C(2) and C(6) of 1, C(2) of 10, as well as C(6) of 9 and 42.Semialdehyde derivatives of L-glutamate afforded C(6) of 10 and 5, while the (R)-configurated C(2) of 9 and 42 were derived from L-serine.For this purpose, the synthesis of the Garner aldehyde 32 has been improved.As chromatographic purifications and the low temperatures for the reduction of the carboxylic acid are eliminated, this valuable intermediate can now be prepared in bulk quantities.An enantio- and diastereoselective aldol addition of a glycine titanium-enolate was applied for the construction of 5(C(2) and C(3)).As all chiral building blocks and reagents used are available in both enantiomeric forms, these routes should also be suitable for the selective synthesis of the other stereoisomers of these bis(α-amino acids).
Bold, Guido,Allmendinger, Thomas,Herold, Peter,Moesch, Luzia,Schaer, Hans-Peter,et al.
p. 865 - 882
(2007/10/02)

Asymmetric Synthesis via Heterocyclic Intermediates, XLVII. Asymmetric Synthesis of (+)-(1R,2S)-allo-Coronamic Acid
allo-Coronamic acid (1) was synthesized in five steps enantiomerically and diastereomerically virtually pure by starting from the bislactim ethers of cyclo(-L-Val-Gly-) (3a) or cyclo(-L-tert-Leu-Gly-) (3b) in an overall yield of 31percent.The key step of this synthesis is the intramolecular alkylation of the lithium azaenolate derived from the allylic chloride 4. Key Words: Amino acids / Cyclopropanes / Cyclopropanation, diastereoselective / Bislactim ether method
Groth, Ulrich,Halfbrodt, Wolfgang,Schoellkopf, Ulrich
p. 351 - 356
(2007/10/02)

ASYMMETRIC SYNTHESIS OF D-erythro-SPHINGOSINE
D-erythro-Sphingosine 9 is a building block of cerebrosides and glycosphingolipids and was synthesized in 5 steps via an asymmetric aldol addition of the lithiated bislactim ether of cyclo-(L-Val-Gly) 4 to (2E)-hexadecenal (3) in an overall yield of 21percent.
Groth, Ulrich,Schoellkopf, Ulrich,Tiller, Thomas
p. 2835 - 2842
(2007/10/02)

Asymmetric Syntheses of Diastereomerically and Enantiomerically Pure (2R,3S)-threo-3-Arylserine Methyl Esters by the Bislactim Ether Method Asymmetric Synthesis of Chloramphenicol
The titanium derivative 3 of the bislactim ether 1 of cyclo(-L-Val-Gly-) reacts with arylaldehydes 4 highly diastereoselectively to give the syn-addition products of type 5.On hydrolysis, these yield besides methyl L-valinate (6) and small amounts of the
Schoellkopf, Ulrich,Beulshausen, Tessa
p. 223 - 226
(2007/10/02)

Asymmetric Syntheses via Heterocyclic Intermediates, XL. - Studies on the Acylation of Lithiated Bislactim Ethers of cyclo(-L-Val-Ala-) and cyclo(-L-Val-Gly-). - Asymmetric Synthesis of (R)-α-Alkenyl and (R)-α-Ethinyl Alanine Methyl Esters by the Bislactim Ether Method
The lithiated bislactim ether 2a of cyclo(-L-Val-Ala-) reacts with acyl chlorides 3 highly diastereoselectively to yield the compounds 4 with (2S,5S)-configuration.With acetyl chloride (3a) the N-acetyl compound 7 is formed as a sideproduct.Alternatively, the compounds 4 can be obtained by oxidation of the carbinols 8.From 4a and b, the olefins 11a and b are obtained by Wittig reaction.These are precursors of methyl (R)-α-alkenyl alanine methyl esters of type 13. (R)-α-ethinyl alanine methyl ester 17 is obtainable from 4a and 4e via the intermediates 14 or 15 and16a.The lithiated bislactim ether 2c of cyclo(-L-Val-Gly-) reacts with benzoyl chloride (3b) to give the "bis adduct" 18.However, 6b is obtained from 2c and the benzamide 19, though as a 1:1 diastereomeric mixture.Presumably, 6b epimerizes via the enol 21a subsequently to its diastereoselective formation.
Schoellkopf, Ulrich,Westphalen, Karl-Otto,Schroeder, Juergen,Horn, Klaus
p. 781 - 786
(2007/10/02)

Enantioselektive Synthese von (R)-N-Boc-1-amino-2-arylcyclopropen-1-carbonsaeuremethylester
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Schoellkopf, Ulrich,Hupfeld, Bernd,Kueper, Stephan,Egert, Ernst,Dyrbusch, Michael
p. 438 - 439
(2007/10/02)

ASYMMETRIC SYNTHESIS VIA HETEROCYCLIC INTERMEDIATES - XXXIX. ASYMMETRTIC SYNTHESIS OF (ENANTIOMERICALLY AND DIASTEREOMERICALLY VIRTUALLY PURE) METHYL 2-AMINO-4,5-EPOXY-3-HYDROXY-ALKANOATES AND METHYL 2-AMINO-3-HYDROXY-4,5-METHYLENE-ALKANOATES BY THE BISLA
α,β-Unsaturated aldehydes react with the titanated bislactim ether 6 of cyclo-(L-val-gly) to give the (2R,1'S)-syn-addition products of type 8.With TBHP (catalyzed by Ti(OiPr)4 with and without (+)- or (-)-DET) these furnish the epoxides 10 or 11 with 1',
Schoellkopf, Ulrich,Tiller, Thomas,Bardenhagen, Juergen
p. 5293 - 5306
(2007/10/02)

Enantio- und diastereoselektive Synthese von (2R)-2-Amino-5-oxocarbonsaeure-methylestern aus Enonen und Bislactimether-Cupraten
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Schoellkopf, Ulrich,Pettig, Dagmar,Schulze, Edda,Klinge, Michael,Egert, Ernst,et al.
p. 1238 - 1239
(2007/10/02)

Asymmetric synthesis via heterocyclic intermediates; XXXVII. Asymmetric synthesis of dimethyl (R)-2-amino-(E)-hept-4-enedioates by the Bislactim ether method
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Pettig,Schollkopf
p. 173 - 175
(2007/10/02)

Optisch aktive α-Arylglycinester durch asymmetrische Friedel-Crafts-Alkylierung mit dem chiralen Kation des Bislactimethers von cyclo-(L-Val-Gly)
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Schoellkopf, Ulrich,Gruettner, Sabine,Anderskewitz, Ralf,Egert, Ernst,Dyrbusch, Michael
p. 717 - 719
(2007/10/02)

Asymmetric synthesis via heterocyclic intermediates; XXX. Asymmetric synthesis of glutamic acids and derivatives thereof by the bislactim-ether method. Michael-addition of methyl 2-alkenoates to the lithiated bislactim-ether of cyclo-(L-Val-Gly)
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Schollkopf,Pettig,Busse,et al.
p. 737 - 740
(2007/10/02)

Asymmetric Syntheses via Heterocyclic Intermediates, XXXI.- Asymmetric Synthesis of Various Non-Proteinogenic Amino Acid Methyl Esters (Functionalized in the Carbon Chain) and Amino Acids by the Bislactim Ether Method
The lithiated bislactim ethers 5, 10, 12, and 23 were alkylated with a variety of alkylating agents 6 to give the alkylated bislactim ethers 7, 11, 13, and 24 with a high degree of asymmetric induction (up to 99percent).Upon hydrolysis these furnished the optically active amino acid methyl esters of type 8, 14, or 25.Some of these amino acid esters were further hydrolyzed to yield the amino acids.
Schoellkopf, Ulrich,Busse, Ulrich,Lonsky, Ralph,Hinrichs, Rolf
p. 2150 - 2163
(2007/10/02)

Asymmetric Syntheses via Heterocyclic Intermediates, XXVI. - Asymmetric Synthesis of an Amino Acid Ester with a 3,4-Epoxy Function (β,γ-Epoxy Function) by the Bislactim Ether Method
α-Chlorketone 3 reagieren mit dem lithiierten Bislactimether 2 von cyclo(L-Val-Gly) zu den Verbindungen 4 mit (3R,1'RS)-Konfiguration.Diese liefern beim Behandeln mit NaOH die Oxirane 5.Aus 5b erhaelt man bei der sauren Hydrolyse ein Epimerengemisch von (2R,3R)- und (2R,3S)-2-Amino-3,4-epoxy-3-phenylbutansaeure-methylester (7).
Neubauer, Hans-Juergen,Baeza, Jaime,Freer, Juanita,Schoellkopf, Ulrich
p. 1508 - 1512
(2007/10/02)

Asymmetric Syntheses via Heterocyclic Intermediates, XXIV. - Enantioselective Synthesis of (R)-α-Methyltryptophane Methyl Ester and D-Tryptophane Methyl Ester by the Bislactim Ether Route
Die Titelverbindungen wurden durch asymmetrische Synthese nach der Bislactimether-Methode hergestellt (e.e. ueber 95percent bzw. etwa 90percent).
Schoellkopf, Ulrich,Lonsky, Ralph,Lehr, Philipp
p. 413 - 417
(2007/10/02)

Process for recovering a dipeptide derivative
A process for recovering a dipeptide derivative comprises admixing an aqueous mixture of a solid dipeptide ester derivative of the formula STR1 wherein R1 is a lower alkyl group, R2 is a side chain group of an amino acid, n is 1 or 2, X is a benzyloxycarbonyl group which can have a nuclear substituent and Y is a hydrogen ion or an ammonium derivative ion of the formula STR2 wherein R3 is a side chain group of an amino acid and R4 is a lower alkyl group with an organic solvent capable of forming a binary phase system with water; said solvent being present in an amount effective to obtain the transfer of said peptide in the form of a solid from the aqueous phase to the organic solvent phase, settling the resulting admixture to form (1) an organic solvent phase containing in a solid state a substantial amount of dipeptide derivative of the formula STR3 wherein R1, R2, n and X are as defined above and Z is a hydrogen ion or an ammonium derivative ion of the formula STR4 wherein R3 and R4 are as defined above, and (2) an aqueous phase, separating the organic solvent phase from the aqueous phase, and recovering the dipeptide derivative from the organic solvent phase.
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(2008/06/13)

ASYMMETRIC SYNTHESES VIA HETEROCYCLIC INTERMEDIATES-XXII; ENANTIOSELECTIVE SYNTHESIS OF α-ALKENYL GLYCINE METHYL ESTERS AND α-ALKENYL GLYCINES (β,γ-UNSATURATED AMINO ACIDS)
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.
Schoellkopf, Ulrich,Nozulak, Joachim,Groth, Ulrich
p. 1409 - 1418
(2007/10/02)

ENANTIOSELECTIVE SYNTHESIS OF NON-PROTEINOGENIC AMINO ACIDS VIA METALLATED BIS-LACTIM ETHERS OF 2,5-DIKETOPIPERAZINES
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.
Schoellkopf, Ulrich
p. 2085 - 2092
(2007/10/02)