- Synthesis of chiral cyclic nitrones via a nitrosoketene intermediate and their use for the complete EPC synthesis of nonproteinogenic amino acids
-
New cyclic chiral nitrones constituting two diastereomers were synthesized by the reaction of isonitroso Meldrum's acid with l-menthone via a nitrosoketene intermediate. Both nitrones reacted with allyltrimelhylsilane diastereoselectively to give the corresponding isoxazolidine derivatives as sole products, which were converted to (S)- and (R)-allylglycines in ca. 100% ee, respectively.
- Katagiri, Nobuya,Okada, Makoto,Kaneko, Chikara,Furuya, Toshio
-
-
Read Online
- Asymmetric [2,3]-rearrangement of glycine-derived allyl ammonium ylids
-
The first examples of highly enantioselective [2,3]-sigmatropic rearrangements of acyclic allylic ammonium ylids are reported. Thus, a range of N-{2′-[(N′-allyl-N′,N′-dialkyl)ammonium]}acetyl camphor sultams undergo rearrangement at 0 °C in DME solution with high diastereofacial control (up to 99:1 dr) to give allylglycines in generally high yield. The power of the method has been demonstrated in a rapid and efficient synthesis of (R)-allyl glycine. Copyright
- Workman, James A.,Garrido, Neil P.,Sancon, Julien,Roberts, Edward,Wessel, Hans Peter,Sweeney
-
-
Read Online
- Epoxy amino acids produced from allylglycines intramolecularly cyclised to yield four stereoisomers of 4-hydroxyproline derivatives
-
Derivatives of 2-amino-4-pentenoic acid (allylglycine) were efficiently resolved using Subtilisin or acylase. The side-chain unsaturated bond of the enantiomerically pure amino acid with tert-butoxycarbonyl (Boc) protection was smoothly epoxidized with m-chloroperbenzoic acid. When the Boc protection of the amino group was removed, the amino group intramolecularly attacked the side-chain epoxide, generating compounds with five-membered rings: the 4-hydroxyproline derivatives. Two diastereomeric products were formed through the cyclisation reaction, for example, (2S,4S)-4-hydroxyproline benzyl ester (cis-8) and (2S,4R)-4-hydroxyproline benzyl ester (trans-8) were formed from (2S)-amino acid with a side-chain epoxide. Compound (2S,4S)-4-hydroxyproline benzyl ester (cis-8) was transformed to a lactone (cis-hydroxyproline lactone, 10) with the removal of benzyl alcohol. The cis-conformation was essential for the intramolecular ester exchange reaction; in fact, no lactone formation was observed for the trans isomer (trans-8). The separation of cis-hydroxyproline lactone and the trans-isomeric hydroxyproline benzyl ester was facile and clear, in contrast to the difficult separation of cis- and trans-hydroxyproline derivatives. Thus, two diastereomers of hydroxyproline derivatives for l-hydroxyproline and also for d-hydroxyproline were obtained, i.e., four diastereomers of hydroxyproline derivatives.
- Krishnamurthy, Suvratha,Arai, Toru,Nakanishi, Kanae,Nishino, Norikazu
-
p. 2482 - 2490
(2014/01/06)
-
- Diastereoselective amidoallylation of glyoxylic acid with chiral tert-butanesulfinamide and allylboronic acid pinacol esters: Efficient synthesis of optically active γ,δ-unsaturated α-amino acids This work is dedicated to Dr. Masanori Sakamoto, Professor Emeritus of Meiji Pharmaceutical University, on the occasion of his 77th birthday (KIJU)
-
A convenient synthesis of δ,γ-unsaturated amino acids has been developed. After a mixture of (R)-tert-butanesulfinamide and glyoxylic acid with molecular sieves in CH2Cl2 was stirred for 42 h at room temperature, allylboronic acid pinacol ester was added to the mixture to give (R)-2-((R)-tert-butanesulfinamido)pent-4-enoic acid with high diastereoselectivity. The corresponding reaction of (Z)-crotylboronic acid pinacol ester produced no product; however, that of (E)-crotylboronic acid pinacol ester produced (2R,3S)-2-((R)-tert-butylsulfinamido)-3-methylpent-4- enoic acid with excellent diastereoselectivity.
- Sugiyama, Shigeo,Imai, Saori,Ishii, Keitaro
-
p. 1069 - 1074
(2013/10/08)
-
- Novel preparation of chiral α-amino acids using the Mitsunobu-Tsunoda reaction
-
An efficient synthesis of racemic or optically active α-amino acids by modified-Mitsunobu alkylation of a racemic or chiral glycine template from alcohols was developed. Libraries of amino acids were prepared in moderate to good yield with good to high enantioselectivity. This simple method widens the scope for preparation of structurally diverse amino acids.
- Noisier, Anais F. M.,Harris, Craig S.,Brimble, Margaret A.
-
supporting information
p. 7744 - 7746
(2013/09/02)
-
- An improved racemase/acylase biotransformation for the preparation of enantiomerically pure amino acids
-
Using directed evolution, a variant N-acetyl amino acid racemase (NAAAR G291D/F323Y) has been developed with up to 6-fold higher activity than the wild-type on a range of N-acetylated amino acids. The variant has been coupled with an enantiospecific acylase to give a preparative scale dynamic kinetic resolution which allows 98% conversion of N-acetyl-dl-allylglycine into d-allylglycine in 18 h at high substrate concentrations (50 g L-1). This is the first example of NAAAR operating under conditions which would allow it to be successfully used on an industrial scale for the production of enantiomerically pure α-amino acids. X-ray crystal analysis of the improved NAAAR variant allowed a comparison with the wild-type enzyme. We postulate that a network of novel interactions that result from the introduction of the two side chains is the source of improved catalytic performance.
- Baxter, Scott,Royer, Sylvain,Grogan, Gideon,Brown, Fraser,Holt-Tiffin, Karen E.,Taylor, Ian N.,Fotheringham, Ian G.,Campopiano, Dominic J.
-
supporting information
p. 19310 - 19313
(2013/02/23)
-
- Phase-transfer enantioselective monoalkylation of prochiral nickel(ii) complexes catalyzed by 3,3′-bis[hydroxy(diphenyl)methyl]-1,1′- binaphthyl-2,23′-diol (BIMBOL) as a route to α-amino acids
-
An achiral nickel complex with a Schiff base derived from glycine was alkylated with alkyl halides under conditions of asymmetric phase-transfer catalysis. The chiral tetraol (R)-BIMBOL was employed as a catalyst. The enantiomeric purity of the alkylation products was up to 88%. Subsequent decomposition of the complexes afforded the corresponding a-amino acids.
- Belokon,Maleev,Samoilichenko,Moskalenko,Hakobyan,Saghyan
-
p. 2344 - 2349
(2013/10/01)
-
- Rapid asymmetric synthesis of amino acids via NiII complexes based on new fluorine containing chiral auxiliaries
-
New fluorine-containing chiral auxiliaries (S)-N-(2-benzoylphenyl)-1-(2- fluorobenzyl)-, (S)-N-(2-benzoylphenyl)-1-(3-fluorobenzyl)-, and (S)-N-(2-benzoylphenyl)-1-(4-fluorobenzyl)-pyrrolidine-2-carboxamide and their NiII complexes of Schiff bases with glycine and alanine have been synthesized. The greater efficiency of the complexes in terms of faster reaction rates and stereoselectivities in the asymmetric synthesis of (S)-α-amino acids has also been demonstrated.
- Saghyan, Ashot S.,Dadayan, Ani S.,Dadayan, Slavik A.,Mkrtchyan, Anna F.,Geolchanyan, Arpine V.,Manasyan, Luiza L.,Ajvazyan, Hrant R.,Khrustalev, Victor N.,Hambardzumyan, Hasmik H.,Maleev, Victor I.
-
experimental part
p. 2956 - 2965
(2011/03/19)
-
- Remarkable salt effect on in-mediated allylation of N-tert-butanesulfinyl imines in aqueous media: Highly practical asymmetric synthesis of chiral homoallylic amines and isoindolinones
-
A highly practical and efficient asymmetric synthesis of chiral homoallylic amines by In-mediated allylation of chiral N-tert-butanesulfinyl imines in aqueous media at room temperature was developed. With 2-formylbenzoate imine substrates, the method allows the highly enantioselective achievement of a variety of pharmacologically important 3-allyl isoindolinone compounds.
- Sun, Xing-Wen,Liu, Min,Xu, Ming-Hua,Lin, Guo-Qiang
-
supporting information; experimental part
p. 1259 - 1262
(2009/04/06)
-
- Large scale enantiomeric synthesis, purification, and characterization of ω-unsaturated amino acids via a Gly-Ni(II)-BPB-complex
-
The enantiomeric syntheses of ω-unsaturated amino acids and β-substituted ω-unsaturated amino acids were accomplished by using Gly-Ni-2[N-(N′-benzylprolyl)amino]benzophenone (BPB) as a chiral auxiliary. The synthesis provides excellent yields and high diastereoselectivities. The product crystallization followed by isomer epimerization strategy makes the reaction practical and useful for large-scale preparations. Dialkylation of the Ni(II)-complex, which was designed for mechanistic considerations, revealed that high diastereoselectivity is obtained due to the thermodynamic conformational stability of the Ni(II)-complex. The assignment of absolute configuration was accomplished by NMR, which is supported by corresponding X-ray structure and optical rotation data. Both enantiomerically pure amino acids can be synthesized in this alkylation-hydrolysis two-step strategy in multi gram scales.
- Gu, Xuyuan,Ndungu, John M.,Qiu, Wei,Ying, Jinfa,Carducci, Michael D.,Wooden, Hank,Hruby, Victor J.
-
p. 8233 - 8243
(2007/10/03)
-
- Asymmetric synthesis with 6-tert-butyl-5-methoxy-6-methyl-3,6-dihydro-2H-1,4-oxazin-2-one as a new chiral glycine equivalent: Preparation of enantiomerically pure α-tertiary and α-quaternary α-amino acids
-
The chiral oxazinone 2 has been developed as a new chiral glycine equivalent for the asymmetric synthesis of mono- and disubstituted α-amino acids. It is derived from the α-hydroxycarboxylic acid 1, which serves as a chiral auxiliary, and is easily accessible in enantiomerically pure form by optical resolution of the racemic compound (RS)-1. For alkylation reactions, 2 was deprotonated with sBuLi or phosphazenic base. Subsequent treatment with alkyl halides yielded the monosubstituted compounds 13/14a-c, e, f, (ent)-13d, (ent)-14d, while a second alkylation step, via the corresponding enolates, provided the disubstituted compounds 17/18a-d. Both alkylation steps proceeded with good yields and excellent diastereoselectivities (up to 99% de) and even less reactive electrophiles such as isopropyl iodide could be used. The results obtained in this reaction supported the assumption that the enolate of 2, as well as those of the monosubstituted derivatives of 2, have less tendency to form the aggregates that hamper alkylation reactions with other systems with higher oxygen content. From the major diastereomers of both the mono- and the disubstituted derivatives of 2 the corresponding α-amino acids 33a-c and 34a-d were obtained in high enantiomeric purity by hydrolytic cleavage of the oxazinone ring, accomplished either in two steps with aqueous TFA and aqueous NaOH or in one with either aqueous NaOH or 3 N HBr. Alkylation of the enolate ions of (S)-2 or (R)-2 with epichlorohydrins as bifunctional electrophiles provided the hydroxymethylenecyclopropyl derivatives 21 and 22. Hydrolysis of 21 and 22 afforded the free amino acids 35 and (ent)-35. Reductive amination with aniline after oxidation of 21 and 22 to the corresponding aldehydes 24 and 26 provided the compounds 25 and 27, whereas Mitsunobu treatment of 21 and 22 with 1-phenyl-3-(trifluoroacetyl)urea (28) afforded the urea derivatives 29 and 31. Hydrolysis of these compounds yielded the corresponding 1-aminocylopropanecarboxylic acid derivatives 36/(ent)-36 and (ent)-37. Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2003.
- Koch, Claus-Juergen,Simonyiova, Sona,Pabel, Joerg,Kaertner, Annerose,Polborn, Kurt,Wanner, Klaus Theodor
-
p. 1244 - 1263
(2007/10/03)
-
- Selective synthesis of either enantiomer of α-amino acids by switching the regiochemistry of the tricyclic iminolactones prepared from a single chiral source
-
Preparation of L-α-amino acids was easily accomplished simply by exchanging the position of the lactone group of our recently reported chiral template I from C2 to C3. The new chiral template 7 was prepared in 54% overall yield over five steps from (1R)-(+)-camphor. Alkylation of iminolactone 7 afforded the α-monosubstituted products in good yields and excellent diastereoselectivities (>98%). Hydrolysis of the alkylated iminolactones furnished the desired L-α-amino acids in good yields and ee with nearly quantitative recovery of chiral auxiliary 4.
- Xu, Peng-Fei,Lu, Ta-Jung
-
p. 658 - 661
(2007/10/03)
-
- Amine-boranes: Effective reducing agents for the deracemisation of DL-amino acids using L-amino acid oxidase from Proteus myxofaciens
-
The deracemisation of DL-α-amino acids using L-amino acid oxidase from Proteus myxofaciens and amine-boranes as chemical reducing agents has been investigated. Amine-boranes were found to be of particular interest in terms of reactivity and chemoselectivity compared to sodium borohydride and cyanoborohydride. Starting from the racemate, a range of D-amino acids were obtained in yields of up to 90% and e.e. >99%.
- Alexandre, Fran?ois-René,Pantaleone, David P.,Taylor, Paul P.,Fotheringham, Ian G.,Ager, David J.,Turner, Nicholas J.
-
p. 707 - 710
(2007/10/03)
-
- Chiral tricyclic iminolactone derived from (1R)-(+)-camphor as a glycine equivalent for the asymmetric synthesis of α-amino acids
-
The development of a highly efficient and stereoselective methodology for the preparation of α-amino acids is described. The chiral template, tricyclic iminolactone 7, was synthesized from (1R)-(+)-camphor in five steps in 50% overall yield. Alkylation of iminolactone 7 afforded the α-monosubstituted products in good yields (74-96%) and excellent diastereoselectivities (>98%). Hydrolysis of the alkylated iminolactones furnished the desired α-amino acids in good yields and enantioselectivities with nearly quantitative recovery of the chiral auxiliary 4.
- Xu, Peng-Fei,Chen, Yuan-Shek,Lin, Shu-I,Lu, Ta-Jung
-
p. 2309 - 2314
(2007/10/03)
-
- Highly efficient catalytic synthesis of α-amino acids under phase-transfer conditions with a novel catalyst/substrate pair
-
A facile and fast enantioselective synthesis of α-amino acids with high ee values was achieved by the asymmetric alkylation of the glycine derivative 1 under phase-transfer conditions with (R)-2-amino-2′-hydrozy-1,1′-binaphthyl (NOBIN; see sceme). The ee value of the amino acid products. This occures as a results of a significant positive nonlinear effect in the alkylation reaction.
- Belokon, Yuri N.,Kochetkov, Konstantin A.,Churkina, Tatiana D.,Ikonnikov, Nikolai S.,Larionov, Oleg V.,Harutyunyan, Syuzanna R.,Vyskocil, Stepan,North, Michael,Kagan, Henri B.
-
p. 1948 - 1951
(2007/10/03)
-
- The imine (+)-pseudoephedrine glycinamide: A useful reagent for the asymmetric synthesis of (R)-α-amino acids
-
The new imine derived from Myers (+)-pseudoephedrine glycinamide can be diastereoselectively alkylated with alkyl halides at room temperature using NaOEt or LiO-tert-Bu as bases under phase transfer conditions. Hydrolysis to the corresponding alkylated products was easily achieved under mild conditions to afford (R)-α-amino acids.
- Guillena, Gabriela,Najera, Carmen
-
p. 181 - 183
(2007/10/03)
-
- A Biocatalytic Route to Enantiomerically Pure Unsaturated α-H-α-Amino Acids
-
A set of both enantiomeric forms of non-proteinogenic, unsaturated α-H-α-amino acids was efficiently synthesized using a biocatalytic pathway. This route involved the straightforward synthesis of the required unsaturated amino acid amides, followed by resolution with an aminopeptidase present in Pseudomonas putida ATCC 12633 and/or a genetically modified organism, leading to the (S)-acids and (R)-amides. Undesired amino acid racemase activity was identified in the wild-type strain, which was absent in the newly developed organism. The (R)-amides were hydrolyzed under mild conditions using an amidase present in whole cells from Rhodococcus erythropolis NCIMB 11540 to the (R)-acids. The viability of this procedure was demonstrated with the multi-gram synthesis of a variety of unsaturated amino acids in excellent enantiopurity.
- Wolf, Larissa B.,Sonke, Theo,Tjen, Kim C. M. F.,Kaptein, Bernard,Broxterman, Quirinus B.,Schoemaker, Hans E.,Rutjes, Floris P. J. T.
-
p. 662 - 674
(2007/10/03)
-
- Chiral salen-metal complexes as novel catalysts for the asymmetric synthesis of α-amino acids under phase transfer catalysis conditions
-
Chiral salen-metal complexes have been tested as catalysts for the C-alkylation of Schiff's bases of alanine and glycine esters with alkyl bromides under phase-transfer conditions (solid sodium hydroxide, toluene, ambient temperature, 1-10 mol% of the catalyst). The best catalyst, which was derived from a Cu(II) complex of (1R, 2R or 1S,2S)-[N,N′-bis(2′-hydroxybenzylidene)]-1,2-diaminocyclohexane, gave α-amino and α-methyl-α-amino acids with enantiomeric excesses of 70-96%.
- Belokon, Yuri N,North, Michael,Churkina, Tatiana D,Ikonnikov, Nikolai S,Maleev, Victor I
-
p. 2491 - 2498
(2007/10/03)
-
- 1,5-dimethyl-4-phenylimidazolidin-2-one-derived iminic glycinimides: Useful new reagents for practical asymmetric synthesis of α-amino acids
-
New 1,5-dimethyl-4-phenylimidazolidin-2-one-derived acyclic chiral iminic glycine reagents have been prepared and diastereoselectively alkylated with activated alkyl halides and electrophilic olefins in the presence of lithium chloride under (a) strong bases (LHMDS, KOBu(t)) and low temperature (-78 °C,) conditions; (b) solid-liquid phase-transfer catalysis reaction (LiOH, TBAB, -20 °C) conditions, and (c) in the presence of organic bases (DBU, BEMP, TMG, -20 °C). In the case of dielectrophiles C- and N-alkylation takes place to afford heterocyclic derivatives. Hydrolysis of alkylated products has been carried out (a) in two-step procedures with LiOOH or LiOH followed by acidic hydrolysis or Dowex purification, (b) in one single-step under refluxing water to give the corresponding α-amino acid, (c) in the presence of DBU in methanol to provide N-protected α-amino acids methyl esters, or (d) by a protection-hydrolysis procedure to afford N-Boc-protected α-amino acids. The chiral imidazolidinone has generally been recovered in good yield. This methodology has been shown to be useful for the synthesis of acyclic and heterocyclic (S)- and (R)-α-amino acids.
- Guillena,Najera
-
p. 7310 - 7322
(2007/10/03)
-
- Synthesis of enantiopure functionalized pipecolic acids via amino acid derived N-acyliminium ions
-
The synthesis and enzymatic resolution of a novel vinylsilane-containing amino acid is described. Derivatization of this and other olefinic amino acids followed by subjection to standard N-acyliminium ion cyclization conditions provides the corresponding pipecolic acid derivatives with - in most cases - complete conservation of enantiopurity. In addition to studying the scope of this reaction, details of the N-acyliminium ion cyclization including an aza Cope equilibrium are highlighted.
- Rutjes, Floris P. J. T.,Veerman, Johan J. N.,Meester, Wim J. N.,Hiemstra, Henk,Schoemaker, Hans E.
-
p. 1127 - 1135
(2007/10/03)
-
- Electrogenerated chiral cationic glycine equivalents - Part 1: The 6-methoxy derivative of cyclo(L-Pro-Gly)
-
The cyclic N,O-acetal cyclo(L-Pro-Gly(OMe)OMe (8) has proved to be an effective chiral electrophilic glycine equivalent which is applicable in nucleophilic substitution reactions not only under Broenstedt acid catalysis but also under Lewis acid catalysis with excellent diastereoselectivities. This chiral building block can easily be obtained by electrochemical methoxylative decarboxylation of the cyclic dipeptide 6 generated from L-proline and aminomalonic diester. Thus, enantiomerically pure D-allyl glycine has been generated.
- Kardassis, Georgios,Brungs, Peter,Steckhan, Eberhard
-
p. 3471 - 3478
(2007/10/03)
-
- Electrogenerated chiral cationic glycine equivalents - Part 2: Chiral 3-methoxy-2,5-morpholinediones from (S)-α-hydroxy acids and dimethyl aminomalonate
-
Chiral 3-methoxy-2,5-morpholinediones which are cyclic N,O-acetals have proved to be excellent chiral cationic amino acid equivalents, especially if larger nucleophiles are employed. They are easily obtained from dipeptolides formed between chiral α-hydroxy acids and dimethyl amino malonate via regioselective electrochemical methoxylation followed by intramolecular lactonizatian after decarboxylation. The lactonization can be performed quantitatively from the open-chain peptolide by condenzation under reduced pressure at elevated temperature. The easy separation of the desired amino acid and the α-hydroxy acid being the chiral auxiliary by extraction is valuable.
- Kardassis, Georgios,Brungs, Peter,Nothhelfer, Christoph,Steckhan, Eberhard
-
p. 3479 - 3488
(2007/10/03)
-
- Highly practical methodology for the synthesis of D- and L-α-amino acids, N-protected α-amino acids, and N-methyl-α-amino acids
-
Full details are provided for an exceedingly practical method to synthesize D- and L-α-amino acids, N-protected α-amino acids, and N-methyl-α-amino acids, employing as a key step the asymmetric alkylation of pseudoephedrine glycinamide (1) or pseudoephedrine sarcosinamide (2). Practical procedures for the synthesis of 1 and 2 from pseudoephedrine and glycine methyl ester or sarcosine methyl ester, respectively, are presented. Optimum protocols for the enolization and subsequent alkylation of 1 and 2 are described. Alkylation reactions of 1 and 2 are found to be quite efficient with a wide range of alkyl halide substrates, and the products are formed with high diastereoselectivity. The products of these alkylation reactions are hydrolyzed efficiently and with little to no racemization simply by heating in water or water-dioxane mixtures. This protocol provides an exceedingly practical method for the preparation of salt-free α-amino acids of high enantiomeric purity. Alternatively, the alkylation products may be hydrolyzed in high yield and with little to no racemization by heating with aqueous sodium hydroxide. The alkaline hydrolyzate can then be treated with an acylating reagent to provide directly highly enantiomerically enriched N-protected derivatives such as N-Boc and N-Fmoc. Key features necessary for the successful execution of these experimental procedures are identified.
- Myers, Andrew G.,Gleason, James L.,Yoon, Taeyoung,Kung, Daniel W.
-
p. 656 - 673
(2007/10/03)
-
- Synthesis of chiral spiro 3-oxazolin-5-one 3-oxides (Chiral nitrones) via a nitrosoketene intermediate and their asymmetric 1,3-dipolar cycloaddition reactions leading to the EPC synthesis of modified amino acids,
-
Cycloaddition of chiral cyclic ketones such as (-)-menthone, (+)-nopinone, and (+)-camphenilone to nitrosokelene generated by thermolysis of 5-hydroxyimino-2,2-dimethyl-1,3-dioxane-4,6 dione gave the corresponding chiral spiro 3-oxazolin-5-one 3-oxides (chiral cyclic nitrones). These nitrones underwent asymmetric 1,3-dipolar cycloddition reactions with electron rich olefins to give the corresponding oxazolidine derivatives with high diastereoselectivity, which were converted to optically pure amino acids.
- Katagiri, Nobuya,Okada, Makoto,Morishita, Yoshihiro,Kaneko, Chikara
-
p. 5725 - 5746
(2007/10/03)
-
- Electrogenerated chiral building blocks for diastereoselective amidoalkylation reactions
-
Three different electrochemical methods have been applied for the synthesis of chiral building blocks for diastereoselective amidoalkylation reactions. These are A. the direct anodic α-methoxylation of amides and carbamates; B. anodic methoxylative decarboxylation of α-amino acid derivatives (Hofer-Moest reaction) C. indirect NaCl mediated anodic α-methoxylation of α-amino acid derivatives. The application of these building blocks for the synthesis of enantiomerically pure α-amino acids, dichiral 1,2-amino alcohols and chiral 1,3-diamines is described.
- Brungs,Danielmeier,Jakobi,Nothhelfer,Stahl,Zietlow,Steckhan
-
p. 575 - 590
(2007/10/03)
-
- Asymmetric Induction in Acyclic Radical Reactions: Enantioselective Syntheses of α-Amino Acids via Carbon-Carbon Bond Forming Radical Reactions.
-
The derivative of glycine, 8-phenylmenthyl N-Boc-2-bromoglycinate 1 reacted with allyltri-n-butylstannanes via the corresponding radical 2 by the SH2' mechanism to give (2S) allyl amino acid derivatives with high diastereoselectivity.The reaction of 1 with triphenyl(1,2-propadienyl)stannane and triphenyl(2-propynyl)stannane gave the (2S) allenyl and (2S) propargyl amino acid derivatives respectively also with high diastereoselectivity but by a different mechanism.
- Hamon, David P. G.,Massy-Westropp, Ralph A.,Razzino, Pasquale
-
p. 4183 - 4194
(2007/10/02)
-
- Asymmetric Alkylation of 8-Phenylmenthyl N-glycinate Enolates. Synthesis of D- and L-α-Amino Acids from a Single Chiral Precursor
-
The herein described studies on the enolization and subsequent alkylation of the acyclic glycine title ester evidence the involvement of the kinetics of the alkylation step on the stereochemical outcome of the overall process, apart from that of the deprotonation sequence itself.Careful choice of reaction conditions allow for the selective obtention of α-amino acids either of the L- or the D-series without the need of changing the chiral inducer: deprotonation with LDA or t-BuLi followed by reaction with alkyl triflates gives rise to the 2R- α-amino acids, whereas the 2S isomers can be obtained by deprotonation with KO-t-Bu followed by reaction with alkyl halides.
- Alvarez-Ibarra, Carlos,Csaky, Aurelio G.,Maroto, Raquel,Quiroga, M. Luz
-
p. 7934 - 7940
(2007/10/03)
-
- (3R)- AND (3S)-METHYLPIPERAZINE-2,5-DIONE DERIVATIVES AS USEFUL INTERMEDIATES IN THE ENANTIOSELECTIVE SYNTHESIS OF α-AMINO ESTERS
-
Treatment of (3S)-3-methylpiperazine-2,5-dione 1 with lithium hexamethyldisilazide (LHMDS) followed by alkylation with several alkyl bromides affords (3S,6S)-3-methyl-6-alkyl derivatives 3 (a-e) in d.e. greater than 98percent.The same reaction sequence carried out on the (3R)-derivative 2 leads to a diastereoisomeric mixture of (3R,6S)-4 (a-e) and (3R,6R)-5 (a-e), the ratio 5 : 4 depending on the alkylating reagent.The configuration at C-6 (of 3, 4 and 5) has been assigned on the basis of 1H-NMR spectroscopic data and conformational analysis performed by the MMPMI program.Cleavage of the heterocyclic ring of 3 (b, d) and 5 (b, d) leads to the corresponding (S)- and (R)-α-amino esters respectively.
- Orena, Mario,Porzi, Gianni,Sandri, Sergio
-
p. 2125 - 2152
(2007/10/02)
-
- Synthesis of (Optically Active) Sulfur-Containing Trifunctional Amino Acids by Radical Addition to (Optically Active) Unsaturated Amino Acids
-
Sulfur-based radicals, generated from R-S-H-type precursors (R = alkyl, acyl) with AIBN, smoothly add to α-allylglycines protected at none, one, or both of the amino acid functions (NH2 and/or CO2H).Sulfur-containing trifunctional amino acids were obtained in good to excellent yields (64-100 percent).The solvent used for the reaction is critical.Optimal results were obtained when both the unsaturated amino acid and RSH dissolve completely in the medium (dioxane/water or methanol/water are good solvent systems).The scope of the reaction includes α-substituted α-allylglycine derivative and derivatives as well as β-substituted β-allyl-β-amino alcohols.In the case of optically active α-allylglycine derivatives, radical addition is accompanied by a small amount of racemization, the amount depending on the type of protection and R-S-H.The products are easily optically enriched by crystallization.Addition of sulfur-based radicals to α-allylglycine is believed to be an example of a general method for synthesizing optically active trifunctional amino acids from unsaturated amino acids.
- Broxterman, Quirinus B.,Kaptein, Bernard,Kamphuis, Johan,Schoemaker, Hans E.
-
p. 6286 - 6294
(2007/10/02)
-
- Asymmetric Synthesis of α-Amino Acids and α-N-Hydroxyamino Acids from N-Acylbornane-10,2-sultams: 1-Chloro-1-nitrosocyclohexane as a Practical +> Equivalent
-
Successive treatment of N-acylsultams 3 with sodium hexamethyldisilazide, 1-chloro-1-nitrosocyclohexane (1), and aq.HCl gave diastereoisomerically pure, crystalline N-hydroxyamino-acid derivatives 5.These were converted into various amino acids 7, N-hydroxyamino acids 8, and an N-Boc-amino acid 9. (S,S)-Isoleucine (17) and (S,S)-2-acetamido-3-phenylbutyric acid (23) were obtained from N-crotonoylsultam 15 via 1,4-addition of an organomagnesium or organocopper reagent followed by enolate 'amination' with 1.
- Oppolzer, Wolfgang,Tamura, Osamu,Deerberg, Joerg
-
p. 1965 - 1978
(2007/10/02)
-
- Asymmetric synthesis of α-amino acids and α-N-hydroxyamino acids via electrophilic amination of bornanesultam-derived enolates with 1-chloro-1-nitrosocyclohexane
-
Successive treatment of N-acylsultams 3 with NaN(TMS)2, 1-chloro-1-nitrosocyclohexane (1) and 1N aq. HCl gave diastereomerically pure, crystalline N-hydroxyamino acid derivatives 4. Products 4 were converted to various amino acids 6, an N-BOC-amino acid 8 and to N-hydroxyamino acids 9. (S,S)-Isoleucine (16) was obtained from N-crotonoylsultam 13 via an organomagnesium-1,4-addition/enolate trapping process generating two stereogenic centers.
- Oppolzer,Tamura
-
p. 991 - 994
(2007/10/02)
-
- ASYMMETRIC SYNTHESIS VII: DOUBLE STEREODIFFERENTATION IN ALLYLYTION OF KETIMINES BEARING TWO CHIRAL AUXILIARIES. APPLICATION TO ENANTIOSELECTIVE SYNTHESIS OF α-ALLYLGLYCINE
-
A diuble asymmetric induction has been observed in allylation of the imines derived from (+)-camphor, (+)- and (-)-2-hydroxypinan-3-ones with (+)- and (-)-menthyl glycinates.After hydrolysis of the allylated intermediates, (R)- and (S)-α-allylglycines are obtained in 3-90percent optical yields.
- Yaozhong, Jiang,Changyou, Zhou,Huri, Piao
-
p. 881 - 888
(2007/10/02)
-
- Practical Asymmetric Syntheses of α-Amino Acids through Carbon-Carbon Bond Constructions on Electrophilic Glycine Templates
-
The optically active D- and L-erythro-4-(benzyloxycarbonyl)-5,6-diphenyl-2,3,5,6-tetrahydro-4H-1,4-oxazin-2-ones (3) and D- and L-erythro-4-(tert-butoxycarbonyl)-5,6-diphenyl-2,3,5,6-tetrahydro-4H-1,4-oxazin-2-ones (3) can be efficiently brominated to serve as electrophilic glycine templates for the asymmetric synthesis of amino acids.It was found that coupling to these templates can proceed with either net retention or net inversion of stereochemistry.The final deblocking to the amino acids is accomplished with either dissolving-metal reduction or catalytic hydrogenolysis.The syntheses of β-ethyl aspartic acid, norvaline, allylglycine, alanine, norleucine, homophenylalanine, p-methoxyhomophenylalanine, cyclopentylglycine, and cyclopentenylglycine and a formal synthesis of clavalanine are described.In addition, the direct asymmetric syntheses of N-t-BOC-allylglycine and N-t-BOC-cyclopentenylglycine are described.
- Williams, Robert M.,Sinclair, Peter J.,Zhai, Dongguan,Chen, Daimo
-
p. 1547 - 1557
(2007/10/02)
-
- A General and Practical Synthesis of (R)-Phthalimido Aldehydes and D-α-Amino Acids from D-Mannitol
-
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.
- Mulzer, Johann,Angermann, Alfred,Schubert, Boris,Seilz, Carsten
-
p. 5294 - 5299
(2007/10/02)
-