- Synthesis of Enantiomerically Pure γ-Amino-β-hydroxybutyric Acid Using Malic Acid as the Chiral Precursor
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The synthesis of enantiomerically pure γ-amino-β-hydroxybutyric acid using malic acid as the chiral precursor is described.The key step involves the regioselective carboxamidation of the β-carboxyl group (adjacent to the hydroxyl) in malic acid.This was achieved by converting (S)-malic acid to its cyclic anhydride 8, which was then treated with ammonia.Protection of the alcoholic group in the ester amide 9 as a tert-butyl ether followed by LiAlH4 reduction gave 3-(tert-butyloxy)-4-aminobutanol (11c).The amino group in 11c was protected as the tert-butyl carbamate to give (S)-3-(tert-butyloxy)-4-butanol (12c).The oxidation of the primary alcoholic group was successfully carried out with zinc permanganate to give the desired acid (S)-3-(tert-butyloxy)-4-butyric acid (13c).Removal of the protecting groups gave (S)-(+)-γ-amino-β-hydroxybutyric acid, the optical rotation measurements of which indicated no racemization during the six-step synthesis.The R isomer could be synthesized starting from (R)-malic acid.Thus a short and efficient route to chirally pure (R)- and (S)-γ-amino-β-hydroxybutyric acid is presented.Furthermore, this work also highlights zinc permanganate as a useful oxidant for the preparation of carboxylic acids.
- Rajashekhar, Betageri,Kaiser, Emil Thomas
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- FURTHER INFORMATION ON THE STERIC COURSE OF THE BAKER'S YEAST REDUCTION OF 4-SUBSTITUTED-3-OXOBUTANOATES
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Yeast reduction of (6), (7), (8), (12) and (13) affords (3R)(9) and (3R)(10) of high optical purity, racemic (11), and (3S)(14) and (3S)(15).
- Fuganti, Claudio,Grasselli, Piero,Seneci, P. Fausto,Casati, Paolo
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- An efficient transformation of cyclic ene-carbamates into ω-(N-formylamino)carboxylic acids by ruthenium tetroxide oxidation
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The ruthenium tetroxide (RuO4) oxidation of cyclic ene-carbamates resulted in the endo-cyclic carbon-carbon double bond cleavage to afford the corresponding ω-(N-formylamino)carboxylic acids in good yields. Substituted cyclic ene-carbamates der
- Kaname, Mamoru,Yoshifuji, Shigeyuki,Sashida, Haruki
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- A short synthesis of 4-amino-3-hydroxybutyric acid (GABOB) via allyl cyanide
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4-Amino-3-hydroxybutyric acid was synthesized from allyl cyanide in four steps in an overall yield of 38%. Ultrasonically promoted epoxidation of allyl cyanide with m-chloroperoxybenzoic acid giving oxiranylacetonitrile was used as a key step.
- Mete,Maras,Secen
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- Novel amide-functionalized chloramphenicol base bifunctional organocatalysts for enantioselective alcoholysis of meso-cyclic anhydrides
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A family of novel chloramphenicol base-amide organocatalysts possessing a NH functionality at C-1 position as monodentate hydrogen bond donor were developed and evaluated for enantioselective organocatalytic alcoholysis of meso-cyclic anhydrides. These structural diversified organocatalysts were found to induce high enantioselectivity in alcoholysis of anhydrides and was successfully applied to the asymmetric synthesis of (S)-GABOB.
- Xu, Lingjun,Han, Shuwen,Yan, Linjie,Wang, Haifeng,Peng, Haihui,Chen, Fener
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supporting information
p. 309 - 317
(2018/02/19)
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- Design, synthesis, and biological evaluation of simplified side chain hybrids of the potent actin binding polyketides rhizopodin and bistramide
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The natural products rhizopodin and bistramide belong to an elite class of highly potent actin binding agents. They show powerful antiproliferative activities against a range of tumor cell lines, with IC50 values in the low-nanomolar range. At the molecular level they disrupt the actin cytoskeleton by binding specifically to a few critical sites of G-actin, resulting in actin filament stabilization. The important biological properties of rhizopodin and bistramide, coupled with their unique and intriguing molecular architectures, render them attractive compounds for further development. However, this is severely hampered by the structural complexity of these metabolites. We initiated an interdisciplinary approach at the interface between molecular modeling, organic synthesis, and chemical biology to support further biological applications. We also wanted to expand structure-activity relationship studies with the goal of accessing simplified analogues with potent biological properties. We report computational analyses of actin-inhibitor interactions involving molecular docking, validated on known actin binding ligands, that show a close match between the crystal and modeled structures. Based on these results, the ligand shape was simplified, and more readily accessible rhizopodin-bistramide mimetics were designed. A flexible and modular strategy was applied for the synthesis of these compounds, enabling diverse access to dramatically simplified rhizopodin-bistramide hybrids. This novel analogue class was analyzed for its antiproliferative and actin binding properties.
- Herkommer, Daniel,Dreisigacker, Sandra,Sergeev, Galina,Sasse, Florenz,Gohlke, Holger,Menche, Dirk
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p. 470 - 489
(2015/04/21)
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- Synthesis of GABOB and GABOB-Based Chiral Units Possessing Distinct Protecting Groups
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In addition to the varied biological activity of GABOB (4-amino-3-hydroxybutanoic acid), the structure of its protected derivatives makes them interesting chiral intermediates for the synthesis of more complex compounds. A stereoselective route to GABOB derivatives with three different protecting groups is presented, using anhydride desymmetrization as a chirality-inducing step. Selective removal of the protecting groups gave compounds with a free carboxylic acid or hydroxy group. Removal of all of the protecting groups allowed GABOB to be isolated in good yield and with excellent ee.
- Ivic, Trpimir,Dokli, Irena,Rimac, Ana,Hamerak, Zdenko
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p. 631 - 638
(2015/10/05)
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- Synthesis of GABOB and GABOB-based chiral units possessing distinct protecting groups
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In addition to the varied biological activity of GABOB (4-amino-3- hydroxybutanoic acid), the structure of its protected derivatives makes them interesting chiral intermediates for the synthesis of more complex compounds. A stereoselective route to GABOB derivatives with three different protecting groups is presented, using anhydride desymmetrization as a chirality-inducing step. Selective removal of the protecting groups gave compounds with a free carboxylic acid or hydroxy group. Removal of all of the protecting groups allowed GABOB to be isolated in good yield and with excellent ee. A stereoselective route to GABOB (4-amino-3-hydroxybutanoic acid) derivatives with three different protecting groups is presented. Selective deprotection produced diprotected chiral building blocks with a free carboxylic acid or hydroxy group. Removal of all the protecting groups allowed GABOB to be isolated. Copyright
- Ivsic, Trpimir,Dokli, Irena,Rimac, Ana,Hamersak, Zdenko
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p. 631 - 638
(2014/02/14)
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- Thalassospiramide G, a new γ-amino-acid-bearing peptide from the marine bacterium Thalassospira sp
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In the chemical investigation of marine unicellular bacteria, a new peptide, thalassospiramide G (1), along with thalassospiramides A and D (2-3), was discovered from a large culture of Thalassospira sp. The structure of thalassospiramide G, bearing γ-amino acids, such as 4-amino-5-hydroxy- penta-2-enoic acid (AHPEA), 4-amino-3,5-dihydroxy-pentanoic acid (ADPA), and unique 2-amino-1-(1H-indol-3-yl) ethanone (AIEN), was determined via extensive spectroscopic analysis. The absolute configuration of thalassospiramide D (3), including 4-amino-3-hydroxy-5-phenylpentanoic acid (AHPPA), was rigorously determined by 1H-1H coupling constant analysis and chemical derivatization. Thalassospiramides A and D (2-3) inhibited nitric oxide (NO) production in lipopolysaccharide (LPS)-stimulated mouse macrophage RAW 264.7 cells, with IC50 values of 16.4 and 4.8 μM, respectively.
- Um, Soohyun,Pyee, Yuna,Kim, Eun-Hee,Lee, Sang Kook,Shin, Jongheon,Oh, Dong-Chan
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p. 611 - 622
(2013/05/23)
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- Stereoselective synthesis of (S)-oxiracetam and (S)-GABOB from (R)-glyceraldehyde acetonide
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Synthetic routes to (S)-oxiracetam and (S)-GABOB have been developed starting from (R)-glyceraldehyde acetonide through its conversion to an appropriate aldehyde intermediate followed by reductive amination using glycinamide hydrochloride/benzyl amine and subsequent chemical transformations.
- Sanyal, Ishita,Shukla, Brajesh,Barman, Piyali Deb,Banerjee, Asish Kumar
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supporting information
p. 2637 - 2640
(2013/06/26)
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- Total synthesis of (+)-negamycin and its 5-epi-derivative
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(+)-Negamycin was prepared in 13 steps in an overall yield of 31% from commercially available ethyl (R)-(+)-4-chloro-3-hydroxybutanoate. The key step in the reaction sequence was a highly stereoselective asymmetric Michael addition of chiral amine (-)-21
- Nishiguchi, Shigenobu,Sydnes, Magne O.,Taguchi, Akihiro,Regnier, Thomas,Kajimoto, Tetsuya,Node, Manabu,Yamazaki, Yuri,Yakushiji, Fumika,Kiso, Yoshiaki,Hayashi, Yoshio
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experimental part
p. 314 - 320
(2010/03/01)
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- Short synthesis of (R)- and (S)-4-amino-3-hydroxybutyric acid (GABOB)
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A simple and stereospecific synthesis of both (R)- and (S)-GABOB has been developed. The synthetic approach involves the conversion, through organoselenium intermediates, of commercially available ethyl (R)- and (S)-4-chloro-3-hydroxybutyrate into a protected 1,2-amino alcohol with retention of the original configuration.
- Tiecco, Marcello,Testaferri, Lorenzo,Temperini, Andrea,Terlizzi, Raffaella,Bagnoli, Luana,Marini, Francesca,Santi, Claudio
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p. 579 - 582
(2007/10/03)
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- Asymmetric synthesis of (R)-(-)-carnitine
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A TiCl4-promoted Mukaiyama-type aldol reaction of the ketenesilyl acetal of ethyl acetate with the lactone carbonyl of (5R,6S)-4-(benzyloxycarbonyl)-5,6-diphenyl-2,3,5,6-tetrahydro-4H-1,4-oxazin- 2-one (1) proceeds with a high degree of diastereoselectivity. The TBDMS-protected hemiketal thus obtained was efficiently converted into highly enantiomerically enriched (R)-(-)-carnitine by following an elimination-reduction protocol. This approach further demonstrates the utility of commercially available glycine template 1 as a potential substrate for the asymmetric synthesis of both enantiomers of carnitine.
- Jain, Rajendra P.,Williams, Robert M.
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p. 4437 - 4440
(2007/10/03)
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- Asymmetric synthesis of (S)-(+)-carnitine and analogs
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A general asymmetric route to enantiomerically pure (S)-(+)-carnitine and analogs has been investigated that involves mono-addition of organometallic reagents to the lactone carbonyl group of (5R,6S)-4-(benzyloxycarbonyl)-5,6-diphenyl-2,3,5,6-tetrahydro-4H-1,4-oxazin- 2-one and Lewis acid promoted stereoselective allylation of the resulting hemiacetals. The diastereomerically pure allyl oxazines thus obtained were readily converted into enantiomerically pure (S)-(+)-carnitine and two substituted analogs.
- Jain, Rajendra P,Williams, Robert M
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p. 6505 - 6509
(2007/10/03)
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- Efficient syntheses of (S)-4-hydroxy-2-pyrrolidinone derivatives
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Efficient syntheses of (S)-4-hydroxy-2-pyrrolidinone ((5)-2) and (R)4- acetylthio-2-pyrrolidinone (S), which are key intermediates of oral carbapenem CS-834, were studied. The most efficient route to (S)-2 from (S)- 3-hydroxybutyrolactone (8) was accomplished in high yield via (S)-N-allyl-3- (1-ethoxy)ethoxy-4-hydroxybutyramide (14).
- Kanno, Osamu,Miyauchi, Masao,Kawamoto, Isao
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p. 173 - 181
(2007/10/03)
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- Stereospecific synthesis of functionalized ether phospholipids
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A new stereospecific synthesis of functionalized alkyl ether phospholipids is reported. The synthesis is based upon the following: (1) the use of (R)-glycidyl tosylate as a chiral glycerol precursor; (2) the opening of a boron trifluoride catalyzed epoxide ring to introduce the functionalized sn-1-alkyl substituents; (3) the role of tetrahydropyranyl in protecting the sn-2-glycerol position; and (4) the elaboration of the sn-3-carbinol function, via the base hydrolysis of the acetoxy intermediate, obtained from the displacement of the toluenesulfonyl group of the substrate in dipolar aprotic media. Phosphorylation, using two different methods, has led to the development of two major classes of alkyllysophospholipids. For preparation of 'modulator-phospholipid' analogues, the substituted glycerol is coupled with 2,2,2-trichloro-tert-butyl phosphodichloridite and an N-protected amino acid ester, while elaboration of the phosphocholine headgroup of the target platelet-activating factor (PAF) analogues is achieved via the 2-chloro-2- oxo-1,3,2-dioxaphospholane/trimethylamine sequence. The synthesis provides rapid and efficient access to both types of phospholipids: (1) construction of the functionalized/substituted glycerol skeleton is achieved in a straightforward four-step sequence in better than 50% overall yield, and (2) phosphitylation or phosphorylation of the respective glycerol intermediates relies on reagents that require minimal use of protecting groups. The phospholipid compounds prepared include (1) the first synthetic analogue exhibiting modulator activity in conjunction with the glucocorticoid-receptor complex and (2) an sn-1-(ωamino)alkyl derivative of PAF, suitable for introduction of chain-terminal spectroscopic labels for biological and physicochemical studies to elucidate the mechanism of action of this highly potent alkyl ether phospholipid. The synthetic methods described herein have a great deal of flexibility, thus providing convenient general routes to a wide range of alkyl ether phospholipids.
- Kazi, Abul B.,Shidmand, Sean,Hajdu, Joseph
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p. 9337 - 9347
(2007/10/03)
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- General asymmetric synthesis of hydroxymethylene and hydroxyethylene peptide isosteres
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The Lewis acid-promoted coupling reactions of (5R, 6S)-2-acetoxy-4- (benzyloxycarbonyl)-5,6-diphenyl-2,3,5,6-tetrahydro-4H-1,4-oxazines (11a-e, and 21), which are prepared easily from (+)-(5R, 6S)-4(benzyloxycarbonyl)- 5,6-diphenyl-2,3,5,6-tetrahydro-4H-1,4-oxazin-2-one (9), with allyltrimethylsilane proceeded to give the corresponding coupling products with moderate to excellent stereoselectivity in good yields. These coupling products (13a, b, and d) were converted to hydroxymethylene-(25a, b, and d) and hydroxyethylene (28) peptide isosteres.
- Aoyagi, Yutaka,Williams, Robert M.
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p. 10419 - 10433
(2007/10/03)
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- A Facile Synthesis of (R)-4-Amino-3-hydroxybutanoic Acid (GABOB) from 3-Hydroxypyridine
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(R)-4-Amino-3-hydroxybutanoic acid (GABOB) has been synthesized facilely from 3-hydroxypyridine via 1-carbobenzoxy-1,2,3,4-tetrahydro-3-hydroxypyridine employing lipase-mediated kinetic resolution.
- Sakagami, Hideki,Kamikubo, Takashi,Ogasawara, Kunio
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p. 221 - 222
(2007/10/03)
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- A convenient preparation of optically pure 3-hydroxyglutaric acid derivatives
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The diastereomeric monoamides resulting from condensation of (L)-cysteine with 3-hydroxyglutarodinitrile have been separted by chromatography then transformed in a few steps into either (+) or (-) methyl ester of 4-cyano-3-hydroxybutyric acid.
- Leclerc,Uguen
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p. 1999 - 2002
(2007/10/02)
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- A simple total synthesis of naturally occurring hydroxy-amino acids by enzymatic kinetic resolution
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Both optically pure enantiomers of GABOB and isoserine were obtained by enzymatic kinetic resolution of acetylated precursors in three or four steps. The key intermediates were cyanohydrins available from simple aldehydes. This procedure can be applied to other unusual hydroxy amino acids widely distributed in biologically important peptides.
- Lu,Miet,Kunesch,Poisson
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p. 893 - 902
(2007/10/02)
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- Short and Practical Syntheses of (R)-(-)-Carnitine and (R)-(-)-γ-Amino-β-hydroxybutyric Acid (GABOB)
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Short and practical syntheses of (R)-(-)-carnitine and (R)-(-)-γ-amino-β-hydroxybutyric acid have been developed, both commencing with the catalytic asymmetric dihydroxylation of allyl bromide.
- Kolb, Hartmuth C.,Bennani, Youssef L.,Sharpless, K. Barry
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p. 133 - 141
(2007/10/02)
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- Baker's yeast reduction of N-protected methyl 4-amino-3-oxobutanoates and 3-oxopentanoates
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Baker's yeast reduction of N-tert-butoxycarbonyl (Boc) or N-benzyloxycarbonyl (Cbz) protected methyl 4-amino-3-oxopentanoates 4b-e and 4-amino-3-oxobutanoates 7a,b stereoselectively afforded the erythro-hydroxy esters 5b-e and (R)-hydroxy esters 8a,b, res
- Hashiguchi,Kawada,Natsugari
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p. 403 - 408
(2007/10/02)
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- Oxaziridine-mediated ring expansions of substituted cyclobutanones: Synthesis of (-)-γ-amino-β-hydroxybutyric acid (GABOB)
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The synthesis and photochemical rearrangement chemistry of oxaziridines derived from 3-benzyloxy- and 3-phenylcyclobutanone were examined. The oxaziridines were prepared by condensation of the ketones with α-methylbenzylamine followed by oxidation. Photolysis at 254 nm afforded good yields of readily separable lactams; 4-benzyloxy-pyrrolidin-2-one obtained in this way was converted to 4-amino-3-hydroxybutanoic acid (GABOB) by catalytic hydrogenolysis followed by acid hydrolysis.
- Aube,Wang,Ghosh,Langhans
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p. 693 - 701
(2007/10/02)
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- A New Synthesis of (R)-GABOB and (R)-Oxiracetam
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The synthesis of both (R)-GABOB 1 and (R)-Oxiracetam 2 through the same diastereomer intermediate 8a is reported.
- Orena, Mario,Porzi, Gianni,Sandri, Sergio
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p. 2701 - 2711
(2007/10/02)
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- Enantiomerically pure β,γ-epoxyesters from β-hydroxylactones: Synthesis of β-hydroxyesters and (-)-GABOB
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The preparation of enantiomerically pure β,γ-epoxyesters was achieved by chemoselective opening of β-hydroxybutanolides with trimethylsilyliodide followed by cyclisation of the resulting iodohydrins with silver oxide. The reaction of these epoxyesters with lithio or magnesiocuprates afforded stereochemically pure α-substituted β-hydroxyesters. Alternatively, (-)-GABOB was synthesized in optically pure form from the iodohydrin 2′a.
- Larcheveque,Henrot
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p. 4277 - 4282
(2007/10/02)
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- Simple Three-Step Synthesis of (R)- and (S)-4-Amino-3-hydroxybutanoic Acid (GABOB) by Stereoselective Aldol Addition
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A simple synthesis of both (R)- and (S)-GABOB (5) is reported.In the key step, doubly deprotonated (R)- or (S)-2-Hydroxy-1,2,2-triphenylethyl acetate (HYTRA) (1) is added to Cbz-protected glycinal (2).
- Braun, Manfred,Waldmueller, Delia
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p. 856 - 858
(2007/10/02)
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- KINETIC RESOLUTION OF RACEMIC β,γ-EPOXY ESTERS WITH PIG LIVER ESTERASE (PLE, E.C. 3.1.1.1.)
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The β,γ-epoxy esters (+/-)-2 to (+/-)-6 were synthetisized.The E-values of kinetic resolution of 2, 3, 4, and 6 with PLE and the absolute configuration of the products of the hydrolysis were determined by the conversion to known compounds.
- Mohr, Peter,Roesslein, Lukas,Tamm, Christoph
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p. 2513 - 2516
(2007/10/02)
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- Substitution and Addition Reactions of Methyl (R)-2-tert-Butyl-Δ4-1,3-oxazoline-3-carboxylates
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Enantiomerically pure Δ4-1,3-oxazolines (1-5) bearing a tert-butyl group in the position 2 are prepared on a 100-g scale from serine or threonine using an electrochemical key step.They contain highly reactive double bonds, amenable to stereoselective electrophilic (1-3) or nucleophilic attack (4, 5).Thus, Vilsmeier and Friedel-Crafts-type reactions (--> 21, 22) and Michael additions (--> 11, 13) occur at C-5.Furthermore, substituents may be introduced in position 4 (next to the carbamate group) by lithiation and reaction with electrophiles (products 4, 10).Finally, dienolate 16 (from 5) reacts with aldehydes at the exocyclic position (--> 18).Hydrogenations of the tri- or tetrasubstituted double bonds in the oxazolines thus obtained are highly stereoselective (--> 14, 19, 24, 26).In the most cases, the 2-tert-butyl substituent directs reactions to the opposite face of the five-membered ring.The overall transformations achieved are discussed with regard to the bonds of serine and threonine. - Key Words: EPC syntheses / Stereogenic centers, self-regeneration of / Δ4-1,3-Oxazoline, derivatives / Electrochemistry, oxidative decarboxylation (Hofer-Moest)
- Stucky, Gerhard,Seebach, Dieter
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p. 2365 - 2376
(2007/10/02)
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- PRACTICAL SYNTHESIS OF (R)-γ-AMINO-β-HYDROXYBUTANOIC ACID (GABOB) FROM (R)-EPICHLOROHYDRIN
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(R)-Epichlorohydrin has efficiently been converted to the hypotensive and antiepileptic compound, (R)-γ-amino-β-hydroxybutanoic acid (GABOB), in six steps in 57percent overall yield.
- Takano, Seiichi,Yanase, Masashi,Sekiguchi, Yoshinori,Ogasawara, Kunio
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p. 1783 - 1784
(2007/10/02)
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- Hydroxylations microbiologiques de pyrrolidinones-2 (note de laboratoire)
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Microbial hydroxylations of various pyrrolidin-2 ones, especially N-acylated, with Beauveria sulfurescens have been carried out.The regioselectivity depends on the nature of the substituent on the nitrogen atom and the hydroxylation may occur at position 3,4 or 5 of the heterocycle.Hydroxylations at position 3 or 4 occur with low enantioselectivity.
- Srairi, Driss,Maurey, Georges
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p. 297 - 301
(2007/10/02)
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- 3-Hydroxyglutarate and β,γ-Epoxy Esters as Substrates for Pig Liver Esterase (PLE) and α-Chymotrypsin
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The pH dependence of the α-chymotrypsin-catalyzed hydrolysis of dimethyl 3-hydroxyglutarate (3) has been studied.The e.e. was determined by HPLC analysis of diastereoisomeric camphanoic-acid derivatives.Kinetic resolution of the β,γ-epoxy esters 10 and 24 by pig liver esterase has been shown to provide an alternative access to chiral β-hydroxy esters and acids of high optical purity.By this latter method, the unnatural enantiomer of γ-amino-β-hydroxybutyric acid (GABOB) has been sinthesized.Finally, dimethyl meso-3,4-epoxyadipate (19) was hydrolyzed by pig liver esterase with almost 100 percent selectivity.
- Mohr, Peter,Roesslein, Lukas,Tamm, Christoph
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p. 142 - 152
(2007/10/02)
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- A Convenient Synthesis of (R)-γ-Amino-β-hydroxybutanoic Acid (GABOB) from Natural (2S,4R)-4-Hydroxyproline (Short Communication)
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The oxidative decarboxylation sequence (1a --> 2a --> 3a --> 4a --> 5a) affording γ-aminobutanoic acid (5a) is adapted to the synthesis of its hydroxy derivative 5b.A facile high yield conversion of (2S,4R)-4-hydroxyproline-methylester-hydrochloride (7) to (R)-GABOB (5b) on a preparative scale is reported with the hydroxypyrrolidone 8 as the intermediate. - Keywords: Oxidation of amino acid derivatives; γ-Amino-β-hydroxybutanoic acid (GABOB); 1-Pyrroline-2-carboxylic acid derivatives
- Haeusler, Johannes
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p. 865 - 870
(2007/10/02)
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- 201. Reactions of Chiral 2-(tert-Butyl)-2H,4H-1,3-dioxin-4-ones Bearing Functional Groups in the 6-Position and Diastereoselective Catalytic Hydrogenation to cis-2,6-Disubstituted 1,3-Dioxan-4-ones
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(R)-5-Bromo-6-(bromomethyl)-2-(tert-butyl)-2H,4H-1,3-dioxin-4-one (2) derived from (R)-3-hydroxybutanoic acid used for substitutions and chain elongations at the side-chain C-atom in the 6-position of the heterocycle (->3-6, 10-13).Subsequent simultaneous reductive debromination and double-bond hydrogenation (Pd/C, H2) occurs with essentially complete diastereoselectivity (>98percent ds), with H transfer from the face opposite to the t-Bu group (->15-20, Table 1).Hydrolytic cleavages of the dioxanones then lead to enantiomerically pure β-hydroxy-acid derivatives (overall self-reproduction of the stereogenic center of 3-hydroxybutanoic acid or alkylation in the 4-position of this acid with preservation of configuration).
- Noda, Yoshihiro,Seebach, Dieter
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p. 2137 - 2145
(2007/10/02)
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- ON THE STERIC COURSE OF BAKER' S YEAST MEDIATED REDUCTION OF ALKYL 4-AZIDO-AND 4-BROMO-3-OXOBUTYRATE. SYNTHESIS OF (R)- AND (S)-CARNITIN
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Baker's yeast reduction of ethyl 4-azido-and 4-bromo-3-oxobutyrate affords (3R) (8) and (3S) (2), respectively, in high optical purity.
- Fuganti, Claudio,Grasselli, Piero
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p. 101 - 104
(2007/10/02)
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- (-)-β-PINENE AS CHIRAL PROMOTER. STEREOSPECIFIC ACCESS TO (-)-γ-AMINO-β(R)-HYDROXYBUTYRIC ACID (GABOB) AND (R)-CARNITINE. 2
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The stereochemical correlation between the ene adducts 2 and 4a and their products of alkaline hydrolysis is reported.Starting from 2, by using a degradative sequence, a stereocontrolled approach to γ-amino-β(R)-hydroxybutyric acid (GABOB) 8f and (R)-carnitine hydrochloride 8g is described.
- Pellegata, R.,Dosi, I.,Villa, M.,Lesma, G.,Palmisano, G.
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p. 5607 - 5614
(2007/10/02)
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- OXIDATIVE DEGRADATION OF β- AND γ-AMINO ACIDS BY CONTACT GLOW DISCHARGE ELECTROLYSIS
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The degradation of β- and γ-amino acids in aqueous solutions by contact glow discharge electrolysis (CGDE) was studied.It was found that the reaction is actually a stepwise oxidative degradation by hydroxyl radical produced by CGDE.
- Harada, Kaoru,Terasawa, Jun-ichi
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p. 441 - 444
(2007/10/02)
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- Total Synthesis of (R)-Glycerol Acetonide and the Antiepileptic and Hypotensive Drug (-)-γ-Amino-β-hydroxybutyric Acid (GABOB): Use of Vitamin C as a Chiral Starting Material
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Ascorbic acid (Vitamin C) (9) is shown to be a useful, inexpensive chiral starting material for natural products synthesis.It is converted in high yield via two synthetic operations into (R)-glycerol acetonide (7), the more inaccessible enantiomer of glycerol acetonide.Since D-(R)-glyceraldehyde acetonide (4) and the corresponding alcohol 1 have been used in many total syntheses of a wide variety of compounds, the ready availability of the opposite enantiomers L-(S)-glyceraldehyde acetonide (6) and glycerol (7) should be of greate value.As one indication of this potential synthetic utility, the hypotensive, antiepileptic compound (R)-(-)-γ-amino-β-hydroxybutyric acid (GABOB) (8) has been synthesized from ascorbic acid (9) via nine steps in 10percent overall yield.As further evidence of the importance of these synthesis, several useful intermediates for the preparation of the highly active hypotensive agents, the aryloxypropanolamines (5), were prepared from Vitamin C.
- Jung, Michael E.,Shaw, Teresa J.
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p. 6304 - 6311
(2007/10/02)
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