- 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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- 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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- 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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- 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 (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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- 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 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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- 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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- 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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- 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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- 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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- 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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- 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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- 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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- 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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p. 5480 - 5484
(2007/10/02)
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