A convenient synthesis of R-(−)-carnitine from R-(−)-epichlorohydrin

Kabat, Marek; Daniewski, A. R.; Burger, Walter

doi:10.1016/s0957-4166(97)00324-8

Cited by 17 publications

(12 citation statements)

References 19 publications

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“…Optically active epoxides are useful chiral synthons and important building blocks for chiral pharmaceuticals and agrochemical products because of their high reactivity. One such synthon and building block is the optically active epichlorohydrin, which has been used in the synthesis of numerous chiral products such as pheromones, ( R )‐carnitine, and antibacterial agents 1,2.…”

Section: Introductionmentioning

confidence: 99%

Nitrite‐mediated synthesis of chiral epichlorohydrin using halohydrin dehalogenase from Agrobacterium radiobacter AD1

Jin

Liu

et al. 2012

Biotech and App Biochem

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In the current study, the haloalcohol dehalogenase HheC gene from Agrobacterium radiobacter AD1 was synthesized and expressed in Escherichia coli. After purification using Ni-nitrilotriacetic acid affinity chromatography, HheC was used in the synthesis of chiral epichlorohydrin in the presence of NO₂⁻. The optimal pH, temperature, and NO₂⁻ concentration for enantioselectivity are 5.0, 37°C, and 60 mM, respectively. The maximum velocity and Michaelis constant values for (S)-epichlorohydrin are 714.3 µmol min⁻¹ mg⁻¹ and 17.2 mM, respectively, whereas those for (R)-epichlorohydrin are 166.8 µmol min⁻¹ mg⁻¹ and 29.0 mM, respectively. Under optimal conditions, (R)-epichlorohydrin with 99% enantiomeric excess was obtained after an 18 Min reaction; the yield reached 41%, which is the highest amount obtained for chiral epichlorohydrin synthesis using haloalcohol dehalogenase. In addition, (R)-epichlorohydrin with 99% enantiomeric excess was successfully obtained from 1,3-dichloro-2-propanol by the ring opening of racemic epichlorohydrin in the presence of NO₂⁻ after the ring closure of 1,3-dichloro-2-propanol with HheC. To the best of our knowledge, the current study is the first report on the kinetic resolution of epichlorohydrin with NO₂⁻ and synthesis of chiral epichlorohydrin with 99% enantiomeric excess from 1,3-dichloro-2-propanol by combining ring closure of 1,3-dichloro-2-propanol and ring opening of racemic epichlorohydrin.

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Section: Introductionmentioning

confidence: 99%

Nitrite‐mediated synthesis of chiral epichlorohydrin using halohydrin dehalogenase from Agrobacterium radiobacter AD1

Jin

Liu

et al. 2012

Biotech and App Biochem

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“…Alternatively, reaction of pyrrolidine-derived lithium enolates (176) with cinnamyl bromide yields the anti-disubstituted g-lactams (177) with high diastereoselectivities (Scheme 14.50). Basic hydrolysis affords the anti-2,4-disubstituted N-Boc-g-amino acids (178) [146].…”

Section: Ab-disubstituted G-amino Acidsmentioning

confidence: 99%

“…Similarly, opening of the epoxide (R)-(66) with vinyl Grignard/cuprate and reaction of the resulting chloride (242) with trimethylamine yields the ammonium salt (243). Ozonolysis and oxidation produces enantiomerically pure (R)-(7) in 67% overall yield [176]. (R)-Glycidyl tosylate has also been converted in eight steps via the corresponding oxazoline to enantiopure (R)-GABOB (R)- (6) in good overall yield [177].…”

Section: B-hydroxy-g-amino Acidsmentioning

confidence: 99%

Synthesis of γ‐Aminobutyric Acid Analogs

Hanrahan

Johnston

2009

Amino Acids, Peptides and Proteins in Organic Chemistry

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“…Treatment of (R)-533 with aqueous trimethylamine produced chlorohydrate (R)-534 in 99% yield, which upon oxidative ozonolysis gave enantiomerically pure (R)-carnitine 22 in 81% yield (Scheme 138). 208 The reaction of commercially available (R)-glycidyl tosylate 535 with acetonitrile in the presence of boron trifluoride diethyl etherate gave the corresponding oxazoline 536, which upon acidic hydrolysis followed by tritylation of the amino group afforded the tosylate derivative (S)-537 in 67% yield. The reaction of (S)-537 with sodium iodide and subsequent nucleophilic displacement with sodium cyanide led to cyano derivative (S)-538 in 33% yield, which upon treatment with potassium carbonate produced cyano-alcohol (S)-539 in 93% yield.…”

Section: Ab-disubstituted C-amino Acidsmentioning

confidence: 99%