- Synthesis method of O-methyl-D-serine
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The invention discloses a synthesis method of O-methyl-D-serine. The synthesis method includes the following steps that 1, acrylic acid methyl ester is added into a reaction bottle, after the temperature is raised, bromine is dropwise added, after an addition reaction is conducted, decompression and distillation are conducted to remove excessive bromine, methyl alcohol is added to residues, after the temperature is lowered, sodium methylate is added, after an alcoholysis reaction, decompression and distillation are conducted to remove methyl alcohol, ammonium hydroxide is added, after an ammonium hydroxide, concentrated crystallization is conducted, and O-methyl-DL-serine is obtained; 2, acetic acid is added into the reaction bottle, the O-methyl-DL-serine, D-tartaric acid and salicylaldehyde are added in sequence, after the temperature is raised for a reaction, cooling and crystallization are conducted, separation is conducted, and O-methyl-D-serine double salt is obtained; 3, the O-methyl-D-serine double salt is dissolved in a methyl alcohol aqueous solution, ammonium hydroxide is added to regulate PH to be 7-8, crystallization and separation are conducted, and the O-methyl-D-serine is obtained. The synthesis method is mild in reaction temperature, safe to operate, low in cost and high in chirality purity, and raw materials are easy to obtain.
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Paragraph 0042; 0043
(2017/01/02)
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- An efficient chemoenzymatic method to prepare optically active O-methyl-D-serine
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Lacosamide is an important anti-epilepsy drug and O-methyl-D-serine is a relevant intermediate in the synthesis of lacosamide. Optically active O-methyl-D-serine was prepared by using a chemoenzymatic method from inexpensive acrylamide. Our method is a four-step reaction sequence: bromination of acrylamide; etherification of dibromopropionamide; ammonolysis of α-bromo-β-methoxy-propionamide; enzymatic racemization and selective hydrolysis. The double-enzyme catalyst system, which consists of α-amino-ε-caprolactam racemase (Locus, E01594) and D-stereospecific amino-acid amidase (Locus, AB026907), was successfully applied to produce enantiopure O-methyl-D-serine (ee >99.8%) in high yield (>98.5%). Optically active O-methyl-D-serine was obtained with a total yield of 81.3%.
- Wang, Zhi-Yuan,Lv, Peng-Mei,Yuan, Zhen-Hong,Luo, Wen,Liu, Shu-Na
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p. 6991 - 6994
(2015/03/14)
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- Process for the preparation of Lacosamide including resolution of O-methyl-DL-serine
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The present invention provides a process for the preparation of lacosamide in substantially optically pure form, which in one aspect comprises the following steps: (i) resolution of O-methyl-D,L-serine to provide O-methyl-D-serine in substantially optically pure form; (ii) acetylation of O-methyl-D-serine thereby obtained to provide the N-acetyl derivative thereof in substantially optically pure form; (iii) activating the carboxy group of the compound thereby obtained; and (iv) reacting the compound thereby obtained with benzylamine.
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Page/Page column 12
(2012/08/28)
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- PROCESS FOR PREPARING LACOSAMIDE
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The present invention provides a process for the preparation of lacosamide in substantially optically pure form, which in one aspect comprises the following steps: (i) resolution of O-methyl-D,L-serine to provide O-methyl-D-serine in substantially optically pure form; (ii) acetylation of O-methyl-D-serine thereby obtained to provide the N-acetyl 10 derivative thereof in substantially optically pure form; (iii) activating the carboxy group of the compound thereby obtained; and (iv) reacting the compound thereby obtained with benzylamine.
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Page/Page column 23
(2012/06/01)
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- An efficient chemoenzymatic method to prepare optically active O-methyl-l-serine
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O-Methyl-l-serine and its derivatives are relevant in peptide synthesis (food, pharmaceuticals, and cosmetics). Optically active O-methyl-l-serine was prepared using a chemoenzymatic method from inexpensive acrylamide. Our method is a four step reaction sequence; bromination of acrylamide; etherification of dibromopropionamide; ammonolysis of α-bromo-β-methoxy-propionamide; enzymatic racemization; and selective hydrolysis. The double-enzyme catalyst system, which consists of α-amino-*-caprolactam racemase (Locus, E01594) and peptidase B (Locus, D84499), was successfully applied to produce enantiopure O-methyl-l-serine (ee >99.9%) in high yield (>99.7%). Optically active O-methyl-l-serine was obtained with a total yield of 82.4%.
- Wang, Zhi-Yuan,Xu, Li-Sheng,Gao, Ji,Liu, Jun-Zhong,Zhang, Hong-Juan,Liu, Qian,Jiao, Qing-Cai
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p. 1653 - 1656
(2013/02/23)
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- Calyxamides A and B, cytotoxic cyclic peptides from the marine sponge Discodermia calyx
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Cyclic peptides containing 5-hydroxytryptophan and thiazole moieties were isolated from the marine sponge Discodermia calyx collected near Shikine-jima Island, Japan. The structures of calyxamides A (1) and B (2), including the absolute configurations of all amino acids, were elucidated by spectroscopic analyses and degradation experiments. The structures are similar to keramamides F and G, previously isolated from Theonella sp. The analysis of the 16S rDNA sequences obtained from the metagenomic DNA of D. calyx revealed the presence of Candidatus Entotheonella sp., an unculturable δ-proteobacterium inhabiting the Theonella genus and implicated in the biosynthesis of bioactive peptides.
- Kimura, Miki,Wakimoto, Toshiyuki,Egami, Yoko,Tan, Karen Co,Ise, Yuji,Abe, Ikuro
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experimental part
p. 290 - 294
(2012/05/05)
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- Mirabamides E-H, HIV-inhibitory depsipeptides from the sponge Stelletta clavosa
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Four new depsipeptides, mirabamides E-H (1-4), and the known depsipeptide mirabamide C (5) have been isolated from the sponge Stelletta clavosa, collected from the Torres Strait. The planar structures were determined on the basis of extensive 1D and 2D NMR and HRESIMS. The absolute configurations were established by the advanced Marfey's method, NMR, and GC-MS. The four new compounds all showed strong inhibition of HIV-1 in a neutralization assay with IC50 values of 121, 62, 68, and 41 nM, respectively.
- Lu, Zhenyu,Van Wagoner, Ryan M.,Harper, Mary Kay,Baker, Heather L.,Hooper, John N. A.,Bewley, Carole A.,Ireland, Chris M.
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experimental part
p. 185 - 193
(2011/04/26)
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- Neomastoidin A, a novel monoacylglycerol with an amino acid moiety from Macrolepiota neomastoidea
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A novel monoacylglycerol with an amino acid moiety, neomastoidin A (1), was isolated from the fruiting bodies of the poisonous mushroom Macrolepiota neomastoidea. The structure of 1 was established by extensive spectroscopic analysis and further confirmed
- Kim, Ki Hyun,Choi, Sang Un,Lee, Kang Ro
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scheme or table
p. 894 - 895
(2010/03/04)
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- Synthesis and anticonvulsant activities of (R)-(O)-methylserine derivatives
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Efficient procedures for the synthesis of (R)-N-benzyl-2-amino-3- methoxypropionamide ((R)-3), 2-acetamido-3-methoxypropionic acid (4), and O- methylserine (5) are described beginning from (R)-Cbz-serine ((R)-7). The reactions proceeded with little or no racemization and permitted the synthesis of the potent anticonvulsant (R)N-benzyl-2-acetamido-3- methoxypropionamide ((R)-2). The anticonvulsant activities of 2-4 were determined revealing the surprising activity of (R)-2.
- Andurkar, Shridhar V.,Stables, James P.,Kohn, Harold
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p. 3841 - 3854
(2007/10/03)
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- ASYMMERTIC SYNTHESIS OF Β-SUBSTITUTED α-AMINO ACIDS VIA A CHIRAL Ni(II) COMPLEX OF DEHYDROALANINE
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An efficient approach to the asymmetric synthesis of β-substituted (S)-alanines is describen.The chiral Ni(II) complex of a Schiff base derived from (S)-o-N-(N-benzylpropyl)aminobenzophenone (BBP) and glycine was treated with formaldehyde and sodium methoxide to give a corresponding (R)-serine complex which, in turn, was converted to the chiral Ni(II) dehydroalanine complex.Michael type base catalyzed addition of nucleophiles (including MeOH, Me2NH, PhCH2NH2, imidazole, PhSH, PhCH2SH,, malonic ester and benzylmagnesium chloride) produced a mixture of diastereoisomeric complexes with a 70-90percent excess of S,S (or L,L) isomers over the S,R (or L,D) ones.The cleavage of pure diastereoisomers with aqueous HCl gave, in good yields, β-substituted (S) (or L)-alanines and regenerated the chiral auxiliary (BBP).
- Belokon, , Yuri N.,Sagyan, Ashot S.,Djamgaryan, Silva M.,Bakhmutov, Vladimir I.,Belikov, Vasili M.
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p. 5507 - 5514
(2007/10/02)
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- Mechanism of Asymmetric Production of L-Aromatic Amino Acids from the Corresponding Hydantoins by Flavobacterium sp.
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The mechanism of asymmetric production of L-aromatic amino acids from the corresponding hydantoins by Flavobacterium sp.AJ-3912 was examined by investigating the properties of the enzymes involved in the hydrolysis of 5-substituted hydantoins corresponding to aromatic amino acids (AAH).The enzymatic hydrolysis of AAH by Flavobacterium sp.AJ-3912 consisted of the following two successive reactions; a hydrolytic ring opening reaction of DL-AAH to L- and D-form N-carbamyl aromatic amino acids (NCA), involving an enzyme (hydantoin hydrolase) followed by a hydrolytic cleaving reaction of the L-form NCA to L-aromatic amino acids involving another enzyme (N-carbamyl-L-aromatic amino acid hydrolase, abbreviated as L-NCA hydrolase).The ring opening reaction involving hydantoin hydrolase was not stereospecific, but the NCA cleaving reaction involving L-NCA hydrolase was completely L-specific.The pathway for the conversion of the by-produced D-form NCA to L-aromatic amino acids was as follows; conversion of D-form NCA to D-AAH through the reverse reaction of hydantoin hydrolase, and then conversion of the D-AAH to L-AAH through spontaneous racemization, followed by the successive hydrolysis of the L-AAH to L-aromatic amino acids by hydantoin hydrolase and L-NCA hydrolase.
- Yokozeki, Kenzo,Hirose, Yoshiteru,Kubota, Koji
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p. 737 - 746
(2007/10/02)
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- Mechanism of formation of serine β-lactones by Mitsunobu cyclization: synthesis and use of L-serine stereospecifically labelled with deuterium at C-3
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The ring closure of N-benzyloxycarbonyl-L-serine (1) under Mitsunobu conditions (Ph3P, dimethyl azodicarboxylate, -78 deg C) to give the corresponding β-lactone (2) is shown by deuterium and oxygen-18 labelling studies to proceed by hydroxy group activation, in contrast to analogous cyclizations of more hindered β-hydroxy acids, which usually occur by carboxy group activation.Samples of 1 stereospecifically labelled with deuterium at C-3 were prepared by hydrogenation of (Z)-2-acetamido-3-methoxyacrylic acid (9) with deuterium, followed by selective Acylase I deacetylation of the 2S isomer, removal of the protecting groups, and N-acylation of the resulting L-serine with benzyl chloroformate.Mitsunobu cyclizations of this 3R deuterated N-acyl serine, of the analog lg, and of the derivative 1f show that lactonization occurs with inversion of configuration at C-3, loss of the hydroxy oxygen, and retention of the carboxy oxygens.Similar labelling experiments demonstrate that aqueous sodium hydroxide opens the β-lactone ring by exclusive attack at the carbonyl to regenerate 1, whereas acidic hydrolysis proceeds primarily by attack of water at the C-3 methylene group of 2.This information allows interconversion of L-serines that are stereospecifically labelled at C-3 with hydrogen isotopes and affords access to other labelled β-substituted alanines.
- Ramer, Shawn E.,Moore, Richard N.,Vederas, John C.
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p. 706 - 713
(2007/10/02)
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