cas 5874-57-7, D-Serine methyl ester hydrochloride

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Synthesis of Novel Lysophosphatidylcholine Analogues Using Serine as Chiral Template
Four novel lysophosphatidylcholine (lysoPC) analogues, (S)-N-stearoyl-O-phosphocholineserine methyl ester [(S)-1a], (R)-1-lyso-2-stearoylamino-2-deoxy-sn-glycero-3-phosphatidylcholine [(R)-2a], (R)-N-stearoyl-O-phosphocholineserine methyl ester [(R)-1b], and (S)-1-lyso-2-stearoyl-amino-2-deoxy-sn-glycero-3-phosphatidylcholine [(S)-2b], were synthesized starting from serine as a chiral template. These synthetic compounds exhibited greatly enhanced hyphal transition inhibitory activity in Candida as compared to the natural lysoPC.
Kim, Young-Ah,Chung, Hae-Mi,Park, Jin-Seon,Choi, Wonja,Min, Juyoung,Park, Nok-Hyun,Kim, Ki-Hwan,Jhon, Gil-Ja,Han, So-Yeop
p. 10162 - 10165
(2003)
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Method for preparing high-purity (R)-4-formyl-2,2-dimethyl-3-oxazoline tert-butyl carboxylate
The invention discloses a method for preparing high-purity (R)-4-formyl-2,2-dimethyl-3-oxazoline tert-butyl carboxylate. The method comprises the following steps: carrying out a reaction on D-serine and thionyl chloride in methanol to obtain a compound 2; carrying out a reaction on the compound 2 and Boc anhydride under triethylamine to obtain a compound 3; carrying out a reaction on the compound3 and 2,2-dimethoxypropane under the action of boron trifluoride diethyl ether to obtain a compound 4; and reducing the compound 4 and DIBAL-H are at a temperature of -60 DEG C to -80 DEG C to obtaina crude product, carrying out a reaction on the crude product and sodium sulfite to form salt, and purifying to obtain the high-purity (R)-4-formyl-2,2-dimethyl-3-oxazoline tert-butyl carboxylate. According to the invention, the salt forming is performed by using the properties of sodium sulfite and an aldehyde group, so that the purity of the salified product can reach 98%, the industrial standard is met, and the production operation is well facilitated.
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Paragraph 0061; 0063-0066

(2020/03/09)

Total synthesis method for xinaomycin
The invention belongs to the technical field of pharmaceutical chemistry and organic synthesis, and aims to provide a chemical total synthesis method for xinaomycin. The method comprises the steps of:using D-galactose and the like as raw materials, firstly carrying out 8 steps of reactions to obtain a compound 14, then performing condensation on the compound 14 and uracil to obtain a compound 15,performing 4 steps of reactions to obtain a compound 19, performing condensation on the compound 19 and a compound 6 to obtain a compound 20, and finally removing an ester protecting group and a Cbzprotecting group in turn, so as to obtain the natural product xinaomycin. The total synthesis method of the present invention is a method for synthesizing the natural product xinaomycin for the firsttime. The total synthesis method has the advantages of high product purity, low cost, simple operation and the like.
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Paragraph 0033; 0047; 0049; 0051

(2018/05/16)

Crystal form of cyclic serine esterified product hydrochloride and preparation method
The invention relates to a novel crystal form of a cyclic serine esterified product hydrochloride and a preparation method. The crystal form has excellent properties in terms of chemical stability andprocessing adaptability.
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Paragraph 0055; 0056; 0080; 0081

(2018/10/19)

Industrial preparation method of lacosamide
The invention relates to an industrial preparation method of lacosamide. Esterification is performed on D-serine for generating D-serine methyl ester hydrochloride; the D-serine methyl ester hydrochloride reacts with acetyl chloride for generating N-acetyl-D-serine methyl ester; the N-acetyl-D-serine methyl ester reacts with benzylamine for obtaining (R)-2-acetamido-N-benzyl-3-hydroxypropionamide;the (R)-2-acetamido-N-benzyl-3-hydroxypropionamide reacts with methyl p-toluenesulfonate under an alkaline condition for obtaining (R)-2-acetamido-N-benzyl-3-methoxypropionamide. The preparation method provide by the invention has relatively mild reaction conditions in each steps; the raw materials are easy to obtain; no high-toxicity reagent is used; a safe and environment-friendly green chemistry idea is met; and the method is suitable for industrial amplification.
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Paragraph 0018-0020; 0027

(2018/03/26)

Generating Stereodiversity: Diastereoselective Fluorination and Highly Diastereoselective Epimerization of α-Amino Acid Building Blocks
Diastereoselective fluorination of N-Boc (R)- and (S)-2,2-dimethyl-4-((arylsulfonyl)methyl)oxazolidines and a previously unknown diastereoselective epimerization at the fluorine-bearing carbon atom α to the sulfone was realized. Diastereoselectivities of both reactions were excellent for benzothiazolyl sulfones, allowing access to two enantiomerically pure diastereomers from one chiral precursor. To demonstrate synthetic utility, the benzothiazolyl sulfones were converted to diastereomerically pure (S,S)- and (R,S)-benzyl sulfones via sulfinate salts and to amino acids. To understand the diastereoselectivities, DFT analysis was performed.
Wei, Wei,Khangarot, Rama Kanwar,Stahl, Lothar,Veresmortean, Cristina,Pradhan, Padmanava,Yang, Lijia,Zajc, Barbara
supporting information
p. 3574 - 3578
(2018/06/26)

FUSED MORPHOLINOPYRIMIDINES AND METHODS OF USE THEREOF
The present disclosure relates to Fused Morpholinopyrimidines, pharmaceutical compositions comprising an effective amount of a Fused Morpholinopyrimidine and methods for using a Fused Morpholinopyrimidine in the treatment of a neurodegenerative disease, comprising administering to a subject in need thereof an effective amount of a Fused Morpholinopyrimidine.
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Paragraph 1067

(2017/05/14)

Process for the preparation of lacosamide
A novel process for the preparation of (R)-2-acetamido-N-benzyl-3-methoxypropionamide (Lacosamide) is described. It comprises reacting N-acetyl-D-serine methyl ester with benzylamine catalyzed by a non-nucleophilic base to obtain (R)-2-acetamido-2-N-benzyl-3-hydroxy propionamide followed by its methylation.
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Page/Page column 11

(2016/10/17)

Incorporation and visualization of azido-functionalized: N -oleoyl serinol in Jurkat cells, mouse brain astrocytes, 3T3 fibroblasts and human brain microvascular endothelial cells
The synthesis and biological evaluation of azido-N-oleoyl serinol is reported. It mimicks biofunctional lipid ceramides and has shown to be capable of click reactions for cell membrane imaging in Jurkat and human brain microvascular endothelial cells.
Walter,Collenburg,Japtok,Kleuser,Schneider-Schaulies,Müller,Becam,Schubert-Unkmeir,Kong,Bieberich,Seibel
supporting information
p. 8612 - 8614
(2016/07/13)

Structure-activity relationships of lysophosphatidylserine analogs as agonists of G-protein-coupled receptors GPR34, P2Y10, and GPR174
Lysophosphatidylserine (LysoPS) is an endogenous lipid mediator generated by hydrolysis of membrane phospholipid phosphatidylserine. Recent ligand screening of orphan G-protein-coupled receptors (GPCRs) identified two LysoPS-specific human GPCRs, namely, P2Y10 (LPS2) and GPR174 (LPS3), which, together with previously reported GPR34 (LPS1), comprise a LysoPS receptor family. Herein, we examined the structure-activity relationships of a series of synthetic LysoPS analogues toward these recently deorphanized LysoPS receptors, based on the idea that LysoPS can be regarded as consisting of distinct modules (fatty acid, glycerol, and l-serine) connected by phosphodiester and ester linkages. Starting from the endogenous ligand (1-oleoyl-LysoPS, 1), we optimized the structure of each module and the ester linkage. Accordingly, we identified some structural requirements of each module for potency and for receptor subtype selectivity. Further assembly of individually structure-optimized modules yielded a series of potent and LysoPS receptor subtype-selective agonists, particularly for P2Y10 and GPR174.
Ikubo, Masaya,Inoue, Asuka,Nakamura, Sho,Jung, Sejin,Sayama, Misa,Otani, Yuko,Uwamizu, Akiharu,Suzuki, Keisuke,Kishi, Takayuki,Shuto, Akira,Ishiguro, Jun,Okudaira, Michiyo,Kano, Kuniyuki,Makide, Kumiko,Aoki, Junken,Ohwada, Tomohiko
supporting information
p. 4204 - 4219
(2015/06/08)

Synthesis and antibacterial activities of Yanglingmycin analogues
The synthesis of Yanglingmycin and its enantiomer, along with eighteen Yanglingmycin analogues is reported. The structures were confirmed mainly by analyses of NMR spectral data. Antibacterial activity assays showed that Yanglingmycin and some of its analogues exhibited significant antibacterial activities against two important agricultural pathogenic bacteria, Ralstonia solanacearum and Pseudomonas syringae pv. actinidiae, with minimum inhibitory concentration (MIC) values ranging from 3.91 to 15.62 μg/mL. The antibacterial activities exhibited by Yanglingmycin and its analogues are promising, suggesting potential in the development of compounds for novel bactericides.
Li, Long-Bo,Dan, Wen-Jia,Tan, Fang-Fang,Cui, Li-Hui,Yuan, Zhi-Peng,Wu, Wen-Jun,Zhang, Ji-Wen
p. 33 - 37
(2015/01/30)

FUSED MORPHOLINOPYRIMIDINES AND METHODS OF USE THEREOF
The present disclosure relates to Fused Morpholinopyrimidines, pharmaceutical compositions comprising an effective amount of a Fused Morpholinopyrimidine and methods for using a Fused Morpholinopyrimidine in the treatment of a neurodegenerative disease, comprising administering to a subject in need thereof an effective amount of a Fused Morpholinopyrimidine.
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Paragraph 0775

(2015/08/03)

Decarbonylative radical coupling of α-aminoacyl tellurides: Single-step preparation of γ-amino and α,β-diamino acids and rapid synthesis of gabapentin and manzacidin A
A new radical-based coupling method has been developed for the single-step generation of various γ-amino acids and α,β-diamino acids from α-aminoacyl tellurides. Upon activation by Et3B and O2 at ambient temperature, α-aminoacyl tellurides were readily converted into α-amino carbon radicals through facile decarbonylation, which then reacted intermolecularly with acrylates or glyoxylic oxime ethers. This mild and powerful method was effectively incorporated into expeditious synthetic routes to the pharmaceutical agent gabapentin and the natural product (-)-manzacidin A.
Nagatomo, Masanori,Nishiyama, Hayato,Fujino, Haruka,Inoue, Masayuki
supporting information
p. 1537 - 1541
(2015/01/30)

Lewis acid facilitated regioselective synthesis of τ-histidinoalanine
τ-Histidinoalanine, with an unusual cross-link between His and Ala, is the central component of theonellamides, a family of bioactive peptidic natural products. Previous syntheses of this residue were plagued with low regioselectivity in the alkylation step. Herein, we report two novel routes to τ-histidinoalanine, involving alkylation of Boc-His-OMe with a serine-derived β-lactone and β-bromoalanine, respectively, as the electrophiles. The use of Mg(OTf)2 as a catalyst was found to be essential to ensure high regioselectivity for the τ-isomer, presumably due to the formation of a six-membered ring chelation involving the π-nitrogen atom of histidine.
Wu, Ju,Ma, Bing,Wang, Yuehui,Zhang, Yue,Yan, Shenghu,Castle, Steven L.
p. 3114 - 3116
(2014/05/20)

Synthesis of d -abrines by palladium-catalyzed reaction of ortho-iodoanilines with N -Boc- N -methylalanyl-substituted acetaldehyde and acetylene
A novel strategy to N-Boc-N-methyl - tryptophans (abrine derivatives) was developed that relies on the palladium-catalyzed annulation of ortho-iodoanilines 12 with either N-Boc-N-methyl-propargylglycine 16 or aldehyde 11. Both 11 and 16 can be prepared from d-serine. An alternative route to propargylglycine 16 utilizes an enantioselective propargylation reaction of glycine imine 17.
Danner, Paulami,Morkunas, Marius,Maier, Martin E.
supporting information
p. 2474 - 2477
(2013/07/04)

Simple and efficient synthetic routes to d-cycloserine
d-Cycloserine has been successfully synthesized in good yields through three new synthetic routes from a readily available d-serine. In each synthesis, cyclization served as the key step, and two of the routes employed one-pot operations for the preparation of the target product. These methods featured the use of mild reaction conditions and simple treatments.
Kim, Hee-Kwon,Park, Kyoung-Joo Jenny
experimental part
p. 1668 - 1670
(2012/04/10)

Novel practical synthesis of d-cycloserine
The synthesis of d-cycloserine has been successfully accomplished from the readily available d-serine through three simple and efficient routes. In each synthetic strategy, cyclization reactions are involved as the key step, and one-pot processes are employed. The simple treatment and mild reaction conditions are attractive features in this methodology.
Kim, Hee-Kwon,Park, Kyoung-Joo Jenny
scheme or table
p. 4090 - 4092
(2012/09/07)

Asymmetric induction afforded by chiral azolylidene N-heterocyclic carbenes (NHC) catalysts
Screening studies of new chiral imidazolium and triazolium based NHC salts I-VIII as ligands in asymmetric organometallic catalysis and as organocatalysts showed that these catalysts efficiently promoted the reactions. Moderate enantioselectivities (55-57% ee) were obtained in the asymmetric Cu-NHC catalysed conjugate additions of diethylzinc to cyclohexenone, in accordance with most previous studies. The chiral induction afforded in the gold(I)-NHC catalysed cyclopropanation reactions was low (28% ee). However, these results represent the first reported chiral gold(I)-NHC catalysed olefin cyclopropanation. The NHC-organocatalysed asymmetric cross-annulation of cinnamaldehyde and trifluoroacetophenone gave lower enantioselectivity (50% ee) but higher yields of the γ-lactone product relative to previous reports. The enantioselectivities obtained varied considerably, even within a group of structurally closely related NHCs. This study demonstrates the challenge of designing NHCs with a general ability to induce asymmetry in a broader range of reactions.
Strand, Ragnhild B.,Helgerud, Trygve,Solvang, Tina,Dolva, Amund,Sperger, Christian A.,Fiksdahl, Anne
p. 1350 - 1359,10
(2012/12/11)

Asymmetric induction afforded by chiral azolylidene N-heterocyclic carbenes (NHC) catalysts
Screening studies of new chiral imidazolium and triazolium based NHC salts I-VIII as ligands in asymmetric organometallic catalysis and as organocatalysts showed that these catalysts efficiently promoted the reactions. Moderate enantioselectivities (55-57% ee) were obtained in the asymmetric Cu-NHC catalysed conjugate additions of diethylzinc to cyclohexenone, in accordance with most previous studies. The chiral induction afforded in the gold(I)-NHC catalysed cyclopropanation reactions was low (28% ee). However, these results represent the first reported chiral gold(I)-NHC catalysed olefin cyclopropanation. The NHC-organocatalysed asymmetric cross-annulation of cinnamaldehyde and trifluoroacetophenone gave lower enantioselectivity (50% ee) but higher yields of the γ-lactone product relative to previous reports. The enantioselectivities obtained varied considerably, even within a group of structurally closely related NHCs. This study demonstrates the challenge of designing NHCs with a general ability to induce asymmetry in a broader range of reactions.
Strand, Ragnhild B.,Helgerud, Trygve,Solvang, Tina,Dolva, Amund,Sperger, Christian A.,Fiksdahl, Anne
p. 1350 - 1359
(2013/01/15)

Synthesis and biological evaluation (in Vitro and in Vivo) of cyclic arginine-glycine-aspartate (RGD) peptidomimetic-paclitaxel conjugates targeting integrin αvβ3
A small library of integrin ligand-paclitaxel conjugates 10-13 was synthesized with the aim of using the tumor-homing cyclo[DKP-RGD] peptidomimetics for site-directed delivery of the cytotoxic drug. All the paclitaxel-RGD constructs 10-13 inhibited biotinylated vitronectin binding to the purified αVβ3 integrin receptor at low nanomolar concentration and showed in vitro cytotoxic activity against a panel of human tumor cell lines similar to that of paclitaxel. Among the cell lines, the cisplatin-resistant IGROV-1/Pt1 cells expressed high levels of integrin αVβ3, making them attractive to be tested in in vivo models. cyclo[DKP-f3-RGD]-PTX 11 displayed sufficient stability in physiological solution and in both human and murine plasma to be a good candidate for in vivo testing. In tumor-targeting experiments against the IGROV-1/Pt1 human ovarian carcinoma xenotransplanted in nude mice, compound 11 exhibited a superior activity compared with paclitaxel, despite the lower (about half) molar dosage used.
Colombo, Raffaele,Mingozzi, Michele,Belvisi, Laura,Arosio, Daniela,Piarulli, Umberto,Carenini, Nives,Perego, Paola,Zaffaroni, Nadia,De Cesare, Michelandrea,Castiglioni, Vittoria,Scanziani, Eugenio,Gennari, Cesare
supporting information
p. 10460 - 10474
(2013/02/22)

PROCESS FOR PREPARING (R)-2-ACETAMIDO-N-BENZYL-3-METHOXY-PROPIONAMIDE
Processes for preparing and purifying (R)-2-acetamido-N-benzyl-3-methoxy- propionamide of formula-1 and intermediates thereof are provided.
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Page/Page column 34-35

(2011/09/15)

Efficient and stereoselective syntheses of DAB-1 and D-fagomine via chiral 1,3-oxazine
The concise, stereocontrolled syntheses of DAB-1 and d-fagomine were achieved utilizing chiral oxazine. The key features in these strategies are the stereoselective intramolecular oxazine formation catalyzed by palladium(0), and pyrrolidine and piperidine formation by catalytic hydrogenation of oxazine.
Kim, Ji-Yeon,Mu, Yu,Jin, Xiangdan,Park, Seok-Hwi,Pham, Van-Thoai,Song, Dong-Keun,Lee, Kee-Young,Ham, Won-Hun
experimental part
p. 9426 - 9432
(2011/12/14)

The structure?activity relationship of the 3-Oxy site in the anticonvulsant (R)- N -benzyl 2-acetamido-3-methoxypropionamide
Lacosamide ((R)-N-benzyl 2-acetamido-3-methoxypropionamide, (R)-1) is a low molecular weight anticonvulsant recently introduced in the United States and Europe for adjuvant treatment of partial-onset seizures in adults. In this study, we define the structure?activity relationship (SAR) for the compound's 3-oxy site. Placement of small nonpolar, nonbulky substituents at the 3-oxy site provided compounds with pronounced seizure protection in the maximal electroshock (MES) seizure test with activities similar to (R)-1. The anticonvulsant activity loss that accompanied introduction of larger moieties at the 3-oxy site in (R)-1 was offset, in part, by including unsaturated groups at this position. Our findings were similar to a recently reported SAR study of the 4?-benzylamide site in (R)-1 (J. Med. Chem. 2010, 53, 1288 ?1305). Together, these results indicate that both the 3-oxy and 4?-benzylamide positions in (R)-1 can accommodate nonbulky, hydrophobic groups and still retain pronounced anticonvulsant activities in rodents in the MES seizure model.
Morieux, Pierre,Salomé, Christophe,Park, Ki Duk,Stables, James P.,Kohn, Harold
scheme or table
p. 5716 - 5726
(2010/10/03)

An expedient synthesis of orthogonally protected lysinoalanine from Aloc-protected Garner's aldehyde
An expedient synthesis of orthogonally protected lysinoalanine has been developed. We have prepared a novel Garner's aldehyde derivative bearing an Aloc group; reductive amination of this aldehyde with Fmoc-Lys-OPMB gave the lysinoalanine skeleton. This was then transformed into an orthogonally protected lysinoalanine derivative suitable for the synthesis of side-chain bridged cyclic peptides by solid phase peptide synthesis methods.
K?rner, Cindy,Raiber, Eun-Ang,Keegan, Samuel E.M.,Nicolau, Daniel C.,Sheppard, Tom D.,Tabor, Alethea B.
supporting information; experimental part
p. 6381 - 6383
(2011/01/03)

Hydrogen-bond-induced hysteresis in the compression/relaxation of monolayer films
Two stereoisomers of surfactants were synthesized in which a diketopiperazine ring was inserted between a hydrocarbon chain (of variable length) and an anionic headgroup. It was found (by HPLC, conductivity, surface tension, and diffusion NMR) that these compounds have low solubilities in water, remarkably high Krafft temperatures, and low critical micelle concentrations. Of particular interest were the pressure/area isotherms of insoluble monolayers of nonionic analogues of the amphiphiles. These isotherms showed an unprecedented hysteresis but only during the first compression/relaxation cycle. Additional cycles were normal in that they lacked the original hysteresis. These results were attributed to diketopiperazine rings that initially lie flat on the water surface at the air/water interface. Compression flips the diketopiperazine rings so that they now reside roughly perpendicular to the interface in a stable hydrogen-bonded orientation where the rings occupy far less space. Copyright
Sorrells, Jennifer L.,Menger, Fredric M.
supporting information; experimental part
p. 10072 - 10073
(2009/02/04)

Synthesis and biological activity of S-oxo-[(methylthio)-methyl]cysteinols
A convenient route was developed to synthesize S-oxo-[(methylthio)-methyl]cysteinols on a large scale from cheap l-serine as the starting material. The structures of diastereoisomers were determined by NMR, CD spectra, and X-ray diffraction analysis. All four diastereoisomers were examined for their ability to inhibit certain bacteria from growing.
Xi, Zhen,Cheng, Xiao-Feng,Chen, Wen-Bin,Cao, Li-Qiang
p. 3337 - 3339
(2007/10/03)

Synthesis of a perhydroindolic analog of kainic acid
Synthesis of perhydroindolyl-2-carboxy-3-acetic acid, a strained analog of kainic acid, is described. This compound was obtained in 7 steps by the use of the Barco procedure from nitrocyclohexene.
Danel, Mathieu,Hijazi, Akram,Barret, Roland
p. 343 - 346
(2007/10/03)

Versatile approach for the synthesis of novel seven-membered iminocyclitols via ring-closing metathesis dihydroxylation reaction
Seven-membered iminocyclitols with diverse diastereomers were prepared starting with D- and L-serines and employing ring-closing olefin metathesis and dihydroxylation reaction sequence. The iminocyclitols were assayed for glycosidase inhibition and compound 20 was found to be a competitive inhibitor for β-glucosidase with Ki 26.3μM.
Lin, Chang-Ching,Pan, Yi-Shin,Patkar, Laxmikant N.,Lin, Hsiu-Mei,Tzou, Der-Lii M.,Subramanian, Thangaiah,Lin, Chun-Cheng
p. 3259 - 3267
(2007/10/03)

The synthesis of (2S)-4,4-difluoroglutamyl γ-peptides based on Garner's aldehyde and fluoro-reformatsky chemistry
The development of optically active fluorinated synthetic building blocks of general utility is a current goal of organo-fluorine chemists. The serine-derived Garner aldehyde was converted to a general 4,4-difluoroamino acid building block via fluoro-Reformatsky reaction with ethyl bromodifluoroacetate. The utility of this building block was demonstrated by the synthesis of derivatives of (2S)-4,4-difluoroglutamine, (2S)-4,4-difluoroglutamic acid, and its incorporation into a fluorophore-containing isopeptide 2 designed as a mechanistic probe of γ-glutamyl hydrolase. Compound 2 proved to be a substrate for γ-glutamyl hydrolase and was hydrolyzed at a rate significantly slower than the corresponding non-fluorinated analog.
Konas, David W.,Pankuch, Jessica J.,Coward, James K.
p. 2616 - 2626
(2007/10/03)

First stereocontrolled synthesis of (S)-cleonin and related cyclopropyl-substituted amino acids.
[reaction: see text]. Enantiomerically pure (S)-cleonin, a key component of the antitumor antibiotic cleomycin, was prepared starting from (R)-serine. The Kulinkovich cyclopropanation of the methyl ester of N-Cbz serine acetonide gave the hydroxycyclopropyl moiety. The amino alcohol region was further oxidized to amino acid. The Kulinkovich cyclopropanation allowed also the preparation of other non-natural substituted cyclopropylglycines.
Esposito,Piras,Ramazzotti,Taddei
p. 3273 - 3275
(2007/10/03)

A flexible and efficient synthesis of the pyrrolidine α-glycosidase inhibitor 1,4-dideoxy-1,4-imino-D-arabinitol (DAB-1)
The synthesis of the pyrrolidine α-glycosidase inhibitor 1,4-dideoxy-1,4-imino-D-arabinitol (DAB-1) was discussed. The synthesis used serine-derived α-dibenzylamino aldehyde in a highly diastereoselective glycolate aldol reaction. The glycolate derivative of Evans' oxazolidinone compound was found to be prepared using benzyl-oxyacetyl chloride and 4-benzyloxazolidin-2-one. The analysis showed that the deprotection of the N-benzyl protecting groups was completed within the first 2-3 h of the reaction.
Hulme, Alison N.,Montgomery, Charles H.,Henderson, David K.
p. 1837 - 1841
(2007/10/03)

The efficient, enantioselective synthesis of aza sugars from amino acids. 1. The polyhydroxylated pyrrolidines
Beginning with (+)-serine or (-)-serine, as appropriate, convenient, high-yield, enantioselective synthesis of all eight stereoisomeric 2-hydroxymethyl-3,4-dihydroxypyrrolidines (the enantiomeric pairs of iminoribitol, -arabinitol, -xylitol, and -lyxitol) can be effected. The absolute configuration of the starting amino acid defines the set of azasugars produced.
Huang, Yifang,Dalton, David R.,Carroll, Patrick J.
p. 372 - 376
(2007/10/03)

Synthesis and anticonvulsant activities of N-benzyl-2-acetamidopropionamide derivatives
Studies have demonstrated that 2-substituted N-benzyl-2-acetamidoacetamides (2) are potent anticonvulsants. A recent investigation has led to the hypothesis that an important structural feature in 2 for maximal anticonvulsant activity is the placement of a small, substituted heteroatom moiety one atom from the C(2) site. This paper validates this hypothesis. Twelve derivatives of N-benzyl-2-acetamidopropionamide have been prepared in which six different heteroatom substituents (chloro, bromo, iodo, oxygen, nitrogen, and sulfur) were incorporated at the C(3) site. Highly potent activities were observed for the two oxygen-substituted derivatives, N-benzyl-2-acetamido-3-methoxypropionamide (18) and N-benzyl-2-acetamido-3-ethoxypropionamide (19). The ED50 values in mice following intraperitoneal (ip) dosing for the maximal electroschock-induced seizure test for 18 and 19 were 8.3 and 17.3 mg/kg, respectively. These values compared favorably to the ED50 value found for phenytoin (ED50 = 6.5 mg/kg). Comparable activities were observed for 18 and 19 upon oral (po) administration to rats (18, ED50 = 3.9 mg/kg; 19, ED50 = 19 mg/kg; phenytoin, ED50 = 23 mg/kg). Evaluation of the individual stereoisomers for 18 demonstrated that the principal anticonvulsant activity resided in the (R)-stereoisomer. The ED50 value for (R)-18 was 4.5 mg/kg, and the ED50 for (S)-18 exceeded 100 mg/kg. This difference in activity for the two stereochemical isomers surpassed comparable values for other members within this class of compounds. The protective indices (PI = TD50/ED50) (where TD50 represents a neurotoxic dose impairing rotorod performance) for (R)-18 in mice (ip) and in rats (po) were 6.0 and > 130, respectively.
Choi, Daeock,Stables, James P.,Kohn, Harold
p. 1907 - 1916
(2007/10/03)

SYNTHESIS OF A SIMPLE KAINIC ACID ANALOGUE BY MEANS OF CARBAMOYLMETHYL RADICAL CYCLIZATION
A new approach to (-)-(2S,3R)-2-carboxy-3-pyrrolidineacetic acid (6) starting from D-serine is described.The key step is a radical cyclization of tert-butyl (S)-3-oxazolidin-4-yl>-(E)-propenoate (15b), which gave tert-butyl (6S,7R,7aS)-5,6,7,7a-tetrahydro-3,3-dimethyl-5-oxo-6-phenylthio-1H,3H-pyrrolooxazol-7-ylacetate (16b) in a highly regio- and diastereo-selective manner.The compound (16b) was then coverted into tert-butyl (4R,5S)-5-(tert-butyldimethylsilyloxymethyl)-1-methoxycarbonyl-2-oxopyrrolidin-4-ylacetate (19) by standard chemical manipulations, which has already been transformed to 6.
Sato, Tatsunori,Matsubayashi, Ken-ichiro,Yamamoto, Kazumi,Ishikawa, Hiroko,Ishibashi, Hiroyuki,Ikeda, Masazumi
p. 261 - 270
(2007/10/02)

Asymmetric addition to chiral aromatic and unsaturated oxazolines using a novel chiral auxillary
By utilizing S-serine, both enantiomers of the reduced methoxyamino alcohol (12) were efficiently prepared. The corresponding oxazolines, prepared from these auxiliaries, showed favorable properties toward additions to naphthalenes 22 and cyclohexene, 27.
Meyers,Schmidt,McKennon
p. 250 - 262
(2007/10/02)

Stereoselective synthesis of novel centrally active benzomorphan-type tricycles with 2-phenylethylamine substructure
Addition of the LDA-deprotonated glycine ester 6 to the homophthalaldehyde monoacetal 5 yields the β-hydroxyester 7 which is cyclized after reduction to give the racemic 2,6-epoxy-3-benzoxocin-5-amines (+/-)-12 and (+/-)-13. The key intermediates for the synthesis of 12 and 13 in enantiometrically pure form are the hydroxyacetals (R,S,R)-22 and (R,S,S)-23: (R,S,R)-22 is stereoselectively prepared by addition of the aryllithium-compound 21b or the aryltitan-compound 21c to the new serinal equivalent (R,S)-20; reduction of the ketone (R,S)-24 with LiAlH4 at -78°C affords the diastereomeric hydroxyacetal (R,S,S)-23 predominantly (>95%). With acid (R,S,R)-22 and (R,S,S)-23 are transformed into the tricyclic ure-thanes (S,S,R)-25 and (R,S,S)-30, which are reduced and methylated to yield the dimethylamines (S,S,R)-12 and (R,S,S)-13 (ee > 97%), respectively. Analogously the enantiomeric amines (R,R,S)-12 and (S,R,R)-13 are prepared starting from (R)-serine. The relative configuration of (R,S,R)-22 is confirmed by molecular dynamics calculations (Sybyl 5.4) combined with NOE-measurement. Symptoms typical for sedation are observed after application of both enantiomers of 12, 13, 27, and 32 to mice. In the acetic acid writhing test (mouse) (S,S,R)-12, (S,R,R)-13, (R,S,S)-13, (S,S,R)-27, (R,R,S)-27, and (R,S,S)-32 exhibit strong analgesic effects with ED50-values in the range of the ED50-value of tramadol-HCl.
Wunsch,Hofner,Bauschke
p. 101 - 113
(2007/10/02)

ENANTIOSELECTIVE KAINOID SYNTHESIS BY COBALT-MEDIATED CYCLISATION OF AN AMINO ACID DERIVATIVE
A new synthesis of (-)-kainic acid is described based on a cobalt mediated cyclisation reaction of an appropriately modified serine precursor.
Baldwin, Jack E.,Moloney, Mark G.,Parsons, Andrew F.
p. 7263 - 7282
(2007/10/02)

Synthesis and Biological Activity of the Isomers and Analogs of (4E,8E,2S,3R,2'R)-N-2'-Hydroxyhexadecanoyl-9-methyl-4,8-sphingadienine, the Ceramide Portion of the Fruiting-inducing Cerebroside in a Basidiomycete Schizophyllum commune
The title compounds were synthesized by employing 2-aminohexadecanoic acid and serine as the chiral sources, and served for an assay of fruiting-inducing activity on Schizophyllum commune.The structure-bioactivity relationship among closely related synthetic ceramides is discussed.
Funaki, Yuji,Kawai, Genshiro,Mori, Kenji
p. 615 - 624
(2007/10/02)

Enzyme-Catalyzed Irreversible Formation of Peptides Containing D-Amino Acids
Procedures have been developed for the preparation of dipeptides Z-L-Tyr-D-X and Z-L-Phe-D-X using Z-L-Tyr-OMe (or Z-L-Phe-OMe) and D-amino acid esters or amides (D-X) as substrates and soluble or immobilized α-chymotrypsin as a catalyst.The formation of each of these peptides in miscible or immiscible organic solvent-water systems in a kinetically controlled approach is virtually irreversible with no side reactions or racemization.Kinetic studies indicate that D-amino acid esters are about 100 times that of water and 10percent that of L-amino acid esters as a nucleophile in deacylation reactions.The effects of pH, organic solvents, temperature, and substrate and enzyme concentrations on the yield and the stability of the enzyme in syntheses have been studied and the results compared with those in the enzyme-catalyzed formation of L-L-dipeptides.
West, J. Blair,Wong, Chi-Huey
p. 2728 - 2735
(2007/10/02)

Synthesis of Polymers of Isocyanides Derived from Tripeptides Containing Imidazolyl, Carboxyl, and Hydroxymethyl Groups
Three optically active polymers of isocyanides, n, which contain imidazolyl, carboxyl, and hydroxymethyl functions in their side chains R, are described.The polymers are derived from the following diastereomeric tripeptides: L-Ala-L-His-L-Ser, L-Ala-L-His-D-Ser, and D-Ala-L-His-L-Ser.The terminal amino groups of these tripeptides are converted into isocyano functions, which are subsequently polymerized with catalytic amounts of nickel(II) chloride.The molecular weights of the polymers are in the Mv range 20000-35000.The CD spectra reveal that the polymers derived from L-Ala-L-His-L-Ser and L-Ala-L-His-D-Ser have right-handed helical configuractions.The pKa values of the imidazolyl and carboxyl groups in the polymers have increased as compared to model compounds.This suggests that strong electrostatic interactions exist between these groups.
Visser, H. G. J.,Nolte, R. J. M.,Zwikker, J. W.,Drenth, W.
p. 3133 - 3137
(2007/10/02)