- Asymmetric recognition of 1-arylethylamines by (R)-phenylglycyl-(R)-phenylglycine and its mechanism
-
An unprotected dipeptide, (R)-phenylglycyl-(R)-phenylglycine, which is insoluble in water, was shown to be an excellent resolving reagent for racemic 1-arylethylamines. By simply stirring the mixture of the dipeptide and racemic 1-phenylethylamine in presence of water, asymmetric recognition occurred to give a salt of (S)-1-phenylethylamine (95% ee) and the dipeptide. X-Ray crystallographic study of the salt elucidated the crystal structure of the diastereomeric salt, where hydrogen bonding and hydrophobic interaction between the dipeptide and amines play important roles in the construction of layers.
- Akazome, Motohiro,Matsuno, Hirozumi,Ogura, Katsuyuki
-
-
Read Online
- Design and synthesis of novel symmetric fluorene-2,7-diamine derivatives as potent hepatitis C virus inhibitors
-
Hepatitis C virus (HCV) is an international challenge. Since the discovery of NS5A direct-acting antivirals, researchers turned their attention to pursue novel NS5A inhibitors with optimized design and structure. Herein we explore highly potent hepatitis C virus (HCV) NS5A inhibitors; the novel analogs share a common symmetrical prolinamide 2,7-diaminofluorene scaffold. Modification of the 2,7-diaminofluorene backbone included the use of (S)-prolinamide or its isostere (S,R)-piperidine-3-caboxamide, both bearing different amino acid residues with terminal carbamate groups. Compound 26 exhibited potent inhibitory activity against HCV genotype (GT) 1b (effective concentration (EC50) = 36 pM and a selectivity index of >2.78 × 106). Compound 26 showed high selectivity on GT 1b versus GT 4a. Interestingly, it showed a significant antiviral effect against GT 3a (EC50 = 1.2 nM). The structure-activity relationship (SAR) analysis revealed that picomolar inhibitory activity was attained with the use of S-prolinamide capped with R- isoleucine or R-phenylglycine residues bearing a terminal alkyl carbamate group.
- Mousa, Mai H. A.,Ahmed, Nermin S.,Schwedtmann, Kai,Frakolaki, Efseveia,Vassilaki, Niki,Zoidis, Grigoris,Weigand, Jan J.,Abadi, Ashraf H.
-
-
- Symmetric benzidine derivatives as anti-HCV agents: Insight into the nature, stereochemistry of the capping amino acid and the size of the terminal capping carbamates
-
Novel symmetric molecules, bearing a benzidine prolinamide core, two terminal carbamate caps of variable sizes and nature, including natural and unnatural amino acids were developed. Several terminal N-carbamate substituents of the core structure, ranging from linear methyl, ethyl and butyl groups to branching isobutyl group; and an aromatic substituent were also synthesized. Series 1 has hydrophobic AA residues, namely S and R phenylglycine and a terminal carbamate capping group, whereas Series 2 bears sulphur containing amino acids, specifically S and R methionine and the natural R methylcysteine. The novel compounds were tested for their inhibitory activity (EC50) and their cytotoxicity (CC50), using an HCV 1b (Con1) reporter replicon cell line. Compound 4 with the unnatural capping residue, bearing D-Phenylglycine amino acid residue and N-isobutyloxycarbonyl capping group, was the most active within the two series, with EC50 = 0.0067 nM. Moreover, it showed high SI50 > 14788524 and was not cytotoxic at the highest tested concentration (100 μΜ), indicating its safety profile. Compound 4 also inhibited HCV genotypes 2a, 3a and 4a. Compared to the clinically approved NS5A inhibitor Daclatasvir, compound 4 shows higher activity against genotypes 1b and 3a, as well as improved safety profile.
- Abadi, Ashraf H.,Abdel Karim, Shereen E.,Abdel-Halim, Mohammad,Ahmed, Nermin S.,Frakolaki, Efseveia,Vassilaki, Niki,Youssef, Youssef H.,Zoidis, Grigoris
-
-
- Enantioselective Michael reaction of anthrone catalyzed by chiral tetraoxacalix[2]arene[2]triazine derivatives
-
A highly enantioselective Michael addition reaction of anthrone with nitroalkenes by chiral tetraoxacalix[2]arene[2]triazine catalysts was investigated as a novel topic. The stereoselective conversion progressed smoothly by employing 10 mol% of the catalyst and afforded the corresponding Michael adducts with acceptable to high enantioselectivities (up to 97% ee) and very high yields (up to 96%).
- Genc, Hayriye Nevin
-
p. 21063 - 21069
(2019/07/12)
-
- Effective asymmetric Michael addition of anthrone to nitroalkenes using chiral tetraoxacalix[2]arene[2]triazines as organocatalysts
-
Novel chiral secondary amines bearing a tetraoxacalix[2]arene[2]triazine scaffold were created and used for catalytic asymmetric Michael reaction of anthrone with nitroalkenes. The relevant adducts were obtained in good to excellent yields (82%-98%) and enantioselectivities (75%-98%).
- Genc, Hayriye Nevin
-
p. 711 - 718
(2019/07/16)
-
- THERAPEUTIC USE OF LEVOROTATORY ?-LACTAMS IN HEMATOPOIESIS, IMMUNO-ONCOLOGY THERAPY, AND REGULATION OF LIPOPROTEIN AND APOLIPOPROTEIN LEVELS
-
A method for increasing the number of CD4+ T-lymphocytes in the serum of a subject in need of such treatment comprising administering to the subject a pharmaceutical composition comprising an amount of an L-isomer of β-lactam effective to increase the number of CD4+ T-lymphocytes in said patient's serum.
- -
-
Page/Page column 29-30
(2018/08/20)
-
- N-METHYL-N-(1-PHENYL-2-(1-PYRROLIDINYL)ETHYL)-2-AMINOPHENYLACETAMIDE DERIVATIVES AGONISTS FOR THE KAPPA OPIOID RECEPTOR
-
Compounds and pharmaceutically acceptable salts and solvates thereof are described. The compounds relate to and/or have application(s) in (among others) the fields of drug discovery, pharmacotherapy, physiology and organic chemistry.
- -
-
Paragraph 00158-00159
(2016/07/27)
-
- COMPOUNDS USEFUL AS CSF1 MODULATORS
-
This invention relates to novel compounds and to pharmaceutical compositions comprising the novel compounds. More specifically, the invention relates to compounds useful as Colony Stimulating Factor 1 Receptor (cFMS) modulators (e.g. cFMS inhibitors). This invention also relates to processes for preparing the compounds, uses of the compounds in treatment and methods of treatment employing the compounds. Specifically, the invention relates to the use of the compounds for the treatment of cancer and autoimmune diseases.
- -
-
-
- KAPPA OPIOID AGONISTS AND USES THEREOF
-
Provided are compounds of Formula I; and pharmaceutically acceptable salts and solvates thereof. The compounds of Formula I described herein relate to and/or have application(s) in (among others) the fields of drug discovery, pharmacotherapy, physiology, organic chemistry and polymer chemistry.
- -
-
Paragraph 00520; 00521
(2015/01/16)
-
- METHOD FOR PRODUCING CARBOXYLIC ACID AND ALCOHOL BY HYDROLYSIS OF ESTER
-
As shown by the following formula (1), after methyl laurate (2 mmol) and water (8 mL) are added to an ammonium pyrosulfate catalyst (5 mol%), a hydrolysis reaction of methyl laurate is carried out by heating for 24 hours at 60°C while stirring is performed, so that lauric acid can be obtained with a yield of 86%.
- -
-
Paragraph 0069; 0070
(2014/11/13)
-
- SUBSTITUTED HETEROCYCLIC ACETAMIDES AS KAPPA OPIOID RECEPTOR (KOR) AGONISTS
-
The present invention relates to a series of substituted compounds having the general formula (I), including their ste reoisomers and/or their pharmaceutically acceptable salts, wherein R1, R2, R3. R4, R5, and R6 are as defined herein. This invention also relates to methods of making these compounds including intermediates. The compounds of this invention are effective at the kappa (κ) opioid receptor (KOR) site. Therefore, the compounds of this invention are useful as pharmaceutical agents, especially in the treatment and/or prevention of a variety of central nervous system disorders (CNS), including but not limited to acute and chronic pain, and associated disorders, particularly functioning peripherally at the CNS.
- -
-
Page/Page column 122
(2013/09/26)
-
- Retention of stereochemistry in the microwave assisted synthesis of 1H-tetrazole bioisosteric moiety from chiral phenyl-acetic acid derivatives
-
Chiral substituted phenylethyl-1H-tetrazoles were built-up from the corresponding carboxylic acid derivatives by a useful three-step synthesis. The procedure, that preserves the chiral center from racemization, was successfully applied to a selection of several hit compounds by conversion of the carboxylic acid moiety to the nitrile derivatives and subsequent reaction with trimethylstannyl azide, under microwave conditions. A useful application to the corresponding tetrazole analogue has been found also in the conversion of the aminoacidic moiety like (R)-N-Cbz-phenylglycine showing a wide potential synthetic application.
- Tomassetti, Mara,Fanì, Michela,Bianchini, Gianluca,Giuli, Sandra,Aramini, Andrea,Colagioia, Sandro,Nano, Giuseppe,Lillini, Samuele
-
supporting information
p. 6247 - 6250
(2013/10/22)
-
- KAPPA OPIOID RECEPTOR AGONISTS
-
The present invention relates to a series of substituted compounds having the general formula (I), including their stereoisomers and/or their pharmaceutically acceptable salts. (I) Wherein A, m, Rls R2, R3, R4 are as defined herein. This invention also relates to methods of making these compounds including intermediates. The compounds of this invention are effective at the kappa (κ) opioid receptor (KOR) site. Therefore, the compounds of this invention are useful as pharmaceutical agents, especially in the treatment and/or prevention of a variety of central nervous system disorders (CNS), including but not limited to acute and chronic pain, and associated disorders, particularly functioning peripherally at the CNS.
- -
-
Page/Page column 44
(2012/02/05)
-
- Enantioselective organocatalytic α-alkylation of ketones by S N1-type reaction of alcohols
-
The enantioselective α-alkylation reaction of cyclic ketones is described. Our catalyst, based on a "privileged" pyrrolidine ring bearing a chiral thioxotetrahydropyrimidinone ring, is a highly reactive catalyst for cyclic ketones. When this catalyst was coupled with in situ generated carbocations derived from alcohols, the corresponding α-alkylated adducts were obtained in moderate to quantitative yields and low to high enantioselectivities (up to 80% ee). The catalyst loading can be efficiently reduced to 10%, which is the lowest value reported in the literature for such an organocatalytic transformation.
- Trifonidou, Maria,Kokotos, Christoforos G.
-
supporting information; experimental part
p. 1563 - 1568
(2012/04/23)
-
- N,N-diarylammonium pyrosulfate as a highly effective reverse micelle-type catalyst for hydrolysis of esters
-
Reverse micelle-type N,N-diarylammonium pyrosulfate (3-5 mol %) efficiently catalyzes the hydrolysis of esters (up to 100 mmol scale) under organic solvent-free conditions. The present method is successfully applied to the hydrolysis of various esters without the decomposition of the base-sensitive moieties and without any loss of optical purity for α-heterosubstituted carboxylic acids.
- Koshikari, Yoshiki,Sakakura, Akira,Ishihara, Kazuaki
-
experimental part
p. 3194 - 3197
(2012/07/31)
-
- PROCESS FOR PRODUCTION OF DISULFONIC ACID COMPOUND, ASYMMETRIC MANNICH CATALYST, PROCESS FOR PRODUCTION OF -AMINOCARBONYL DERIVATIVE, AND NOVEL DISULFONATE SALT
-
Hexamethylphosphoramide (HMPA) was added to a reaction vessel containing (R)-1,1'-binaphthyl-2,2'-dithiol and potassium hydroxide. The vessel was purged with oxygen and stirred at 80°C for 5 days under 7 atmospheres of oxygen. After being cooled to room temperature, the reaction product was purified to yield potassium (R)-1,1'-binaphthyl-2,2'-disulfonate. The (R)-1,1'-binaphthyl-2,2'-disulfonic acid obtained from the disulfonate and 2,6-diphenylpyridine were stirred in acetonitrile, and then the solvent was evaporated under reduced pressure. Subsequently, magnesium sulfate and distilled CH2Cl2 were added to the reaction product, and the mixture was stirred at room temperature for 30 minutes. The resulting solution was cooled to 0°C. Benzaldehyde imine whose nitrogen is protected with Cbz and subsequently acetyl acetone were dropped into the solution over a period of 1 hour. The resulting mixture was further stirred at 0°C for 30 minutes. A corresponding β-aminocarbonyl derivative was thus produced with an yield of 91% and an enantiomeric excess of 90% ee.
- -
-
Page/Page column 9-10
(2010/08/07)
-
- Pyridinium 1,1′-binaphthyl-2,2′-disulfonates as highly effective chiral Br?nsted acid-base combined salt catalysts for enantioselective mannich-type reaction
-
We have established, for the first time, a practical synthesis of chiral 1,1′-binaphthyl-2,2′-disulfonic acid (BINSA 1) from inexpensive BINOL. An efficient enantioselective catalysis in the Mannich-type reactions of diketones and ketoester equivalents with aldimines was developed using chiral 1?achiral 2,6-diarylpyridine (2) combined salts, which acted as convenient chiral tailor-made Br?nsted acid?base organocatalysts in situ. Copyright
- Hatano, Manabu,Maki, Toshikatsu,Moriyama, Katsuhiko,Arinobe, Manabu,Ishihara, Kazuaki
-
supporting information; experimental part
p. 16858 - 16860
(2009/04/13)
-
- Aqueous phase mono-protection of amines and amino acids as N-benzyloxycarbonyl derivatives in the presence of β-cyclodextrin
-
A simple and selective protection of amines/amino acids with Cbz-Cl has been achieved in aqueous phase with catalytic amounts of β-cyclodextrin in high yields at room temperature. This reaction proceeds without the formation of any by-products and has advantages over existing methods.
- Pavan Kumar,Somi Reddy,Narender,Surendra,Nageswar,Rama Rao
-
p. 6393 - 6396
(2007/10/03)
-
- DIPEPTIDE CASPASE INHIBITORS AND THE USE THEREOF
-
The present invention is directed to novel dipeptides represented by the general Formula I: where R1-R2 and AA are defined herein. The present invention relates to the discovery that compounds having Formula I are potent inhibitors of caspases and apoptotic cell death. Therefore, the inhibitors of this invention can retard or block cell death in a variety of clinical conditions in which the loss of cells, tissues or entire organs occurs.
- -
-
Page/Page column 9; 13
(2008/06/13)
-
- Development of a rapid, room-temperature dynamic kinetic resolution for efficient asymmetric synthesis of α-aryl amino acids
-
equation presented A rapid, highly efficient and general dynamic kinetic resolution (DKR) of racemic α-aryl UNCAs with the dual-function catalysis of modified cinchona alkaloid was accomplished at room temperature. This DKR led to the development of a highly enantioselective catalytic method for the practical synthesis of a wide range of α-aryl and α-heteroaryl amino acids in 89-92% ee and 86-95% yield from racemic UNCAs.
- Hang, Jianfeng,Li, Hongming,Deng, Li
-
p. 3321 - 3324
(2007/10/03)
-
- A general synthesis of enantiopure 1,2-aminoalcohols via chiral morpholinones
-
Eleven optically active 1,2-aminoalcohols 20a-i and 26b-c were prepared from D-phenylglycine via cyclic imines 7b-i (or enamine 7a). The key step of the strategy is the diastereoselective reduction of chiral oxazinones 7a-i.
- Segat-Dioury, Fabienne,Lingibé, Olivier,Graffe, Bernadette,Sacquet, Marie-Claude,Lhommet, Gérard
-
p. 233 - 248
(2007/10/03)
-
- Chiral oxime ethers in asymmetric synthesis. 3. Asymmetric synthesis of (R)-N-protected α-amino acids by the addition of organometallic reagents to the ROPHy oxime of cinnamaldehyde
-
A new asymmetric synthesis of α-amino acids is described in which the key step is the diastereoselective addition of organometallic reagents to (R)-O-(1-phenylbutyl)cinnamaldoxime 5 to give hydroxylamines 6. Subsequent reductive cleavage of the N-O bond in the hydroxylamine 6 followed by N- protection gave the carbamates 7, which upon oxidation with ruthenium(III) chloride/periodate gave the N-protected amino acids 8. The method was also adapted to the synthesis of a quaternary amino acid 15 from the ketoxime ether 9.
- Moody, Christopher J.,Gallagher, Peter T.,Lightfoot, Andrew P.,Slawin, Alexandra M. Z.
-
p. 4419 - 4425
(2007/10/03)
-
- From styrenes to enantiopure α-arylglycines in two steps
-
Direct enantioselective synthesis of (R)- and (S)-N-Cbz- or N- BOC-protected α-arylglycinols from styrenes via catalytic asymmetric aminohydroxylation, with enantioselective up to 99% and isolated yields up to 80%, is described. In a subsequent oxidation step, these glycinols yield the corresponding carbamate-protected α-arylglycines.
- Laxma Reddy,Barry Sharpless
-
p. 1207 - 1217
(2007/10/03)
-
- Synthesis and use of amino acid fluorides as peptide coupling reagents
-
The present invention is directed to the process of preparing a peptide comprising reacting a first amino acid or peptide with an amino acid fluoride of the formula: STR1 or the acid fluoride salts thereof wherein BLK is an N-amino protecting group AA is an amino acid residue and X is H or a protecting group useful, and the first amino and peptide have a free amino group and a blocked carboxy end.
- -
-
-
- Addition of Organolithiums to the (R)-O-(1-Phenylbutyl)hydroxylamine (ROPHy) Oxime of Cinnamaldehyde. Asymmetric Synthesis of α-Aminoacids
-
A new asymmetric synthesis of α-aminoacids is described in which the key step is the diastereoselective addition of organolithium reagents to (R)-O-(1-phenylbutyl) cinnamaldoxime.
- Moody, Christopher J.,Lightfoot, Andrew P.,Gallagher, Peter T.
-
p. 659 - 660
(2007/10/03)
-
- Asymmetric synthesis with chiral hydrogenolysable amines : A new route to enantiomerically pure amino diols
-
Enantiomerically pure amino diols are obtained via diastereoselective reduction of chiral enamino and imino esters (3a), (3b), and (3c).
- Segat, Fabienne,Lingibe, Olivier,Graffe, Bernadette,Sacquet, Marie-Claude,Lhommet, Gerard
-
p. 1451 - 1455
(2007/10/03)
-
- Poststatin, a new inhibitor of prolyl endopeptidase. V. Endopeptidase inhibitory activity of poststatin analogues
-
Thirty analogues of poststatin were synthesized, and their inhibitory activities against prolyl endopeptidase, human leukocyte elastase and cathepsin B were measured. The α-ketone was essential and the S configuration was preferable to the R configuration in the β-substituted-β-amino-α-oxopropionic acid moiety of poststatin analogues for endopeptidase inhibitory activity. The analogue in which the D-leucine residue of poststatin was replaced by L-leucine showed strong inhibitory activity to cathepsin B. Introduction of an aromatic group into the P4 position and proline into the P2 position increased inhibitory activity to elastase. Benzyloxycarbonyl-L-homophenylalanyl-(RS)-3-amino-2-oxovaleryl-D- leucyl-L-valine was about 6 times more active to prolyl endopeptidase than natural poststatin.
- Tsuda, Makoto,Muraoka, Yasuhiko,Nagai, Machiko,Aoyagi, Takaaki,Takeuchi, Tomio
-
p. 890 - 899
(2007/10/03)
-
- Synthesis of α-Methyldopa Prodrugs Containing Dipeptide Moieties as Tools for Intestinal Delivery
-
Dipeptides containing D-phenylglycine or D-p-hydroxyphenylglycine were attached onto the antihypertensive agent α-methyldopa to form prodrugs 1a,1b and 1c.The nonessential amino acids were introduced into the prodrug molecules as tools of chemical delivery to improve the intestinal absorption of the parent drug.Preliminary tests revealed that the prodrugs were stable in phosphate buffer solutions at pH 7.4(t1/2>10 h).These compounds also demonstrated satisfactory stability toward enzymatic degradation in a mucosa preparation isolated from rat intestine, indicating that they might be feasibly formulated as an oral prodrug of α-methyldopa.Key Words α-Methyldopa prodrugs; Dipeptides as tools for intestinal delivery.
- Wang, Hui-Po,Cheng, Chih-Yuan,Ma, Jin-Ran,Lee, Jia-Shuai
-
p. 561 - 568
(2007/10/02)
-
- A new route to homochiral piperidines
-
The synthesis of an enantiomeric pair of enaminoesters from phenylglycine is described. Conjugate addition to α,β-enones, reductive cyclization-fragmentation to octahydroimidazopyridines and further reduction to remove the auxiliary atoms, completes a new route to homochiral piperidines in which the enaminoesters function as homochiral 'ethanal enamines'.
- Jones,Turner,Howard
-
p. 6329 - 6332
(2007/10/02)
-
- Synthesis of the Alkaloid Homaline in (+/-) and Natural (S,S)-(-) Forms, using Amination and Transamidative Ring Expansion in Liquid Ammonia
-
Synthesis of the alkaloid homaline in (+/-) and natural (S,S)-(-) forms is reported.Linking of 2-azacyclooctanone units either directly or successively using 1,4-dihalogenobutanes or 1,4-dihalogenobut-2-ynes is examined. (+/-)-5-Methyl-4-phenyl-1,5-diazacyclooctan-2-one is first made by a 2,2'-dithiodipyridine/triphenylphosphine-mediated cyclisation, and then by amination and transamidative ring expansion from N-(3-chloropropyl)-4-phenylazetidin-2-one in liquid ammonia, followed by N-methylation.Coupling through a 1,4-dihalogenobutane of either the N-methylated azalactam, or the unmethylated azalactam followed by methylation, gave homaline in (+/-) and meso forms. (R)-(-)-Phenylglycine was converted via (S)-β-phenyl-β-alanine into an (S)-β-lactam which was then alkylated with 1-bromo-3-chloropropane, and aminated and ring expanded in liquid ammonia.Coupling of the homochiral azalactam (2 mol) so formed with 1,4-dibromobutane, followed by N-methylation, gave (S,S)-(-)-homaline identical with the natural material.
- Crombie, Leslie,Haigh, David,Jones, Raymond C. F.,Mat-Zin, Ab. Rasid
-
p. 2047 - 2054
(2007/10/02)
-
- High potency dipeptide sweeteners. 1. L-aspartyl-D-phenylglycine esters
-
Twenty esters of L-aspartyl-D-phenylglycine, as well as two substituted analogues, an o-fluoro and a p-hydroxyphenylglycine ester, were prepared. The L-aspartyl-D-phenylglycine (-)-α- and (+)-β-fenchyl esters had the highest sweetness potency at 1200 and 3700 times that of sucrose, respectively. The high potency of these sweeteners is surprising as the phenyl group occupies a position previously believed to accommodate only much smaller groups.
- Janusz,Gardklik,Young,Burkes,Stoll,Estelle,Riley
-
p. 1052 - 1061
(2007/10/02)
-
- Porcine Pancreatic Lipase Catalyzed Enantioselective Hydrolysis of Esters of N-Protected Unusual Amino Acids
-
Porcine pancreatic lipase catalyzed the highly enantioselective hydrolysis of a kind of α-substituted carboxylic esters, i.e., the 2,2,2-trifluoroethyl esters of the N-benzyloxycarbonyl derivatives of unusual amino acids.
- Miyazawa, Toshifumi,Iwanaga, Hitoshi,Ueji, Shinichi,Yamada,Takashi,Kuwata, Shigeru
-
p. 2219 - 2222
(2007/10/02)
-
- Direct Optical Resolution of Carboxylic Acids by Chyral HPLC on Tris(3,5-dimethylphenylcarbamate)s of Cellulose and Amylose
-
A variety of racemic carboxylic acids have been for the first time directly resolved by normal-phase, high-performance liquid chromatography using a hexane-2-propanol eluting system containing a small amount (ca. 1percent) of a strong carboxylic acid, like formic acid, trichloroacetic acid, and trifluoroacetic acid.
- Okamoto, Yoshio,Aburatani, Ryo,Kaida, Yuriko,Hatada, Koichi
-
p. 1125 - 1128
(2007/10/02)
-
- Analogues of 2'(3')-O-L-phenylalanyladenosine as substrates and inhibitors of ribosomal peptidyltransferase
-
The chemical syntheses of 2'(3')-O-(L-3-amino-3-phenylpropionyl)adenosine (2e), the corresponding D stereoisomer 2f, 2'(3')-O-(DL-phenylglycyl)adenosine (2g), 2'(3')-O-(N-benzylglycyl)adenosine (2h), and 9-(2-O-L-phenylalanyl-β-D-xylofuranosyl)adenine (3b) are described. Compounds 2e-h were obtained by acylation of 5'-O(4-methoxytrityl)adenosine with the appropriate N-benzyloxycarbonyl or N-tert-butoxycarbonyl amino acids with dicyclohexylcarbodiimide in pyridine. The corresponding reaction of N-(benzyloxycarbonyl)-D-phenylglycine led to an almost complete racemization of the aminoacyl residue (compounds 2c and 2g). Subsequent chromatographic separation and deprotection of intermediates 2a-d afforded the desired target derivatives 2e-h. Product 3b was obtained by a similar acylation of 9-(3,5-O-isopropylidene-β-D-xylofuranosyl)adenine with N-(benzyloxycarbonyl)-L-phenylalanine, followed by deblocking. The NMR spectra of 2' and 3' isomers of stereoisomers 2a and 2b are discussed. Compounds 2g and 3b are both substrates and inhibitors of Escherichia coli ribosomal peptidyltransferase, although the activity of 3b is low. Derivatives 2e,f,h do not accept AcPhe from N-AcPhe-tRNA in a peptidyltransferase-catalyzed reaction, but they inhibit the puromycin reaction in the same system. The order of inhibitory activity is 2e>2f>2h. The implications of these findings for the mechanism of peptidyltransferase and comparison of the latter with the action of chymotrypsin are discussed.
- Zemlicka,Bhuta,Bhuta
-
p. 167 - 174
(2007/10/02)
-