- carba Nicotinamide Adenine Dinucleotide Phosphate: Robust Cofactor for Redox Biocatalysis
-
Here we report a new robust nicotinamide dinucleotide phosphate cofactor analog (carba-NADP+) and its acceptance by many enzymes in the class of oxidoreductases. Replacing one ribose oxygen with a methylene group of the natural NADP+ was found to enhance stability dramatically. Decomposition experiments at moderate and high temperatures with the cofactors showed a drastic increase in half-life time at elevated temperatures since it significantly disfavors hydrolysis of the pyridinium-N?glycoside bond. Overall, more than 27 different oxidoreductases were successfully tested, and a thorough analytical characterization and comparison is given. The cofactor carba-NADP+ opens up the field of redox-biocatalysis under harsh conditions.
- D?ring, Manuel,Sieber, Volker,Simon, Robert C.,Tafertshofer, Georg,Zachos, Ioannis
-
supporting information
p. 14701 - 14706
(2021/05/13)
-
- Alcohols as Latent Hydrophobes: Entropically Driven Uptake of 1,2-Diol Functionalized Ligands by a Porous Capsule in Water
-
Alcohols, with hydroxyl groups compositionally identical to water itself, are consummate hydrophiles, whose high solubilities preclude spontaneous self-assembly in water. Nevertheless, the solute-solvent interactions associated with their highly favorable solvation enthalpies impose substantial entropic costs, similar in magnitude to those that drive the hydrophobic assembly of alkanes. We now show that under nanoconfined conditions this normally dormant "hydrophobicity" can emerge as the driving force for alcohol encapsulation. Using a porous molecular capsule, the displacement of endohedrally coordinated formate ligands (HCO2-) by 1,2-hydroxyl-functionalized l-glycerate (l-gly, l-HOCH2(HO)CHCO2-) was investigated by van't Hoff analysis of variable-temperature 1H NMR in D2O. At pD 5.8, l-gly uptake is enthalpically inhibited. Upon attenuation of this unfavorable change in enthalpy by cosequestration of protons within the alcoholic environment provided by encapsulated diol-functionalized ligands, -TΔS° dominates over ΔH°, spontaneously filling the capsule to its host capacity of 24 l-gly ligands via an entropically driven hydrophobic response.
- Chakraborty, Sourav,Shnaiderman Grego, Alina,Garai, Somenath,Baranov, Mark,Müller, Achim,Weinstock, Ira A.
-
supporting information
p. 9170 - 9174
(2019/06/21)
-
- Synthesis of Phosphatidylserine and Its Stereoisomers: Their Role in Activation of Blood Coagulation
-
Natural phosphatidylserine (PS), which contains two chiral centers, enhances blood coagulation. However, the process by which PS enhanced blood coagulation is not completely understood. An efficient and flexible synthetic route has been developed to synthesize all of the possible stereoisomers of PS. In this study, we examined the role of PS chiral centers in modulating the activity of the tissue factor (TF)-factor VIIa coagulation initiation complex. Full length TF was relipidated with phosphatidylcholine, and the synthesized PS isomers were individually used to estimate the procoagulant activity of the TF-FVIIa complex via a FXa generation assay. The results revealed that the initiation complex activity was stereoselective and had increased sensitivity to the configuration of the PS glycerol backbone due to optimal protein-lipid interactions.
- Mallik, Suman,Prasad, Ramesh,Bhattacharya, Anindita,Sen, Prosenjit
-
supporting information
p. 434 - 439
(2018/05/23)
-
- Synthesis of macrocyclic precursors of the vioprolides
-
The vioprolides are novel depsipeptides that have not been synthesized. However, they have been identified as important targets for synthesis because of their novel biological activities and challenging chemical structures. Following early work on the synthesis of a modified tetrapeptide that contained both the (E)-dehydrobutyrine and thiazoline components of vioprolide D, problems were encountered in taking an (E)-dehydrobutyrine containing intermediate further into the synthesis. A second approach to vioprolides and analogues was therefore investigated in which (E)- and (Z)-dehydrobutyrines were to be introduced by selenoxide elimination very late in the synthesis. A convergent approach to advanced macrocyclic precursors of the vioprolides was then completed using a modified hexapeptide and a dipeptidyl glycerate. In this work, it was necessary to protect the 2-hydroxyl group of the glycerate as its acetate and not as its 2,2,2-trichloroethoxycarbonate. Preliminary studies were carried out on the introduction of the required dehydrobutyrine and thiazoline components into advanced intermediates.
- Butler, Eibhlin,Florentino, Lucia,Cornut, Damien,Gomez-Campillos, Gonzalo,Liu, Hao,Regan, Andrew C.,Thomas, Eric J.
-
p. 6935 - 6960
(2018/10/17)
-
- Samholides, Swinholide-Related Metabolites from a Marine Cyanobacterium cf. Phormidium sp.
-
Cancer cell cytotoxicity was used to guide the isolation of nine new swinholide-related compounds, named samholides A-I (1-9), from an American Samoan marine cyanobacterium cf. Phormidium sp. Their structures were determined by extensive analysis of 1D and 2D NMR spectroscopic data. The new compounds share an unusual 20-demethyl 44-membered lactone ring composed of two monomers, and they demonstrate structural diversity arising from geometric isomerization of double bonds, sugar units with unique glyceryl moieties and varied methylation patterns. All of the new samholides were potently active against the H-460 human lung cancer cell line with IC50 values ranging from 170 to 910 nM. The isolation of these new swinholide-related compounds from a marine cyanobacterium reinvigorates questions concerning the evolution and biosynthetic origin of these natural products.
- Tao, Yiwen,Li, Pinglin,Zhang, Daojing,Glukhov, Evgenia,Gerwick, Lena,Zhang, Chen,Murray, Thomas F.,Gerwick, William H.
-
p. 3034 - 3046
(2018/03/25)
-
- Chemical constituents and biological activities of Viburnum macrocephalum f. keteleeri
-
Three new compounds (1–3) and seven known compounds (4–10) have been isolated from the ethanolic extract of Viburnum macrocephalum f. keteleeri using bioactivity-guided fractionation and identified as methyl (2-α-L-rhamnopyranosyloxy)acetate (1), methyl (2R-3-α-L-rhamnopyranosyloxy)glycerate (2), methyl (3R-4-α-L-rhamnopyranosyloxy-3-hydroxy)butanoate (3), bridelionoside B (4), (6S,7E,9R)-roseoside (5), linarionoside A (6), 3,7,11-trimethyl-1,6-dodecadien-3,10,11-triol (7), (+)-8-hydroxylinalool (8), β-sitosterol (9) and daucosterol (10). The structures of 1–3, including absolute configurations, were determined by spectroscopic data (1H and 13C NMR, HSQC, HMBC and ORD) and chemical methods. In addition, compounds 1–8 were assayed for their insecticidal and antimicrobial activities. Compounds 7 and 8 exhibited moderately insecticidal effects against Mythimna separata with LD50 values of 180 and 230?μg?g?1, respectively. Compounds 2, 3, 7 and 8 showed varying antimicrobial activities with IC50 values ranging from 125 to 529?μM.
- Shao, Jian-Hua,Chen, Jia,Xu, Xiao-Qing,Zhao, Chun-Chao,Dong, Zi-Ling,Liu, Wen-Yan,Shen, Jie
-
-
- Deinococcucins A-D, Aminoglycolipids from Deinococcus sp., a Gut Bacterium of the Carpenter Ant Camponotus japonicus
-
Four new aminoglycolipids, deinococcucins A-D (1-4), were discovered from a Deinococcus sp. strain isolated from the gut of queen carpenter ants, Camponotus japonicus. The structures of deinococcucins A-D were elucidated as a combination of N-acetyl glucosamine, 2,3-dihydroxypropanoic acid, and an alkyl amine with a C16 or C17 hydrocarbon chain primarily based on 1D and 2D NMR and mass spectroscopic data. The exact location of the olefinic double bond in deinococcucins C and D (3 and 4) was assigned based on the liquid chromatography-mass spectroscopy data obtained after olefin metathesis. The absolute configurations of the N-acetyl glucosamine and 2,3-dihydroxy moieties were determined through gas chromatography-mass spectroscopy analysis of authentic samples and phenylglycine methyl ester-derivatized products, respectively. Deinococcucins A and C displayed significant induction of quinone reductase in murine Hepa-1c1c7 cells.
- Shin, Bora,Park, So Hyun,Kim, Byung-Yong,Jo, Shin-Il,Lee, Sang Kook,Shin, Jongheon,Oh, Dong-Chan
-
p. 2910 - 2916
(2017/12/01)
-
- Serinolamides and Lyngbyabellins from an Okeania sp. Cyanobacterium Collected from the Red Sea
-
NMR- and MS-guided fractionation of an extract of an Okeania sp. marine cyanobacterium, collected from the Red Sea, led to the isolation of four new metabolites, including serinolamides C (1) and D (2) and lyngbyabellins O (3) and P (4), together with the three known substances lyngbyabellins F (5) and G (6) and dolastatin 16 (7). The planar structures of the new compounds were determined using NMR and MS analyses. The absolute configurations of 1 and 2 were determined by Marfey's analysis of their hydrolysates. The absolute configuration of 3 was ascertained by chiral-phase chromatography of degradation products, while that of 4 was determined by comparison to 3 and 5. The cytotoxic and antifouling activities of these compounds were evaluated using MCF7 breast cancer cells and Amphibalanus amphitrite larvae, respectively. Compounds 3, 4, and 7 exhibited strong antifouling activity, and 3 and 7 were not cytotoxic. A structure-activity relationship was observed for the cytotoxicity of the lyngbyabellins with the presence of a side chain (4 is more active than 3) leading to greater activity. For the antifouling activity, the acyclic form without a side chain (3) was the most active.
- Petitbois, Julie G.,Casalme, Loida O.,Lopez, Julius Adam V.,Alarif, Walied M.,Abdel-Lateff, Ahmed,Al-Lihaibi, Sultan S.,Yoshimura, Erina,Nogata, Yasuyuki,Umezawa, Taiki,Matsuda, Fuyuhiko,Okino, Tatsufumi
-
p. 2708 - 2715
(2017/11/06)
-
- Synthesis and biological evaluation of enantiomerically pure glyceric acid derivatives as LpxC inhibitors
-
Inhibitors of the UDP-3-O-[(R)-3-hydroxymyristoyl]-N-acetylglucosamine deacetylase (LpxC) represent a promising class of novel antibiotics, selectively combating Gram-negative bacteria. In order to elucidate the impact of the hydroxymethyl groups of diol (S,S)-4 on the inhibitory activity against LpxC, glyceric acid ethers (R)-7a, (S)-7a, (R)-7b, and (S)-7b, lacking the hydroxymethyl group in benzylic position, were synthesized. The compounds were obtained in enantiomerically pure form by a chiral pool synthesis and a lipase-catalyzed enantioselective desymmetrization, respectively. The enantiomeric hydroxamic acids (R)-7b (Ki = 230 nM) and (S)-7b (Ki = 390 nM) show promising enzyme inhibition. However, their inhibitory activities do not substantially differ from each other leading to a low eudismic ratio. Generally, the synthesized glyceric acid derivatives 7 show antibacterial activities against two Escherichia coli strains exceeding the ones of their respective regioisomes 6.
- Tangherlini, Giovanni,Torregrossa, Tullio,Agoglitta, Oriana,K?hler, Jens,Melesina, Jelena,Sippl, Wolfgang,Holl, Ralph
-
p. 1032 - 1044
(2016/02/19)
-
- Total Synthesis of (-)-Isoamericanin A and (+)-Isoamericanol A
-
The enantioselective total synthesis of the biologically active 1,4-benzodioxane lignans isoamericanin A (2) and isoamericanol A (3) has been achieved in 11 and 12 steps, respectively. These benzodioxane lignan natural products, and others that contain 9-hydroxymethyl group, show a wide range of biological properties. The 1,4-benzodioxane ring was formed by an acid-catalysed cyclisation, which gave the desired trans isomer exclusively. This method will allow the synthesis of a number of benzodioxane compounds containing a 9-hydroxymethyl group The total syntheses of (-)-isoamericanin A and (+)-isoamericanol A are described. The key steps were a Mitsunobu etherification and the acid-catalysed formation of the 1,4-benzodioxane moiety with exclusive formation of the desired trans isomer.
- Pilkington, Lisa I.,Barker, David
-
p. 1037 - 1046
(2015/10/05)
-
- Total synthesis of (-)-isoamericanin A and (+)-isoamericanol A
-
The enantioselective total synthesis of the biologically active 1,4-benzodioxane lignans isoamericanin A (2) and isoamericanol A (3) has been achieved in 11 and 12 steps, respectively. These benzodioxane lignan natural products, and others that contain 9-hydroxymethyl group, show a wide range of biological properties. The 1,4-benzodioxane ring was formed by an acid-catalysed cyclisation, which gave the desired trans isomer exclusively. This method will allow the synthesis of a number of benzodioxane compounds containing a 9-hydroxymethyl group The total syntheses of (-)-isoamericanin A and (+)-isoamericanol A are described. The key steps were a Mitsunobu etherification and the acid-catalysed formation of the 1,4-benzodioxane moiety with exclusive formation of the desired trans isomer. Copyright
- Pilkington, Lisa I.,Barker, David
-
p. 1037 - 1046
(2014/03/21)
-
- Cystomanamides: Structure and biosynthetic pathway of a family of glycosylated lipopeptides from myxobacteria
-
Cystomanamides A-D were isolated as novel natural product scaffolds from Cystobacter fuscus MCy9118, and their structures were established by spectroscopic techniques including 2D NMR, LC-SPE-NMR/-MS, and HR-MS. The cystomanamides contain β-hydroxy amino acids along with 3-amino-9-methyldecanoic acid that is N-glycosylated in cystomanamide C and D. The gene cluster for cystomanamide biosynthesis was identified by gene disruption as PKS/NRPS hybrid incorporating an iso-fatty acid as starter unit and including a reductive amination step at the interface of the PKS and NRPS modules.
- Etzbach, Lena,Plaza, Alberto,Garcia, Ronald,Baumann, Sascha,Mueller, Rolf
-
supporting information
p. 2414 - 2417
(2014/05/20)
-
- Stereoselective synthesis of the C5-C18 fragment of halichomycin
-
An efficient and convergent synthesis of the C5-C18 fragment of halichomycin is reported. Butanolide fragment 6 was readily prepared stereoselectively from (R)-Roche ester through catalyst control; dienylic bromide domain 7 was synthesized from (S)-serine by substrate control. C 5-C18 fragment 2 was rapidly assembled through a stereoselective alkylation of the butanolide with the dienylic bromide, followed by functional group transformations.
- Li, Qingjiang,Mao, Shiyong,Cui, Yuxin,Jia, Yanxing
-
scheme or table
p. 4111 - 4116
(2012/06/18)
-
- Kinetic resolution of glyceraldehyde using an aldehyde dehydrogenase from Deinococcus geothermalis DSM 11300 combined with electrochemical cofactor recycling
-
Glyceraldehyde and glyceric acid are both valuable chiral starting materials. Aldehyde dehydrogenases (ALDHs) accept a broad scope of endo- and exogenous aldehydes, such as glyceraldehyde, and convert them into the corresponding carboxylic acid. Here we present cloning, overexpression and kinetic data on two ALDHs from Escherichia coli BL21 and Deinococcus geothermalis. The two ALDHs have a similar substrate scope and favor short to medium chain aldehydes, both oxidize glyceraldehyde to glyceric acid. The ALDH variant of D. geothermalis shows the higher specific activity towards glyceraldehyde and has an elevated activity optimum compared with the BL21 enzyme. The ALDH of G. geothermalis was also applied to conduct a kinetic resolution of glyceraldehyde with electrochemical cofactor recycling. .
- Wulf,Perzborn,Sievers,Scholz,Bornscheuer
-
experimental part
p. 144 - 150
(2012/05/19)
-
- Orthogonally protected glycerols and 2-aminodiols: Useful building blocks in heterocyclic chemistry
-
The efficient synthesis of orthogonally protected glycerols, 2-aminopropane-1,3-diols and 2-aminobutane-1,4-diols that can constitute useful tools in heterocyclic chemistry, is reported. These interesting tri-functionalized small synthons were easily prepared from serine or aspartic acid. In addition, these substrates can be readily transformed into their iodide derivatives in very good yields. ARKAT USA, Inc.
- Ollivier, Anthony,Goubert, Marlene,Tursun, Ahmatjan,Canet, Isabelle,Sinibaldia, Marie-Eve
-
scheme or table
p. 108 - 126
(2010/10/03)
-
- Cytotoxic halogenated macrolides and modified peptides from the apratoxin-producing marine cyanobacterium Lyngbya bouillonii from Guam
-
Collections of the marine cyanobacterium Lyngbya bouillonii from shallow patch reefs in Apra Harbor, Guam, afforded three hitherto undescribed analogues of the glycosidic macrolide lyngbyaloside, namely, 2-epi-lyngbyaloside (1) and the regioisomeric 18E- and 18Z-lyngbyalosides C (2 and 3). Concurrently we discovered two new analogues of the cytoskeletal actin-disrupting lyngbyabellins, 27-deoxylyngbyabellin A (4) and lyngbyabellin J (5), a novel macrolide of the laingolide family, laingolide B (6), and a linear modified peptide, lyngbyapeptin D (7), along with known lyngbyabellins A and B, lyngbyapeptin A, and lyngbyaloside. The structures of 1-7 were elucidated by a combination of NMR spectroscopic and mass spectrometric analysis. Compounds 1-6 were either brominated (1-3) or chlorinated (4-6), consistent with halogenation being a hallmark of many marine natural products. All extracts derived from these L. bouillonii collections were highly cytotoxic due to the presence of apratoxin A or apratoxin C. Compounds 1-5 showed weak to moderate cytotoxicity to HT29 colorectal adenocarcinoma and HeLa cervical carcinoma cells.
- Matthew, Susan,Salvador, Lilibeth A.,Schupp, Peter J.,Paul, Valerie J.,Luesch, Hendrik
-
experimental part
p. 1544 - 1552
(2010/12/25)
-
- Micropeptins from an Israeli fishpond water bloom of the cyanobacterium microcystis sp
-
Seven new natural products, micropeptin MZ845 (1), micropeptin MZ859 (2), micropeptin MZ939A (3), micropeptin MZ925 (4), micropeptin MZ939B (5), micropeptin MZ1019 (6), and micropeptin MZ771 (7), as well as two known micropeptins, cyanopeptolin S (8) and cyanopeptolin SS (9), were isolated from the hydrophilic extract of the cyanobacterium Microcystis sp. that was collected from a fishpond in Kibbutz Ma'ayan Tzvi, Israel, in July 2006. The structures of the pure natural products were elucidated using spectroscopic methods, including UV, 1D and 2D NMR, and MS techniques. The absolute configuration of the chiral centers of the compounds was determined using Marfey's method for HPLC. The inhibitory activity of the compounds was determined for the serine proteases: trypsin, chymotrypsin, thrombin, and elastase. These micropeptins inhibited trypsin with IC50's that varied between 0.6 and 24.2 μM. The SAR of these micropeptins is discussed.
- Zafrir, Ella,Carmeli, Shmuel
-
experimental part
p. 352 - 358
(2010/08/05)
-
- Degradation of 1-deoxy-d-erythro-hexo-2,3-diulose in the presence of lysine leads to formation of carboxylic acid amides
-
A novel species of amides formed from degradation of one of the most important key intermediates in Maillard hexose chemistry-1-deoxyhexo-2,3- diulose-was investigated. In 1-deoxyhexo-2,3-diulose/Nα-t-BOC- lysine reaction mixtures four amides, Nε-acetyl lysine, N ε-formyl lysine, Nε-lactoyl lysine and N ε-glycerinyl lysine, were identified and their structures verified by authentic reference standards. Amides and corresponding carboxylic acids (acetic acid, formic acid, lactic acid and glyceric acid) accumulated over time. Both Nε-lysine amides and carboxylic acids were thus determined as stable Maillard end products. Results of model incubations suggested the synthesis of amides to be mechanistically closely related to the formation of their corresponding carboxylic acids by β-dicarbonyl cleavage. Due to the different chemical properties of all the compounds monitored, various analytical strategies had to be carried out (LC-MS2, GC-MS, GC-FID, enzymatic determination).
- Smuda, Mareen,Voigt, Michael,Glomb, Marcus A.
-
experimental part
p. 6458 - 6464
(2011/08/09)
-
- Eight novel serine proteases inhibitors from a water bloom of the cyanobacterium Microcystis sp.
-
Eight new secondary metabolites, micropeptin MM836 (1), micropeptin MM850 (2), micropeptin MM916 (3), micropeptin MM932 (4), micropeptin MM978 (5), anabaenopeptin MM823 (6), anabaenopeptin MM850 (7), and anabaenopeptin MM913 (8), as well as the known anabaenopeptin B (9) were isolated from the hydrophilic extract of the cyanobacterium Microcystis sp. that was collected from a fishpond in Kibbutz Ma'agan Michael, Israel, in September 2006. The structure of the pure natural products was established by spectroscopic methods including 1D and 2D NMR, UV, and MS techniques. The absolute configuration of the chiral centers of the compounds was determined using Marfey's method. The inhibitory activity of the compounds was determined against the serine proteases, trypsin, chymotrypsin, thrombin and elastase.
- Zafrir-Ilan, Ella,Carmeli, Shmuel
-
experimental part
p. 9194 - 9202
(2011/02/22)
-
- Production of glyceric acid by gluconobacter sp. NBRC3259 using raw glycerol
-
Gluconobacter sp. NBRC3259 converted glycerol to glyceric acid (GA). The enantiomeric composition of the GA produced was a mixture of DL-forms with a 77% enantiomeric excess of d-GA. After culture conditions, such as initial glycerol concentration, types
- Habe, Hiroshi,ShimActa, Yuko,Fukuoka, Tokuma,Kitamoto, Dai,Itagaki, Masayuki,Watanabe, Kunihiro,Yanagishita, Hiroshi,Sakaki, Keiji
-
experimental part
p. 1799 - 1805
(2010/03/24)
-
- Reactivity of 1-deoxy-D-erythro-hexo-2,3-diulose; A key intermediate in the maillard chemistry of hexoses
-
Degradation of 1-deoxyhexo-2,3-diulose, a key intermediate in Maillard chemistry, in the presence of L-alanine under moderate conditions (37 and 50 °C) was investigated. Different analytical strategies were accomplished to cover the broad range of product
- Voigt, Michael,Glomb, Marcus A.
-
experimental part
p. 4765 - 4770
(2010/06/14)
-
- Reaction pathways of glucose oxidation by ozone under acidic conditions
-
The ozonation of d-glucose-1-13C, 2-13C, and 6-13C was carried out at pH 2.5 in a semi-batch reactor at room temperature. The products present in the liquid phase were analyzed by GC-MS, HPAEC-PAD, and 13C NMR s
- Marcq, Olivier,Barbe, Jean-Michel,Trichet, Alain,Guilard, Roger
-
experimental part
p. 1303 - 1310
(2009/12/01)
-
- Total synthesis and proof of relative stereochemistry of (-)-aureonitol
-
(Chemical Equation Presented) Two trisubstituted epimeric tetrahydrofurans, 1 and 2, have been synthesized in order to confirm the relative stereochemistry in the natural product aureonitol. The key step in the synthesis of 1 and 2 involved a stereoselective intramolecular allylation of an allylsilane with an aldehyde, which introduced the stereotriad in the five-membered ring. The major tetrahydrofuran diastereoisomer 18 from this cyclization reaction was subsequently elaborated to tetrahydrofuran 1. Its 3-epimer (2) was then prepared from 1 via an oxidation-reduction sequence. Compound 1 exhibits identical 1H NMR data to those reported for aureonitol, which was isolated from Helichrysum aureonitons by Bohlmann in 1979, whereas the 1H NMR data for 2 are markedly different. The 1H NMR data (in CDCl3, CD3OD, and C6D6) and 13C NMR data (in CDCl3) for 1 are also identical with those reported for a natural product isolated from various Chaetomium sp. by Abraham, Seto, and Teuscher. These findings support Abraham's conclusion that the structure of aureonitol should be revised from 2 to 1. The enantioselective synthesis of 1 has also confirmed that (-)-aureonitol isolated by Abraham contains the (2S,3R,4S) absolute configuration of stereocenters on the tetrahydrofuran ring.
- Jervis, Peter J.,Cox, Liam R.
-
p. 7616 - 7624
(2008/12/22)
-
- d- and l-Serine, useful synthons for the synthesis of 24-hydroxyvitamin D3 metabolites. A formal synthesis of 1α,24R,25-(OH)3-D3, 24R,25-(OH)2-D3 and 24S,25-(OH)2-D3
-
d- and l-Serine have been used for the enantioselective synthesis of tosylates 7a and 7b, useful building blocks for the synthesis of triols 5a and 5b which have already been obtained via a diastereoselective synthesis and used for the synthesis of 2a, 2b and 2c. We have thus performed a formal synthesis of 24S,25-(OH)2-D3, 24R,25-(OH)2-D3 and 1α,24R,25-(OH)3-D3.
- Fernandez, Carlos,Gándara, Zoila,Gómez, Generosa,Covelo, Berta,Fall, Yagamare
-
p. 2939 - 2942
(2008/02/03)
-
- Synthetic studies towards 4,10-diaza-1,7-dioxaspiro[5.5]undecanes: access to 3-aza-6,8-dioxabicyclo[3.2.1]octan-2-one and 2H-1,4-oxazin-3(4H)-one frameworks
-
Synthetic approaches towards 4,10-diaza-1,7-dioxaspiro[5.5]undecanes starting from 1,3-dichloroacetone and solketal derivatives are explored. The method relies on the preparation of a key bis-substituted dihydroxy-protected oxime, which would undergo a final acidic deprotection-spiroacetalization process. Although the desired diazaspiroketal framework could not be obtained, our conditions led to the unexpected 3-aza-6,8-dioxabicyclo[3.2.1]octan-2-one 18 or to the oxazinone 32 in good yields.
- Goubert, Marlène,Toupet, Lo?c,Sinibaldi, Marie-Eve,Canet, Isabelle
-
p. 8255 - 8266
(2008/02/08)
-
- Lyngbyastatins 5-7, potent elastase inhibitors from Floridian marine cyanobacteria, Lyngbya spp.
-
Three new analogues of dolastatin 13, termed lyngbyastatins 5-7 (1-3), were isolated from two different collections of marine cyanobacteria, Lyngbya spp., from South Florida. Their planar structures were deduced by a combination of NMR techniques, and the absolute configurations were established by modified Marfey's analysis of the acid hydrolyzates. The related cyclodepsipeptide somamide B (4), previously reported from a Fijian cyanobacterium, has also been found in one of the extracts, and its absolute stereochemistry was unambiguously assigned for the first time. Compounds 1-4 were found to selectively inhibit elastase over several other serine proteases, with IC50 values for porcine pancreatic elastase ranging from 3 to 10 nM.
- Taori, Kanchan,Matthew, Susan,Rocca, James R.,Paul, Valerie J.,Luesch, Hendrik
-
p. 1593 - 1600
(2008/03/13)
-
- Synthetic studies of the cyclic depsipeptides bearing the 3-amino-6-hydroxy-2-piperidone (Ahp) unit. Total synthesis of the proposed structure of micropeptin T-20
-
The first total synthesis of a cyclic depsipeptide possessing the 3-amino-6-hydroxy-2-piperidone (Ahp) unit was successfully achieved in a convergent manner by the oxidative construction of the Ahp unit at the later stage of the synthesis. This synthetic work provides data indicating that the structure of the target Ahp-depsipeptide, micropeptin T-20, should be re-examined.
- Yokokawa, Fumiaki,Inaizumi, Akiko,Shioiri, Takayuki
-
p. 1459 - 1480
(2007/10/03)
-
- Kinetics and mechanism of oxidation of D-fructose and D-glucose by sodium salts of N-(chloro)-mono/di-substituted benzenesulfonamides in aqueous alkaline medium
-
In an effort to introduce N-chloroarylsulfonamides of different oxidizing strengths, nine sodium salts of mono- and di-substituted N- chloroarylsulfonamides are employed as oxidants for studying the kinetics of oxidation of D-fructose and D-glucose in aqueous alkaline medium. The results are analyzed along with those by the sodium salts of N-chlorobenzenesulfonamide and N-chloro-4-methylbenzenesulfonamide. The reactions show first-order kinetics each in [oxidant], [Fru/Glu], and [OH-]. The rates slightly increase with increase in ionic strength of the medium. Further, the rate of oxidation of fructose is higher by 4 to 5 times than that of the glucose oxidation, by the same oxidant. Similarly, Ea values for glucose oxidations are higher by about 1.5 times the Ea values for fructose oxidations. The results have been explained by a plausible mechanism, and the related rate law deduced. The significant changes in the kinetics and thermodynamic data are observed with change of substituent in the benzene ring. It is because Cl + is the effective oxidizing species in the reactions of N-chloroarylsulfonamides. The oxidative strengths of the latter therefore depend on the ease with which Cl+ is released from them. The ease with which Cl+ is released from N-chloroarylsulfonamides depends on the electron density of the nitrogen atom of the sulfonamide group, which in turn depends on the nature of the substituent in the benzene ring. The following Hammett equations are valid for the oxidation of fructose and glucose, log kobs = -3.13 + 0.54 σ ρ and log kobs = -3.81 + 0.28 σ ρ, respectively. The enthalpies and entropies of activations for oxidations by all the N-chloroarylsulfonamides correlate well with isokinetic temperatures of 301 K and 299 K, for fructose and glucose oxidations, respectively. The effect of substitution in the oxidants on the Ea and log A for the oxidations is also considered.
- Gowda, B. Thimme,Damodara,Jyothi
-
p. 572 - 582
(2007/10/03)
-
- Inhibition of the severe acute respiratory syndrome 3CL protease by peptidomimetic α,β-unsaturated esters
-
The proteolytic processing of polyproteins by the 3CL protease of severe acute respiratory syndrome coronavirus is essential for the viral propagation. A series of tripeptide α,β-unsaturated esters and ketomethylene isosteres, including AG7088, are synthesized and assayed to target the 3CL protease. Though AG7088 is inactive (IC50 > 100 μM), the ketomethylene isosteres and tripeptide α,β-unsaturated esters containing both P1 and P2 phenylalanine residues show modest inhibitory activity (IC50 = 11-39 μM). The Phe-Phe dipeptide inhibitors 18a-e are designed on the basis of computer modeling of the enzyme-inhibitor complex. The most potent inhibitor 18c with an inhibition constant of 0.52 μM is obtained by condensation of the Phe-Phe dipeptide α,β-unsaturated ester with 4-(dimethylamino)cinnamic acid. The cell-based assays also indicate that 18c is a nontoxic anti-SARS agent with an EC50 value of 0.18 μM.
- Shie, Jiun-Jie,Fang, Jim-Min,Kuo, Tun-Hsun,Kuo, Chih-Jung,Liang, Po-Huang,Huang, Hung-Jyun,Wu, Yin-Ta,Jan, Jia-Tsrong,Cheng, Yih-Shyun E.,Wong, Chi-Huey
-
p. 5240 - 5252
(2007/10/03)
-
- Kinetics and mechanism of oxidation of D-ribose, D-glucose, and D-fructose by dichloroisocyanuric acid in aqueous acetic acid-perchloric acid mixtures catalyzed by Ru(III)
-
The kinetics and mechanism of oxidation of D-ribose, D-glucose, and D-fructose by dichloroisocyanuric acid (DCICA) in aqueous acetic acid-perchloric acid mixtures catalyzed by Ru(III) have been investigated. The oxidation of D-ribose and D-glucose has the following kinetic orders: first order in oxidant, first order in Ru(III), and zeroth order in substrates and H+. The D-fructose exhibits a different behavior: zeroth order in oxidant, first order in catalyst, and zeroth order in substrate and H+. The results have been rationalized by postulating an active Ru(V) species, which oxidizes the pentose and hexose in a fast step to products. D-fructose reacts by complexation with Ru(III) in an equilibrium step, and the complex breaks down into products without involvement of DCICA. The Ru(III) species is regenerated by DCICA in a fast step, which acts as a catalyst continuously. The mechanistic pathway seems to be different in aldose and ketose systems. It is presumed that β-anomer in all cases is reacting with either Ru(V) or Ru(III) species, yielding products. The corresponding lactones are the products in each case along with formaldehyde in case of D-fructose under the conditions of [sugar] > [DCICA].
- Madhavi,Sundar, B. Syama,Radhakrishnamurti
-
p. 1579 - 1585
(2007/10/03)
-
- Synthesis and CB1 receptor activities of novel arachidonyl alcohol derivatives
-
Novel derivatives of arachidonyl alcohol were synthesized and evaluated for their CB1 receptor activity by [35S]GTPγS assay using rat cerebellar membranes.
- Parkkari, Teija,Savinainen, Juha R.,Rauhala, Anu L.,Tolonen, Tiina L.,Nevalainen, Tapio,Laitinen, Jarmo T.,Gynther, Jukka,Jaervinen, Tomi
-
p. 3231 - 3234
(2007/10/03)
-
- Oxidation of threose-series, pentose and hexoses by N-arylbromosulphonamides in alkaline medium
-
Kinetic studies of the oxidation of D-galactose, L-sorbose and D-xylose by bromamine-T (sodium-N-bromo-p-toluenesulphonamide or BAT) and bromamine-B (sodium-N-bromobenzene sulphonamide or BAB) in alkaline medium has been investigated at 303 K. The rate of the reaction is first order both with respect to oxidant and sugar, and second order with respect to [HO-]. The addition of the reaction product p-toluenesulphonamide (PTS) or benzenesulphonamide (BSA) and the variation of ionic strength of the medium have no effect on the rate. The rate decreases with the decrease in dielectric constant of the medium and values of dAB, the size of activated complex are calculated. Proton inventory studies in H2O · D2O mixtures suggest a single transition state. Product analysis for D-galactose, L-sorbose and D-xylose reveal that hexoses give mainly mixture of lyxonic and threonic acids with minor proportions of hexonic, xylonic and glyceric acids, whereas xylose yields a mixture of lyxonic, threonic and glyceric acids with minor amounts of xylonic and hexonic acids. From the results of kinetic studies, reaction stoichiometry and product analysis, a possible mechanism for the oxidation of threose-series sugars is suggested.
- Shashikala,Rangappa
-
p. 1907 - 1914
(2007/10/03)
-
- A novel mechanism for the oxidation of erythro-series pentoses and hexoses by N-arylbromosulphonamides in alkaline medium
-
Kinetic studies of the oxidation of D-mannose, D-glucose, D-fructose, L-arabinose and D-ribose by bromamine-T (sodium N-bromo-p-toluenesulphonamide or BAT) and bromamine-B (sodium N-bromobenzenesulphonamide or BAB) in alkaline medium were investigated at 30°C. The rate of the reaction was first order both with respect to the oxidant and the sugar and second order with respect to [HO-]. The addition of the reaction product, p-toluenesulphonamide (PTS) or benzenesulphonamide (BSA), and the variation of ionic strength of the medium have no effect on the rate. The rate decreases with decrease in dielectric constant of the medium and values of dAB, the size of activated complex, were calculated. Proton inventory studies were made in H2O-D2O mixtures. The activation parameters of the reaction were computed from Arrhenius plots. HPLC and GLC-MS analysis of the products indicated that the sugars were oxidized to a mixture of aldonic acids consisting of arabinonic, ribonic, erythronic and glyceric acids. A general mechanism consistent with the observed results has been proposed.
- Shashikala,Rangappa
-
p. 219 - 234
(2007/10/03)
-
- Synthetic studies of micropeptin T-20, a novel 3-amino-6-hydroxy-2-piperidone (Ahp)-containing cyclic depsipeptide
-
The synthetic studies of micropeptin T-20 including the late installation of the Ahp (3-amino-6-hydroxy-2-piperidone) residue through oxidation and cyclization of a homoserine to the requisite hemiaminal are described.
- Yokokawa, Fumiaki,Inaizumi, Akiko,Shioiri, Takayuki
-
p. 5903 - 5908
(2007/10/03)
-
- Kinetics and mechanism of oxidation of hexoses by bromamine-T in alkaline medium
-
The kinetics and mechanism of oxidation of D-glucose and D-mannose with bromamine-T in alkaline medium have been studied and the rate = κ[BAT][sugar][OH-]2, is observed. The rate of the reaction is influenced by a change in ionic strength of the medium and the dielectric effect is found to be positive. The latter enables the computation of dAB, the size of the activated complex. Proton inventory studies are made for the reactions in H2O-D2O mixtures. Activation parameters are calculated from the Arrhenius plots. The product analyses indicates that the sugars are oxidized to a mixture of aldonic acids, consisting of arabinonic, ribonic, erythronic and glyceric acids. A mechanism consistent with the observed kinetics has been proposed.
- Prashanth,Mantelingu,Murthy, A. S. Ananda,Anitha,Rangaswamy,Rangappa
-
p. 241 - 245
(2007/10/03)
-
- Asymmetric total synthesis of Taxol
-
The asymmetric total synthesis of Taxol was achieved by way of B to BC to ABC to ABCD ring construction. Optically active 8-membered ring enones 1 and 2 corresponding to the B ring of Taxol have been synthesized in high yields from the linear precursors 28 and 32, respectively, by intramolecular aldol cyclization using SmI2. The optically active linear polyoxy compounds 28 and 32 were obtained by way of diastereoselective aldol reaction between aldehyde 4 and ketene silyl acetal 8 catalyzed by MgBr2 · OEt2. The chiral pentanal 4 was synthesized either by asymmetric aldol reaction of achiral aldehyde 7 and ketene silyl acetal 8 by means of a chiral Lewis acid or by diastereoselective aldol reaction between the chiral aldehyde 16, derived from L-serine, and the lithium enolate derived from methyl isobutyrate. Optically active bicyclo[6.4.0]dodecanone 38β, corresponding to the BC ring system of Taxol, was prepared from 8-membered ring enone 2 in high yield by stereoselective Michael addition and successive intramolecular aldol cyclization. Furthermore, baccatin III, the ABCD ring system of Taxol, was efficiently synthesized from the BC ring system 38β by successive construction of the A and D rings by intramolecular pinacol coupling cyclization, introduction of the C-13 hydroxyl group and an oxetane-forming reaction. Finally, the total synthesis of Taxol was accomplished by dehydration condensation between a protected N-benzoylphenylisoserine 70 or 75 and 7-TES baccatin III, prepared from baccatin III. Taxol side chains 70, 73, 75, and 77, optically active protected N-benzoylphenylisoserines, were synthesized by enantioselective aldol reaction from two achiral starting materials, benzaldehyde and an enol silyl ether 65 derived from S-ethyl benzyloxyethanethioate.
- Mukaiyama, Teruaki,Shiina, Isamu,Iwadare, Hayato,Saitoh, Masahiro,Nishimura, Toshihiro,Ohkawa, Naoto,Sakoh, Hiroki,Nishimura, Koji,Tani, Yu-Ichirou,Hasegawa, Masatoshi,Yamada, Koji,Saitoh, Katsuyuki
-
p. 121 - 161
(2007/10/03)
-
- Electrooxidation of mesoerythritol on platinum, modified or not by adatoms, in acid medium
-
The electrocatalytic oxidation of meso-erythritol has been studied in 0.1 M HClO4 on platinum and on adatoms modified platinum. Preliminary investigations by cyclic voltammetry showed that erythritol was not reactive on a Pt electrode. Underpotential deposition of lead or thallium adatoms at platinum allowed to increase significantly the current densities. Long-time electrolyses were carded out using a three potential plateau program with different values of the oxidation potentials. Chromatographic analyses showed that the oxidation of erythritol led mainly to erythrose, erythrulose and to erythronic acid. Otherwise, electrolysis of erythritol on a Pt-Tl modified electrode orientated selectively the distribution of the reaction products towards the formation of erythrulose.
- Cherqaoui,Chbihi,Takky,Kokoh,Leger,Lamy
-
p. 510 - 521
(2007/10/03)
-
- Synthesis of (S)-1-(1H-indol-4-yloxy)-3[4-(3-methoxyphenyl)-4- hydroxypiperidin-1-yl]-propan-2-ol (LY333068) succinate, and its 3-[14C]- isotopomer based on chiral glycerol-[14C] derivatives
-
The 3-[14C]-isotopomer of (S)-1-(1H-indol-4-yloxy)-3-[4-(3- methoxyphenyl)-4-hydroxypiperidin-1-yl]-propan-2-ol (LY333068), a 5HT(1A) antagonist, was prepared in 10 steps and 8.2% radiochemical yield from (L)- serine-[3-14C]. Deamination, esterification, and protection of the resulting diol gave methyl (R)2,2-dimethyl-1,3-dioxolane-4-carboxylate-[3- 14C], as a chiral and radiolabeled building block, which then was subsequently coupled with 4-hydroxyindole and 4-(3-methoxyphenyl)-4- hydroxypiperidine to give the titled product with 99.4% radiochemical purity.
- Czeskis, Boris A.
-
p. 465 - 475
(2007/10/03)
-
- Sodium N-Chlorobenzenesulfonamide as a Selective Oxidant for Hexosamines in Alkaline Medium: A Kinetic and Mechanistic Study
-
Oxidation of D-mannosamine (1), D-glucosamine (2), and D-galctosamine (3) by sodium N-chlorobenzenesulfonamide or chloramine-B (CAB) at 313 K is followed by a shortening of carbon chain and obeys the rate law, rate = k[CAB][sugar][HO-]x, where x is less than unity. The products are arabinonic acid, ribonic acid, and erythronic acid for 1 and 2 with smaller amounts of glyceric and hexonic acids, while lyxonic and threonic acids are predominant in the oxidation of 3 with smaller amounts of glyceric and hexonic acids. Proton inventory studies made in a H2)O-D2)O mixture point toward a single transition state. In the proposed mechanism the alkoxy anion (S-) of the hexosamine formed in a base-catalyzed reaction at C-1 carbon is subjected to an electrophilic rate-limiting attack by Cl+ of the oxidant. The hexonic acid formed is decarboxylated with loss of ammonia to form the respective pentose, which is further converted into the corresponding pentonic acid. The breaking of the bond between C-1 and C-2 carbons in pentose yields tetronic acids. The thermodynamic parameters for sugar alkoxy anion formation and activation parameters for the rate-limiting step have been evaluated.
- Rangappa, Kanchugarakoppal S.,Raghavendra, Manikanahally P.,Mahadevappa, Dandinasivara S.,Channegowda, Doddegowda
-
p. 531 - 536
(2007/10/03)
-
- Kinetics and mechanism of oxidation of erythro-series pentoses and hexoses by N-chloro-p-toluenesulfonamide
-
The kinetics and mechanism of oxidation of D-glucose, D-mannose, D- fructose, D-arabinose, and D-ribose with chloramine-T in alkaline medium were studied. The rate law, rate = k [Chloramine-T] [Sugar] [HO-]2, was observed. The rate of the reaction was influenced by a change in ionic strength of the medium, and the dielectric effect was found to be negative. The latter enabled the computation of d(AB), the size of the activated complex. The reaction rate was almost doubled in deuterium oxide. Activation energies were calculated from the Arrhenius plots. HPLC and GLC-MS analyses of the products indicated that the sugars were oxidized to a mixture of aldonic acids, consisting of arabinonic, ribonic, erythronic, and glyceric acids. Based on these data, a plausible mechanism involving the aldo-enolic anions of pentoses and keto-enolic anions of hexoses is suggested.
- Rangappa, Kanchugarakoppal S.,Raghavendra, Manikanahally P.,Mahadevappa, Dandinasivara S.,Gowda, D. Channe
-
-
- Oxidation of erythrose series sugars by sodium N-chlorobenzenesulphonamide in alkaline medium : A kinetic study
-
The kinetics of oxidation of D-glucose, D-mannose, D-fructose, D-arabinose, and D-ribose, with sodium N-chlorobenzenesulphonamide (chloramine-B or CAB) in alkaline medium have been studied at 35°C and the rate law, rate = κ′ [CAB] [Sugar] [OH-]2 is observed. The rate of reaction is influenced by a change in ionic strength of the medium, and the dielectric effect is negative. The solvent isotope studies in D2O show that the rate is almost doubled in heavy water. HPLC and GLC-MS analyses of the products indicated that the erythrose-series sugars are oxidized to a mixture of aldonic acids consisting of arabinonic, ribonic, erythronic, and glyceric acids in varying proportions. Based on these data, a mechanism involving the aldoenolic anions of pentoses and keto-enolic anions of hexoses is suggested.
- Raghavendra,Rangappa,Mahadevappa,Channe Gowda
-
p. 783 - 792
(2007/10/03)
-
- Kinetics and mechanism of oxidation of D-mannosamine by sodium N-chloro-p-toluenesulphonamide in alkaline medium
-
The kinetics of oxidation of D-mannosamine (S) to the aldonic acids by sodium N-chloro-p-toluenesulphonamide or chloramine-T (CAT) in the presence of alkali at 40°C follows the rate law d[CAT]/dt=k[CAT] [S] [HO-]x, where x2O)/k(H2O) was found to be 1.62. The mechanism assumes stepwise, the formation of sugar alkoxy anion, followed by a rate limiting complexation with oxidant resulting in the formation of the respective pentose through decarboxylation and deammation. The latter is oxidised to arabonic, ribonic, erythronic and glyceric acids. A mechanism involving the reaction of enolanion of sugar with the oxidant in the rate limiting step is proposed.
- Rangappa,Mahadevappa,Raghavendra
-
p. 890 - 896
(2007/10/03)
-
- Oxidation of methyl and n-octyl α-D-glucopyranoside over graphite-supported platinum catalysts: Effect of the alkyl substituent on activity and selectivity
-
The oxidation of methyl and n-octyl α-D-glucopyranoside to methyl and n-octyl α-D-glucopyranosiduronate with molecular oxygen over a graphite-supported platinum catalyst was investigated. An increase of the length of the n-alkyl substituent from methyl to n-octyl resulted in a ten-fold decrease of the catalyst activity and an increase of the selectivity at pH 8.0 and 323 K. The selectivity decreased with increasing pH. The lower activity for a longer n-alkyl substituent is attributed to steric effects upon adsorption on the platinum surface and not to internal diffusion limitations. A tentative reaction scheme is presented, which describes the formation of side products through oxidation of secondary hydroxyl groups, ring cleavage and hydrolysis. Major side products are mono- and di-carboxylates with 2, 4, and 6 carbon atoms and mono-carboxylates, resulting from the oxidation of the alkyl substituent. C-C-Bond cleavage mainly occurs between C-2 and C-3 or C-4 and C-5, the former being less important for a longer alkyl substituent. The higher selectivity for a longer alkyl substituent is attributed to its protecting ability against hydrolysis and the exposition of neighboring hydroxyl groups to the platinum surface.
- Vleeming, Johannes H.,Kuster, Ben F.M.,Marin, Guy B.
-
p. 175 - 183
(2007/10/03)
-
- OXIDATION OF MONOSACCHARIDES WITH OXYGEN IN ALKALINE SOLUTION. SEPARATION, IDENTIFICATION AND ESTIMATION OF THE ALDONIC ACIDS PRODUCED BY LIQUID CHROMATOGRAPHY
-
A reliable liquid chromatographic method has been developed for the separation, identification and estimation of the products formed when saccharides are oxidized in alkaline solution with oxygen.The technique was then used to quantitate the acids produced when glucose is subjected to such an oxidation.The Bio-Rad cation exchange column HPX-87H(1+), when eluted with 0.01 N H2SO4 and attached to a UV detector, was found to be satisfactory.Quantitative estimation of the products formed during the oxidation of glucose was achieved by withdrawing aliquots from the reaction mixture and injecting them directly into the chromatographic system.It was found that about 90percent of the oxidation products formed were produced via a 1,2-enediol and less than 10percent via a 2,3-enediol.The results confirmed the mechanism proposed by Isbell to account for the acids produced.
- Shalaby, M. Ashraf,Isbell, Horace S.,Khadem, Hassan S. El
-
p. 429 - 438
(2007/10/02)
-
- On the factors controlling the structural specificity and stereospecificity of the L-lactate dehydrogenase from Bacillus stearothermophilus: Effects of Gln102→Arg and Arg171→Trp/Tyr double mutations
-
The factors determining the L-stereospecificity of the L-lactate dehydrogenase from Bacillus stearolhermophilus have been probed by introducing Arg171Trp/Tyr and Gln 102Arg mutations. These changes preclude normal 2-keto acid substrate binding via an Arg171-COO- electrostatic interaction and are positioned to induce a reversal of the natural substrate binding mode, thereby leading to D-2-hydroxy acid formation. However, the L-stereospecificities of the mutant enzymes remain unchanged, showing that there are important fail-safe stereospecificity determinants that take over when the key Arg171-COO- binding interaction is removed. The effects of the mutations on structural specificity are approximately additive, resulting in the broad 2-keto acid specificity of the wild-type enzyme being changed to give catalysts highly selective for the dicarboxylic substrate oxalacetate.
- Kallwass, Helmut K.W.,Hogan, James K.,Macfarlane, Emma L.A.,Martichonok, Valeri,Partis, Wendy,Kay, Cyril M.,Gold, Marvin,Bryan Jones
-
p. 10704 - 10710
(2007/10/02)
-
- Polyfunctional (R)-2-Hydroxycarboxylic Acids by Reduction of 2-Oxo Acids with Hydrogen Gas or Formate and Resting Cells of Proteus vulgaris
-
Various (R)-2-hydroxy acids such as (R)-2-hydroxy-3-enoic-, 3,5-dienoic-, 4-oxo-, (R,S)-3-hydroxy and some others were prepared on a scale up to 0.12 mol by biocatalytic reduction of the corresponding 2-oxo acids with P. vulgaris and hydrogen gas and/or formate as electron donors.With the exception of the 2-hydroxy-4-oxo acids it could be proved that the enantiomeric excess is >97 percent.For the 4-oxo derivatives this enantiomeric excess can be assumed.The yields of isolated products are high because they were isolated from rather small amounts of biocatalyst and low buffer concentrations.Product concentrations in the range of 0.1- 0.24 M were obtained.For 1 mmol of product formation in 15-20 h about 20-40 mg (dry weight) of P. vulgaris cells are necessary.
- Schummer, Anita,Yu, Hongtao,Simon, Helmut
-
p. 9019 - 9034
(2007/10/02)
-
- S-2-Hydroxyacylglutathione-Derivatives: Enzymatic Preparation, Purification and Characterisation
-
S-2-Hydroxyacylglutathione derivatives have been prepared by enzymatic synthesis from α-oxoaldehydes and reduced glutathione in the presence of glyoxalase I.S-D-Lactoylglutathione, S-D-mandelylglutathione, S-glycolylglutathione and S-L-glyceroylglutathione were prepared from methylglyoxal, phenylglyoxal, glyoxal and hydroxypyruvaldehyde, respectively.They were purified by ion exchange chromatography on Dowex 1 on a gram scale.Analytical data and re-evaluated extinction coefficients for these compounds are presented.The method described provides a reliable, large-scale procedure for the preparation and purification of S-acylglutathiones of increasing biological and pharmacological interest.
- Clelland, James D.,Thornalley, Paul J.
-
p. 3009 - 3016
(2007/10/02)
-
- Intermediates for preparing optically active carboxylic acids
-
A process is described for preparing optically active alpha-arylalkanoic acids consisting of rearranging an optically active ketal of formula STR1 in which the substituents have the meaning given in the description of the invention.
- -
-
-