28305-26-2Relevant articles and documents
carba Nicotinamide Adenine Dinucleotide Phosphate: Robust Cofactor for Redox Biocatalysis
D?ring, Manuel,Sieber, Volker,Simon, Robert C.,Tafertshofer, Georg,Zachos, Ioannis
supporting information, p. 14701 - 14706 (2021/05/13)
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.
Alcohols as Latent Hydrophobes: Entropically Driven Uptake of 1,2-Diol Functionalized Ligands by a Porous Capsule in Water
Chakraborty, Sourav,Shnaiderman Grego, Alina,Garai, Somenath,Baranov, Mark,Müller, Achim,Weinstock, Ira A.
supporting information, p. 9170 - 9174 (2019/06/21)
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.
Synthesis of Phosphatidylserine and Its Stereoisomers: Their Role in Activation of Blood Coagulation
Mallik, Suman,Prasad, Ramesh,Bhattacharya, Anindita,Sen, Prosenjit
supporting information, p. 434 - 439 (2018/05/23)
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.
Synthesis of macrocyclic precursors of the vioprolides
Butler, Eibhlin,Florentino, Lucia,Cornut, Damien,Gomez-Campillos, Gonzalo,Liu, Hao,Regan, Andrew C.,Thomas, Eric J.
, p. 6935 - 6960 (2018/10/17)
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.
Samholides, Swinholide-Related Metabolites from a Marine Cyanobacterium cf. Phormidium sp.
Tao, Yiwen,Li, Pinglin,Zhang, Daojing,Glukhov, Evgenia,Gerwick, Lena,Zhang, Chen,Murray, Thomas F.,Gerwick, William H.
, p. 3034 - 3046 (2018/03/25)
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.
Chemical constituents and biological activities of Viburnum macrocephalum f. keteleeri
Shao, Jian-Hua,Chen, Jia,Xu, Xiao-Qing,Zhao, Chun-Chao,Dong, Zi-Ling,Liu, Wen-Yan,Shen, Jie
, p. 1 - 5 (2018/02/06)
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.
Deinococcucins A-D, Aminoglycolipids from Deinococcus sp., a Gut Bacterium of the Carpenter Ant Camponotus japonicus
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)
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.
Serinolamides and Lyngbyabellins from an Okeania sp. Cyanobacterium Collected from the Red Sea
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)
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.
Synthesis and biological evaluation of enantiomerically pure glyceric acid derivatives as LpxC inhibitors
Tangherlini, Giovanni,Torregrossa, Tullio,Agoglitta, Oriana,K?hler, Jens,Melesina, Jelena,Sippl, Wolfgang,Holl, Ralph
, p. 1032 - 1044 (2016/02/19)
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.
Total Synthesis of (-)-Isoamericanin A and (+)-Isoamericanol A
Pilkington, Lisa I.,Barker, David
, p. 1037 - 1046 (2015/10/05)
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.
