612-05-5Relevant articles and documents
Positional specificity of Flavobacterium johnsoniae acetylxylan esterase and acetyl group migration on xylan main chain
Puchart, Vladimír,Gjermansen, Morten,Mastihubová, Mária,M?rkeberg Krogh, Kristian B.R.,Biely, Peter
, (2020/01/09)
A new Flavovacterium johnsoniae isolate encodes an enzyme that is essentially identical with a recently discovered novel acetylxylan esterase, capable of liberating 3-O-acetyl group from 4-O-methyl-D-glucuronic acid-substituted xylopyranosyl (Xylp) residues (Razeq et al., 2018). In addition to deesterification of the 2-O-MeGlcA-substituted Xylp residues in acetylglucuronoxylan, the enzyme acts equally well on doubly acetylated Xylp residues from which it liberates only the 3-O-acetyl groups, leaving the 2-O-acetyl groups untouched. 3-O-Monoacetylated Xylp residues are attacked with a significantly reduced affinity. The resulting 2-O-acetylated xylan was used to investigate for the first time the migration of the 2-O-acetyl group to position 3 within the polysaccharide. In contrast to easy acetyl group migration along the monomeric xylopyranosides or non-reducing-end terminal Xylp residues of xylooligosaccharides, such a migration in the polymer required much longer heating at 100 °C. The specificity of the xylan 3-O-deacetylase was, however, no so strict on acetylated methyl and 4-nitrophenyl xylopyranosides.
Synthesis and structural insights into the binding mode of the albomycin δ1 core and its analogues in complex with their target aminoacyl-tRNA synthetase
De Graef, Steff,Gadakh, Bharat,Nautiyal, Manesh,Pang, Luping,Strelkov, Sergei V.,Van Aerschot, Arthur,Vondenhoff, Gaston,Weeks, Stephen D.
, (2020/07/21)
Despite of proven efficacy and well tolerability, albomycin is not used clinically due to scarcity of material. Several attempts have been made to increase the production of albomycin by chemical or biochemical methods. In the current study, we have synthesized the active moiety of albomycin δ1 and investigated its binding mode to its molecular target seryl-trna synthetase (SerRS). In addition, isoleucyl and aspartyl congeners were prepared to investigate whether the albomycin scaffold can be extrapolated to target other aminoacyl-tRNA synthetases (aaRSs) from both class I and class II aaRSs, respectively. The synthesized analogues were evaluated for their ability to inhibit the corresponding aaRSs by an in vitro aminoacylation experiment using purified enzymes. It was observed that the diastereomer having the 5′S, 6′R-configuration (nucleoside numbering) as observed in the crystal structure, exhibits excellent inhibitory activity in contrast to poor activity of its companion 5′R,6′S-diasteromer obtained as byproduct during synthesis. Moreover, the albomycin core scaffold seems well tolerated for class II aaRSs inhibition compared with class I aaRSs. To understand this bias, we studied X-ray crystal structures of SerRS in complex with the albomycin δ1 core structure 14a, and AspRS in complex with compound 16a. Structural analysis clearly showed that diastereomer selectivity is attributed to the steric restraints of the active site of SerRS and AspRS.
Methyl glycosides via Fischer glycosylation: translation from batch microwave to continuous flow processing
Aronow, Jonas,Stanetty, Christian,Baxendale, Ian R.,Mihovilovic, Marko D.
, p. 11 - 19 (2018/11/27)
Abstract: A continuous flow procedure for the synthesis of methyl glycosides (Fischer glycosylation) of various monosaccharides using a heterogenous catalyst has been developed. In-depth analysis of the isomeric composition was undertaken and high consistency with corresponding results observed under microwave heating was obtained. Even in cases where addition of water was needed to achieve homogeneity—a prerequisite for the flow experiments—no detrimental effect on the conversion was found. The scalability was demonstrated on a model case (mannose) and as part of the target-oriented synthesis of d-glycero-d-manno heptose, both performed on multigram scale.
Biosynthetic Origin of the Atypical Stereochemistry in the Thioheptose Core of Albomycin Nucleoside Antibiotics
Ushimaru, Richiro,Liu, Hung-Wen
supporting information, (2019/02/14)
Albomycins are peptidyl thionucleoside natural products that display antimicrobial activity against clinically important pathogens. Their structures are characterized by a thioheptose with atypical stereochemistry including a d-xylofuranose ring modified with a d-amino acid moiety. Herein it is demonstrated that AbmH is a pyridoxal 5′-phosphate (PLP)-dependent transaldolase that catalyzes a threo-selective aldol-type reaction to generate the thioheptose core with a d-ribofuranose ring and an l-amino acid moiety. The conversion of l-to d-amino acid configuration is catalyzed by the PLP-dependent epimerase AbmD. The d-ribo to d-xylo conversion of the thiofuranose ring appears according to gene deletion experiments to be mediated by AbmJ, which is annotated as a radical S-adenosyl-l-methionine (SAM) enzyme. These studies establish several key steps in the assembly of the thioheptose core during the biosynthesis of albomycins.
Simultaneous Conversion of C5 and C6 Sugars into Methyl Levulinate with the Addition of 1,3,5-Trioxane
Lyu, Xilei,Zhang, Zihao,Okejiri, Francis,Chen, Hao,Xu, Mai,Chen, Xujie,Deng, Shuguang,Lu, Xiuyang
, p. 4400 - 4404 (2019/09/09)
The simultaneous conversion of C5 and C6 mixed sugars into methyl levulinate (MLE) has emerged as a versatile strategy to eliminate costly separation steps. However, the traditional upgrading of C5 sugars into MLE is very complex as it requires both acid-catalyzed and hydrogenation processes. This study concerns the development of a one-pot, hydrogenation-free conversion of C5 sugars into MLE over different acid catalysts at near-critical methanol conditions with the help of 1,3,5-trioxane. For the conversion of C5 sugars over zeolites without the addition of 1,3,5-trioxane, the MLE yield is quite low, owing to low hydrogenation activity. The addition of 1,3,5-trioxane significantly boosts the MLE yield by providing an alternative conversion pathway that does not include the hydrogenation step. A direct comparison of the catalytic performance of five different zeolites reveals that Hβ zeolite, which has high densities of both Lewis and Br?nsted acid sites, affords the highest MLE yield. With the addition of 1,3,5-trioxane, the hydroxymethylation of furfural derivative and formaldehyde is a key step. Notably, the simultaneous conversion of C5 and C6 sugars catalyzed by Hβ zeolite can attain an MLE yield as high as 50.4 % when the reaction conditions are fully optimized. Moreover, the Hβ zeolite catalyst can be reused at least five times without significant change in performance.
TRITERPENE SAPONIN SYNTHESIS, INTERMEDIATES AND ADJUVANT COMBINATIONS
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Page/Page column 82; 83; 84, (2018/11/10)
The present application relates to triterpene glycoside saponin-derived adjuvants, syntheses thereof, and intermediates thereto. The application also provides pharmaceutical compositions comprising compounds of the present invention and methods of using said compounds or compositions in the treatment of and immunization for infectious diseases.
Ring-opened 4-hydroxy-δ-valerolactone subunit as a key structural fragment of polyesters that degrade without acid formation
Nifant'ev, Ilya E.,Shlyakhtin, Andrey V.,Bagrov, Vladimir V.,Ezhov, Roman N.,Lozhkin, Boris A.,Churakov, Andrei V.,Ivchenko, Pavel V.
, p. 629 - 631 (2018/12/13)
Random copolymers of ?-caprolactone with O-benzyl-protected 4-hydroxy- or 2,4-dihydroxy-δ-valerolactone after hydrogenation form γ-hydroxy functionalized polyesters that degrade via the cyclization to γ-butyrolactone fragments without carboxylic acid formation.
Selective C?O Bond Cleavage of Sugars with Hydrosilanes Catalyzed by Piers’ Borane Generated In Situ
Zhang, Jianbo,Park, Sehoon,Chang, Sukbok
supporting information, p. 13757 - 13761 (2017/10/09)
Described herein is the selective reduction of sugars with hydrosilanes catalyzed by using Piers’ borane [(C6F5)2BH] generated in situ. The hydrosilylative C?O bond cleavage of silyl-protected mono- and disaccharides in the presence of a (C6F5)2BH catalyst, generated in situ from (C6F5)2BOH, takes place with excellent chemo- and regioselectivities to provide a range of polyols. A study of the substituent effects of sugars on the catalytic activity and selectivity revealed that the steric environment around the anomeric carbon (C1) is crucial.
Synthesis of a novel polyester building block from pentoses by tin-containing silicates
Elliot,Andersen,Tolborg,Meier,Sádaba,Daugaard,Taarning
, p. 985 - 996 (2017/01/13)
We report here the direct formation of the new chemical product trans-2,5-dihydroxy-3-pentenoic acid methyl ester from pentoses using tin-containing silicates as catalysts. The product is formed under alkali-free conditions in methanol at temperatures in the range 140-180 °C. The highest yields are found using Sn-Beta as the catalyst. Under optimised conditions, a yield of 33% is achieved. Purified trans-2,5-dihydroxy-3-pentenoic acid methyl ester was used for co-polymerisation studies with ethyl 6-hydroxyhexanoate using Candida antarctica lipase B as the catalyst. The co-polymerisation yields a product containing functional groups originating from trans-2,5-dihydroxy-3-pentenoic acid methyl ester in the polyester backbone. The reactivity of the incorporated olefin and hydroxyl moieties was investigated using trifluoroacetic anhydride and thiol-ene chemistry, thus illustrating the potential for functionalising the new co-polymers.
Binding pattern of intermediate UDP-4-keto-xylose to human UDP-xylose synthase: Synthesis and STD NMR of model keto-saccharides
Puchner, Claudia,Eixelsberger, Thomas,Nidetzky, Bernd,Brecker, Lothar
, p. 50 - 58 (2016/12/14)
Human UDP-xylose synthase (hUXS1) exclusively converts UDP-glucuronic acid to UDP-xylose via intermediate UDP-4-keto-xylose (UDP-Xyl-4O). Synthesis of model compounds like methyl-4-keto-xylose (Me-Xyl-4O) is reported to investigate the binding pattern thereof to hUXS1. Hence, selective oxidation of the desired hydroxyl function required employment of protecting group chemistry. Solution behavior of synthesized keto-saccharides was studied without enzyme via1H and13C NMR spectroscopy with respect to existent forms in deuterated potassium phosphate buffer. Keto-enol tautomerism was observed for all investigated keto-saccharides, while gem-diol hydrate forms were only observed for 4-keto-xylose derivatives. Saturation transfer difference (STD) NMR was used to study binding of synthesized keto-gylcosides to wild type hUXS1. Resulting epitope maps were correlated to earlier published molecular modeling studies of UDP-Xyl-4O. STD NMR results of Me-Xyl-4O are in good agreement with simulations of the intermediate UDP-Xyl-4O indicating a strong interaction of proton H3 with the enzyme, potentially caused by active site residue Ala79. In contrast, pyranoside binding pattern studies of methyl uronic acids showed some differences compared to previously published STD NMR results of UDP-glycosides. In general, obtained results can contribute to a better understanding in binding of UDP-glycosides to other UXS enzyme family members, which have high structural similarities in the active site.
