6752-48-3Relevant articles and documents
Reactivity–Stereoselectivity Mapping for the Assembly of Mycobacterium marinum Lipooligosaccharides
Hansen, Thomas,Ofman, Tim P.,Vlaming, Joey G. C.,Gagarinov, Ivan A.,van Beek, Jessey,Goté, Tessa A.,Tichem, Jacoba M.,Ruijgrok, Gijs,Overkleeft, Herman S.,Filippov, Dmitri V.,van der Marel, Gijsbert A.,Codée, Jeroen D. C.
, p. 937 - 945 (2020/12/09)
The assembly of complex bacterial glycans presenting rare structural motifs and cis-glycosidic linkages is significantly obstructed by the lack of knowledge of the reactivity of the constituting building blocks and the stereoselectivity of the reactions i
Total syntheses of the non-peptide bradykinin B1 receptor antagonist velutinol a and its analogs, seco-pregnanes with a cage-like moiety
Tamiya, Minoru,Isaka, Nobuhisa,Kitazawa, Takaaki,Hasegawa, Atsushi,Ishizawa, Kazuya,Ikeda, Mayu,Kawada, Saki,Ishiguro, Masaji
supporting information, p. 1474 - 1494 (2019/09/30)
We describe here the syntheses of velutinol A (1) and the structurally similar compounds 24 sharing a highly oxygenated seco-pregnane cage-like structure. The synthesis of velutinol A (1, 15,16-seco-pregnane) features the highly regioselective construction of |14 silyl enol ether from 15-keto-21,22-diol, followed by stereoselective introduction of a sterically hindered β-hydroxy group at the C14 position by Rubottom oxidation. Prolonged reaction time and the use of an excess amount of mCPBA at this step allowed double Rubottom oxidation, enabling us to introduce the requisite hydroxy groups at the C14 and C16 positions in one pot. Subsequent oxidative cleavage of the C1516 bond, deprotection, and intramolecular acetalization allowed the concise total synthesis of velutinol A (1). Utilization of α,α-dihydroxy-ketone, the double Rubottom oxidation product, for formation of the ether F-ring by 5-exo-cyclization, and subsequent C1421 oxidative cleavage, effectively achieved the synthesis of pentalinonside-aglycon (2). Construction of the 14,15-seco-structures of two other analogs, argeloside aglycon (3) and illustrol (4), was achieved by BaeyerVilliger oxidation of 15(21)-keto derivatives. Introduction of the 20-oxo group potentially embedded in argeloside aglycon was accomplished by Wacker oxidation of |20, which was constructed by GriecoNishizawa syn-β-elimination of the C21-primary alcohol obtained by reduction of the BaeyerVilliger product. Intra-molecular double acetalization of the 15,16-dihydroxy-14,20-oxo derivative to form the cage-like structure of the DEF-rings required a moderately weak acid. This step was the key to accessing argeloside aglycon (3), as otherwise the easily aromatized β,γ-dihydroxyketone moiety was transformed to furan. Sharpless asymmetric dihydroxylation of |20 to set the C20 stereocenter, followed by intramolecular double acetalization, achieved the stereoselective synthesis of illustrol With all synthesized compounds, structural requirements of steroidal bradykinine B1 receptor antagonist would be revealed.
Synthesis of MeON-neoglycosides of digoxigenin with 6-deoxy- and 2,6-dideoxy-D-glucose derivatives and their anticancer activity
Wang, Dong-dong,Li, Xiao-san,Bao, Yu-zhou,Liu, Jie,Zhang, Xiao-kun,Yao, Xin-sheng,Sun, Xue-Long,Tang, Jin-Shan
supporting information, p. 3359 - 3364 (2017/07/07)
Cardiac glycosides show anticancer activities and their deoxy-sugar chains are vital for their anticancer effects. In order to study the structure-activity relationship (SAR) of cardiac glycosides toward cancers and get more potent anticancer agents, a series of MeON-neoglycosides of digoxigenin was synthesized and evaluated. First, ten 6-deoxy- and 2,6-dideoxy-D-glucopyranosyl donors were synthesized starting from methyl α-D-glucopyranoside and 2-deoxy-D-glucose. Meanwhile, the digoxigenin was obtained by acidic hydrolysis of commercially available digoxin as glycosyl acceptor. Then, a 22-member MeON-neoglycoside library of digoxigenin was successfully synthesized by neoglycosylation method. Finally, the induction of Nur77 expression and its translocation from the nucleus to cytoplasm together with cytotoxicity of these MeON-neoglycosides were evaluated. The SAR analysis revealed that C3 glycosylation is required for their induction of Nur77 expression. Moreover, some MeON-neoglycosides (2b and 8b) could significant induce the expression of Nur77 and its translocation from the nucleus to cytoplasm. However, these compounds showed no inhibitory effects on the proliferation of cancer cells, suggesting that they may not induce apoptosis of NIH-H460 cancer cells and their underlying potential and application toward cancer cells deserves future study.
Site-Selective Acylations with Tailor-Made Catalysts
Huber, Florian,Kirsch, Stefan F.
supporting information, p. 5914 - 5918 (2016/04/26)
The acylation of alcohols catalyzed by N,N-dimethylamino pyridine (DMAP) is, despite its widespread use, sometimes confronted with substrate-specific problems: For example, target compounds with multiple hydroxy groups may show insufficient selectivity for one hydroxyl, and the resulting product mixtures are hardly separable. Here we describe a concept that aims at tailor-made catalysts for the site-specific acylation. To this end, we introduce a catalyst library where each entry is constructed by connecting a variable and readily tuned peptide scaffold with a catalytically active unit based on DMAP. For selected examples, we demonstrate how library screening leads to the identification of optimized catalysts, and the substrates of interest can be converted with a markedly enhanced site-selectivity compared with only DMAP. Furthermore, substrate-optimized catalysts of this type can be used to selectively convert "their" substrate in the presence of structurally similar compounds, an important requisite for reactions with mixtures of substances. Substrate-optimized catalysts: Site- selective acylations were achieved using substrate-optimized catalysts (see scheme) as identified from a library screening. The catalysts are composed of low-molecular-weight peptides that are readily tuned through variation of the amino acid sequence, and one amino acid was connected to DMAP to ensure catalytic activity. These substrate-optimized catalysts were also applied to selectively convert one substrate in the presence of a structurally similar compound.
Stereoselective synthesis of α-linked 2-deoxy glycosides enabled by visible-light-mediated reductive deiodination
Wang, Hao,Tao, Jinyi,Cai, Xinpei,Chen, Wei,Zhao, Yueqi,Xu, Yang,Yao, Wang,Zeng, Jing,Wan, Qian
, p. 17319 - 17323 (2015/02/19)
2-Deoxy sugars and their derivatives occur abundantly in many pharmaceutically important natural products. However, the construction of specific 2-deoxy-glycosidic bonds remains as a challenge. Herein, we report an efficient way to prepare 2-deoxy-a-glycosides by glycosylation of 2-iodo-glycosyl acetate and subsequent visible-light-mediated tin-free reductive deiodination. We have successfully applied the postglycosylational-deiodination strategy in the synthesis of more than 30 mono-, di-, tri-, tetra- and pentadeoxysaccharides with excellent stereoselectivity and efficiency. This method has also been applied to the synthesis of a 2-deoxy-tetrasac-charide containing four a-linkages.
Synthesis of ribo-hexopyranoside- and altrose-based azacrown ethers and their application in an asymmetric Michael addition
Rapi, Zsolt,Bakó, Péter,Keglevich, Gy?rgy,Sz?llsy, áron,Drahos, László,Hegeds, László
, p. 61 - 68 (2013/02/22)
The synthesis of four new ribo-hexopyranoside-based chiral lariat ethers of monoaza-15-crown-5 type and two altropyranoside-based crown ethers were elaborated. Our syntheses utilized the regioselective ring opening of the oxiran moiety of the 2,3-anhydro sugars by nucleophilic reagents to afford the key intermediates. The reaction of methyl-2,3-anhydro-4,6-O-benzylidene-α-d- mannopyranoside with ethanolamine is especially of interest to afford a 3-substituted altropyranoside. One of the ribo-hexopyranoside-based lariat ethers with a 4-methoxyphenyl substituent induced an enantioselectivity of 80% when used as catalyst in the Michael addition of diethyl acetamidomalonate to trans-β-nitrostyrene under phase transfer catalytic conditions.
Assembly of digitoxin by gold(I)-catalyzed glycosidation of glycosyl o-alkynylbenzoates
Ma, Yuyong,Li, Zhongzhen,Shi, Hefang,Zhang, Jian,Yu, Biao
, p. 9748 - 9756 (2012/01/04)
Digitoxin, a clinically important cardiac trisaccharide, was assembled efficiently from digitoxigenin and 3,4-di-O-tert-butyldiphenylsilyl-d- digitoxosyl o-cyclopropylethynylbenzoate in 9 steps and 52% overall yield via alternate glycosylation and protecting group manipulation. The present synthesis showcases the advantage of the gold(I)-catalyzed glycosylation protocol in the synthesis of glycoconjugates containing acid-labile 2-deoxysugar linkages.
Chiral pool synthesis of calystegine A3 from 2-deoxyglucose via a Brown allylation
Rasmussen, Tina Secher,Jensen, Henrik Helligs?
scheme or table, p. 2855 - 2861 (2012/01/04)
Calystegine A3 is a naturally occurring nortropane iminosugar of which there previously have been three total syntheses. Inspired by our previous work we here report on a fourth approach using 17 steps from 2-deoxy-d-glucose applying a diastereoselective allylation protocol.
Site-selective catalysis of phenyl thionoformate transfer as a tool for regioselective deoxygenation of polyols
Sanchez-Rosello, Maria,Puchlopek, Angela L. A.,Morgan, Adam J.,Miller, Scott J.
, p. 1774 - 1782 (2008/09/18)
(Chemical Equation Presented) We report the application of peptide-embedded imidazoles as catalysts for the site-selective delivery of the phenyl thionoformate unit as a prelude to deoxygenation reactions of polyols. Methodology was developed that allows for the synthesis of thiocarbonyl derivatives based on a combination of additives that include N-alkylimidazoles and FeCl3 as co-catalysts. The use of this reagent combination leads to increased reaction rates and efficient yields relative to those of simple base-mediated reactions. In terms of controlling regioselectivity during the course of polyol modification, we found that histidine-containing peptides, in combination with FeCl3, could lead to modulation of the product distribution. Through screening of peptides and control of reaction conditions, products could be observed that reflected both the inherent preference of substrates and also reversal of inherent selectivity.
Substrate flexibility of vicenisaminyltransferase VinC involved in the biosynthesis of vicenistatin
Minami, Atsushi,Eguchi, Tadashi
, p. 5102 - 5107 (2008/02/04)
A glycosyltransferase VinC is involved in the biosynthesis of antitumor β-glycoside antibiotic vicenistatin. It catalyzes a glycosyl transfer reaction between dTDP-α-D-vicenisamine and vicenilactam. Previous identification of its broad substrate specifici
