212265-19-5Relevant academic research and scientific papers
Total Synthesis of Hispidulin and the Structural Basis for Its Inhibition of Proto-oncogene Kinase Pim-1
Chao, Shi-Wei,Su, Ming-Yuan,Chiou, Lih-Chu,Chen, Liang-Chieh,Chang, Chung-I,Huang, Wei-Jan
, p. 1969 - 1976 (2015/09/08)
(Figure Presented). A new method is applied to synthesize hispidulin, a natural flavone with a broad spectrum of biological activities. Hispidulin exhibits inhibitory activity against the oncogenic protein kinase Pim-1. Crystallographic analysis of Pim-1 bound to hispidulin reveals a binding mode distinct from that of quercetin, suggesting that the binding potency of flavonoids is determined by their hydrogen-bonding interactions with the hinge region of the kinase. Overall, this work may facilitate construction of a library of hispidulin-derived compounds for investigating the structure-activity relationship of flavone-based Pim-1 inhibitors.
Probing the catalytic promiscuity of a regio- and stereospecific C-glycosyltransferase from Mangifera indica
Chen, Dawei,Chen, Ridao,Wang, Ruishan,Li, Jianhua,Xie, Kebo,Bian, Chuancai,Sun, Lili,Zhang, Xiaolin,Liu, Jimei,Yang, Lin,Ye, Fei,Yu, Xiaoming,Dai, Jungui
supporting information, p. 12678 - 12682 (2015/10/28)
The catalytic promiscuity of the novel benzophenone C-glycosyltransferase, MiCGT, which is involved in the biosynthesis of mangiferin from Mangifera indica, was explored. MiCGT exhibited a robust capability to regio- and stereospecific C-glycosylation of 35 structurally diverse druglike scaffolds and simple phenolics with UDP-glucose, and also formed O- and N-glycosides. Moreover, MiCGT was able to generate C-xylosides with UDP-xylose. The OGT-reversibility of MiCGT was also exploited to generate C-glucosides with simple sugar donor. Three aryl-C-glycosides exhibited potent SGLT2 inhibitory activities with IC50 values of 2.6×, 7.6×, and 7.6×10-7-M, respectively. These findings demonstrate for the first time the significant potential of an enzymatic approach to diversification through C-glycosidation of bioactive natural and unnatural products in drug discovery. C-glycodiversification: MiCGT, as the first benzophenone C-glycosyltransferase (CGT) from Mangifera indica, showed robust regio- and stereospecific C-glycosylation activity for 35 structurally diverse acceptors with UDP-glucose or xylose. The aryl-C-glycoside 1 exhibited potent antidiabetic activity toward SGLT2.
First total synthesis of a polyunsaturated chromone metabolite isolated from the brown algae Zonaria tournefortii
Anwar, Many F.,Hansen, Trond Vidar
supporting information; experimental part, p. 587 - 588 (2009/07/30)
(Chemical Equation Presented) Starting from the ethyl ester of eicosapentaenoic acid, the first total synthesis of the marine natural product all-(Z)-5,7-dihydroxy-2-(4Z,7Z,10Z,13Z,16Z-nonadecapentaenyl)chromone has been achieved in six steps and in 14% o
Synthesis and fate of o-carboxybenzophenones in the biosynthesis of aflatoxin
Henry, Kevin M.,Townsend, Craig A.
, p. 3300 - 3309 (2007/10/03)
o-Carboxybenzophenones have long been postulated to be intermediates in the oxidative rearrangement of anthraquinone natural products to xanthones in vivo. Many of these Baeyer-Villiger-like cleavages are believed to be carried out by cytochrome P450 enzymes. In the biosynthesis of the fungal carcinogen, aflatoxin, six cytochromes P450 are encoded by the biosynthetic gene cluster. One of these, AflN, is known to be involved in the conversion of the anthraquinone versicolorin A (3) to the xanthone demethylsterigmatocystin (5) en route to the mycotoxin. An aryl deoxygenation, however, also takes place in this overall transformation and is proposed to be due to the requirement that an NADPH-dependent oxidoreductase, AflM, be active for this process to take place. What is known about other fungal anthraquinone → xanthone conversions is reviewed, notably, the role of the o-carboxybenzophenone sulochrin (25) in geodin (26) biosynthesis. On the basis of mutagenesis experiments in the aflatoxin pathway and these biochemical precedents, total syntheses of a tetrahydroxy-o-carboxybenzophenone bearing a fused tetrahydrobisfuran and its 15-deoxy homologue are described. The key steps of the syntheses entail rearrangement of a 1,2-disubstituted alkene bearing an electron-rich benzene ring under Kikuchi conditions to give the 2-aryl aldehyde 43 followed by silyltriflate closure to a differentially protected dihydrobenzofuran 44. Regiospecific bromination, conversion to the substituted benzoic acid, and condensation with an o-bromobenzyl alcohol gave esters 47 and 50. The latter could be rearranged with strong base, oxidized, and deprotected to the desired o-carboxybenzophenones. These potential biosynthetic intermediates were examined in whole-cell and ground-cell experiments for their ability to support aflatoxin formation in the blocked mutant DIS-1, defective in its ability to synthesize the first intermediate in the pathway, norsolorinic acid. Against expectation, neither of these compounds was converted into aflatoxin under conditions where the anthraquinones versicolorin A and B readily afforded aflatoxins B1 and B2. This outcome is evaluated further in a companion paper appearing later in this journal.
Biological activities of α-mangostin derivatives against acidic sphingomyelinase
Hamada, Motoko,Iikubo, Kazuhiko,Ishikawa, Yuichi,Ikeda, Aya,Umezawa, Kazuo,Nishiyama, Shigeru
, p. 3151 - 3153 (2007/10/03)
Deprenyl and benzofenone-type congeners of α-mangostin 1 have been synthesized to understand their role for the inhibitory activity against sphingomyelinase (SMase). While removal of the prenyl group of the right side (11 and 12) caused loss of the selectivity between ASMase (acidic sphingomyelinase) and NSMase (neutral sphingomyelinase), the prenyl group of the left side appeared to increase the inhibitory activities (16 and 17).
Silyl triflate-mediated ring-closure and rearrangement in the synthesis of potential bisfuran-containing intermediates of aflatoxin biosynthesis
Graybill, Todd L.,Casillas, Eduard G.,Pal, Kollol,Townsend, Craig A.
, p. 7729 - 7746 (2007/10/03)
The biosynthetic pathway to the potent mycotoxin aflatoxin B1 is unusually long and complex, proceeding from anthraquinone to xanthone to coumarin nuclear types bearing fused tetrahydro- and bisdihydrofuran rings. A synthetic strategy is described involving two silyl triflate-mediated cyclization and rearrangement processes that have enabled both furofuran oxidation states to be readily achieved and undesired but thermodynamically favorable side reactions to be avoided in the preparation of these ring systems. In the first an o-methoxymethyl phenylacetaldehyde is cyclized directly to the five-membered, differentially protected hemiacetal, while in the second this group, appropriately substituted, can be rearranged to a 4- trialkylsilyloxy-2,5-methano-1,3-benzodioxepane. The latter masked dialdehyde is sufficiently stable to strong base, mild acid, and oxidants to allow all needed aryl ring systems to be constructed. Using these methods, total syntheses of (±)-versicolorin B, (±)-versicolorin A, its hemiacetal, and its 6-deoxy derivative, (±)-6-deoxyversicolorin A, have been achieved, and these are reported herein, as well as preparation of the methyl ester of a putative o-carboxybenzophenone biosynthetic intermediate. In work described elsewhere, incorporation experiments with 13C-labeled forms of these compounds have made possible the complete elucidation of bisfuran biosynthesis characteristic of the first major phase of aflatoxin formation in vivo.
First total synthesis of (±)-kenusanone b
Xiao, Li,Tan, Wenfei,Li, Yulin
, p. 2861 - 2869 (2007/10/03)
The first total synthesis of a natural prenylflavanone, (±)-kenusanone B (1) has been achieved by condensation of acetophenone 4 and benzaldehyde 6 followed by cyclization and deprotection. Chloromethyl methyl ether was used as a facile protecting reagent of free hydroxy groups for the synthesis of polyhydroxylated flavanones.
