136883-91-5Relevant academic research and scientific papers
Stereoselective synthesis of natural product inspired carbohydrate fused pyrano[3,2-: C] quinolones as antiproliferative agents
Kumari, Priti,Narayana, Chintam,Dubey, Shraddha,Gupta, Ashish,Sagar, Ram
, p. 2049 - 2059 (2018)
Pyrano[3,2-c]quinolone structural motifs are commonly found in natural products with diverse biological activities. As part of a research programme aimed at developing the efficient synthesis of natural product-like small molecules, we designed and developed the microwave assisted, facile stereoselective synthesis of two series of carbohydrate fused pyrano[3,2-c]quinolone derivatives (n = 23) starting from 2-C-formyl galactal and 2-C-formyl glucal, reacting with various 4-hydroxyquinolones in shorter reaction times (15-20 min). The antiproliferative activity of these synthesized pyrano[3,2-c]quinolones was determined against MCF-7 (breast) and HepG2 (liver) cancer cells. The selected library members displayed low micromolar (3.53-9.68 μM) and selective antiproliferative activity. These findings on carbohydrate fused pyrano[3,2-c]quinolone derivatives are expected to provide new leads for anticancer drug discovery.
Palladium catalysed carbonylation of 2-iodoglycals for the synthesis of C-2 carboxylic acids and aldehydes taking formic acid as a carbonyl source
Ahmed, Ajaz,Hussain, Nazar,Bhardwaj, Monika,Chhalodia, Anuj Kumar,Kumar, Amit,Mukherjee, Debaraj
, p. 22227 - 22231 (2019)
Pd catalyzed carbonylative reaction of 2-iodo-glycals has been developed taking formic acid as a carbonyl source for the synthesis of 2-carboxylic acids of sugars by the hydroxycarbonylation strategy. The methodology was successfully extended to the synthesis of 2-formyl glycals by using a reductive carbonylation approach. Both ester and ether protected glycals undergo the reaction and furnished sugar acids in good yield which is otherwise not possible by literature methods. The C-2 sugar acids were successfully utilized for the construction of 2-amido glycals, 2-dipeptido-glycal by Ugi reaction and C-1 and C-2 branched glycosyl esters.
Mechanistic Studies on the Base-Promoted Ring Opening of Glycal-Derived gem-Dibromocyclopropanes
Lepage, Romain J.,Moore, Peter W.,Hewitt, Russell J.,Teesdale-Spittle, Paul H.,Krenske, Elizabeth H.,Harvey, Joanne E.
, p. 301 - 315 (2022/01/03)
In the presence of a nucleophilic base, ring-fused gem-dibromocyclopropanes derived from d-glycals undergo ring opening to give 2-deoxy-2-(E-bromomethylene)glycosides. Such cleavage of an exocyclic cyclopropane bond contrasts with the more usual silver-promoted ring-expansion reactions in which endocyclic bond cleavage occurs. Experimental and theoretical studies are reported which provide insights into the reaction mechanism and the origin of its kinetic selectivity for E-configured bromoalkene products. Density functional theory computations (M06-2X) predict that the reaction commences with alkoxide-induced HBr elimination from the dibromocyclopropane to form a bromocyclopropene. Ring opening then gives a configurationally stable zwitterionic (oxocarbenium cation/vinyl carbanion) intermediate, which undergoes nucleophilic addition and protonation to give the bromoalkene. There are two competing sources of the proton in the final step: One is the alcohol (co)solvent, and the other is the molecule of alcohol produced during the initial deprotonation step. The roles of the formed alcohol molecule and the bulk (co)solvent are demonstrated by isotope-labeling studies performed with deuterated solvents. The acid-promoted isomerization of the E-bromoalkene product into the corresponding Z-bromoalkene is also described. The mechanistic knowledge gained in this investigation sheds light on the unusual chemistry of this system and facilitates its future application in new settings.
Regio- And diastereoselective Pd-catalyzed synthesis of C2-aryl glycosides
Alami, Mouad,Franco, Rémi,Gandon, Vincent,Ghouilem, Juba,Messaoudi, Samir,Retailleau, Pascal
supporting information, p. 7175 - 7178 (2020/07/14)
An efficient regio- and diastereoselective arylation method of readily available 2,3-glycals with various aryl iodides has been established. Using the Pd(OAc)2/AsPh3 precatalytic system, this protocol proved to be general to prepare a variety of substituted C2-aryl glycosides in good yields with complete diastereoselectivity.
Use of XtalFluor-E as an Alternative to POCl3 in the Vilsmeier-Haack Formylation of C-2-Glycals
Roudias, Majdouline,Vallée, Frédéric,Martel, Julien,Paquin, Jean-Fran?ois
, p. 8731 - 8738 (2018/08/10)
We report the use of XtalFluor-E ([Et2NSF2]BF4) as an alternative to POCl3 in the Vilsmeier-Haack formylation reaction of C-2-glycals. Employing a XtalFluor-E/DMF combination allowed the desired C-2-formyl glyca
Diversity-Oriented Synthetic Endeavors of Newly Designed Ferrier and Ferrier-Nicholas Systems Derived from 1-C-Alkynyl-2-deoxy-2-C-Methylene Pyranosides
Miranda, Silvia,Gómez, Ana M.,López, J. Cristóbal
, p. 5355 - 5374 (2018/09/10)
Novel pyranose derivatives that display Ferrier- and Ferrier-Nicholas-like reactivity have been designed. These systems: 1-C-alkynyl-2-deoxy-2-C-methylene pyranosides (Ferrier), and their corresponding dicobalthexacarbonyl alkenyl derivatives (Ferrier-Nic
Stereoselective synthesis of carbohydrate fused pyrano[3,2-c]pyranones as anticancer agents
Kumari, Priti,Gupta, Sonal,Narayana, Chintam,Ahmad, Shakeel,Vishnoi, Nidhi,Singh, Shailja,Sagar, Ram
supporting information, p. 13985 - 13997 (2018/08/21)
Pyrano[3,2-c]pyranone is an important structural motif present in many natural products exhibiting diverse biological activities. Two series of carbohydrate fused pyrano[3,2-c]pyranone derivatives (n = 20) were efficiently synthesized starting from 2-C-formyl galactal and 2-C-formyl glucal, reacting with various 4-hydroxycoumarins in a very short reaction time (10 min) under microwave assisted conditions. The anticancer activity of these synthesized pyrano[3,2-c]pyranones was determined in detail through cellular assays against MCF-7 (breast), MDA-MB-231 (breast) and HepG2 (liver) cancer cell lines. The newly synthesized pyrano[3,2-c]pyranones were screened for their cell-viability and anti-proliferative activity against MCF-7, MDA-MB-231 and HepG2 cell lines. Compounds 12, 13 and 14 exhibited high growth inhibitory potencies selectively against MCF-7 cells with half-maximal inhibitory concentration (IC50) values of 19.9, 14.5 and 10.9 μM respectively. Compounds 12, 13, 14, 15 and 19 inhibited the growth of MDA-MB-231 cells (breast) by 43, 44, 37, 31 and 45% respectively. However, no inhibitory effect was observed for these compounds in the human liver cancer cell line (HepG2) and normal cell lines (HEK293, human embryonic kidney cells). Mechanistic studies showed that these compounds alter the cell morphology and cause G2/M arrest in MCF-7. Further studies showed that compounds 12, 13 and 14 significantly inhibited cell migration which was accompanied by altered microtubule distribution. An enhanced accumulation of these compounds in cells was observed as compared to the 4-hydroxycoumarins precursor in the intracellular uptake assay. These findings confirm that carbohydrate fused pyrano[3,2-c]pyranones are better candidates for anticancer activity.
Polyunsaturated C-Glycosidic 4-Hydroxy-2-pyrone Derivatives: Total Synthesis Shows that Putative Orevactaene Is Likely Identical with Epipyrone A
Preindl, Johannes,Schulthoff, Saskia,Wirtz, Conny,Lingnau, Julia,Fürstner, Alois
supporting information, p. 7525 - 7530 (2017/06/13)
Orevactaene and epipyrone A were previously thought to comprise the same polyunsaturated tail but notably different C-glycosylated 4-hydroxy-2-pyrone head groups. Total synthesis now shows that the signature bicyclic framework assigned to orevactaene is a chimera; the compound is almost certainly identical with epipyrone A, whose previously unknown stereochemistry has also been established during this study. Key to success was the ready formation of the bicyclic core of putative orevactaene by a sequence of two alkyne cycloisomerization reactions using tungsten and gold catalysis. Equally important was the flexibility in the assembly process gained by the use of heterobimetallic polyunsaturated modules whose termini could be selectively and consecutively addressed in a practical one-pot cross-coupling sequence.
Gold- or Silver-Catalyzed Syntheses of Pyrones and Pyridine Derivatives: Mechanistic and Synthetic Aspects
Preindl, Johannes,Jouvin, Kvin,Laurich, Daniel,Seidel, Günter,Fürstner, Alois
supporting information, p. 237 - 247 (2016/01/25)
3-Oxo-5-alkynoic acid esters, on treatment with a carbophilic catalyst, undergo 6-endo-dig cyclization reactions to furnish either 2-pyrones or 4-pyrones in high yields. The regiochemical course can be dialed in by the proper choice of the alcohol part of the ester and the π-acid. This transformation is compatible with a variety of acid-sensitive groups as witnessed by a number of exigent applications to the total synthesis of natural products, including pseudopyronine A, hispidine, phellinin A, the radininol family, neurymenolide, violapyrone, wailupemycin and an unnamed brominated 4-pyrone of marine origin. Although the reaction proceeds well in neutral medium, the rate is largely increased when HOAc is used as solvent or co-solvent, which is thought to favor the protodeauration of the reactive alkenyl-gold intermediates as the likely rate-determining step of the catalytic cycle. Such intermediates are prone to undergo diauration as an off-cycle event that sequesters the catalyst; this notion is consistent with literature data and supported by the isolation of the gem-diaurated complexes 12 and 15. Furthermore, silver catalysis allowed access to be gained to 2-alkoxypyridine and 2-alkoxyisoquinoline derivatives starting from readily available imidate precursors.
Divergent synthesis of 2-C-branched pyranosides and oxepines from 1,2-gem-dibromocyclopropyl carbohydrates
Moore, Peter W.,Schuster, Julia K.,Hewitt, Russell J.,Stone, M. Rhia L.,Teesdale-Spittle, Paul H.,Harvey, Joanne E.
supporting information, p. 7032 - 7043 (2015/02/19)
The ring opening of 1,2-(gem-dibromo)cyclopropyl carbohydrates by two different modes leads to either 2-C-(bromomethylene)pyranosides (using base) or 2-bromooxepines (using silver salts), as shown previously by us for a D-glucal-derived cyclopropane. The base-promoted ring opening is extended to encompass additional alcohol, thiol and amine nucleophiles, and diastereoisomeric cyclopropane precursors. Cross-coupling of the 2-C-(bromomethylene)pyranosides leads to extended 2-C-branched pyranosides. Silver-promoted ring expansion of the cyclopropyl carbohydrates in the presence of various alcohols is described. Cross-coupling of the resulting benzyl 2-bromooxepines affords 2-C-substituted oxepines.
