81446-31-3Relevant academic research and scientific papers
A sterically encumbered photoredox catalyst enables the unified synthesis of the classical lignan family of natural products
Alfonzo, Edwin,Beeler, Aaron B.
, p. 7746 - 7754 (2019/08/30)
Herein, we detail a unified synthetic approach to the classical lignan family of natural products that hinges on divergence from a common intermediate that was strategically identified from nature's biosynthetic blueprints. Efforts toward accessing the common intermediate through a convergent and modular approach resulted in the discovery of a sterically encumbered photoredox catalyst that can selectively generate carbonyl ylides from electron-rich epoxides. These can undergo concerted [3 + 2] dipolar cycloadditions to afford tetrahydrofurans, which were advanced (2-4 steps) to at least one representative natural product or natural product scaffold within all six subtypes in classical lignans. The application of those synthetic blueprints to the synthesis of heterolignans bearing unnatural functionality was demonstrated, which establishes the potential of this strategy to accelerate structure-activity-relationship studies of these natural product frameworks and their rich biological activity.
Ni-Catalyzed Regioselective Dicarbofunctionalization of Unactivated Olefins by Tandem Cyclization/Cross-Coupling and Application to the Concise Synthesis of Lignan Natural Products
Kc, Shekhar,Basnet, Prakash,Thapa, Surendra,Shrestha, Bijay,Giri, Ramesh
, p. 2920 - 2936 (2018/03/09)
We disclose a (terpy)NiBr2-catalyzed reaction protocol that regioselectively difunctionalizes unactivated olefins with tethered alkyl halides and arylzinc reagents. The reaction shows an excellent functional group tolerance (such as ketones, es
Modular synthesis and biological investigation of 5-hydroxymethyl dibenzyl butyrolactones and related lignans
Davidson, Samuel J.,Pilkington, Lisa I.,Dempsey-Hibbert, Nina C.,El-Mohtadi, Mohamed,Tang, Shiying,Wainwright, Thomas,Whitehead, Kathryn A.,Barker, David
, (2018/11/30)
Dibenzyl butyrolactone lignans are well known for their excellent biological properties, particularly for their notable anti-proliferative activities. Herein we report a novel, efficient, convergent synthesis of dibenzyl butyrolactone lignans utilizing the acyl-Claisen rearrangement to stereoselectively prepare a key intermediate. The reported synthetic route enables the modification of these lignans to give rise to 5-hydroxymethyl derivatives of these lignans. The biological activities of these analogues were assessed, with derivatives showing an excellent cytotoxic profile which resulted in programmed cell death of Jurkat T-leukemia cells with less than 2% of the incubated cells entering a necrotic cell death pathway.
Design and synthesis of novel arctigenin analogues for the amelioration of metabolic disorders
Duan, Shudong,Huang, Suling,Gong, Jian,Shen, Yu,Zeng, Limin,Feng, Ying,Ren, Wenming,Leng, Ying,Hu, Youhong
supporting information, p. 386 - 391 (2015/04/27)
Analogues of the natural product (-)-arctigenin, an activator of adenosine monophosphate activated protein kinase, were prepared in order to evaluate their effects on 2-deoxyglucose uptake in L6 myotubes and possible use in ameliorating metabolic disorders. Racemic arctigenin 2a was found to display a similar uptake enhancement as does (-)-arctigenin. As a result, the SAR study was conducted utilizing racemic compounds. The structure-activity relationship study led to the discovery of key substitution patterns on the lactone motif that govern 2-deoxyglucose uptake activities. The results show that replacement of the para-hydroxyl group of the C-2 benzyl moiety of arctigenin by Cl has a pronounced effect on uptake activity. Specifically, analogue 2p, which contains the p-Cl substituent, stimulates glucose uptake and fatty acid oxidation in L6 myotubes.
A chemoenzymatic synthesis of both enantiomers of a cis-lignan lactone
Chenevert, Robert,Rose, Yannick Stephane
, p. 2827 - 2831 (2007/10/03)
The stereoselective acetylation of meso-2,3-bis(3,4- dimethoxybenzyl)butanediol by vinyl acetate in the presence of Candida antarctica lipase in benzene gave the corresponding (+)-(2S,3R) monoester (ee ≥98%). Transesterification of meso-2,3-bis(3,4-dimethoxybenzyl)butyl diacetate, in the presence of the same enzyme, by ethanol in benzene/isopropyl ether gave the corresponding (-)-(2R,3S) monoester (ee ≥98%). Both enantiomers of the known cis-2,3-bis(3,4- dimethoxybenzyl)butyrolactone were synthesized from these monoesters.
Asymmetric synthesis of a lignan lactone from a meso anhydride
Ward, Robert S.,Pelter, Andrew,Edwards, Mark I.,Gilmore, Jeremy
, p. 12799 - 12814 (2007/10/03)
The synthesis of a meso-2,3-dibenzylbutanedioic acid anhydride is given. Reaction of this with (+)-α-methylbenzylamide proceeds diastereoselectively to give a butanedioic acid monoamide which is converted into an enantiomerically enriched cis-2,3-dibenzyl
Asymmetric synthesis of a lignan lactone from a meso anhydride
Ward,Pelter,Edwards,Gilmore
, p. 843 - 844 (2007/10/02)
Reaction of the anhydride of a meso-2,3-dibenzylbutanedioic acid with (+)-α-methylbenzylamine proceeds diastereoselectively to give an acid-amide which can be converted into an enantiomerically enriched cis-2,3-dibenzylbutyrolactone.
Ruthenium dioxide in fluoro acid medium V. Application to the non phenolic oxidative coupling of diarylbutanes. Conformational studies of cis and trans deoxyschizandrins
Dhal,Landais,Lebrun,Lenain,Robin
, p. 1153 - 1164 (2007/10/02)
Ruthenium (IV) dioxide dihydrate in fluoro acidic medium was found to be a very efficient agent for the non phenolic oxidative coupling of diarylbutanes. We observed along with the expected aryl-aryl coupling, an unusual aryl-benzyl coupling, leading to a known class of lignans, the aryltetralins. Conformational studies of resultant cis and trans deoxyschizandrins were performed using high resolution NMR and molecular models.
STEREOSELECTIVE SYNTHESIS OF METHOXY SUBSTITUTED 2,3-DIBENZYL-γ-BUTYROLACTONES USING ORGANIC PHOSPHONATES AS INTERMEDIATES
Compagnone, Reinaldo S.,Suarez, Alirica
, p. 35 - 38 (2007/10/02)
A stereoselective, short and convergent synthesis of methoxy substituted 2,3-dibenzyl-γ-butyrolactones was developed using organic phosphonates as key intermediates.
FORMATION OF (-)-ARCTIGENIN IN FORSYTHIA INTERMEDIA
Ozawa, Shuji,Davin, Laurence B.,Lewis, Norman G.
, p. 643 - 652 (2007/10/02)
Forsythia intermedia cell-free extracts were examined for their ability to catalyse the enantioselective and regiospecific O-methylation of matairesinol.In contrast to the enzymatic steps defined from (+)-pinoresinol to (-)-matairesinol, the conversion of matairesinol into arctigenin was not highly enenatioselective; both (+)- and (-)-antipodes of matairesinol served as substrates for methylation, with the naturally occuring (-)-enantiomer slightly preferred.But the cell-free extracts also catalyses the synthesis of (+)- and (-)-isoarctigenins, with (-)-matairesinol again the preferred substrate.Thus the O-methylation of matairesinol, catalysed by F. intermedia cell-free extracts, is neither highly enantioselective nor regiospecific.No evidence that subsequent methylation of either arctigenin or isoarctigenin occured to afford dimethyl matairesinol was obtained, i.e. the O-methyltransferase(s) only catalysed monomethylation.Taken together, it is proposed that post-coupling methylation does not proceed via regiospecific methylation of matairesinol to give arctigenin directly.Instead, regiospecific glucosylation first occurs to afford matairesinoside; subsequent methylation affords arctiin, which is then converted into arctigenin via action of a β-glucosidase. Key Word Index - Forsythia; Oleaceae; O-methyltransferases; glucosyltransferases; lignans; neolignans; biosynthesis; enantioselectivity; regiospecifity; chiral separation.
