- A sterically encumbered photoredox catalyst enables the unified synthesis of the classical lignan family of natural products
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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.
- Alfonzo, Edwin,Beeler, Aaron B.
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p. 7746 - 7754
(2019/08/30)
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- Modular synthesis and biological investigation of 5-hydroxymethyl dibenzyl butyrolactones and related lignans
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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.
- Davidson, Samuel J.,Pilkington, Lisa I.,Dempsey-Hibbert, Nina C.,El-Mohtadi, Mohamed,Tang, Shiying,Wainwright, Thomas,Whitehead, Kathryn A.,Barker, David
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- Radical one-pot α,β-dual and β-mono-oxymethylation of alkylidenemalonate
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Dimethylzinc-mediated radical conjugate addition reaction of dimethyl alkylidenemalonates with iodomethyl pivalate gave a high yield of the α,β-dual oxymethylation product in one pot under air and the β-pivaloyloxymethylation product under argon.
- Yamada, Ken-Ichi,Konishi, Takehito,Nakano, Mayu,Fujii, Shintaro,Cadou, Romain,Yamamoto, Yasutomo,Tomioka, Kiyoshi
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p. 5775 - 5780
(2012/09/07)
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- Synthesis, anti-virus and anti-tumour activities of dibenzylbutyrolactone lignans and their analogues
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An efficient synthesis of dibenzylbutyrolactone lignans and their analogues has been developed. Based on a Stobbe condensation of piperonal or veratraldehyde with diethylsuccinate and alkylation with 3,4- methylenedioxybenzyl bromide to give the skeleton
- Xia, Yamu,You, Jia,Zhang, Yuanyuan,Su, Zhongliang
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experimental part
p. 565 - 569
(2010/03/03)
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- An efficient oxidative lactonization of 1,4-diols catalyzed by Cp*Ru(PN) complexes
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An efficient oxidative lactonization of 1,4-diols in acetone is accomplished by the well-defined ruthenium catalyst, whose bifunctional nature underlies the high efficiency as well as unique chemo- and regioselectivity of the reaction which provides a rapid access to γ-butyrolactones including flavor lactones hinokinin, and muricatacin.
- Ito, Masato,Osaku, Akihide,Shiibashi, Akira,Ikariya, Takao
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p. 1821 - 1824
(2008/02/02)
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- Double coupling reactions of 3,4-bis(stannyl)furanone: Facile preparation of diaryl- and dibenzylfuranones
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The palladium-catalyzed cross-coupling reaction of 3,4-bis(tributylstannyl) furan-2(5H)-one using chelating ligand or polar solvent gives mixtures of single and double coupled products, even when one equivalent of halide coupling partner is used. After optimization, the double coupling reaction was shown to be general, with the use of two equivalents of aryl iodides giving 3,4-disubstituted furanones, The reaction using benzyl bromides proceeds at lower temperatures than the corresponding coupling using aryl iodides, giving dibenzylfuranones. The methodology has been exemplified in a synthesis of (±)-hinokinin. Georg Thieme Verlag Stuttgart.
- Carter, Neil B.,Mabon, Ross,Walmsley, Rachel,Richec?ur, Alexandre M. E.,Sweeney
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p. 1747 - 1749
(2008/02/03)
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- Lipase-catalyzed esterification of a (±)-2,3-di(arylmethyl)-1,4- butanediol and its application to the synthesis of (S,S)-(+)-hinokinin
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Racemic trans-2,3-di[(3,4-methylenedioxy)benzyl]-1,4-butanediol (dihydrocubebin) 6 was enantioselectively esterified using lipases as catalysts with vinyl acetate. Optically active (S,S)-1,4-butanediol 6 obtained was selectively oxygenated with a Fetizon reagent, affording (S,S)-(+)-hinokinin 9 in a high yield.
- Morimoto, Toshiaki,Nagai, Hazuki,Achiwa, Kazuo
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p. 857 - 865
(2007/10/03)
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- A novel asymmetric route to succinimides and derived compounds: Synthesis of the lignan lactone (+)-hinokinin
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A novel approach to chiral succinimides and derived compounds has been developed that involves chiral lithium amide desymmetrisation of an N-ortho-tert-butylphenyl succinimide to generate a putative atropisomeric intermediate enolate, alkylation of which
- Bennett, D. Jonathan,Pickering, Paula L.,Simpkins, Nigel S.
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p. 1392 - 1393
(2007/10/03)
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- A short synthesis of biologically active lignan analogues
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β-Benzyl-γ-butyrolactones were synthesized in four transition metal catalysed reactions from butynediol, and alkylated to afford new, biologically active lignan analogues.
- Kamlage,Sefkow,Pool-Zobel,Peter
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p. 331 - 332
(2007/10/03)
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- 3-Phenylselanylfuran-2(5H)-one: A versatile building block in the synthesis of lignans. A new approach towards 3,4-dibenzyl γ-butyrolactones
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Ready available 3-phenylselanylfuran-2(5H)-one undergoes tandem conjugate addition-alkylation by organocopper reagents to afford, with good yields and diastereoselectivities, 3,4-disubstituted-3-phenylselanyl-γ- butyrolactones, which can be transformed into naturally occurring compounds, such as lignans.
- Bella, Marco,Piancatelli, Giovanni,Pigro, Maria Cristina
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p. 12387 - 12398
(2007/10/03)
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- Intramolecular regioselective insertion into unactivated prochiral carbon-hydrogen bonds with diazoacetates of primary alcohols catalyzed by chiral dirhodium(II) carboxamidates. Highly enantioselective total synthesis of natural lignan lactones
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Intramolecular insertion into unactivated prochiral C-H bonds of 3-aryl-1-propyl diazoacetates catalyzed by dirhodium(II) tetrakis[methyl 1-(3-phenyl propanoyl)imidazolidin-2-one-4(R or S)-carboxylate], Rh2(4R-MPPIM)4 or Rh2(4S-MPPIM)4, occurs in 91-96% ee and with virtually complete regiocontrol for the formation of β-benzyl-γ-butyrolactones. This methodology has been applied to the total synthesis of dibenzylbutyrolactone lignans (-)- and (+)-enterolactone, (-)- and (+)-hinokinin, and (+)-arctigenin from substituted cinnamic acids in 19-27% overall yields. Aryltetralin lignan (+)-isodeoxypodophyllotoxin was prepared from the reactant 3,4-(methylenedioxy)cinnamic acid in 36% yield overall, and the lactone precursor to (+)-isolauricerisinol was formed in 96.5% ee and 23% yield overall. Applications of the chiral Rh2(MPPIM)4 catalysts to fully aliphatic systems resulting in the formation of β-substituted-γ-butyrolactones with high regiocontrol and with 93-96% ee have demonstrated the generality of this methodology. A model that provides accurate predictions of β-substituted-γ-butyrolactone absolute configurations in these asymmetric metal carbene transformations is described.
- Bode,Doyle,Protopopova,Zhou
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p. 9146 - 9155
(2007/10/03)
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- Chiral Synthesis of Lignan Lactones, (-)-Hinokinin, (-)-Deoxypodorhizone, (-)-Isohibalactone and (-)-Savinin by Means of Enantioselective Deprotonation
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Chiral synthesis of lignan lactones, (-)-hinokinin, (-)-deoxypodorhizone, (-)-isohibalactone and (-)-savinin, has been achieved by employing an enantioselective deprotonation of 3-(3,4-methylenedioxybenzyl)cyclobutanone with lithium (S,S')-α,α'-dimethylbenzylamide, as a key step.
- Honda, Toshio,Kimura, Nobuaki,Sato, Shigeki,Kato, Daishiro,Tominaga, Hideo
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p. 1043 - 1046
(2007/10/02)
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- Oxidative Coupling of Carboxylic Acid Dianions: The Total Synthesis of (+/-)-Hinokinin and (+/-)-Fomentaric Acid
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The oxidative coupling of carboxylic acid dianion derivatives provides the key intermediates needed for efficient syntheses of the symmetrical lignan hinokinin (9) and the unsymmetrical fungal metabolite fomentaric acid (22).Racemic hinokinin (9), a targed chosen to test the facility of dianion oxidative coupling in the presence of electron-rich aromatic rings, is prepared in an overall conversion of 61 percent from 3,4-(methylenedioxy)hydrocynnamic acid.Racemic fomentaric acid (22), a trisubstituted succinic acid derivative, results from a straightforward two-stepsequence that proceeds in an overall yield of 40 percent from eicosanoic acid.Preliminary studies demonstrate the utility of oxidative coupling in the synthesis of novel surfactant prototypes.
- Belletire, John L.,Fry, Douglas F.
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p. 2549 - 2555
(2007/10/02)
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- α-Diethoxyphosphinyl-γ-butenolide, a Versatile Reagent for the Synthesis of α,β-Difunctionalized γ-Lactones
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α-Diethoxyphosphinyl-γ-butenolide was synthesized in good yield by phenylselenenylation of an α-diethoxyphosphinyl -γ-butyrolactone carbanion and subsequent oxidative elimination of the phenylseleno residue.The butenolide 2 underwent the Michael addition of various nucleophiles to generate the phosphoryl-stabilized carbanions, which reacted with carbonyl compounds to give α,β-difunctionalized γ-butyrolactones, ligands, and a γ-butyrolactone annelated compound.
- Minami, Toru,Kitajima, Yoshiyuki,Chkugo, Tsuguhiko
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p. 1229 - 1232
(2007/10/02)
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