Total Synthesis of 2‴,5‴-Diepisilvestrol and Its C1‴ Epimer: Key Structure Activity Relationships at C1‴ and C2‴

Chambers, Jennifer M.; Huang, David C.S.; Lindqvist, Lisa; Savage, G. Paul; White, Jonathan M.; Rizzacasa, Mark A.

doi:10.1021/np300376f

Cited by 19 publications

(12 citation statements)

References 23 publications

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“…Silvestrols, featuring an unprecedented dioxanyloxy unit attached to phenyl ring A of the cyclopenta[ b ]benzofuran skeleton, is a rare subtype of rocaglate, mostly of marked cytotoxicity 8 11 13 . The structure complexity and the potent activities of silvestrols have attracted significant interest in their biosynthesis and total synthesis 16 17 18 19 .…”

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confidence: 99%

Cytotoxic Rocaglate Derivatives from Leaves of Aglaia perviridis

Wang

et al. 2016

Sci Rep

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Rocaglates are a series of structurally complex secondary metabolites with considerable cytotoxicity that have been isolated from plants of the Aglaia genus (Meliaceae). A new rocaglate (aglapervirisinRocaglate, a class of structurally complex secondary metabolites from plants of the Aglaia genus (Meliaceae), have attracted great attentions for their considerable cytotoxicity [1][2][3][4][5] . Rocaglates could block cell cycle progression 6-13 from G2 to M and exhibited promising activity in human tumor cell lines and xenograft models. Their cytostatic effects are comparable to those of established anticancer drugs such as vinblastine sulphate, actinomycin D, and hydroxycamptothecine 14,15 . Rocaglates possess cyclopenta [b]benzofuran skeleton, which originates from the [3 + 2] cyclization products of flavonol and diamide (cyclopenta[bc]benzofurans). Silvestrols, featuring an unprecedented dioxanyloxy unit attached to phenyl ring A of the cyclopenta[b]benzofuran skeleton, is a rare subtype of rocaglate, mostly of marked cytotoxicity 8,11,13 . The structure complexity and the potent activities of silvestrols have attracted significant interest in their biosynthesis and total synthesis [16][17][18][19] .In the plant kingdom, silvestrol analogues are characteristically and exclusively present in Aglaia species, and only four silvestrols have been reported 4 as yet. Certain Aglaia species have been used as traditional medicines for treating fever, cough, diarrhoea, and contused wounds 4,5 . In continuation of the discovery of novel and bioactive natural products from plants of the Meliaceae family [20][21][22] , the species A. perviridis, a wild shrub indigenous to Yunnan Province of China 20-22 , was investigated to find cytotoxic rocaglates, particularly silvestrols. As a result, three silvestrol analogues including a new one (aglapervirisin A, 1), eight new biosynthetic precursors of rocaglates (cyclopenta[bc]benzopyrans, 2-9), and three known precursors (12-14) were isolated and purified from the leaves of A. perviridis (Fig. 1). Their structures were mainly elucidated through comprehensive analysis using spectroscopic methods, including IR, UV, MS, HRESIMS, 1D-NMR and 2D-NMR. The absolute configuration of 1 was determined by ECD analysis and chemical conversion, and that of 2 was established by single-crystal X-ray diffraction using Cu Kα radiation. These isolates (except for 6 and 12) were evaluated for their cytotoxicity against four human cancer cell lines: three silvestrol analogues (1, 10 and 11) showed potent activity with IC 50 values between 8.0 and 15.0 nM. Of them, 1 induced cell cycle arrest by reducing the Cdc2 and Cdc25C expression levels in a dose-dependent manner and induced the apoptosis of these cells at concentrations over 160 nM. Herein, we report the separation and structural elucidation of these isolated rocaglate derivatives, as well as the bioassay results.

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confidence: 99%

Cytotoxic Rocaglate Derivatives from Leaves of Aglaia perviridis

Wang

et al. 2016

Sci Rep

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“…This rearrangement, however, was of no consequence because addition of sodium methoxide to the mixture of 38 and 39 induced a second α-ketol rearrangement to 40 as a tautomeric mixture. The same research group later utilized the same [3 + 2] cycloaddition and α-ketol rearrangement approach to prepare the 2′′′-epimer of 35, which bears an inverted methyl acetal in the dioxane ring, but this compound was less active at inhibiting protein translation [14]. Triumphalone (41) and isotriumphalone (42) represent a class of oxidized phloroglucinol natural products isolated from the Australian plant Melaleuca triumphalis.…”

Section: α-Ketol Rearrangements Implemented In Total Synthesesmentioning

confidence: 99%

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

Benz¹,

Murkin²

2021

Beilstein J. Org. Chem.

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In the presence of a suitable acid or base, α-hydroxyaldehydes, ketones, and imines can undergo isomerization that features the 1,2-shift of an alkyl or aryl group. In the process, the hydroxy group is converted to a carbonyl and the aldehyde/ketone or imine is converted to an alcohol or amine. Such α-ketol/α-iminol rearrangements are used in a wide variety of synthetic applications including asymmetric synthesis, tandem reactions, and the total synthesis and biosynthesis of natural products. This review explores the use of α-ketol rearrangements in these contexts over the past two decades.

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“…The total synthesis of 2‴,5‴‐Diepisilvestrol ( 91) has been achieved and reported by Chambers and co‐workers in 2012. This strategy started by Mitsunobu coupling of already reported of lactol 92 and phenol 93 , in the presence of di‐2‐ methoxyethyl azodicarboxylate (DMEAD) and triphenyl phosphine (PPh 3 ) along with 4Å molecular sieves, to afford the coupled product 94 in good yield (55%) as an inseparable ∼2.5:1 mixture (determined by NMR data analysis) (Scheme ).…”

Section: Applications Of Mitsunobu Reaction In Total Synthesis Of Natmentioning

confidence: 99%

Applications of Mitsunobu Reaction in total synthesis of natural products

Heravi

Ghalavand

Ghanbarian

et al. 2018

Applied Organom Chemis

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The Mitsunobu Reaction allows the conversion of primary and secondary alcohols to esters, phenyl ethers, thioethers and some other compounds. The nucleophile employed should be acidic, since one of the reagents, diethylazodicarboxylate (DEAD) must be protonated during the course of the reaction, preventing from the formation of unwanted side products. In this review, we try to focus on the scope and preparative synthetic applications of Mitsunobu reaction as a key step in the total synthesis of biologically active natural products.

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Total Synthesis of 2‴,5‴-Diepisilvestrol and Its C1‴ Epimer: Key Structure Activity Relationships at C1‴ and C2‴

Cited by 19 publications

References 23 publications

Cytotoxic Rocaglate Derivatives from Leaves of Aglaia perviridis

Cytotoxic Rocaglate Derivatives from Leaves of Aglaia perviridis

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

Applications of Mitsunobu Reaction in total synthesis of natural products

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