Total synthesis of the potent anticancer Aglaia metabolites (-)-silvestrol and (-)-episilvestrol and the active analogue (-)-4'-desmethoxyepisilvestrol.

  title={Total synthesis of the potent anticancer Aglaia metabolites (-)-silvestrol and (-)-episilvestrol and the active analogue (-)-4'-desmethoxyepisilvestrol.},
  author={Tim E. Adams and Mariana El Sous and Bill C. Hawkins and Sebastian Hirner and Georgina A. Holloway and Mui Ling Khoo and David J. Owen and G Paul Savage and Peter J. Scammells and Mark A. Rizzacasa},
  journal={Journal of the American Chemical Society},
  volume={131 4},
Total synthesis of the anticancer 1,4-dioxane containing natural products silvestrol (1) and episilvestrol (2) is described by an approach based on the proposed biosynthesis of these novel compounds. The key steps included an oxidative rearrangement of the protected d-glucose derivative 11 to afford the 1,4-dioxane 12, which could be elaborated to the coupling partner 5 and a photochemical [3 + 2]-cycloadditon between the 3-hydroxyflavone 27 and methyl cinnamate followed by base-induced alpha… Expand
Structurally Modified Cyclopenta[b]benzofuran Analogues Isolated from Aglaia perviridis.
Four new cyclopenta[b]benzofuran derivatives based on an unprecedented carbon skeleton (1-4), with a dihydrofuran ring fused to dioxanyl and aryl rings, along with a new structural analogue (5) ofExpand
Biomimetic photocycloaddition of 3-hydroxyflavones: synthesis and evaluation of rocaglate derivatives as inhibitors of eukaryotic translation.
The scope of the photocycloaddition with various dipolarophiles, mechanistic and photophysical studies, and evaluation of the rocaglates produced as inhibitors of eukaryotic protein translation are described. Expand
Comparative phytochemistry of flavaglines (= rocaglamides), a group of highly bioactive flavolignans from Aglaia species (Meliaceae)
  • H. Greger
  • Medicine
  • Phytochemistry reviews : proceedings of the Phytochemical Society of Europe
  • 2021
Broad-based comparison revealed characteristic substitution trends which contribute as chemical markers to natural delimitation and grouping of taxonomically problematic Aglaia species and were shown to be not only promising anticancer agents but gained now also high expectations as agents against emerging RNA viruses like SARS-CoV-2. Expand
Bioactive flavaglines and other constituents isolated from Aglaia perviridis.
Eight new compounds, including two cyclopenta[b]benzopyran derivatives (1, 2), two cycloartane triterpenoids (5-7), and an apocarotenoid (8), together with 16 known compounds, were isolated from the chloroform-soluble partitions of separate methanol extracts of a combination of the fruits, leaves, and twigs and of the roots of Aglaia perviridis collected in Vietnam. Expand
Pd‐Catalyzed Reactions of Allenylphosphonates and Related Allenes with Functionalized 2‐Iodophenols, 2‐Iodobenzoic Acid, and 2‐Iodobenzyl Alcohol Leading to Functionalized Benzofurans, Isocoumarins, and Benzopyrans
Regioselective, palladium-catalyzed coupling reactions of allenylphosphonates (OCH2CMe2CH2O)P(O)CH=C=CRR′ [R, R′ = H (1a), R = H, R′ = Me (1b), R = R′ = Me (1c)] and phenyl allenes PhCH=C=CR2 [R = HExpand
All-carbon [3 + 2] cycloaddition in natural product synthesis
The development of all-carbon [3 + 2] cycloadditions is presented and their application in natural product synthesis reported in the last decade covering 2011–2020 (inclusive). Expand
Total synthesis of (±)-rocaglamide via oxidation-initiated Nazarov cyclization.
A sequence of experiments that led to an understanding of the unexpected reactivity of this key intermediate is described, which culminated in the successful total synthesis of (+)-rocaglamide. Expand
Delitschiapyrone A, a Pyrone–Naphthalenone Adduct Bearing a New Pentacyclic Ring System from the Leaf-Associated Fungus Delitschia sp. FL1581
Delitschiapyrone A (1), an α-pyrone–naphthalenone adduct with an unprecedented pentacyclic ring system, was isolated from a solid culture of the leaf-associated fungus Delitschia sp. FL1581. TheExpand
Synthesis and Isolation of Enantiomerically Enriched Cyclopenta[b]benzofurans Based on Products from Anodic Oxidation of 2,4‐Dimethylphenol
The anodic treatment of 2,4-dimethylphenol offers a powerful and direct method for the construction of a dehydrotetramer with four contiguous stereocentres on a multigram scale. The installation ofExpand
Chemistry and biology of rocaglamides (= flavaglines) and related derivatives from aglaia species (meliaceae).
This chapter reviews the chemistry and biology of the rocaglamide-type derivatives and related compounds, with emphasis on their structural diversity, biosynthesis, pharmacological significance and total synthesis. Expand


Silvestrol and episilvestrol, potential anticancer rocaglate derivatives from Aglaia silvestris.
Two cytotoxic rocaglate derivatives possessing an unusual dioxanyloxy unit, silvestrol (1) and episilvestrol (2), were isolated from the fruits and twigs of Aglaia silvestris by bioassay-guidedExpand
1-O-Alkylation of D-Glucopyranose
Abstract Direct 1-O-methylation of 1-O-metalated 2,3,4,6-tetra-O-benzyl-d-glucose (1) with methyl trifluoromethanesulfonate (3a) as a strong alkylating agent led to the methyl gluco-pyranosides 4aExpand
A Practical Synthesis of Mannosaminyl-β(1→4)-glucosyl-α(1→2)-rhamnose, the Trisaccharide Repeating Unit of a Streptococcus pneumoniae Capsular Polysaccharide
An efficient chemical synthesis is described for the title trisaccharide repeating unit of the capsular polysaccharide of Streptococcus pneumoniae Type 19F. The key intermediate was a well-accessibleExpand
Synthesis of the novel anti-leukaemic tetrahydrocyclopenta[b]benzofuran, rocaglamide and related synthetic studies
Two approaches to the rocaglamide tricyclic skeleton are described. The first, which employs an unusual intramolecular dithianyl anion to carbonyl addition reaction, provides access to α-phenylExpand
Stereoselective synthesis of (+/-)-rocaglaol analogues.
An intramolecular hydroxy epoxide opening was used to access the cyclopenta[b]benzofuran ring system of the natural product rocaglaol and this strategy is well-suited for the production of analogues with variation of the western ring. Expand
Epoxidation of alkenes by dioxirane intermediates generated in the reaction of potassium caroate with ketones
Kinetics and 180-labeling experiments have provided evidence for the involvment of dioxirane intermediates 2a (Scheme I) in the ketone-catalyzed decomposition of potassium peroxomonosulfate (KHS05,Expand
Total synthesis of (±)-rocaglamide and some aryl analogues
Abstract The insecticidal activity found for rocaglamide and its congeners, prompted us to establish a short and efficient synthesis of the natural product and some synthetic ‘halo-aryl’ analogues.Expand
A new analogue of rocaglamide by an oxidative dihydrofuran synthesis
Abstract A new analogue of rocaglamide 1 has been synthesised. The tricyclic core structure that is lacking the C-8b hydroxy group was generated in an oxidative addition of 1,3-cyclohexanedione to aExpand
Stereospecific synthesis of (+/-)-1,2-anhydro methyl rocaglate.
This letter shows that 14 is converted into 5 as a single stereoisomer and subsequently transformed into 1,2-anhydro methyl rocaglate 20. Expand
Several 4- protected D-glucopyranosides were synthesized and cleaved by sodium metaperiodate. Depending on the protection pattern the resulting dialdehydes showed different types of structures.Expand