960365-65-5

Usage

Uses

Used in Cancer Treatment:
Silvestrol aglycone is used as an antitumor agent for its ability to selectively target and induce the death of cancer cells. Its mechanism of action involves binding to the ribosome and inhibiting protein synthesis, which is crucial for the survival and proliferation of cancer cells.
Used in Pharmaceutical Research:
Silvestrol aglycone is used as a research compound in the development of new cancer therapies. Its unique mechanism of action and selectivity for cancer cells make it an attractive candidate for further investigation and potential incorporation into novel drug formulations.
Used in Drug Delivery Systems:
To enhance the therapeutic potential and bioavailability of silvestrol aglycone, various drug delivery systems are being explored. These systems aim to improve the delivery of silvestrol aglycone to cancer cells, increasing its efficacy and reducing potential side effects. Organic and metallic nanoparticles, among other carriers, are being investigated for their ability to transport silvestrol aglycone effectively to the target cells.

Upstream product

• 960365-75-7 C₂₉H₃₀O₉ 
• 1112993-16-4 C₃₄H₃₂O₈ 
• 1402931-29-6 1-(4-(benzyloxy)-2-hydroxy-6-methoxyphenyl)-2-hydroxyethanone 
• 39548-89-5 1-(4-(benzyloxy)-2-hydroxy-6-methoxyphenyl)ethan-1-one 
• 681294-57-5 1-(4-(benzyloxy)-2-hydroxy-6-methoxyphenyl)ethanone 
• 110506-85-9 7-(benzyloxy)-5-hydroxy-2-phenyl-4H-chromen-4-one 
• 480-40-0 5,7-dihydroxy-2-phenyl-chromen-4-one 
• 1402931-30-9 7-(benzyloxy)-5-methoxy-2-(4-methoxyphenyl)-4-oxo-4H-chromen-3-yl 4-methoxybenzoate 
• 103-26-4 Methyl cinnamate 
• 874202-33-2 7-(benzyloxy)-3-hydroxy-5-methoxy-2-(4-methoxyphenyl)-4H-chromen-4-one 

Downstream Products

• 960505-99-1 C₄₆H₆₆O₁₃Si₂ 
• 143901-35-3 aglafoline 
• 1402931-62-7 (1R,2R,3S,3aR,8bS)-methyl 1,8b-dihydroxy-8-methoxy-3a-(4-methoxyphenyl)-3-phenyl-6-(trifluoromethylsulfonyloxy)-2,3,3a,8b-tetrahydro-1H-benzo[b]cyclopenta[d]furan-2-carboxylate 
• 1402931-74-1 (1R,2R,3S,3aR,8bS)-methyl 6-acetyl-1,8b-dihydroxy-8-methoxy-3a-(4-methoxyphenyl)-3-phenyl-2,3,3a,8b-tetrahydro-1H-benzo[b]-cyclopenta[d]furan-2-carboxylate 
• 1402931-75-2 (1R,2R,3S,3aR,8bS)-methyl 6-cyano-1,8b-dihydroxy-8-methoxy-3a-(4-methoxyphenyl)-3-phenyl-2,3,3a,8b-tetrahydro-1H-benzo[b]-cyclopenta[d]furan-2-carboxylate 
• 1402931-76-3 (1R,2R,3S,3aR,8bS)-methyl 6-chloro-1,8b-dihydroxy-8-methoxy-3a-(4-methoxyphenyl)-3-phenyl-2,3,3a,8b-tetrahydro-1H-benzo[b]-cyclopenta[d]furan-2-carboxylate 
• 1402931-96-7 C₄₇H₄₈O₁₂ 
• 1402931-82-1 C₃₉H₄₀O₁₁ 
• 1402931-59-2 (1R,2R,3S,3aR,8bS)-methyl 1,8b-dihydroxy-6-((2S,6R)-6-(hydroxymethyl)tetrahydro-2H-pyran-2-yloxy)-8-methoxy-3a-(4-methoxyphenyl)-3-phenyl-2,3,3a,8b-tetrahydro-1H-benzo[b]-cyclopenta[d]furan-2-carboxylate 

Relevant academic research and scientific papers

Synthetic silvestrol analogues as potent and selective protein synthesis inhibitors

Misregulation of protein translation plays a critical role in human cancer pathogenesis at many levels. Silvestrol, a cyclopenta[b]benzofuran natural product, blocks translation at the initiation step by interfering with assembly of the eIF4F translation complex. Silvestrol has a complex chemical structure whose functional group requirements have not been systematically investigated. Moreover, silvestrol has limited development potential due to poor druglike properties. Herein, we sought to develop a practical synthesis of key intermediates of silvestrol and explore structure-activity relationships around the C6 position. The ability of silvestrol and analogues to selectively inhibit the translation of proteins with high requirement on the translation-initiation machinery (i.e., complex 5′-untranslated region UTR) relative to simple 5′UTR was determined by a cellular reporter assay. Simplified analogues of silvestrol such as compounds 74 and 76 were shown to have similar cytotoxic potency and better ADME characteristics relative to those of silvestrol.

Total synthesis of 2?,5?-diepisilvestrol and its C1''' epimer: Key structure activity relationships at C1''' and C2'''

The first total synthesis of the low-abundance natural product 2?,5?-diepisilvestrol (4) is described. The key step involved a Mitsunobu coupling between cyclopenta[b]benzofuran phenol 7 and dioxane lactol 6. Deprotection then gave a 1:2.6 ratio of natural product 2?,5?- diepisilvestrol (4) and its C1 epimer 1?,2?,5?- triepisilvestrol (15) in 50% overall yield. An in vitro protein translation inhibition assay showed that 2?,5?-diepisilvestrol (4) was considerably less active than episilvestrol (2), while the unnatural isomer 1?,2?,5?-triepisilvestrol (15) was essentially inactive, showing that the configuration at C1''' and C''' has a large effect on the biological activity.

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

Total synthesis of the anticancer 1,4-dioxane containing natural products silvestrol (1) and episilvestrol (2) is described by an approach basedon the proposed biosynthesis of these novel compounds. The key steps in cluded 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 α-ketol rearrangement and reduction to give the cyclopentabenzofuran core 33. The core (-)-6 and 1,4-dioxane fragment 5 were united by a highly stereoselective Mitsunobu coupling with the modified azodicarboxylate DMEAD toafford the axial coupled product 36. Deprotection then gave episilvestr ol (2). Silvestrol (1) was synthesized by a coupling between core (-)-6 and the dioxane 44 followed by deprotection. Compound 1 was also synthesized from episilvestrol (2) by a Mitsunobu inversion. In addition, the analogue 4-desmethoxyepisilvestrol (46) was synthesized via the same route. It was found that 46 and episilvestrol 2 displayed an unexpected concentration-dependent chemical shift variation for the nonexchangeable dioxane protons. Synthetic compounds 1, 2, 38, 46, and 54 were tested against cancer cells lines, and it was found that the stereochemistry of the core was critical for activity. Synthetic analogue 4-desmethoxyepisilvestrol (46) was also active against lung and colon cancer cell lines.

Enantioselective synthesis of the complex rocaglate (-)-silvestrol

The total synthesis of the natural product (-)-silvestrol (1) has been accomplished and features enantioselective [3+2] photocycloaddition of a substituted 3-hydroxyflavone and methyl cinnamate promoted by a chiral Bronsted acid. Initial biological studies indicate a 5-10-fold greater activity of silvestrol as an inhibitor of protein synthesis in HeLa cells than its 1″″ diastereomer.