827348-01-6

Upstream product

• 501-36-0 (E)-5-[2-4-(hydroxyphenyl)ethenyl]-1,3-benzenediol 
• 18162-48-6 tert-butyldimethylsilyl chloride 
• 69739-34-0 t-butyldimethylsiyl triflate 

Downstream Products

• 387372-17-0 (E)-resveratrol-3-O-β-D-glucuronide 
• 1228999-17-4 resveratrol potassium 3-sulfate 
• 1185745-14-5 (E)-1-[3-tert-butyldimethylsilyloxy-5-O-(2,3,4-tri-O-acetyl-β-D-glucopyranoside)phenyl]-2-(4'-tert-butyldimethylsilyloxyphenyl)ethene methyl ester 
• 1185745-15-6 (E)-1-[3-tert-butyldimethylsilyloxy-5-O-(2,3,4-tri-O-pivaloyl-β-D-glucopyranoside)phenyl]-2-(4'-tert-butyldimethylsilyloxyphenyl)ethene methyl ester 
• 27208-80-6 polydatin 
• 892402-77-6 (E)-1-[3-{[tert-butyl(dimethyl)silyl]oxy}-5-(2,3,4,6-tetra-O-benzoyl-β-D-glucopyranosyloxy)phenyl]-2-(4-{[tert-butyl(dimethyl)silyl]oxy}phenyl)ethene 

Relevant academic research and scientific papers

Silyl resveratrol derivatives as potential therapeutic agents for neurodegenerative and neurological diseases

Natural phenolic compounds found in food have demonstrated interesting preventive and therapeutic effects on a large variety of pathologies. Indeed, some of them, such as resveratrol (RES), have been examined in clinical trials. Nevertheless, their success has been scarce mainly due to their low bioavailability. In this study, we found serendipitously that O-silyl RES derivatives exerted a better neuroprotective activity than resveratrol itself and decided to explore them as potential drugs for neurodegenerative and neurological diseases. We have also designed and prepared a series of O-silyl RES prodrugs to improve their bioavailability. We found that di-triethylsilyl and di-triisopropylsilyl RES derivatives were better in vitro neuroprotective and anti-inflammatory agents than RES. Among these derivatives and their corresponding acyl-, glycosyl- and carbamoyl-prodrugs, 3,5-triethylsilyl-4’-(6″-octanoylglucopyranosyl) resveratrol 26 showed the best profile on toxicity and neuroprotective activity in zebra fish embryo. Compound 26 was also capable of reducing the loss of motor coordination in a 3-nitropropionic acid mice model of Huntington's disease, in a similar way to RES. However, 26 diminished pro-inflammatory cytokine IL-6 to a higher extent than RES and improved the latency to fall in the rotarod test by 10% with respect to RES. Finally, we investigated 26 and RES as potential treatments on an experimental autoimmune encephalomyelitis (EAE) multiple sclerosis mice model. We observed that, in a therapeutic regimen, 26 significantly diminished the progression of EAE severity and reduced the percentage of animals with moderate to severe clinical score, whereas RES showed no improvement.

Resveratrol glucoside derivative as well as preparation method and application

The invention relates to the field of medicinal chemistry, in particular to a resveratrol glucoside derivative which can be used for treating osteoarthritis, and further discloses a preparation methodof the resveratrol glucoside derivative and pharmaceutical compositions of the resveratrol glucoside derivative. The compounds I and II disclosed by the invention can be used for treating articular cartilage degeneration injury, articular edge and subchondral bone reactive proliferative osteoarthritis diseases caused by multiple factors such as aging, obesity, strain, trauma, joint congenital abnormality, joint deformity, immune function abnormality and the like.

SILYLATED DERIVATIVES OF RESERVATROL AND THE USE THEREOF IN NEURODEGENERATIVE, NEUROLOGICAL OR INFLAMMATORY DISEASES

The present invention relates to a group of compounds derived from resveratrol having as substituents at least one silyl group which, in turn, can be substituted by different groups. The invention also relates to the therapeutic use of these compounds in inflammatory, neurological, and neurodegenerative diseases.

Cytotoxic, Antiangiogenic and Antitelomerase Activity of Glucosyl- and Acyl- Resveratrol Prodrugs and Resveratrol Sulfate Metabolites

Resveratrol (RES) is a natural polyphenol with relevant and varied biological activity. However, its low bioavailability and rapid metabolism to its glucuronate and sulfate conjugates has opened a debate on the mechanisms underlying its bioactivity. RES prodrugs are being developed to overcome these problems. We have synthesized a series of RES prodrugs and RES sulfate metabolites (RES-S) and evaluated their biological activities. RES glucosylated prodrugs (RES-Glc) were more cytotoxic in HT-29 and MCF-7 cells than RES itself whereas RES-S showed similar or higher cytotoxicity than RES. VEGF production was decreased by RES-Glc, and RES-disulfate (RES-diS) diminished it even more than RES. Finally, RES-Glc and RES-diS inhibited hTERT gene expression to a higher extent than RES. In conclusion, resveratrol prodrugs are promising candidates as anticancer drugs. In addition, RES-S showed distinct biological activity, thus indicating they are not simply RES reservoirs.

Design, synthesis and evaluation of a series of non-steroidal anti-inflammatory drug conjugates as novel neuroinflammatory inhibitors

Neuroinflammation is involved in the process of several central nervous system (CNS) diseases such as Parkinson's disease, Alzheimer's disease, ischemia and multiple sclerosis. As the macrophages in the central nervous system, microglial cell function in

Influence of glucuronidation and reduction modifications of resveratrol on its biological activities

Resveratrol (3,5,4′-trihydroxystilbene, RES), a star among dietary polyphenols, shows a wide range of biological activities, but it is rapidly and extensively metabolized into its glucuronide and sulfate conjugates as well as to the corresponding reduced

Preventive oral treatment with resveratrol pro-prodrugs drastically reduce colon inflammation in rodents

There is no pharmaceutical or definitive surgical cure for inflammatory bowel diseases (IBDs). The naturally occurring polyphenol resveratrol exerts anti-inflammatory properties. However, its rapid metabolism diminishes its effectiveness in the colon. The design of prodrugs to targeting active molecules to the colon provides an opportunity for therapy of IBDs. Herein we explore the efficacy of different resveratrol prodrugs and pro-prodrugs to ameliorate colon inflammation in the murine dextran sulfate sodium (DSS) model. Mice fed with a very low dose (equivalent to 10 mg for a 70 kg-person) of either resveratrol-3-O-(6′-O-butanoyl)-β-d-glucopyranoside (6) or resveratrol-3-O-(6′-O-octanoyl)-β-d-glucopyranoside (7) did not develop colitis symptoms and improved 6-fold the disease activity index (DAI) compared to resveratrol. Our results indicate that these pro-prodrugs exerted a dual effect: (1) they prevented the rapid metabolism of resveratrol and delivered higher quantities of resveratrol to the colon and (2) they reduced mucosal barrier imbalance and prevented diarrhea, which consequently facilitated the action of the delivered resveratrol in the colon mucosa.

Selective synthesis and biological evaluation of sulfate-conjugated resveratrol metabolites

Five resveratrol sulfate metabolites were synthesized and assessed for activities known to be mediated by resveratrol: inhibition of tumor necrosis factor (TNF) α induced NFkB activity, cylcooxygenases (COX-1 and COX-2), aromatase, nitric oxide

Synthesis of mono- and di-O-β-D-glucopyranoside conjugates of (E)-resveratrol

Starting from the commercially available natural product (E)-resveratrol (1), the four selectively tert-butyldimethylsilyl (TBS) protected (E)-resveratrols 6-9 were prepared by one reaction. Using 6-9 as glucosyl acceptors and trifluoroacetimidate 11 as glucosyl donor, three bioactive natural glucopyranoside conjugates of (E)-resveratrol 2-4 and one novel compound (5) were efficiently prepared in two steps. Georg Thieme Verlag Stuttgart.