2871-84-3

Basic information

• Product Name: (R)-3,4-bis(benzyloxy)-5-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)furan-2(5H)-one
• Synonyms: (R)-3,4-bis(benzyloxy)-5-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)furan-2(5H)-one
• CAS NO: 2871-84-3
• Molecular Weight: 396.44
• Mol File: 2871-84-3.mol

Chemical Properties

• CAS DataBase Reference: (R)-3,4-bis(benzyloxy)-5-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)furan-2(5H)-one(CAS DataBase Reference)
• NIST Chemistry Reference: (R)-3,4-bis(benzyloxy)-5-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)furan-2(5H)-one(2871-84-3)
• EPA Substance Registry System: (R)-3,4-bis(benzyloxy)-5-((S)-2,2-dimethyl-1,3-dioxolan-4-yl)furan-2(5H)-one(2871-84-3)

Safety Data

• Hazardous Substances Data: 2871-84-3(Hazardous Substances Data)

Upstream product

• 15042-01-0 5,6-O-isopropylidene-L-ascorbic acid 
• 100-39-0 benzyl bromide 
• 50-81-7 ascorbic acid 
• 100-44-7 benzyl chloride 
• 15042-01-0 5,6-isopropylidene L-ascorbate 

Downstream Products

• 136767-82-3 3,4-dibenzyloxy-5-(2-hydroxyethylidene)-2(5H)-furanone 
• 185683-68-5 (S)-3,4-Bis-benzyloxy-5-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-5H-furan-2-one 
• 86404-07-1 O³-benzyl-O⁵,O⁶-(1-methylethylidene)-L-ascorbic acid 
• 185675-41-6 3,4-bis(benzyloxy)-5-(2-hydroxyethyl)furan-2(5H)-one 
• 185675-57-4 (Z)-3,4-bis(benzyloxy)-5-(2-hydroxyethylidene)furan-2(5H)-one 
• 185675-42-7 Oxalic acid benzyl ester (R)-benzyloxycarbonyl-((S)-2,2-dimethyl-[1,3]dioxolan-4-yl)-methyl ester 
• 914771-19-0 [(2S)-2-[(2R)-3,4-dibenzyloxy-5-oxo-2H-furan-2-yl]-2-hydroxyethyl] hexadecanoate 

Relevant articles and documents

ANTITUMORAL ASCORBIC ACID ESTERS

The present invention provides a compound of formula (I), or a pharmaceutically acceptable salt thereof, or a stereoisomer thereof or mixture of stereoisomers, wherein n is an integer from 0 to 10; R1 is a biradical selected from the group consisting of CH2, O, NH and SH; and R2 is a (C3-C15)alkyl radical. The present invention also provides pharmaceutical compositions comprising the compound of formula (I), and said compound and pharmaceutical compositions for use as a medicament, more particularly, for use in the treatment or prevention of a neoplastic disease, such as pancreatic cancer.

Antitumor and antiviral activities of 4-substituted 1,2,3-triazolyl-2,3-dibenzyl-L-ascorbic acid derivatives

Two series of 6-(1,2,3-triazolyl)-2,3-dibenzyl-L-ascorbic acid derivatives with the hydroxyethylene (8a?8u) and ethylidene linkers (10c?10p) were synthesized and evaluated for their antiproliferative activity against seven malignant tumor cell lines and antiviral activity against a broad range of viruses. Conformationally unrestricted spacer between the lactone and 1,2,3-triazole units in 8a?8u series had a profound effect on antitumor activity. Besides, the introduction of a long side chain at C-4 of 1,2,3-triazole that led to the synthesis of decyl-substituted 2,3-dibenzyl-L-ascorbic acid 8m accounted for a selective and potent antiproliferative activity on breast cancer MCF-7 cells cells in the nM range. Further analysis showed that compound 8m strongly enhanced expression of hypoxia inducible transcription factor 1 α (HIF-1α) and to some extent decreased expression of nitric oxide synthase 2 (NOS2) suggesting its role in regulating HIF-1α signalling pathway. The p-methoxyphenyl-substituted derivative 10g displayed specific anti-cytomegalovirus (CMV) potential, whereas aliphatic-substituted derivatives 8l and 8m had the most potent, yet relatively non-specific, anti-varicella-zoster (VZV) activity.

Design, synthesis, and neuroprotective effects of dual-brain targeting naproxen prodrug

A new dual-targeting naproxen prodrug conjugated with glucose and ascorbic acid for central nervous system (CNS) drug delivery was designed and synthesized in order to effectively deliver naproxen to the brain. Naproxen could be released from the prepared prodrugs when incubated with various buffers, mouse plasma, and brain homogenate. Also, the prodrug showed superior neuroprotective effect in vivo over naproxen. Our results suggest that chemical modification of therapeutics with warheads of glucose and ascorbic acid represents a promising and efficient strategy for the development of brain targeting prodrugs by utilizing the endogenous transportation mechanism of the warheads.

Dual-targeting for brain-specific liposomes drug delivery system: Synthesis and preliminary evaluation

The treatment of glioma has become a great challenge because of the existence of brain barrier (BB). In order to develop an efficient brain targeting drug delivery system to greatly improve the brain permeability of anti-cancer drugs, a novel brain-targeted glucose-vitamin C (Glu-Vc) derivative was designed and synthesized as liposome ligand for preparing liposome to effectively deliver paclitaxel (PTX). The liposome was prepared and its particle size, zeta potential, encapsulation efficiency, release profile, stability, hemolysis and cytotoxicity were also characterized. What's more, the cellular uptake of CFPE-labeled Glu-Vc-Lip on GLUT1- and SVCT2-overexpressed C6 cells was 4.79-, 1.95-, 4.00- and 1.53-fold higher than that of Lip, Glu-Lip, Vc-Lip and Glu + Vc-Lip. Also, the Glu-Vc modified liposomes showed superior targeting ability in vivo evaluation compared with naked paclitaxel, non-coated, singly-modified and co-modified by physical blending liposomes. The relative uptake efficiency was enhanced by 7.53 fold to that of naked paclitaxel, while the concentration efficiency was up to 7.89 times. What's more, the Glu-Vc modified liposomes also displayed the maximum accumulation of DiD-loaded liposomes at tumor sites with the strongest fluorescence in the brain in vivo imaging. Our results suggest that chemical modification of liposomes with warheads of glucose and vitamin C represents a promising and efficient strategy for the development of brain-specific liposomes drug delivery system by utilizing the endogenous transportation mechanism of the warheads.

Continuous flow-ultrasonic synergy in click reactions for the synthesis of novel 1,2,3-triazolyl appended 4,5-unsaturated l-ascorbic acid derivatives

A combination of flow chemistry and batch-based synthetic procedures has been successfully applied to the assembly of novel 4,5-unsaturated l-ascorbic acid series 6a-6n with diverse C-6-substituted 1,2,3-triazole moiety. We report herein the first Cu(i)-catalyzed 1,3-dipolar cycloaddition of azido functionalized l-ascorbic acid derivative and selected alkynes to provide target 1,2,3-triazolyl appended 4,5-didehydro-5,6-dideoxy-l-ascorbic acid library 6a-6n under both micro-flow and batch conditions. Implementation of ultrasound with flow chemistry accelerated hour-scale reaction conditions in batch to the minute range in micro-flow device and considerably improved the yields for the flow syntheses of 6a-6n. Moreover, the synergistic use of microreactor technology and ultrasonic irradiation highlights the sustainable eco-friendly aspect of utilized method.

Design, synthesis and biological evaluation of novel l-ascorbic acid-conjugated pentacyclic triterpene derivatives as potential influenza virus entry inhibitors

Since the influenza viruses can rapidly evolve, it is urgently required to develop novel anti-influenza agents possessing a novel mechanism of action. In our previous study, two pentacyclic triterpene derivatives (Q8 and Y3) have been found to have anti-influenza virus entry activities. Keeping the potential synergy of biological activity of pentacyclic triterpenes and l-ascorbic acid in mind, we synthesized a series of novel l-ascorbic acid-conjugated pentacyclic triterpene derivatives (18-26, 29-31, 35-40 and 42-43). Moreover, we evaluated these novel compounds for their anti-influenza activities against A/WSN/33 virus in MDCK cells. Among all evaluated compounds, the 2,3-O,O-dibenzyl-6-deoxy-l-ascorbic acid-betulinic acid conjugate (30) showed the most significant anti-influenza activity with an EC50 of 8.7 μM, and no cytotoxic effects on MDCK cells were observed. Time-of-addition assay indicated that compound 30 acted at an early stage of the influenza life cycle. Further analyses revealed that influenza virus-induced hemagglutination of chicken red blood cells was inhibited by treatment of compound 30, and the interaction between the influenza hemagglutinin (HA) and compound 30 was determined by surface plasmon resonance (SPR) with a dissociation constant of KD = 3.76 μM. Finally, silico docking studies indicated that compound 30 and its derivative 31 were able to occupy the binding pocket of HA for sialic acid receptor. Collectively, these results suggested that l-ascorbic acid-conjugated pentacyclic triterpenes were promising anti-influenza entry inhibitors, and HA protein associated with viral entry was a promising drug target.

ASCORBIC ACID-RELATED COMPOUND AND ANTI-PLANT-VIRUS AGENT

The present invention provides a compound represented by formula (1) (wherein each of X1 and X2 independently represents -OR1, -NR2R3 or -CR4R5R6 or the like, each of

Design, synthesis and biological evaluation of brain targeting l-ascorbic acid prodrugs of ibuprofen with "lock-in" function

A novel brain targeting l-ascorbic acid derivatives with "lock-in" function were designed and synthesized as prodrugs to achieve the effective delivery of ibuprofen to brain by glucose transporter 1 (GLUT1) and the Na+-dependent vitamin C transporter SVCT2. Ibuprofen-loaded four prodrugs were tested in the animals. Results from the in vivo distribution study after i.v. administration of these four prodrugs and naked ibuprofen indicated that four prodrugs exhibited excellent transport ability across the BBB and significantly increased the level of ibuprofen in brain. Among them, prodrugs 4 showed higher brain concentration. Both biodistribution data and pharmacokinetic parameters suggested that l-ascorbic acid thiamine disulfide delivery system was a promising carrier to enhance CNS drug's delivery ability into brain.

Synthesis and cytotoxic evaluation of novel 2,3-di-O-alkyl derivatives of l-ascorbic acid

A new series of 2,3-di-O-alkyl derivatives of 5,6-O-isopropylidene-l- ascorbic acid were synthesized using phase transfer catalysis in aqueous media. These derivatives were screened for their superoxide radical scavenging activity and anticancer activity against human breast cancer cell line (MCF-7), leukemic cell line (HL-60), and cervical cell line (HeLa). All these derivatives exhibited enhanced scavenging effect than l-ascorbic acid except for the 4-fluorobenzyl or 2/4-chlorobenzyl alkyl group either at 3-O and/or 2-O position displayed pro-oxidant activity. These pro-oxidant derivatives (2c-e, m) exhibited potent anticancer activities against all the cell lines (IC 50 = 25.79-57.21 μM). However, these compounds were also cytotoxic to human normal leukemic macrophages THP-1. On the other hand, antioxidant derivatives displayed albeit slight (2k, IC50 = 57.96-63.45 μM), but selective inhibitory effect toward all tumor cell lines. Thus, pro-oxidant and antioxidant properties can be used to predict the cytotoxic selectivity of drug against normal and cancer cells.

Design, synthesis and preliminary biological evaluation of brain targeting l-ascorbic acid prodrugs of ibuprofen

l-Ascorbic acid (AA, vitamin C) exhibits a high concentration in the brain. The transportation of AA in brain is mainly mediated by the glucose transporter 1 (GLUT1) and the Na+-dependent vitamin C transporter SVCT2. While l-ascorbic acid C6O conjugation has been investigated as a tool to enhance brain drug delivery, C5O conjugation and C5O & C6O conjugation as brain targeting tools have not been reported. In this letter, ibuprofen was linked directly to C5O, C6O and C5O & C6O positions of l-ascorbic acid with eater bonds, providing prodrug 1, 2 and 3, respectively, to improve their targeting abilities in the brain. Prodrug 1, 2 and 3 were synthesized in facile ways with good yields. And the preliminary evaluation in vivo illustrated that prodrug 2 had a better targeting ability than prodrug 1. Moreover, prodrug 3, whose C5O & C6O positions were both modified, had good targeting ability for brain which will provide an important evidence for our further study on C5O- & C6O- di-derivatives of l-ascorbic acid.