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Usage

Uses

Used in Pharmaceutical Industry:
2-(2-hydroxyethyl)hexahydro-1H-4,7-epoxyisoindole-1,3(2H)-dione is used as a potential pharmaceutical agent for its possible biological activity, which may be attributed to its distinctive structural components. 2-(2-hydroxyethyl)hexahydro-1H-4,7-epoxyisoindole-1,3(2H)-dione's specific interactions with biological systems could be harnessed for therapeutic purposes, although further research is required to explore and validate its efficacy and safety.
Used in Medical Research:
In the field of medical research, 2-(2-hydroxyethyl)hexahydro-1H-4,7-epoxyisoindole-1,3(2H)-dione serves as a subject of investigation for its potential to influence biological processes. Its unique structure may allow it to interact with cellular targets or pathways in ways that could be beneficial for understanding disease mechanisms or developing new treatment strategies.

Upstream product

• 141-43-5 ethanolamine 
• 29745-04-8 norcantharidin 
• 6118-51-0 exo-3,6-epoxy-1,2,3,6-tetrahydrophthalic anhydride 
• 5426-09-5 4,10-dioxatricyclo[5.2.1.0^2,6]dec-8-ene-3,5-dione 
• 847757-03-3 (+/-)-(3aR,4S,7R,7aS)-2-(2-hydroxyethyl)-3a,4,7,7a-tetrahydro-1H-4,7-epoxyisoindole-1,3(2H)-dione 
• 1164475-59-5 7-oxabicyclo[2,2,1]heptane-2,3-dicarboxylic acid anhydride 

Relevant academic research and scientific papers

Development of nanodroplets for histotripsy-mediated cell ablation

This report describes the synthesis of amphiphilic copolymers (ABC-1 and ABC-2) composed of a hydrophilic poly(ethylene glycol) (PEG) block, a central poly(acrylic acid) (PAA) block, and a random copolymer of heptadecafluorodecyl methacrylate (HDFMA) and methyl methacrylate (MMA) forming the hydrophobic block, which are used to form nanodroplets for ultrasound-mediated cell ablation. Specifically, the effect of molecular weight of PEG and P(HDFMA-co-MMA) blocks on polymers ability to self-assemble around a variable amount (0%, 1%, and 2% v/v) of perfluoropentane (PFP) forming nanodroplets is investigated. The ability of different nanodroplets formulations embedded with a monolayer of red blood cells (RBCs) in tissue-mimicking agarose phantoms to initiate and sustain a bubble cloud in response to ultrasound treatments with different acoustic pressures and the associated ablation of RBCs were also investigated. Results show that ABC-1 polymer composed of a 2 kDa PEG block and a 6.7 kDa P(HDFMA-co-MMA) block better encapsulate the PFP core compared to ABC-2 polymer composed of a 5 kDa PEG block and 11.4 kDa P(HDFMA-co-MMA) block. Further, the ablative capacity indicated by the damage area in the RBCs monolayer increased with the increase in PFP content and reached its maximum with the nanodroplets formulated using ABC-1 polymer and encapsulating 2% v/v PFP. The nanodroplets formulated using ABC-1 polymer and loaded with 2% PFP produced the cavitation cloud and exhibited their ablative effect at an acoustic pressure that is 2.5-fold lower than the acoustic pressure needed to generate the same effect using a histotripsy (ultrasound) pulse alone, which indicates the ability of these nanodroplets to achieve targeted and self-limiting fractionation of disease cells while sparing neighboring healthy ones. Results also show that effective nanodroplets maintained their size and concentration upon incubation with bovine serum albumin at 37 °C for 24 h, which indicates their stability in physiologic conditions and their promise for in vivo cancer cell ablation.

Structural and theoretical study of four novel norcantharidine derivatives: Two new cases of conditional isomorphism

Structural and theoretical studies of four novel 5,6-dehydronorcantharidine (DNCA)/norcantharidine (NCA) derivatives, namely (3aR,4S,7R,7aS)-2-phenyl-3a,4,7,7a-tetrahydro-4,7-epoxy-1H-isoindole-1,3(2H)-dione, C14H11NO3 (DNCA-A), (3aR,4S,7R,7aS)-2-(4-nitrophenyl)-3a,4,7,7a-tetrahydro-4,7-epoxy-1H-isoindole-1,3(2H)-dione, C14H10N2O5 (DNCA-NA), (3aR,4S,7R,7aS)-2-(4-nitrophenyl)-3a,4,5,6,7,7a-hexahydro-1H-4,7-epoxyisoindole-1,3(2H)-dione, C14H12N2O5 (NCA-NA), and (3aR,4S,7R,7aS)-2-(2-hydroxyethyl)-3a,4,5,6,7,7a-hexahydro-1H-4,7-epoxyisoindole-1,3(2H)-dione, C10H13NO4 (NCA-AE), are reported. The supramolecular interactions and single-crystal structural characteristics of these molecules, together with the crystal structures of four other similar molecules, i.e. NCA-A (the 4-phenyl derivative of NCA-NA), DNCA-AE (the 5,6-unsaturated derivative of NCA-AE), DNCA and NCA, were analysed. Surprisingly, DNCA-A and NCA-A, as well as DNCA-NA and NCA-NA, proved to be isomorphic, while DNCA-AE and NCA-AE, as well as DNCA and NCA, have very different crystal structures. These are very rare isostructural examples between unsaturated and saturated oxanorbornene/oxanorbornane derivatives. To further explore how noncovalent interactions (NCIs) affect the degree of isomorphism in this particular series of rigid molecules where there is a fairly limited conformational degree of freedom, all four pairs of crystal structures were analyzed in parallel. The differentiation in NCIs which entails the packing mode of similar molecules is supported by energy calculations based on real or exchanged crystal structures. Our results show that minor structural differences may result in very different supramolecular interactions, and so lead to altered packing modes in the crystalline solids. Even if isostructurality sometimes occurs, the possibility of various molecular packing types cannot be ruled out. On the other hand, isomorphism may just be the result of kinetic possibilities instead of relative thermodynamic stabilities. Though crystal structure prediction is formidable, the comparison method based on existing crystal structures and quantum calculations can be used to predict the probability of isomorphism. This understanding will help us to design new norbornene derivatives with specified structures.

Norcantharimide analogues possessing terminal phosphate esters and their anti-cancer activity

A family of norcantharidin analogues possessing a terminal alcohol (ethanol, propanol, butanol, pentanol, hexanol and cyclohexanol) moiety were treated with either chlorodiethyl, chlorodiphenyl or chloro-bis-trichloroethyl- phosphate to afford highly focused libraries of the corresponding phosphate esters. Subsequent biological screening against a panel of nine human cancer cell lines identified a trend between the ease of phosphate unmasking (phosphate ester hydrolysis) and cell death. The most potent analogues possessed either a diphenyl or a bis-trichloroethyl moiety. The effect of alkyl spacer was also examined with the hexyl analogues typically more potent. 4-Aza-4-(3-{bis(2,2,2- trichloroethyl)phosphate}propyl)-10-oxatricyclo[5.2.1.0]decane-3,5-dione (10b) was the most potent analogue synthesised with an average GI50 of 11 μM across a panel of nine human carcinoma cell lines: colon carcinoma (HT29 and SW480); breast carcinoma (MCF-7); ovarian carcinoma (A2780); lung carcinoma (H460); skin carcinoma (A431); prostate carcinoma (DU145); neuronal carcinoma (BE2-C) and brain carcinoma (SJ-G2). This represents a fivefold improvement in anti-proliferative activity relative to the lead, norcantharidin.

Norcantharidin analogues with nematocidal activity in Haemonchus contortus

With the major problems with resistance in parasitic nematodes of livestock to anthelmintic drugs, there is an urgent need to develop new nematocides. In the present study, we employed a targeted approach for the design of a series of norcantharidin analogues (n = 54) for activity testing against the barber's pole worm (Haemonchus contortus) of small ruminants in a larval development assay (LDA) and also for toxicity testing on nine distinct human cell lines. Although none of the 54 analogues synthesized were toxic to any of these cell lines, three of them (N-octyl-7-oxabicyclo(2.2.1)heptane-2,3-dicarboximide (B2), N-decyl-7-oxabicyclo(2.2.1)heptane-2,3-dicarboximide (B3) and 4-[(4-methyl)-3-ethyl-2-methyl-5-phenylfuran-10-oxa-4-azatricyclo[5.2.1] decane-3,5-dione (B21) reproducibly displayed 99-100% lethality to H. contortus in LDA, with LD50s of 25-40 μM. The high 'hit rate' (5.6%) indicates that the approach taken here has advantages over conventional drug screening methods. A major advantage of norcantharidin analogues over some other currently available anthelmintics is that they can be produced in one to two steps in large amounts at low cost and high purity, and do not require any additional steps for the isolation of the active isomer. This positions them well for commercial development.

In situ ATRP-mediated hierarchical formation of giant amphiphile bionanoreactors

(Figure Presented) Functional giants: Amphiphilic bioconjugates can be synthesized in situ by grafting polystyrene from a protein (see scheme). The resulting giant amphiphiles display low polydispersities and the characteristic aggregation properties of amphiphilic biomacromolecules. A second, catalytically active guest protein can also be included within the superstructures.

COMPOUNDS, COMPOSITIONS AND METHODS FOR CONTROLLING INVERTEBRATE PESTS

The present application discloses the Tv-stp-1 serine/threonine phosphatase gene from Trichostrongylus vitrinus, and compounds that are useful as invertebrate control agents.

Norcantharimides, synthesis and anticancer activity: Synthesis of new norcantharidin analogues and their anticancer evaluation

A range of amines was reacted with norcantharidin (2) to provide the corresponding norcantharimides (9-43). Treatment of norcantharidin with allylamine afforded the corresponding allyl-norcantharimide (20) which was amenable to epoxidation (mCPBA, 22) and

Design and synthesis of N-maleimido-functionalized hydrophilic polymers via copper-mediated living radical polymerization: A suitable alternative to pegylation chemistry

A series of α-functional maleimide polymethacrylates (Mn = 4.1-35.4 kDa, PDi = 1.06-1.27) have been prepared via copper-catalyzed living radical polymerization (LRP). Two independent synthetic protocols have been successfully developed and the polymers obtained in multigram scale, with an 80-100% content of maleimide reactive chain ends, depending on the method employed. A method for the synthesis of amino-terminated polymers, starting from Boc-protected amino initiators, has also been developed, as these derivatives are key intermediates in one of the two processes studied in the present work. The alternative synthetic pathway involves an initiator containing a maleimide unit "protected" as a Diels-Alder adduct. After the polymerization step, the maleimide functionality has been reintroduced by retro-Diels-Alder reaction, by simply refluxing those polymers in toluene for 7 h. These maleimido-terminated materials, poly(methoxyPEG(475)) methacrylates and poly(glycerol) methacrylates, differ for both the nature and size of the polymer side branches and showed an excellent solubility in water, a property that made them an ideal candidate for the synthesis of new polymer-(poly)peptide biomaterials. These functional polymers have been successfully employed in conjugation reactions in the presence of thiol-containing model substrates, namely, reduced glutathione (γ-Glu-Cys-Gly) and the carrier protein, bovine serum albumin (BSA), in 100 mM phosphate buffer (pH 6.8-7.4) and ambient temperature.

Synthesis of glycerophospholipid conjugates of cantharidin and its analogues

A series of glycerophospholipid conjugates of cantharidin and its analogues were synthesized in a one-pot reaction, using hexaehtyl phosphorus triamide, activated by a catalytic amount of iodine, as the phosphorylating reagent. The structures of the title compounds were confirmed by 1H NMR, 31P NMR, IR and elemental analysis.