Microbial trdrisformation of taxoids was inveStigared: taxoid 2 was transformed into 1β and 14β hydroxylated derivahves 3 and 4, unnatural taxoid 6 was transformed into 1β-hydroxy derivative 7 and 11(15-1) abeotaxa...Microbial trdrisformation of taxoids was inveStigared: taxoid 2 was transformed into 1β and 14β hydroxylated derivahves 3 and 4, unnatural taxoid 6 was transformed into 1β-hydroxy derivative 7 and 11(15-1) abeotaxane 8. Taxoids with an oxetane ring, 11-13 were synthesized from 1 via chemical reachons.展开更多
A compound,3-ethyl-3-hydroxymethyloxetane(EHO),was synthesized with diethyl carbonate and trihydroxypropane as raw materials,3-ethyl-3-allylmethoxy oxetane(EAMO)was synthesized with EHO and allyl bromide,and 1,1,3,3,5...A compound,3-ethyl-3-hydroxymethyloxetane(EHO),was synthesized with diethyl carbonate and trihydroxypropane as raw materials,3-ethyl-3-allylmethoxy oxetane(EAMO)was synthesized with EHO and allyl bromide,and 1,1,3,3,5,5-hexamethyl-1,5-bis[(3-ethyl-3-methoxyoxetane)propyl]trisiloxane(HMBEMOPTS)was synthesized with EAMO and 1,1,3,3,5,5-hexamethyltrisiloxane(HMTS).HMBEMOPTS is a novel UV-curable oligomer.The test of photo-DSC shows the photosensitivity of HMBEMOPTS is better than the ordinary oxetane,3-ethyl-3-[(3-ethyloxetan-3-yl)methoxymethyl]oxetane.HMBEMOPTS was mixed with bisphenol A type epoxy resin E-51 to prepare a cationic UV-curable system,and triarylsulfonium hexafluoroantimonate(UV-6976)was used as a cationic photoinitiator.The mechanical tests of coating films prove that when the mass fraction of HMBEMOPTS is 50%,the mechanical properties of the curing system are the best.The impact strength of the UV-curable films is measured to be 40 kg·cm and the flexibility is 2 mm;the tensile strength and flexural strength of the prepared specimens are 20.74 MPa and 13.43 MPa,respectively.The experimental results show that HMBEMOPTS can effectively improve photosensitivity and flexibility of the photosensitive resin.展开更多
-An oxetane ring can be constructed from 5 α-acyloxy-Δ4(20) -taxoids with osmylation as the first step in the usual manner. The innovation reported here is the use of an intramolecularly available acyl group for the...-An oxetane ring can be constructed from 5 α-acyloxy-Δ4(20) -taxoids with osmylation as the first step in the usual manner. The innovation reported here is the use of an intramolecularly available acyl group for the protection of 20-OH by an unexpected 5-to 20-migration under slightly basic conditions.展开更多
Treatment of health problems that accompany aging often includes pharmacotherapy. It is thus common for older adults—and, increasingly, younger adults—to be on multiple medications, either prescription or over-the-c...Treatment of health problems that accompany aging often includes pharmacotherapy. It is thus common for older adults—and, increasingly, younger adults—to be on multiple medications, either prescription or over-the-counter (OTC). With the consumption of multiple medications, drug-drug interactions (DDIs) are a concern. The site of drug-drug interactions is often at the level of drug metabolism. If a drug inhibits (or enhances) the metabolism of another, the blood level (therapeutic effect) can be decreased below the required level, or adverse effects can increase. Because most currently used drugs are metabolized via cytochrome P450-catalyzed pathways, drug discovers seek drugs that are metabolized by alternate pathways. Medicinal chemists have come upon a strategy—the incorporation of oxetane rings in the drug structure—that increases the likelihood that a drug will not be metabolized via CYP450. The same modification gives other desirable physical properties to the molecule. Although there are no guarantees that there will be fewer DDIs or an absence of other unexpected problems, the strategy could pave the way for new drugs that are safer and easier to use with concomitant medications.展开更多
The divergent synthesis of versatile 3,3′-disubstituted oxetane amino acids by utilizing visible-light-induced photocatalytic decarboxylative Giese-type reaction has been demonstrated.3-Methyleneoxetane-derived subst...The divergent synthesis of versatile 3,3′-disubstituted oxetane amino acids by utilizing visible-light-induced photocatalytic decarboxylative Giese-type reaction has been demonstrated.3-Methyleneoxetane-derived substrates are readily available in a single-step and highly reactive as radical acceptors,allowing the production of versatile oxetaneγ-andα-amino acids in high yields.A distinct ring strain release-driven radical addition mechanism was preliminarily revealed.The preparative power was further highlighted by the application in the synthesis of oxetane-containing dipeptides and azetidine amino acids,as well as the transformation of the product into novel oxetane-containing spiro-heterocycle pharmacophore.展开更多
In this paper, we combined high-end cationic UV-curable material with fluorinated chain obtaining a series of new fluorine-containing aromatic oxetane monomers via a mild nucleophilic substitution reaction. The struct...In this paper, we combined high-end cationic UV-curable material with fluorinated chain obtaining a series of new fluorine-containing aromatic oxetane monomers via a mild nucleophilic substitution reaction. The structures and properties of monomers were characterized using ~1 H-NMR, ^（19） F-NMR, dynamic viscosity tests and differential scanning calorimetry（DSC）. It was determined that all of the fluorinated monomers obtained had much lower viscosity and higher thermostability after the introduction of hexafluorobenzene. Then, UV-curable coatings were prepared using four fluorine-containing aromatic oxetane monomers（FOX1-4）; the UV-curing kinetics, with three kinds of initiators, and properties of the cured films were evaluated using real-time Fourier transform infrared（FTIR） spectroscopy, water and diiodomethane contact angle tests, surface energy calculations and scanning electron microscopy（SEM）. The FTIR spectroscopy results showed that the coatings possessed excellent conversion rate（〉 99% with liquid initiator PAG-201 in 150 s）, and as the fluorine content increased, the monomers exhibited decreased mobility with the increasing viscosity and worse solubility with fluorinated monomers, resulting in a lower conversion rate. Moreover, the coatings possessed favorable hydrophobic and oleophobic properties and low surface energies owing to the fluoride chains floating to the membrane-air interface, which was also confirmed by discrete concave structures in SEM images. These new kinds of monomers can replace traditional fluorinated cationic monomers applied to the fingerprint resistant, fouling resistant, scratch resistant and anti-aging coatings, adhesives or printing ink materials.展开更多
An oxetane ring can be constructed from 5α-acyloxy-Δ4(20)-taxoids. Hie facile intramolecular acyl migration from 5- to 20-position under slightly basic conditions enabled the construction of the oxetane ring in a co...An oxetane ring can be constructed from 5α-acyloxy-Δ4(20)-taxoids. Hie facile intramolecular acyl migration from 5- to 20-position under slightly basic conditions enabled the construction of the oxetane ring in a convenient short cut, whereas the acyl migration from 2- to 20-position left the 2-hydroxyl accessible to a later benzoylation. An unexpected five-mem-bered 4-O, 20- O sulfite ring was formed in the attempted construction of the oxetane ring with 5α-triflate as a leaving group. After the construction of the oxetane ring, treatment with strong base LiHMDS and acetyl chloride gave the expected 4-O-acetate while treatment with acetic anhydride and DMAP gave a 4-O-acetoacetate.展开更多
New D-seco-taxoids were synthesized from 1-deoxybaccatinⅥand their structures were confirmed by 1H NMR,13C NMR, ESIMS and X-ray crystallography.The key step of the synthesis involved the opening of the oxetane ring u...New D-seco-taxoids were synthesized from 1-deoxybaccatinⅥand their structures were confirmed by 1H NMR,13C NMR, ESIMS and X-ray crystallography.The key step of the synthesis involved the opening of the oxetane ring under acid and basic conditions in order to obtain new multidrug resistance（MDR） reversal agents and new synthetic precursors of paclitaxel analogues.展开更多
Two novel taxoids were synthesized from 1-deoxybaccatin Ⅵ and their crystal structures were determined by X-ray crystallographic techniques. The influences of oxetane ring on molecular conformations and bioactivity w...Two novel taxoids were synthesized from 1-deoxybaccatin Ⅵ and their crystal structures were determined by X-ray crystallographic techniques. The influences of oxetane ring on molecular conformations and bioactivity were investigated. The result shows that the oxetane ring plays an important role in the conformation and bioactivity of the diterpenoid core. In the structure of compound 3, the six-membered A ring exhibits the 1,4-di-planar conformation, the eightmembered B ring adopts a boat-chair conformation, and the six-membered C ring exhibits a slightly distorted half-chair conformation. However, in D-seco-taxoid 4, the six-membered C ring exhibits a boat conformation with the release of ring strain for the D-ring opening.展开更多
The photopolymerization kinetics of cycloaliphatic epoxide and oxetane with accelerators were investigated with Real-time Fourier transform infrared spectroscopy(RT-FTIR).The consumption rates of epoxy group and oxeta...The photopolymerization kinetics of cycloaliphatic epoxide and oxetane with accelerators were investigated with Real-time Fourier transform infrared spectroscopy(RT-FTIR).The consumption rates of epoxy group and oxetane group as a function of time were obtained by monitoring of the absorption peaks in the 789 cm-1 and 981 cm-1.The effect of accelerators type and the accelerating mechanism were discussed.In general,benzyl alcohol and its analogues with electron-donating substituents are useful accelerators for the cationic polymerization of cycloaliphatic epoxide and oxetane.Activated monomer mechanism and free-radical chain-induced decomposition of onium salt cationic photoinitiator account for the observed accelerating effect on the polymerization rate.展开更多
Propellants containing micro-aluminium particles have been shown to produce faster burn rates than conventional gun propellants.However,they are also more abrasive than conventional propellants.Nano-material propellan...Propellants containing micro-aluminium particles have been shown to produce faster burn rates than conventional gun propellants.However,they are also more abrasive than conventional propellants.Nano-material propellants have been reported to give similar benefits to micron-material propellants but without the disadvantage of increased abrasion.Tests were conducted to compare the burn rates,ignitability and wear rates of a propellant loaded with 0% aluminium,15% micro-aluminium and 15%nano-aluminium.Closed vessel tests showed a burn rate increase of 39% in the range 30-250 MPa,and 70% at low pressure(50-100MPa)for the nano-aluminium propellant compared with the baseline propellant.The micro-aluminium propellant showed only a 10%increase in the burn rate compared with the standard propellant.The ignition delay for the nano-aluminium propellant was slightly shorter than that of the baseline propellant.Substantially increased wear rates were measured for the micro-aluminium propellant.The nano-aluminium propellant showed reduced wear rates compared with the micro-aluminium propellant but these were still substantially greater than those for the baseline propellant.展开更多
文摘Microbial trdrisformation of taxoids was inveStigared: taxoid 2 was transformed into 1β and 14β hydroxylated derivahves 3 and 4, unnatural taxoid 6 was transformed into 1β-hydroxy derivative 7 and 11(15-1) abeotaxane 8. Taxoids with an oxetane ring, 11-13 were synthesized from 1 via chemical reachons.
基金Funded by the National Natural Science Foundation of China(No.21865017)。
文摘A compound,3-ethyl-3-hydroxymethyloxetane(EHO),was synthesized with diethyl carbonate and trihydroxypropane as raw materials,3-ethyl-3-allylmethoxy oxetane(EAMO)was synthesized with EHO and allyl bromide,and 1,1,3,3,5,5-hexamethyl-1,5-bis[(3-ethyl-3-methoxyoxetane)propyl]trisiloxane(HMBEMOPTS)was synthesized with EAMO and 1,1,3,3,5,5-hexamethyltrisiloxane(HMTS).HMBEMOPTS is a novel UV-curable oligomer.The test of photo-DSC shows the photosensitivity of HMBEMOPTS is better than the ordinary oxetane,3-ethyl-3-[(3-ethyloxetan-3-yl)methoxymethyl]oxetane.HMBEMOPTS was mixed with bisphenol A type epoxy resin E-51 to prepare a cationic UV-curable system,and triarylsulfonium hexafluoroantimonate(UV-6976)was used as a cationic photoinitiator.The mechanical tests of coating films prove that when the mass fraction of HMBEMOPTS is 50%,the mechanical properties of the curing system are the best.The impact strength of the UV-curable films is measured to be 40 kg·cm and the flexibility is 2 mm;the tensile strength and flexural strength of the prepared specimens are 20.74 MPa and 13.43 MPa,respectively.The experimental results show that HMBEMOPTS can effectively improve photosensitivity and flexibility of the photosensitive resin.
文摘-An oxetane ring can be constructed from 5 α-acyloxy-Δ4(20) -taxoids with osmylation as the first step in the usual manner. The innovation reported here is the use of an intramolecularly available acyl group for the protection of 20-OH by an unexpected 5-to 20-migration under slightly basic conditions.
文摘Treatment of health problems that accompany aging often includes pharmacotherapy. It is thus common for older adults—and, increasingly, younger adults—to be on multiple medications, either prescription or over-the-counter (OTC). With the consumption of multiple medications, drug-drug interactions (DDIs) are a concern. The site of drug-drug interactions is often at the level of drug metabolism. If a drug inhibits (or enhances) the metabolism of another, the blood level (therapeutic effect) can be decreased below the required level, or adverse effects can increase. Because most currently used drugs are metabolized via cytochrome P450-catalyzed pathways, drug discovers seek drugs that are metabolized by alternate pathways. Medicinal chemists have come upon a strategy—the incorporation of oxetane rings in the drug structure—that increases the likelihood that a drug will not be metabolized via CYP450. The same modification gives other desirable physical properties to the molecule. Although there are no guarantees that there will be fewer DDIs or an absence of other unexpected problems, the strategy could pave the way for new drugs that are safer and easier to use with concomitant medications.
基金Financial support from the program of the National Natural Science Foundation of China(21871086 and 22171080,Y-Q.Z.)Natural Science Foundation of Shanghai(23ZR1417200,Y.-Q.Z.)isgratefullyacknowledged.
文摘The divergent synthesis of versatile 3,3′-disubstituted oxetane amino acids by utilizing visible-light-induced photocatalytic decarboxylative Giese-type reaction has been demonstrated.3-Methyleneoxetane-derived substrates are readily available in a single-step and highly reactive as radical acceptors,allowing the production of versatile oxetaneγ-andα-amino acids in high yields.A distinct ring strain release-driven radical addition mechanism was preliminarily revealed.The preparative power was further highlighted by the application in the synthesis of oxetane-containing dipeptides and azetidine amino acids,as well as the transformation of the product into novel oxetane-containing spiro-heterocycle pharmacophore.
基金financially supported by the National Natural Science Foundation of China (No. 21574014)
文摘In this paper, we combined high-end cationic UV-curable material with fluorinated chain obtaining a series of new fluorine-containing aromatic oxetane monomers via a mild nucleophilic substitution reaction. The structures and properties of monomers were characterized using ~1 H-NMR, ^（19） F-NMR, dynamic viscosity tests and differential scanning calorimetry（DSC）. It was determined that all of the fluorinated monomers obtained had much lower viscosity and higher thermostability after the introduction of hexafluorobenzene. Then, UV-curable coatings were prepared using four fluorine-containing aromatic oxetane monomers（FOX1-4）; the UV-curing kinetics, with three kinds of initiators, and properties of the cured films were evaluated using real-time Fourier transform infrared（FTIR） spectroscopy, water and diiodomethane contact angle tests, surface energy calculations and scanning electron microscopy（SEM）. The FTIR spectroscopy results showed that the coatings possessed excellent conversion rate（〉 99% with liquid initiator PAG-201 in 150 s）, and as the fluorine content increased, the monomers exhibited decreased mobility with the increasing viscosity and worse solubility with fluorinated monomers, resulting in a lower conversion rate. Moreover, the coatings possessed favorable hydrophobic and oleophobic properties and low surface energies owing to the fluoride chains floating to the membrane-air interface, which was also confirmed by discrete concave structures in SEM images. These new kinds of monomers can replace traditional fluorinated cationic monomers applied to the fingerprint resistant, fouling resistant, scratch resistant and anti-aging coatings, adhesives or printing ink materials.
基金Project supported by Chinese Academy of Medical Science Researeh Grant and Taisho Pharmaceutical Co. Ltd.
文摘An oxetane ring can be constructed from 5α-acyloxy-Δ4(20)-taxoids. Hie facile intramolecular acyl migration from 5- to 20-position under slightly basic conditions enabled the construction of the oxetane ring in a convenient short cut, whereas the acyl migration from 2- to 20-position left the 2-hydroxyl accessible to a later benzoylation. An unexpected five-mem-bered 4-O, 20- O sulfite ring was formed in the attempted construction of the oxetane ring with 5α-triflate as a leaving group. After the construction of the oxetane ring, treatment with strong base LiHMDS and acetyl chloride gave the expected 4-O-acetate while treatment with acetic anhydride and DMAP gave a 4-O-acetoacetate.
基金the National Natural Science Foundation of China(No.30672506)Leading Academic Discipline Project of Shanghai Municipal Education Commission(No.J50102)
文摘New D-seco-taxoids were synthesized from 1-deoxybaccatinⅥand their structures were confirmed by 1H NMR,13C NMR, ESIMS and X-ray crystallography.The key step of the synthesis involved the opening of the oxetane ring under acid and basic conditions in order to obtain new multidrug resistance（MDR） reversal agents and new synthetic precursors of paclitaxel analogues.
基金supported by the National Natural Science Foundation of China(No.21272154 and 81202402)
文摘Two novel taxoids were synthesized from 1-deoxybaccatin Ⅵ and their crystal structures were determined by X-ray crystallographic techniques. The influences of oxetane ring on molecular conformations and bioactivity were investigated. The result shows that the oxetane ring plays an important role in the conformation and bioactivity of the diterpenoid core. In the structure of compound 3, the six-membered A ring exhibits the 1,4-di-planar conformation, the eightmembered B ring adopts a boat-chair conformation, and the six-membered C ring exhibits a slightly distorted half-chair conformation. However, in D-seco-taxoid 4, the six-membered C ring exhibits a boat conformation with the release of ring strain for the D-ring opening.
基金Natural Science Foundation of Hubei Province of China(No.2005ABA181)National Innovation Fund for Small Technology-based Firms(No.05C26214201059)
文摘The photopolymerization kinetics of cycloaliphatic epoxide and oxetane with accelerators were investigated with Real-time Fourier transform infrared spectroscopy(RT-FTIR).The consumption rates of epoxy group and oxetane group as a function of time were obtained by monitoring of the absorption peaks in the 789 cm-1 and 981 cm-1.The effect of accelerators type and the accelerating mechanism were discussed.In general,benzyl alcohol and its analogues with electron-donating substituents are useful accelerators for the cationic polymerization of cycloaliphatic epoxide and oxetane.Activated monomer mechanism and free-radical chain-induced decomposition of onium salt cationic photoinitiator account for the observed accelerating effect on the polymerization rate.
基金funded by the Defence Science and Technology Laboratory(Dstl)part of the UK MoD,under the Hazard Modelling and Simulation task of the UK Energetics(UK-E)programme now consumed by the Weapons Science and Technology Centre(WSTC)
文摘Propellants containing micro-aluminium particles have been shown to produce faster burn rates than conventional gun propellants.However,they are also more abrasive than conventional propellants.Nano-material propellants have been reported to give similar benefits to micron-material propellants but without the disadvantage of increased abrasion.Tests were conducted to compare the burn rates,ignitability and wear rates of a propellant loaded with 0% aluminium,15% micro-aluminium and 15%nano-aluminium.Closed vessel tests showed a burn rate increase of 39% in the range 30-250 MPa,and 70% at low pressure(50-100MPa)for the nano-aluminium propellant compared with the baseline propellant.The micro-aluminium propellant showed only a 10%increase in the burn rate compared with the standard propellant.The ignition delay for the nano-aluminium propellant was slightly shorter than that of the baseline propellant.Substantially increased wear rates were measured for the micro-aluminium propellant.The nano-aluminium propellant showed reduced wear rates compared with the micro-aluminium propellant but these were still substantially greater than those for the baseline propellant.
