THP Group Research Articles

Synthesis of (−)-Cephalosporolide D Using an Iterative Acetylene–Epoxide Coupling Strategy

Abstract The synthesis of an eight-membered lactone, cephalosporolide D is described using an iterative acetylene–epoxide coupling strategy. The terminal triple bond compound prepared in situ from the known epoxy chloride was coupled with (R)-methyloxirane to afford the propargyl alcohol. The selective protection of the propargylic hydroxy group as TBS ether followed by reduction of the triple bond gave the saturated alcohol. Removal of THP group followed by selective oxidation of the primary hydroxy group was achieved using BAIB–TEMPO to furnish the aldehyde, which was converted to the corresponding acid by Pinnick oxidation, followed by Yamaguchi lactonization and finally removal of the TBS group afforded the target molecule. A concise synthesis of (−)-cephalosporolide D is described. The salient features are the utilization of acetylene–epoxide coupling strategy and Yamaguchi lactonization.

Concise Synthesis of Licochalcone A through Water-Accelerated [3,3]-Sigmatropic Rearrangement of an Aryl Prenyl Ether

Claisen-Schmidt condensation of 4-(tetrahydropyran-2-yloxy)acetophenone with 2-methoxy-4-[(3-methylbut-2-en-1-yl)oxy]benzaldehyde gave a THP-protected chalcone ether. Removal of the THP group under mild acidic conditions gave the corresponding chalcone ether, which underwent a water-accelerated Claisen rearrangement under microwave irradiation or heating in a sealed tube in aqueous ethanol to give a good yield of licochalcone A, which has diverse biological activities; no product of deprenylation or abnormal Claisen rearrangement was formed. The abnormal Claisen rearrangement of γ-substituted allyl aryl ethers is known to be a problem in [3,3]-sigmatropic rearrangement reaction; this, however, was not detected in our water-accelerated system.

Additive antitumoral effect of interleukin-12 gene therapy and chemotherapy in the treatment of urothelial bladder cancer in vitro and in vivo

We evaluated antitumoral effect of combined chemotherapy and interleukin-12 (IL-12) gene therapy in in vitro and in vivo experimental urothelial bladder cancer (UBC) model. EJ UBC cells were transfected with recombinant IL-12 genes using a liposomal transfection agent. Pirarubicin (THP) was added to the experimental samples at a final concentration of 20 mg/l. Four groups were assigned in vitro: untreated cells, transfected cells, untransfected cells plus THP and transfected cells plus THP. Death rates (DR) and cellular micromorphologic changes were evaluated. Bladder tumor model was established by subcutaneous injection of EJ cells to the nude mice. Four groups were assigned in vivo: control group; THP group; IL-12 gene group and IL-12 gene plus THP group. After injection of combined THP and IL-12 gene therapy, tumor size and IL-12 levels were evaluated. In vitro study: DR in the THP + IL-12 gene therapy group (58.2 ± 15.8%) was significantly higher than transfected group (12.2 ± 5.6%; P = 0.01) and untransfected cells plus THP group (33.4 ± 7.8; P = 0.046). A higher amount of apoptotic changes and necrosis on transmission electron microscope analysis were observed in transfected cells plus THP group. In vivo study: A significant tumor attenuation was found in IL-12 gene in combination with THP group when compared with any other groups that were treated without Il-12 or THP (P < 0.05). IL-12 levels in serum were significant high in IL-12 gene groups (P < 0.01). The combination of THP chemotherapy and IL-12 gene therapy showed an additive antitumoral effect on bladder cancer cells in vitro and in vivo. Further investigation should be focused on high-level transgene protocols in vivo.

High-Frequency Ultrasound-Responsive Block Copolymer Micelle

Micelles of a diblock copolymer composed of poly(ethylene oxide) and poly(2-tetrahydropyranyl methacrylate) (PEO-b-PTHPMA) in aqueous solution could be disrupted by high-frequency ultrasound (1.1 MHz). It was found that, upon exposure to a high-intensity focused ultrasound (HIFU) beam at room temperature, the pH value of the micellar solution decreased over irradiation time. The infrared spectroscopic analysis of solid block copolymer samples collected from the ultrasound irradiated micellar solution revealed the formation of carboxylic acid dimers and hydroxyl groups. These characterization results suggest that the high-frequency HIFU beam could induce the hydrolysis reaction of THPMA at room temperature resulting in the cleavage of THP groups. The disruption of PEO-b-PTHPMA micelles by ultrasound was investigated by using dynamic light scattering, atomic force microscopy, and fluorescence spectroscopy. On the basis of the pH change, it was found that the disruption process was determined by a number of factors such as the ultrasound power, the micellar solution volume and the location of the focal spot of the ultrasound beam. This study shows the potential to develop ultrasound-sensitive block copolymer micelles by having labile chemical bonds in the polymer structure, and to use the high-frequency HIFU to trigger a chemical reaction for the disruption of micelles.

Synthesis of cyanato-functional polymaleimides and their application in negative-tone photoimaging by post-crosslinking

A cyanato-functional maleimide monomer (CyOPMI) was radically copolymerized with N-[4-(tetrahydropyranyloxy)phenyl]maleimide (THPPMI) and methyl methacrylate (MMA) to obtain reactive cyanate polymers along with acid-labile THP-protecting groups. The soluble copolymers of CyOPMI, employed as cyanato-imidopolymers, were converted to the insoluble polymers by thermal or photo-acid treatment based on the acid-catalyzed deprotection of THP groups and cyclotrimerization of the pendent cyanto groups to form a crosslinked triazine structure (cyanurate). Upon this selective post-crosslinking, the cyanato-polymers were applied to negative-tone photoimaging by photolithography. CyOPMI was radically copolymerized with various vinyl monomers such as MMA, styrenes (St) and alkyl vinyl ethers (R’VE) to obtain soluble polymers by controlling the monomer feed ratios and polymerization conditions. The high thermal properties of the cyanato-imido polymers were attributed to the curing characteristics of the pendant cyanatophenyl and imidophenolic groups.

Reactivity to Helicobacter pylori Antigens in Patients Suffering from Thyroid Gland Autoimmunity

The role of infection in autoimmunity is widely discussed. In this study we concentrated on relationship between HELICOBACTER PYLORI as a very important gastroduodenal pathogen and autoimmune thyroiditis (AT). Forty seven AT patients and 34 healthy controls were enrolled. They were split into: THP ( H.PYLORI positive patients, n=17), THN ( H.PYLORI negative patients, n=30), CP ( H.PYLORI positive controls, n=17) and CN groups ( H.PYLORI negative controls, n=17). By protein microarray we analysed production of 23 cytokines and chemokines prior and post stimulation with H.PYLORI lysate and its lipopolysaccharide (LPS). Reactivity to lysate as well as to bacterial LPS differed within groups. The lowest basal cytokine and chemokine production was observed in CN group but these subjects reacted significantly to specific stimulation by increasing IFN-gamma (in comparison with THP p=0.01 for LPS and p=0.004 for H.PYLORI lysate) and TGF-beta production (p=0.015 for LPS). In contrast, IL-10 and IL-5 were decreased in this group. In CP, THN and THP groups, we observed in general higher chemokine response. THP group increased proinflammatory IL-6 after specific stimulation as well (in comparison with CP p<0.0001 for LPS stimulation). We observed different "reactivity pattern" to H.PYLORI within groups with low basal cytokine and chemokine production in healthy H.PYLORI negative controls but with clear specific response in IFN-gamma and TGF-beta production in this group. Adequate immune reaction which is joined to appropriate immunoregulation leads to prevention of the chronic infection and on the other hand may prevent the development of "connected" diseases such as autoimmune.

Comparative Radiographic and Clinical Outcome of Two-Hole and Multi-Hole Symphyseal Plating

To report on the radiographic and clinical outcome of symphyseal plating techniques, with specific attention to the incidence of implant failure, reoperation secondary to implant complication, and ability to maintain reduction of the pelvic ring. Retrospective chart and radiographic review. Level 1 trauma center. A total of 229 skeletally mature patients with traumatic pelvic disruptions associated with pubic symphysis diastasis requiring open reduction internal fixation. Symphyseal plating: (1) group THP, a two-hole plate; (2) group MHP, a multi-hole plate (minimum 2 holes/screws on either side of the symphysis). Patients were analyzed with respect to technique of anterior ring fixation and posterior ring injury pattern and fixation. Retrospective review of charts and radiographs immediately after the index procedure to latest follow-up was performed. Analysis included pelvic ring injury, type of anterior and/or posterior fixation, maintenance of postoperative reduction, rate of implant failure, and need for reoperation secondary to implant complication. Additionally, logistic regression analysis was performed to detect correlation between any other variable (posterior injury pattern, presence or absence of posterior fixation, time to surgery) and failure or malunion. Statistical analyses were performed using SPSS software. A total of 92 complete data sets were available for review. There were 51 patients in group THP and 41 patients in group MHP. When comparing the results of the 2 different methods of anterior fixation (THP versus MHP), the rate of fixation failure was greater in group THP (17 of 51; 33%) than group MHP (5 of 41; 12%). This was statistically significant (P = 0.018). When evaluating the presence of a malunion as a result of these 2 treatment methods, there were more present in the THP group (29 of 51; 57%) than in the MHP group (6 of 41; 15%). Again, this was highly statistically significant (P = 0.001). Although the reoperation rate was slightly higher in the THP group (16%) as compared to the MHP group (12%), this was not statistically significant (P = 0.67). Logistic regression analysis did not reveal any other variables to correlate as a risk factor for failure or malunion in this group of patients. In this group of patients, the two-hole symphyseal plating technique group had a higher implant failure rate and, more importantly, a significantly higher rate of pelvic malunion. On the basis of these findings, we recommend multi-hole plating of unstable pubic symphyseal disruptions.

A school-based randomized controlled trial to improve physical activity among Iranian high school girls.

BackgroundPhysical activity (PA) rates decline precipitously during the high school years and are consistently lower among adolescent girls than adolescent boys. Due to cultural barriers, this problem might be exacerbated in female Iranian adolescents. However, little intervention research has been conducted to try to increase PA participation rates with this population. Because PA interventions in schools have the potential to reach many children and adolescents, this study reports on PA intervention research conducted in all-female Iranian high schools.MethodsA randomized controlled trial was conducted to examine the effects of two six-month tailored interventions on potential determinants of PA and PA behavior. Students (N = 161) were randomly allocated to one of three conditions: an intervention based on Pender's Health Promotion model (HP), an intervention based on an integration of the health promotion model and selected constructs from the Transtheoretical model (THP), and a control group (CON). Measures were administered prior to the intervention, at post-intervention and at a six-month follow-up.ResultsRepeated measure ANOVAs showed a significant interaction between group and time for perceived benefits, self efficacy, interpersonal norms, social support, behavioral processes, and PA behavior, indicating that both intervention groups significantly improved across the 24-week intervention, whereas the control group did not. Participants in the THP group showed greater use of counter conditioning and stimulus control at post-intervention and at follow-up. While there were no significant differences in PA between the HP and CON groups at follow-up, a significant difference was still found between the THP and the CON group.ConclusionThis study provides the first evidence of the effectiveness of a PA intervention based on Pender's HP model combined with selected aspects of the TTM on potential determinants to increase PA among Iranian high school girls.

Conjugated Polymers as Heterogeneous Catalyst in Organic Synthesis

In this review, we have focused our attention on the application of conjugated polymers as heterogeneous catalyst in organic transformations, which appeared in the literature. Conjugated polymers have attracted interest as promising materials for catalyst support for a decade. Conjugated polymers having heteroatom in their backbone can be easily doped with acids like Bronsted, organic, Lewis and heteropoly acids. These conjugated polymers containing acids can act as polymer based solid acid catalyst in organic synthesis. Use of conjugated polymer salts, complexes and metal composites in organic transformations is discussed and the advantages of conjugated polymers in catalysis field are brought out in this review. Keywords: polyaniline, THP group, oxidizing agents, Mannich-Type Reactions, Pechmann Reaction, Coumarins

Synthesis of an isomeric mixture (24 RS,25 RS) of sodium scymnol sulfate

This is the first reported multistep synthesis of the shark bile sterol sodium scymnol sulfate epimeric at the C-24 hydroxyl and C-27 sulfate positions. The starting cholic acid was protected as the tetrahydropyran ether (THP) derivative, reduced to the C-24 alcohol and oxidized to the protected aldehyde. This aldehyde was then coupled with methyl 3-hydroxypropionate using 2 equiv. of lithium diethylamide at −65 °C to produce methyl (24 RS,25 RS)-24,27-dihydroxy-3α,7α,12α,tris[(tetrahydropyran-2-yl)oxy]-5β-cholestan-26-oate. After protecting the 24 and 27 hydroxyls as the THP derivatives, this fully protected ester was then reduced to the monoalcohol. The monoalcohol was sulfated using the sulfur trioxide–triethylamine complex in dimethylformamide. The protective THP groups were removed with methanolic HCl and the sulfate was converted to the sodium salt with sodium ethoxide in methanol. This general synthetic scheme has application to produce a range of monosulfated sterols.

Mixed-Metal Cluster Chemistry. 30. Syntheses and Optical Limiting Properties of Cluster-Containing Oligo- and Polyurethanes

Molybdenum−iridium clusters Mo2Ir2{μ4-η2-C2[(CH2)6OH]2}(μ-CO)4(CO)4(η-C5H4R)2 [R = H (5), Me (6), (CH2)9O(THP) (7); THP = tetrahydropyranyl] are formed from reaction of Mo2Ir2(μ-CO)3(CO)7(η-C5H4R)2 with the alkyne HO(CH2)6C2(CH2)6OH. Reaction of 6 and 7 with the diisocyanate OCN(CH2)4NCO affords oligourethanes [−O(CH2)6(μ4-η2-C2){Mo2Ir2(μ-CO)4(CO)4(η-C5H4R)2}(CH2)6OC(O)NH(CH2)4NHC(O)−]n [R = Me (12), (CH2)9O(THP) (13)], with transition metal clusters in the backbone, the extent of polymerization being ascertained by size exclusion chromatography and 1H NMR spectroscopy. Characterization of the cluster-containing oligo- and polyurethanes was aided by 1H NMR and IR spectral comparison with model cluster diurethanes Mo2Ir2{μ4-η2-C2[(CH2)6OC(O)NH(CH2)3Me]2}(μ-CO)4(CO)4(η-C5H4R)2 [R = H (8), Me (9), (CH2)9O(THP) (11)], prepared from reaction between the cluster diols 5, 6, and 7 and the isocyanate Me(CH2)3NCO. The diol cluster 5 and cluster diurethane 8 have been characterized by single-crystal X-ray diffraction studies. Removal of the THP groups in 13 gives [−O(CH2)6(μ4-η2-C2){Mo2Ir2(μ-CO)4(CO)4(η-C5H4(CH2)9OH)2}(CH2)6OC(O)NH(CH2)4NHC(O)−]n (14), which has been cross-linked on reaction with OCN(CH2)4NCO. The cluster content of the polyurethanes can be diluted; polymerization of 1:19 6:1,6-hexanediol and OCN(CH2)4NCO affords copolymer [−O(CH2)6(μ4-η2-C2){Mo2Ir2(μ-CO)4(CO)4(η-C5H4Me)2}(CH2)6OC(O)NH(CH2)4NHC(O){O(CH2)6OC(O)NH(CH2)4NHC(O)}m−]n (16). The optical limiting properties of these dimolybdenum-diiridium clusters and cluster-containing polymers, and related molybdenum-triiridium clusters and tungsten-containing homologues, have been assessed by open-aperture Z-scan studies at 527 nm employing ns pulses. Optical limiting merit increases upon increasing group 6 metal content, and replacing the 4d metal molybdenum with the 5d metal tungsten. Some insight into the mechanism by which these clusters function as optical limiters has been gleaned from complementary pump−probe studies, with their behavior consistent with a fast nonlinear absorption process followed by reverse saturable absorption involving metastable excited states of greater than nanosecond lifetime.

Experimental study of hydroxycamptothecine and theprubicine in the treatment of adenoid cystic carcinoma lung metastases

To investigate anticancer effect of hydroxycamptothecine and theprubicine in the treatment of established human adenoid cystic carcinoma (ACC) lung metastasis of nude mice and to determine the best therapy sequence of the two drugs. The model of ACC lung metastasis (60 animals) was established by injecting the ACC-M cells into the nude mice from their tail veins. Animals were divided into six groups: v acuity control group, HCPT group, THP group, HCPT and THP group 1, HCPT and THP group 2, HCPT and THP group 3 (No.1 - No.6). Different treatment sequence was performed on these groups. The lung samples were collected and observed after HE staining. The area of metastases and lung tissue were analyzed by the images analysis system. The size of the metastatic lesion in the treatment groups were smaller than that in the control group (P < 0.01). The treatment effects between the group with simultaneous administration of HCPT and THP and the group with single drug administration were not different (P > 0.05). No.5 and No.6 groups showed better effect of treatment than the other treatment groups (P < 0.05). There are two recommended sequences: (1) HCPT should be used after THP; (2) THP is used 48 hours, After HCPT is administered. Because using two drugs together will decrease the anticancer effect, HCPT and THP should not be used simultaneously.

Long-term Results of a Multicenter Randomized, Comparative Trial of Modified CHOP versus THP-COP versus THP-COPE Regimens in Elderly Patients with Non-Hodgkin's Lymphoma

In treating elderly non-Hodgkin's lymphoma (NHL) patients, it is particularly important to use drugs that have a low incidence of adverse events and high efficacy. In this multicenter study, THP (pirarubicin)-COP (cyclophosphamide, vincristine, and prednisolone) was compared to two thirds dosage of full CHOP (cyclophosphamide, doxorubicin, vincristine, and prednisolone) regimen with regard to both adverse events and efficacy. For a third group, etoposide (E) was added to the THP-COP regimen (THP-COPE) in order to achieve high dose-intensity. Subjects were 486 previously untreated patients, aged 65 or older (range, 65-92 years; median, 74 years), with NHL. Subjects were randomly assigned to receive THP-COP, two thirds CHOP, or THP-COPE. Four hundred and forty-three patients were assessed for response and followed for 8 years after the last subject registered. The complete remission rates for the THP-COP, CHOP, and THP-COPE groups were 42.5%, 41.4%, and 48.0%, respectively. There was no difference in overall survival or progression-free survival among these 3 groups. In aggressive lymphoma, there was also no difference in complete response (CR) rate (45.3% in THP-COP, 44.9% in CHOP, 48.0% in THP-COPE), overall survival, and progression-free survival among these groups. The 5- and 8-year survival rates for all patients were 29.4% and 18.7%, respectively. The 5- and 8-year survival rates for patients with aggressive lymphoma were 27.4% and 17.4%, respectively. Although long-term survival for patients with aggressive lymphoma on our regimens was not worse compared to previous reports, the CR rate was lower. Because severe adverse events were not observed, higher dose chemotherapy may be directed to achieve better CR rates. In patients with T-cell-type lymphoma, the CR rate was greater after treatment with THP-COP (51.4%) or THP-COPE (57.7%) compared to treatment with CHOP (19.4%). Pirarubicin may be more useful for T-cell lymphoma than doxorubicin. Because adverse cardiac events were reported only in CHOP, adverse cardiac events might be low in the THP group.

Functionalized Heptahelicene Bidentate Ligands and Chiral Building Blocks

Syntheses of functionalized heptahelicenes 11-13 disubstituted at positions 3 and 16 by hydroxymethyl or bromomethyl functions are described as a new series of bidentate ligands or chiral building blocks. Those functions are flexible enough and properly positioned for a possible chelate effect onto a metal center. Photocyclodehydrogenation, phase-transfer-catalyzed Wittig reaction, and use of THP groups for increasing solubility and further functional group transformations were key elements in this synthetic route.

Cellulose-Based Polymers with Long-Chain Pendant Ferrocene Derivatives as Organometallic Chromophores

Selective transmetalation reactions via 1,1‘-distannylated ferrocene enables the synthesis of the new ferrocenyl chromophore [Fe(η5-C5H4-CH2OH)(η5-C5H4-CHCH-C7H7)] (6). Coupling reactions of complex 6 with corresponding alkyl halides reveal the sandwich compounds [Fe(η5-C5H4-CH2OCH3)(η5-C5H4-CHCH-C7H7)] (7), [Fe{η5-C5H4-CH2O(CH2)6Br}(η5-C5H4-CHCH-C7H7)] (8), [Fe{η5-C5H4-CH2O(CH2)6OTHP}(η5-C5H4-CHCH-C7H7)] (9) (THP = tetrahydropyranyl), and [Fe{η5-C5H4-CH2O(CH2)6I}(η5-C5H4-CHCH-C7H7)] (10), which are potential precursors for dipolar donor−acceptor complexes, providing nonlinear optical properties. The synthesis of the THP derivative 9 was intended as a precursor for the hydroxy-terminated compound [Fe{η5-C5H4-CH2O(CH2)6OH}(η5-C5H4-CHCH-C7H7)] (11), which would be a suitable starting material for a coupling reaction with modified cellulose. However, an acid-catalyzed cleavage of the THP group of 9 in ethanol solution resulted in the formation of [Fe(η5-C5H4-CH2OCH2CH3)(η5-C5H4-CHCH−C7H7)] (12) instead of 11...

Solid-phase synthesis of a library of hydroxyproline derivatives.

The synthesis of a library of N-alkylated O-arylated hydroxyproline derivatives has been achieved on solid phase. The choice of O-protection and the optimization of the Mitsunobu reaction involving a secondary alcohol were key to the success of this synthesis. First, acylation of resin-bound amines with N-Fmoc-O-THP-hydroxyproline was accomplished readily. Subsequent deprotection of the Fmoc and reductive amination with different aldehydes resulted in the tertiary amine intermediate. The deprotection of the THP group by p-toluenesulfonic acid was followed by a Mitsunobu reaction with a series of phenols. Finally, the products were cleaved from the resin using trifluoroacetic acid to produce a 10 200 member library.

Propylene Glycol Cyclic Sulfate as a Substitute for Propylene Oxide in Reactions with Acetylides.

AbstractFor Abstract see ChemInform Abstract in Full Text.

Propylene Glycol Cyclic Sulfate as a Substitute for Propylene Oxide in Reactions with Acetylides

Lithium acetylides react cleanly with propylene glycol cyclic sulfate to give, after acidic hydrolysis, homopropargylic alcohols in good yield. The benzyl and TBDPS protecting groups are stable to these conditions, but the THP, TBS, acetal and orthoester groups are not. The readily available (S)-cyclic sulfate gives the (S)-alcohol without loss of stereochemical integrity.

Simple, economical and environmentally friendly sulfone synthesis

Chemoselective sulfur oxidation of functionalized sulfides was developed using catalytic amounts of MnSO 4·H 2O (1 mol%) and 30% H 2O 2 in the presence of a buffer solution of NaHCO 3. Aromatic and aliphatic sulfides were oxidized to sulfones in quantitative yields in 15 min. Different functional groups including double bonds, alcohols, ethers of THP and TBDMS groups were tolerated under these mild and green reaction conditions.

A Novel, Efficient, and Highly Selective O-Bn Bond Cleavage Reaction via a Rare K-Induced Electron Transfer Process

A new, efficient and highly selective deprotective method of both benzyl and benzylidene groups for protection of monohydroxyl and dihydroxyl, respectively, has been developed by using the system K-t-BuNH2-t-BuOH-18-crown-6. This method is valuable since it can not only selectively protect the TBDMS and THP groups and the ethylene ketal from cleavage, but also keep the separate or conjugated C=C bonds from reduction. A possible electron transfer reaction process was also suggested.