2), H7N9 split vaccine induced much stronger immune response either in the presence of or without adjuvants (Fig. 4). The low immune response to H7N7 split vaccine was also observed in previous studies in humans and further clarified by conducting the comparison of HA antigen uptake, processing, presentation, and trimer conformation as well

as the EM morphology among influenza vaccines [24]. Interestingly, our TEM observations showed the H7N7 split vaccine primary exhibited the small round (5–20 nm) structures and consistent with the recent report (Fig. 1A vs. Fig. 5, H7N7 [24]). In contrast, the H7N9 split vaccine showed the predominant pieces of viral particles of varying sizes, most of that with external projections of HA and NA (Fig. 1A). This morphology Veliparib molecular weight observed in our H7N9 split vaccine HIF cancer is similar to that of H9N2 split vaccine described in previous findings,

which also indicated that H9N2 split antigen is the most immunogenic to induce immune response among the avian vaccines [24]. All of above observations support the suggestion that the morphology of vaccine may influence immunogenicity of split-virion vaccine in human. The whole virus vaccines were usually used and shown to be more immunogenic than split virus vaccines [25]. In this study, we found that without adjuvants, both H7N9 split and whole virus antigens have compatible immunogenicity (Fig. 4A, lane A vs. lane D). However, with AddaVAX, the H7N9 split virus vaccine exhibited higher HAI titers and neutralizing capacity to both H7-subtype viruses than whole virus

vaccine (Fig. 4, lane C vs. lane F). No obvious difference of vaccine potency was observed among split and whole virus H7N7 vaccines when combined with individual adjuvants (Fig. 2A, lane D vs. lane H and lane F vs. lane J). Overall, the AddaVAX-adjuvanted H7N9 or H7N7 vaccines elicited the highest HAI and neutralizing antibodies titers when compared to Al(OH)3 or without adjuvant (Fig. 2 and Fig. 4). Our results illustrated that squalene-based adjuvant may confer the superior formulation to enhance the H7 subtype vaccine efficacy. To address the cross-reactivity of H7 subtype vaccines, we demonstrated Montelukast Sodium that 0.5 μg of both AddaVAX-H7N7 vaccines strongly confer potent cross-reactive HAI and viral neutralizing titers against H7N9 virus, suggesting the AddaVAX-adjuvantation strategy can enhance the cross-reactivity of H7N7 vaccine (Fig. 2C and D). On the other hand, the antisera from 0.5 μg split- or whole-virion H7N9 antigen exhibited compatible HAI titer (≧1:40) and neutralization titers (≧1:100–300) against both H7-subtype viruses (Fig. 4). It illustrated that even no adjuvantation, the both H7N9 vaccines also provided adequate HAI titer against H7N7 virus in mice might due to their highly structure similarity [26] and more immunogenic characteristic of HA antigen.

Indeed, during the second year of follow-up, 96 cases of severe RVGE were detected. During the second year of follow-up the point estimate of vaccine

efficacy was 19.2%. We surmise that if a similarly intense and culturally compatible surveillance ABT-888 concentration system had also been utilized through the first year of follow-up, the number of cases of severe RVGE detected would have been greatly increased due to the higher burden of severe rotavirus GE in the first year of life. Thus, the estimate of vaccine efficacy may have been higher. The composite of experiences in poorer developing countries in Africa and Asia now provides convincing evidence that the level of efficacy of oral RV vaccines measured in individual subject-randomized,

double-blind, controlled field trials (approximately 50–65% efficacy) is lower [7], [8] and [24] than the efficacy of vaccine documented in controlled field trials in industrialized Cobimetinib concentration and transitional countries [3] and [4]. The reduced immunogenicity and efficacy of both live and non-living oral vaccines in populations in developing countries has been previously described with multiple vaccines, such as oral polio vaccine, cholera vaccine and Shigella vaccines [25], [26], [27], [28], [29], [30], [31], [32], [33] and [34] and is the subject of much discussion and research to understand the basis of this phenomenon. Possibilities include potential vaccine factors, such as restricted immunogenicity or host factors such as gut enteropathy, and co-morbidities as described elsewhere [35], [36] and [37] This has led some to become discouraged about what live oral RV vaccines can accomplish in the world’s least developed countries (where RV vaccines are most needed) and to propose

starting afresh on new vaccine strategies such as parenterally administered inactivated Cediranib (AZD2171) vaccines [38] and [39]. On the other hand, there are also clear reasons for optimism. The immunogenicity in Mali was comparable to that in Ghana and Kenya, where sufficient numbers of cases were captured to yield site-specific efficacies of 65.0% and 83.4%, respectively, through the first year of life [4] and [40]. Moreover, it is likely that the actual impact of widespread immunization of infants in Mali with live oral RV vaccine would result in an impact far greater than anticipated based just on the estimate of vaccine efficacy because of indirect protection and a herd immunity effect. Experiences in the U.S.A. [41], [42], [43] and [44], Australia [45], [46] and [47], and Latin America [48] show an unequivocal herd immunity effect wherein the observed fall in rotavirus disease far exceeds the expectation based just on estimates of direct vaccine efficacy and immunization coverage.

Specific antibodies were observed after a period of one year without Quizartinib reactivity against human heart proteins. No lesions were observed in several organs [29], indicating that StreptInCor is safe and has protection potential. In the present study, we analyzed the in vitro ability of anti-StreptInCor antibodies to neutralize/opsonize S. pyogenes strains frequently found in Sao Paulo. We also analyzed the absence of humoral autoimmune

reactions against human heart valve tissue. The results presented here showed that anti-StreptInCor antibodies were able to neutralize/opsonize M1, M5, M12, M22 and M87 S. pyogenes strains, indicating that the vaccine can be effective against the bacteria, preventing infection and subsequent sequelae without causing autoimmune reactions. The vaccine epitope consists of the following 55 amino acid residues: KGLRRDLDASREAKKQLEAEQQKLEEQNKISEASRKGLRRDLDASREAKKQVEKA. The peptide was synthesized using a 9-α-fluorenylmethoxy-carbonyl (Fmoc) solid-phase strategy, purified by reverse phase high-pressure liquid chromatography (RP-HPLC, Shimadzu, Japan). Peptide quality was assessed by matrix-assisted desorption ionization mass spectrometry (MALDI-ToF, Ettan Maldi Tof Pro, Amersham-Pharmacia, Sweden) as previously described [25]. Patents PCT-BR07/000184. Inbred BALB/c and outbred Swiss mice with mature immune system (6- to 8-week-old) specific pathogen-free from CEMIB (Unicamp,

Campinas, Brazil) were maintained in autoclaved cages (Alesco, Brazil) and handled under sterile conditions in the animal facility at the OTX015 solubility dmso Tropical Medicine Institute, University of São Paulo,

Brazil. Procedures were performed in accordance with the Brazilian Committee for animal care and use (COBEA) guidelines approved by the Tropical Medicine Institute Ethics Committee (project number 002/08). Mice sera previously immunized with 10 μg of StreptInCor adsorbed onto 60 μg of aluminum hydroxide gel (Sigma–Aldrich Corp., USA) in saline via subcutaneous with two doses 14 days apart. Oxymatrine Animals that received saline plus 60 μg of adjuvant were used as negative controls. Positive controls were immunized with recombinant streptococcal M1 full protein (clone kindly provided by Prof. Patrick Cleary, University of Minnesota Medical School, MN, USA), produced and purified in our lab. Sera samples were obtained under light anesthesia by retro-orbital puncture on day 28 following immunization. Samples with high specific antibody titers (>1:1.200) detected by Enzyme-Linked Assay Immunoabsorbent (ELISA) [28] were used. The strains were obtained from patients treated at the Clinical Hospital, University of Medicine – Sao Paulo, between 2001 and 2008 and identified by genotyping [30]. The M1, M5, M6, M12, M22 and M87 specimens were cultured on sheep blood agar (Vetec, Brazil), followed by growth in Todd-Hewitt broth (Himedia, India) until OD600 of 0.

21 Mechanisms of action of such herbicides are the denovo fatty acid biosynthesis pathway. 22 and 23 selleck products Inhibition blocks the synthesis of phospholipids which is essential building block for cell membrane for growth. 24 Shutting down either activity of two catalytic activities, BC and CT should be sufficient to inhibit the overall reaction of the enzyme ACC by herbicides.

Disturbance in the polymerization process, absence of means of synthesizing malonyl-CoA, inhibition by mimicking palmitoyl-CoA, inhibition by bisubstrate analog, structural components of herbicides CoA esters are well studied alternatives for drug targeting using ACC. 25 and 26 Molecular docking studies has been carried for the above mentioned compounds using Molegro Virtual Docker[ Table 3]. Binding sites were identified at positions

95Gly, Asp78, Arg41 etc 27 further found surrounding first cavity in Molegro Virtual Docker. Flexible molecular docking results are found to be considerable when above stated compounds from three classes were docked in the active site of modeled 3D structure of Acetyl-CoA carboxylase (ACC) from J. curcas. Docking scores are produced in  Table 3 which clearly indicates appreciable inhibitory activity profile of compounds screened. Compounds are arranged in descending order of their docking rerank scores belonging to each class. Comparison of candidates in terms of better binding ability shows that Pinoxaden (Phenylpyrazole class) could interact with ACC most effectively (rerank = −81.436 and RMSD = 0.31) selleckchem to inhibit it. Other three members of the same group also indicate better binding affinities towards ACC inhibition as compared to other two classes and their compounds. Quizalofop (Aryloxyphenoxypropionates class) found intermediate position in terms of rerank = −77.4055 Ketanserin and RMSD = 1.713. Sethoxydim (Cyclohexanediones class) was found to have least inhibiting effect on ACC as compared to other two classes and their compounds with

rerank = −71.917 and RMSD = 0.424. Docking scores are mathematical calculations to quantify force-fields between binding site of receptors and interacting ligands. For qualitative discussion, we should identify participation of atoms and groups of ligand with those complimenting atoms and groups of receptor amino acids. In order to map qualitative aspects of molecular docking studies, we have noted various types of atomic and molecular interactions which are reproduced in Fig. 5, Fig. 6 and Fig. 7. Blue dotted lines depict H-bond while maroon dotted lines quote steric interactions. Electrostatic interactions are found absent in current docking studies. Functional characterization of a protein sequence is a frequent problem in biological world. Today’s scenario is focused in identification and exploration of functional knowledge of bio-molecule like protein.

Daily counts by age between 1998 and 2007 were extracted from the database. The ratio of the number of reported cases to the number of symptomatic cases in the population was assumed to be 1 in 35, based on figures from a study in England and Wales looking at under-ascertainment within rotavirus surveillance data [26]. Berkeley Madonna gives the root mean square deviation (RMSD)

between the data and the best fitting model. The deviation is the root mean square of the differences between individual data points in the dataset and the corresponding points in the model. There were 29200 (number of days x number of age groups) data points in the HPA rotavirus surveillance dataset used. We initially investigated the effects of a two-dose rotavirus mass vaccination programme with doses given PLX3397 supplier at two and four months of age [8]. Initial assumptions were that the full vaccine course conferred a protective effect against infection and disease similar to that of a primary natural infection. Studies have shown that vaccine efficacy is comparable in breastfed infants, compared to non-breastfed infants [27], so we assumed vaccinated infants can be successfully immunized prior to waning of maternal antibodies. We assumed that 96% of individuals receiving the full two doses were successfully immunized to a natural primary

infection. This figure was consistent

with the proportion of individuals who seroconverted Epacadostat in vivo following two doses of Rotarix in clinical trials [28]. Thus, 96% of individuals would be successfully immunized against a primary rotavirus infection with two doses of the vaccine and therefore bypass the first infected compartment to enter the second susceptible or recovered compartments. The proportion entering these compartments were equivalent to those entering these compartments after a natural primary infection. Using a method similar to that used by Pitzer et al. [29], this gives a vaccine efficacy after two doses of 36.5% (=0.96 × (1 − 0.62)) against infection and 64.3% (=0.96 × (1 − (0.62 × 0.25/0.47))) against any rotavirus gastroenteritis, an estimate all similar to the 72% vaccine efficacy against any rotavirus gastroenteritis of two doses of Rotarix vaccine in a phase III European clinical trial [30]. We explored a variety of vaccine coverage levels. The long-term relative effects of direct and indirect (herd immunity) protection of the vaccine were determined. The direct effect of vaccination on the incidence of rotavirus gastroenteritis was estimated as 1 − 0.643 × vaccine coverage. This method assumes all individuals receiving the vaccine have protection from birth. Clinical trials have demonstrated a protective effect of the vaccine after a single dose.

Le nombre de décès augmente brutalement après 35 ans pour atteindre un maximum dans la tranche 40–55 ans, la courbe s’abaissant au-delà surtout du fait de la diminution significative du nombre de pratiquants. L’élévation exponentielle après 35 ans est due à l’augmentation des accidents coronariens aigus. Des variations

saisonnières des morts subites sont rapportées avec des pics en période estivale synonyme de « reprise sportive », d’augmentation du nombre de pratiquants moins entraînés [15]. Une possible fréquence plus élevée des accidents matinaux est discutée [16]. Une question selleck compound library souvent posée concerne les sports à risque. Existe-t-il un sport plus « tueur » que d’autres ?

Dans la population générale, la course à pied et le cyclisme sont les plus forts selleckchem pourvoyeurs de mort subite. Bien que très sollicitant sur le plan cardiovasculaire, ces deux sports sont surtout les plus pratiqués, en particulier par les « vétérans » statistiquement plus à risque. Ainsi, d’autres sports très pratiqués comme le baseball et le golf aux États-Unis ou le football en Europe, sont aussi surreprésentés dans les publications. Le risque principal n’est pas le sport en lui-même mais l’intensité avec laquelle il est pratiqué. À partir de toutes ces données peut-on décrire un profil à risque de mort subite liée au sport ? L’âge du pratiquant joue un rôle majeur et cette question concerne surtout les sujets de plus de 35 ans. Dans cette population, d’autres facteurs de risque sont identifiés. Il s’agit surtout de la pratique occasionnelle d’une activité physique intense mafosfamide et d’un niveau de risque cardiovasculaire élevé avec un score coronaire élevé (voir ci-dessous) [17] and [18]. Ainsi, le risque relatif d’infarctus chez un sujet de plus de 35 ans, sédentaire, qui pratique brutalement un effort très intense est multiplié par 100 par rapport au repos [17]. Pour comparaison, ce sur-risque chez le pratiquant régulier d’activité physique est inférieur à 5 [8]. Avant

35 ans, ce sont surtout les antécédents familiaux de mort subite et/ou de cardiopathie à risque et personnels, pathologie cardiovasculaire et/ou symptômes, qui doivent alerter. Dans tous les cas, des comportements inadaptés de pratique sportive, en période fébrile, associés à la prise de cigarette, ou dans des conditions climatiques hostiles ou avec hydratation insuffisante favorisent la survenue de ces accidents [19] and [20]. Un sportif ne meurt pas par hasard et la mort subite liée à l’exercice révèle une pathologie cardiaque ignorée. En effet, les données nécropsiques à notre disposition montrent que la mort subite révèle en règle une cardiopathie méconnue. Le sport, sauf peut-être quelques exceptions, ne crée pas la pathologie cardiovasculaire [21].

After predetermined time point of I/R, the brains were quickly removed and sliced into coronal sections of 2 mm thickness. Each slice was immersed in a 1.0% solution of 2,3,5-triphenyltetrazolium chloride (TTC) for 30 min. Necrotic infarcted tissue was unstained and viable tissue was stained dark red, further separated, weighed and percentage of infarction was determined.19 The stained tissue was not suitable for estimating oxidative and inflammatory biomarkers; hence a separate group of animals were used for estimating the levels of these biochemical parameters (Table 2). The brain tissue of each animal was removed after completion of 4 h reperfusion and used for the estimation of superoxide

dismutase (SOD), catalase (CAT), myeloperoxidase (MPO), tumor necrosis factor-α (TNF-α) and interleukin-10 (IL-10). SOD LY2109761 concentration levels were determined by the method developed by Kakar

et al.20 CAT levels were determined by the method developed by Aebi et al21 MDA levels were determined by the method developed by Ohkawa et al22 MPO levels were determined by the method developed by Mullane et al23 TNF-α levels were determined by using AssayMax Rat Tumor Necrosis Factor-alpha (TNF-alpha) ELISA Kit (Catalog No. ERT2010-1).24 IL-10 levels were determined by using PF-02341066 clinical trial AssayMax Rat Interleukin-10 (IL-10) ELISA Kit (Catalog No. ERI3010-1).25 Statistical analysis was performed using Prism software (Version 6.02). Results of percentage of infarct size are shown in Table 3 and Fig. 2 and Fig. 3. Cerebral Infarct Org 27569 size was found to be 48.34 ± 0.84% in rats subjected to cerebral I/R injury. Significant cerebral damage was observed in I/R control group animals when compared to sham operated group. Pyrimidines (AUCP1 and AUCP2) treatment offered dose dependent cerebroprotection in terms of significant reduction in cerebral infarct size when compared to I/R control group. AUCP2 has offered more degree of cerebroprotection when compared to AUCP1. Results of tissue SOD levels are shown in Table 4 and Fig. 4. Results shown in the above mentioned figure indicate that the cerebral ischemia

and reperfusion significantly decreased antioxidant enzyme (SOD) levels in the injured brain tissue of rats as compared with the sham control group. Results of tissue SOD levels are shown in Table 4 and Fig. 5. Results shown in the above mentioned figure indicate that the cerebral ischemia and reperfusion significantly decreased antioxidant enzyme (CAT) levels in the injured brain tissue of rats as compared with the sham control group. Results of tissue MDA levels are presented in Table 4 and Fig. 6. Results shown in the above mentioned figure indicate that the cerebral ischemia and reperfusion significantly increased lipid peroxidation (MDA) levels in the injured brain tissue of rats as compared with the sham control group. Results of tissue MPO levels are presented in Table 4 and Fig. 7.

Parasite suspension (1 × 106 tachyzoites/ml) was treated with 1% formaldehyde for 30 min at room temperature. After washing twice in PBS, parasites were dry-fixed in microscopic slides and stored at −20 °C. ArtinM and Jacalin from A. integrifolia were prepared in one of our laboratories (MCRB). The total selleck screening library extract preparation of seeds from A. integrifolia, as well as their purification to generate

d-mannose (ArtinM)- and d-galactose (Jacalin)-binding lectins, were performed as previously described [11] and [13]. The homogeneity and purity degree of the lectins were evaluated by electrophoresis in polyacrylamide gel in the presence of sodium dodecyl sulfate (SDS-PAGE at 15%) under non-reducing conditions. All experiments were carried out with 8–12-week-old female C57BL/6 mice maintained under standard

conditions in the Bioterism Center and Animal Experimentation, Federal University of Uberlândia, MG, Brazil. All procedures were conducted according to guidelines for animal ethics and the study received approval of the Ethics Committee for Animal Experimentation of the institution. Six groups of 13 mice were immunized subcutaneously (200 μl/animal) three times Epacadostat purchase at two-week intervals, as follows: 25 μg NLA mixed with 1 μg ArtinM in sterile PBS (NLA + ArtinM group); 25 μg NLA mixed with 100 μg Jacalin in sterile PBS (NLA + JAC group); 25 μg NLA alone (NLA group);

1 μg ArtinM alone (ArtinM group); 100 μg Jacalin alone (JAC group); and diluent only (PBS group). The adopted doses of antigen and lectins were based on previous studies [14], [15] and [29]. Blood samples were collected at 0, 15, 30, 45 and 60 days after immunization (d.a.i.), and the sera stored at −20 °C until to be analyzed for the presence of specific antibodies. Levels of N. caninum-specific total IgG, IgG1 and IgG2a antibodies were measured by ELISA as described elsewhere [29], with modifications. High-affinity microtiter plates were coated with NLA (10 μg/ml), washed with PBS plus 0.05% Tween 20 (PBS-T) and blocked with 5% skim milk in PBS-T for 1 h at room temperature. Serum samples were diluted 1:25 in 1% skim milk-PBS-T and incubated for 1 h (for Rolziracetam IgG detection) or 2 h (for IgG1 and IgG2a detection) at 37 °C. After washing, peroxidase-labeled goat anti-mouse IgG (1:1000; Sigma Chemical Co., St Louis, MO) or biotin-labeled goat anti-mouse IgG1 (1:4000) or anti-mouse IgG2a (1:2000) antibodies (Caltag Lab. Inc., South San Francisco, CA) were added and incubated for 1 h at 37 °C. Next, streptavidin-peroxidase (1:1000; Sigma) was added for IgG1 and IgG2a detection assays. The assays were developed with 0.01 M 2,2-azino-bis-3-ethyl-benzthiazoline sulfonic acid (ABTS; Sigma) and 0.03% H2O2. Optical density (OD) values were determined in a plate reader at 405 nm.

However, it has implications for students whose score is within the borderline pass/fail range. If the pass mark is 40 out of the total 80 marks on the 20 items, then 40 minus 6.5 (33.5) might be considered an outright fail, while 40 plus 6.5 (46.5) might be considered an outright pass. The values in between would require

a process for deciding on further assessment for confidence that the student has an adequate level of professional competence. There are many possible sources of error in assessment scores and these are likely to be related to circumstances, educator, student, and the interaction of these factors. If other indicators of student ability indicated competency, GW786034 in vivo a mark as low as 34 may be acceptable. Alternatively, if other assessments indicate a student consistently performs in the borderline range, further practice and assessment PD98059 concentration (or tailored remediation) may be triggered even by grades as high as 47. Norman et al (2003) reported that for health-related quality of life outcome measures, the change in measures of health outcomes that people typically consider to be important (minimal important difference) is approximately half a standard deviation of raw scores for a representative cohort. If the APP scores behaved as quality of life scores do, then an estimate of the possible minimally important difference would be 6–8 points, a proposal that warrants investigation. There will always be some

lack of agreement between raters and defining the limits of tolerable disagreement is challenging. Some variability would be expected due to the unpredictable challenges of a complex health services environment combined with variable opportunities for

educators to observe student ability across the spectrum of clinical skills. Despite these challenges, in this interrater reliability trial the physiotherapy clinical educators demonstrated a high level of consistency in the assessment and marking of physiotherapy students’ performance on clinical placements when using the Assessment of Physiotherapy Practice. Ethics: Approval for the study was provided by the Human Ethics Committees of Monash University and from the Human Ethics Committees of each of the participating universities. All participants gave written informed either consent before data collection began. Competing interests: Nil. Support: Funding from the Australian Learning and Teaching Council (ALTC) enabled employment of a research assistant and travel to conduct focus groups and training workshops. The authors acknowledge the assistance of Curtin, James Cook, La Trobe, Griffith, Monash, and Sydney Universities and thank the clinical educators and students who participated. “
“Summary of: Hill JC et al (2011) Comparison of stratified primary care management for low back pain with current best practice (STarT Back): a randomised controlled trial. Lancet 378: 1560–1571. Published Online September 29, 2011 DOI:10.

4 (C, C-1′), 154.7 (C, C-4′),

162.8 (C, C-7), 165.0 (C, C-8a), 165.7 (C, C-5), 191.9 (C, C-4); HRMS (EI) calcd for C18H19O5 315.1154, found 315.1224. NaBH4 (0.3 g, 9.5 mmol) was added portion wise to a solution of 5,7-dimethoxy-3-(4-hydroxybenzyl)-4-chromanone (1.0 g, 3.1 mmol) in anhydrous MeOH (15 ml) at a temperature of 0 °C under nitrogen atmosphere. The mixture was then allowed to reach room temperature and stirred for 1 h. The reaction mixture was quenched with water and extracted with ethyl selleck acetate (3 × 30). The organic layer was washed with brine, dried over magnesium sulphate, and concentrated under reduced pressure to produce a viscous oil mixture of (R,R)-6 and (R,S)-6. The residue obtained after evaporation of the solvent was chromatographed over Selleckchem Duvelisib a silicagel column using mixture of ethyl acetate/hexane (30:70) as eluent to produce an oily syrup at an overall yield of 88%. Compound (R,R)-6; Rf = 0.48 (30:70 ethyl acetate/hexane); oily syrup; 1H NMR (400 MHz, CDCl3) δ: 2.08–2.15 (1H, m, H-3), 2.58 (1H, dd, J = 2.6, 7.2 Hz, H-9a), 2.85 (1H, dd, J = 2.6, 7.2 Hz, H-9b), 3.78 (3H, s, Ar–OCH3-5), 3.83 (3H, s, Ar-OCH3-7), 3.99 (2H, d, J = 8.2 Hz, H-2a & 2b), 4.66 (1H, d, J = 2.5 Hz, H-4), 5.99

(1H, d, J = 7.1 Hz, H-8), 6.01 (1H, d, J = 7.1 Hz, H-6), 6.76 (2H, d, J = 8.2 Hz, H-3′,5′), 7.12 (2H, d, J = 8.0 Hz, H-2′,6′); 13C NMR (100 MHz, CDCl3) 31.9 (CH2, C-9), 40.1 (CH, C-3), 55.3 (OCH3, C-7), 55.4 (OCH3, C-5), 59.6 (CH, C-4), 65.2 (CH2, C-2), 91.3 (CH, C-6), 93.0 (CH, C-8), 106.6 (C, C-4a), 115.2 (CH, C-3′,5′), 130.2 (C, C-1′), 131.6 (CH, C-2′,6′), 153.8 (C, C-4′), 155.9 (C, C-5), Sitaxentan 159.2 (C, C-8a), 161.1 (C, C-7); mass m/z = 317 (M + 1)+. Compound (R,S)-6; Rf = 0.45 (30:70 ethyl acetate/hexane); oily syrup; 1H NMR (400 MHz, CDCl3) δ: 2.12-2.18 (1H, m, H-3), 2.40 (1H, dd,

J = 2.9, 7.9 Hz, H-9a), 2.55 (1H, dd, J = 2.9, 7.9 Hz, H-9b), 3.76 (3H, s, Ar–OCH3-5), 3.81 (3H, s, Ar–OCH3-7), 3.90 (1H, dd, J = 1.8, 1.8 Hz, H-2a), 4.07 (1H, dd, J = 1.9, 2.0 Hz, H-2b), 4.62 (1H, s, H-4), 6.06 (1H, d, J = 3.9 Hz, H-6), 6.07 (1H, d, J = 3.9 Hz, H-8), 6.74 (2H, d, J = 8.3 Hz, H-3′,5′), 7.04 (2H, d, J = 8.3 Hz, H-2′,6′); 13C NMR (100 MHz, CDCl3) 33.6 (CH2, C-9), 40.5 (CH, C-3), 55.3 (OCH3, C-7), 55.5 (OCH3, C-5), 62.9 (CH, C-4), 64.3 (CH2, C-2), 91.8 (CH, C-6), 93.2 (CH, C-8), 104.9 (C, C-4a), 115.3 (CH, C-3′,5′), 130.2 (C, C-1′), 131.2 (CH, C-2′,6′), 154.2 (C, C-4′), 155.8 (C, C-5), 159.8 (C, C-8a), 161.0 (C, C-7); mass m/z = 317 (M + 1)+. To a mixture of either (R,R)-6 or (R,S)-6 respectively (0.1 g, 1.0 mmol) in acetic acid (4 ml) was added CrO3 (0.16 g, 5.0 mmol). The reaction mixture was stirred at room temperature and allowed to stand for 0.5 h. The solvent was evaporated and extracted with ethyl acetate (2 × 15 ml). The organic layer was washed with brine (2 × 15 ml) and dried over magnesium sulphate.