Oxetanes as versatile building blocks in the total synthesis of natural products: An overview

Oxetane ring plays an important role as main core in naturally occurring compounds and has many applications in pharmaceutical industries and synthetic organic chemistry. In this review, we report a brief survey of using the oxetane ring as versatile precursors in the total synthesis of natural products. Many approaches such as cyclization, addition, oxidation, reduction, elimination, protection as well as deprotection reactions utilized to synthesize of most important oxetane-containing natural products involving taxol, (±)-merrilactone A, (±)-oxetin, L-oxetanocin, (+)-(Z)-laureatin and L-oxetanocin are also covered. We describe in this review the most common total synthesis approaches have been yet applied to synthesis of most important oxetane-containing natural products. The review is also included isolation, structure Identification of these oxetane-containing natural products. The biological activity of oxetane-containing natural products due to the oxetane ring is also defined

Synthesis of Functionalized Anthraquinones, Phthalates and Quinolines by Site-Selective Suzuki-Miyaura Cross-Coupling Reactions

Based on the methodology of Suzuki-Miyaura cross-coupling reactions, a wide range of substituted anthraquinones are now readily available including a few examples of phthalates and quinolines. The method provides new possibilities in carbon-carbon bond formation for the preparation of new materials. The chemistry of the bis(triflates) of anthraquinones, phthalates and 5,7-dibromo-8-(trifluoromethylsulfonyloxy)quinoline has been investigated in this thesis. The results for the synthesis and characterization of diarylanthraquinones, diarylphthalates and diarylquinolines are presented in this thesis

O6-[(2”,3”-O-Isopropylidene-5”-O-tbutyldimethylsilyl)pentyl]- 5′-O-tbutyldiphenylsilyl-2′,3′-O-isopropylideneinosine

Cyclic adenosine diphosphate ribose (cADPR) is a cyclic nucleotide involved in the Ca2+ homeostasis. In its structure, the northern ribose, bonded to adenosine through an N1 glycosidic bond, is connected to the southern ribose through a pyrophosphate bridge. Due to the chemical instability at the N1 glycosidic bond, new bioactive cADPR derivatives have been synthesized. One of the most interesting analogues is the cyclic inosine diphosphate ribose (cIDPR), in which the hypoxanthine replaced adenosine. The efforts for synthesizing new linear and cyclic northern ribose modified cIDPR analogues led us to study in detail the inosine N1 alkylation reaction. In the last few years, we have produced new flexible cIDPR analogues, where the northern ribose has been replaced by alkyl chains. With the aim to obtain the closest flexible cIDPR analogue, we have attached to the inosine N1 position a 2”,3”-dihydroxypentyl chain, possessing the two OH groups in a ribose-like fashion. The inosine alkylation reaction afforded also the O6-alkylated regioisomer, which could be a useful intermediate for the construction of new kinds of cADPR mimics

Enhanced of Maltenes -Asphalt Blends Specifications via Thermal Catalytic Processes

Abstract: In this article the effects of using maltenes, which have been pre-separated recently from paraffinic base asphalt to modify asphalt pavement in variety of percentages has been investigated. Further modification has been performed by applying chlorine gas using ultra violet and ferric chloride as catalyst at certain temperature in order to increase the homogeneity and performance of paving asphalt. Characterization of asphalt blends has been performed according to ASTM standards. The results showed that addition of 1% of maltenes increases the softening point for the blends from catalytic chlorination, which reflects the benefit of this treatment. The penetration index for blends obtained by catalytic chlorination has also improved compared to unchlorinated samples and to those obtained from treating the asphalt with maltenes alone. Finally the specific gravity of catalytic chlorinated blends increased, thus indicating the influence of chlorination on the improvements of asphalt blends

Does true Gleason pattern 3 merit its cancer descriptor?

Nearly five decades following its conception, the Gleason grading system remains a cornerstone in the prognostication and management of patients with prostate cancer. In the past few years, a debate has been growing whether Gleason score 3 + 3 = 6 prostate cancer is a clinically significant disease. Clinical, molecular and genetic research is addressing the question whether well characterized Gleason score 3 + 3 = 6 disease has the ability to affect the morbidity and quality of life of an individual in whom it is diagnosed. The consequences of treatment of Gleason score 3 + 3 = 6 disease are considerable; few men get through their treatments without sustaining some harm. Further modification of the classification of prostate cancer and dropping the label cancer for Gleason score 3 + 3 = 6 disease might be warranted

Analytical modelling of bond-slip failure between epoxy bonded FRP and concrete substrate

In this paper, a set of explicit theoretical derivations from a generalised bond-slip model for an epoxy bonded fibre reinforced polymer (FRP) sheet to concrete are presented. The derivations address the maximum bond resistance, load-slip response, effective bond length and stress-strain distributions along the FRP. The generalised bond-slip model was compared with the existing bond-slip models to obtain the optimal bond-slip parameter using bond resistance results of single and double lap shear tests results available in the literature. The theoretical predictions using the optimal bond-slip parameters showed good agreement with experimental results of double lap shear tests. Furthermore, in order to understand the influence of the bond-slip parameters, a series of parametric studies are presented. Overall, the proposed bond-slip model and explicit derivations provide complete understanding of bonded FRP on concrete, as opposed to the partial understanding provided by empirical and semi-empirical models available in the literatur

Comparative analysis of 1152 African-American and European-American men with prostate cancer identifies distinct genomic and immunological differences

Racial disparities in prostate cancer have not been well characterized on a genomic level. Here we show the results of a multi-institutional retrospective analysis of 1,152 patients (596 African-American men (AAM) and 556 European-American men (EAM)) who underwent radical prostatectomy. Comparative analyses between the race groups were conducted at the clinical, genomic, pathway, molecular subtype, and prognostic levels. The EAM group had increased ERG (P<0.001) and ETS (P=0.02) expression, decreased SPINK1 expression (P<0.001), and basal-like (P<0.001) molecular subtypes. After adjusting for confounders, the AAM group was associated with higher expression of CRYBB2, GSTM3, and inflammation genes (IL33, IFNG, CCL4, CD3, ICOSLG), and lower expression of mismatch repair genes (MSH2, MSH6) (p<0.001 for all). At the pathway level, the AAM group had higher expression of genes sets related to the immune response, apoptosis, hypoxia, and reactive oxygen species. EAM group was associated with higher levels of fatty acid metabolism, DNA repair, and WNT/beta-catenin signaling. Based on cell lines data, AAM were predicted to have higher potential response to DNA damage. In conclusion, biological characteristics of prostate tumor were substantially different in AAM when compared to EAM. Walter Rayford, Alp Tuna Beksac et al. investigated gene expression alterations in African-American and European-American men who underwent radical prostatectomy for prostate cancer. The observed differences include higher expression of inflammation genes and lower expression of mismatch repair genes in African-American men

The effect of multiple adverse childhood experiences on health: a systematic review and meta-analysis

Background A growing body of research identifies the harmful effects that adverse childhood experiences (ACEs; occurring during childhood or adolescence; eg, child maltreatment or exposure to domestic violence) have on health throughout life. Studies have quantified such effects for individual ACEs. However, ACEs frequently co-occur and no synthesis of findings from studies measuring the effect of multiple ACE types has been done. Methods In this systematic review and meta-analysis, we searched five electronic databases for cross-sectional, case-control, or cohort studies published up to May 6, 2016, reporting risks of health outcomes, consisting of substance use, sexual health, mental health, weight and physical exercise, violence, and physical health status and conditions, associated with multiple ACEs. We selected articles that presented risk estimates for individuals with at least four ACEs compared with those with none for outcomes with sufficient data for meta-analysis (at least four populations). Included studies also focused on adults aged at least 18 years with a sample size of at least 100. We excluded studies based on high-risk or clinical populations. We extracted data from published reports. We calculated pooled odds ratios (ORs) using a random-effects model. Findings Of 11 621 references identified by the search, 37 included studies provided risk estimates for 23 outcomes, with a total of 253 719 participants. Individuals with at least four ACEs were at increased risk of all health outcomes compared with individuals with no ACEs. Associations were weak or modest for physical inactivity, overweight or obesity, and diabetes (ORs of less than two); moderate for smoking, heavy alcohol use, poor self-rated health, cancer, heart disease, and respiratory disease (ORs of two to three), strong for sexual risk taking, mental ill health, and problematic alcohol use (ORs of more than three to six), and strongest for problematic drug use and interpersonal and self-directed violence (ORs of more than seven). We identified considerable heterogeneity (I 2 of > 75%) between estimates for almost half of the outcomes. Interpretation To have multiple ACEs is a major risk factor for many health conditions. The outcomes most strongly associated with multiple ACEs represent ACE risks for the next generation (eg, violence, mental illness, and substance use). To sustain improvements in public health requires a shift in focus to include prevention of ACEs, resilience building, and ACE-informed service provision. The Sustainable Development Goals provide a global platform to reduce ACEs and their life-course effect on health. Funding Public Health Wales. © 2017 The Author(s). Published by Elsevier Ltd. This is an Open Access article under the CC BY-NC-ND 4.0 licens