Mechanism and Application of Baker–Venkataraman O→C Acyl Migration Reactions

This literature review focuses on the O→C acyl migration of aryl esters to yield the corresponding 1,3-dicarbonyl products—a reaction known as the Baker–Venkataraman rearrangement—and outlines their subsequent transformations. The purpose of the review is to highlight the utility of the rearrangement which provides a key step in the synthesis of various heterocyclic motifs. The scope of the Baker–Venkataraman rearrangement is illustrated by way of numerous examples of its application, and in doing so, the review contains over 100 references and covers just over 100 years of the literature, from the first report of the rearrangement by Auwers in 1910 up to more recent examples in the past few years. 1 Introduction 2 Historical Perspective 3 Mechanism 4 Applications: General Routes to Heterocycles 4.1 Flavones and Flavanones 4.2 Xanthones 4.3 Chromones 4.4 Coumarins 4.5 Anthrapyran and Anthracyclin Antibiotics 4.6 Benzopyrans 5 The Retro-Baker–Venkataraman Rearrangement 6 Summary and Outloo

A Baker–Venkataraman retro-Claisen cascade delivers a novel alkyl migration process for the synthesis of amides

A simple extension of the carbamoyl Baker-Venkataraman rearrangement has been developed. If residual water in the reaction is not strictly excluded a Baker-Venkataraman retro-Claisen cascade takes place, giving amide products, in which an alkyl group apparently migrates between two functionalities of the substrate

CONSTRUCTING CHIRAL CENTRES VIA O→C ARYL AND ACYL MIGRATIONS: EXPLORING REACTION POTENTIAL

Detailed within this thesis are the production of diasteromerically enriched α-aryl carbonyl compounds prepared by a new and mild method based on the Truce-Smiles rearrangement; the synthesis of 1,3-dicarbonyl compounds utilising a Baker-Venkataraman rearrangement; and the synthesis of salicylic acid derivatives and amides by a novel Baker-Venkataraman-retro-Claisen cascade. In addition, the in vitro screening of the cyclooxygenase inhibitory activity of some of the diarylethers of the acetamide based substrates prepared, has been undertaken. The introduction summarises the significance and use of both the Truce-Smiles and Baker-Venkataraman rearrangement reactions in the synthesis of α aryl and α acyl carbonyl compounds, respectively. Additionally, a detailed review on some currently available chiral auxiliaries along with their applications is also mentioned. The discussion begins with the application of phase transfer catalysts, based on cinchona alkaloids, for the induction of chirality in ketone-based precursors. Further discussion continues with the synthesis of amide-based substrates from lactones and amines, and the use of C2-symmetric chiral auxiliaries to induce chirality during aryl migration. Using such an approach, a new and mild method for the production of diasteromerically enriched α aryl carbonyl compounds has been achieved. It was found that propanamide-based substrates did not rearrange whilst acetamide-based substrates did, favouring a five-membered transition state during aryl migration. In these initial efforts, only modest diastereoselectivies (dr= max. 1.7:1) were observed. The amide-based substrates did not undergo the Baker-Venkataraman rearrangement, but instead suffered from facile hydrolysis. Thereafter, the section focuses on the investigation of a serendipitously discovered, novel Baker-Venkataraman-retro-Claisen cascade and its subsequent applications in the synthesis of important amides, in which, unusually, the ketone appears to act as an alkyl donor and the carbamoyl moiety as an alkyl acceptor. A separate chapter is given to the cyclooxygenase activity of some of the diarylethers prepared, wherein the diarylethers of certain acetamides were screened for their activities against cyclooxygenase enzymes, COX I and COX II. The preliminary results showed that the best compound was a pyrrolidyl-acetamide based precursor which showed good to modest inhibitory activity against both COX I and COX II (25-37% and 44-70%, respectively) in the in vitro screening assay. The thesis concludes with the experimental section encompassing the experimental details, spectroscopic and analytical analysis of all the compounds prepared and described

Kids' Atlas application to Learn about Geography and Maps

Geography is the study of local and spatial variations in physical and human events on Earth. Studies of the world's geography have grown together with human developments and revolutions. Atlases often present geographic features and boundaries of areas; an atlas is a compilation of different Earth maps or Earth regions, such as the Middle East, and the continents of Asia, and North America. Most teachers still use classical methods of teaching. Geographical concepts and map-reading skills are the most common aspects of learning that early-stage students find challenging. Hence, the objective of this application is to develop a geography application for children between the ages of 9 and 12 years that would allow them to learn maps. Nowadays, smartphones and mobile apps are drawing closer to becoming acceptable learning tools. To facilitate this, Kids' Atlas is an android application, the main purpose of which is to help children to learn easily and test their knowledge. The application improves learning through entertainment by adding technologies that will help children to learning geography. It captures their attention to learn by visualizing objects and allows them to interact more effectively than traditional methods teaching by visualizing the 3D items. The application intends to improve the individual's ability to understand by providing a training section containing simple quizzes, listening/voice recognition capability, and it has the ability to search for a country by voice recognition and zooming for searched country. The methodology involves a set of software development phases, beginning with the planning; analyze data, design, implementation, testing and maintenance phases. The result of this project is a geography learning application that assists children to enjoy learning geography. The result has shown positive indicators that improve children's ability and knowledge of geography. Learning geography also becomes enjoyable; encouraging and motivating children to continue learning. This project contributes to the growth of education in early childhood, which is essential to shape the nation for the future. Therefore, this project is significant and relevant, as it contributes to the knowledge society for Saudi Arabia

Refining colorectal cancer classification and clinical stratification through a single-cell atlas

Background Colorectal cancer (CRC) consensus molecular subtypes (CMS) have different immunological, stromal cell, and clinicopathological characteristics. Single-cell characterization of CMS subtype tumor microenvironments is required to elucidate mechanisms of tumor and stroma cell contributions to pathogenesis which may advance subtype-specific therapeutic development. We interrogate racially diverse human CRC samples and analyze multiple independent external cohorts for a total of 487,829 single cells enabling high-resolution depiction of the cellular diversity and heterogeneity within the tumor and microenvironmental cells. Results Tumor cells recapitulate individual CMS subgroups yet exhibit significant intratumoral CMS heterogeneity. Both CMS1 microsatellite instability (MSI-H) CRCs and microsatellite stable (MSS) CRC demonstrate similar pathway activations at the tumor epithelial level. However, CD8+ cytotoxic T cell phenotype infiltration in MSI-H CRCs may explain why these tumors respond to immune checkpoint inhibitors. Cellular transcriptomic profiles in CRC exist in a tumor immune stromal continuum in contrast to discrete subtypes proposed by studies utilizing bulk transcriptomics. We note a dichotomy in tumor microenvironments across CMS subgroups exists by which patients with high cancer-associated fibroblasts (CAFs) and C1Q+TAM content exhibit poor outcomes, providing a higher level of personalization and precision than would distinct subtypes. Additionally, we discover CAF subtypes known to be associated with immunotherapy resistance. Conclusions Distinct CAFs and C1Q+ TAMs are sufficient to explain CMS predictive ability and a simpler signature based on these cellular phenotypes could stratify CRC patient prognosis with greater precision. Therapeutically targeting specific CAF subtypes and C1Q + TAMs may promote immunotherapy responses in CRC patient

Redefining tumor classification and clinical stratification through a colorectal cancer single-cell atlas

Colorectal cancer (CRC), a disease of high incidence and mortality, exhibits a large degree of inter- and intra-tumoral heterogeneity. The cellular etiology of this heterogeneity is poorly understood. Here, we generated and analyzed a single-cell transcriptome atlas of 49,859 CRC cells from 16 patients, validated with an additional 31,383 cells from an independent CRC patient cohort. We describe subclonal transcriptomic heterogeneity of CRC tumor epithelial cells, as well as discrete stromal populations of cancer-associated fibroblasts (CAFs). Within CRC CAFs, we identify the transcriptional signature of specific subtypes that significantly stratifies overall survival in more than 1,500 CRC patients with bulk transcriptomic data. We demonstrate that scRNA analysis of malignant, stromal, and immune cells exhibit a more complex picture than portrayed by bulk transcriptomic-based Consensus Molecular Subtypes (CMS) classification. By demonstrating an abundant degree of heterogeneity amongst these cell types, our work shows that CRC is best represented in a transcriptomic continuum crossing traditional classification systems boundaries. Overall, this CRC cell map provides a framework to re-evaluate CRC tumor biology with implications for clinical trial design and therapeutic development. Competing Interest Statement: The authors have declared no competing interest

Developing the Scope of O→C Aryl Migrations: Exploring Amide Substrates as Potential Precursors for Asymmetric Reactions

A new and mild method for the production of diasteromerically enriched α-aryl carbonyl compounds has been achieved. Although only modest diastereoselectivies are observed, they demonstrate the potential of the method for further optimisation. It also appears that reactions that proceed through a five-membered spirocyclic transition state rearrange, whereas those proceeding through a six-membered transition state do not, but stop at the diaryl ether stage

Isolation, Culture, and Functional Characterization of Human Embryonic Stem Cells: Current Trends and Challenges

Human embryonic stem cells (hESCs) hold great potential for the treatment of various degenerative diseases. Pluripotent hESCs have a great ability to undergo unlimited self-renewal in culture and to differentiate into all cell types in the body. The journey of hESC research is not that smooth, as it has faced several challenges which are limited to not only tumor formation and immunorejection but also social, ethical, and political aspects. The isolation of hESCs from the human embryo is considered highly objectionable as it requires the destruction of the human embryo. The issue was debated and discussed in both public and government platforms, which led to banning of hESC research in many countries around the world. The banning has negatively affected the progress of hESC research as many federal governments around the world stopped research funding. Afterward, some countries lifted the ban and allowed the funding in hESC research, but the damage has already been done on the progress of research. Under these unfavorable conditions, still some progress was made to isolate, culture, and characterize hESCs using different strategies. In this review, we have summarized various strategies used to successfully isolate, culture, and characterize hESCs. Finally, hESCs hold a great promise for clinical applications with proper strategies to minimize the teratoma formation and immunorejection and better cell transplantation strategies

Extracts of Clove (Syzygium aromaticum) Potentiate FMSP-Nanoparticles Induced Cell Death in MCF-7 Cells

Both nanoparticles and cloves (Syzygium aromaticum) possess anticancer properties, but they do not elicit a significant response on cancer cells when treated alone. In the present study, we have tested fluorescent magnetic submicronic polymer nanoparticles (FMSP-nanoparticles) in combination with crude clove extracts on human breast cancer cells (MCF-7) to examine whether the combination approach enhance the cancer cell death. The MCF-7 cells were treated with different concentrations (1.25 μg/mL, 12.5 μg/mL, 50 μg/mL, 75 μg/mL, and 100 μg/mL) of FMSP-nanoparticles alone and in combination with 50 μg/mL crude clove extracts. The effects of FMSP-nanoparticles alone and combined with clove extracts were observed after 24 hrs and 48 hrs intervals. The response of FMSP-nanoparticles-treated cells was evaluated by Trypan Blue, 4′,6-diamidino-2-phenylindole (DAPI), and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays, respectively. We have demonstrated that cancer cell viability was decreased to 55.40% when treated with FMSP-nanoparticles alone, whereas when cancer cells were treated with FMSP-nanoparticles along with crude clove extracts, the cell viability was drastically decreased to 8.50%. Both morphological and quantitative data suggest that the combination of FMSP-nanoparticles plus crude clove extracts are more effective in treating cancer cells and we suggest that the combination treatment of nanoparticles along with clove extracts hold a great promise for the cancer treatments