Multicomponent Reactions for the Preparation of Fluorous Taged Pyrimidines and Thiopyrimidines and their Derivatisation to Obtain Biaryl-Substituted Heterocycles

This thesis presents a work in the field of multicomponent reactions (MCRs), one-step condensation between a fluorous tagged aldehyde, β-keto ester and urea derivatives. This process in literature is known as Biginelli Reaction . This dissertation describes a new Biginelli reaction element, using fluorous component as a limiting agent. Chapter one is an introduction of MCRs. A brief historical review, key principles as well as applications in different fields such as academic research, synthetic organic chemistry, and medicinal applications are presented. Chapter two discusses the general features of the Biginelli reaction, microwave, and fluorous chemistry with a distinctive look from the perspective of green chemistry. In chapter three our efforts in expanding the procedures to new fluorous components such as fluorous tagged DHMPs are examined. Interesting features for the synthetic process were reveled through multiple types of reagents-controlled synthesis. Suzuki reaction with phenyl boronic acids is explored. The extent of the different structures and the stereochemical preference are discussed. The possibility of Suzuki coupling of thiazolopyrimidine structures by conducting a cycloaddition reaction was investigated. A five member ring was added to the position 2 and 3 of the dihydropyrimidine scaffold to obtain 5H-Thiazolo 2,3 pyrimidines. Two analogues from cycloaddition reaction were obtained for Suzuki couplings to afford eight final products. Another feature that we were able to explore was the synthetic manipulation of thiazolopyrimidine adduct obtained from the Biginelli reaction. The reactivity of the double bonded sulfur toward palladium promoted transformations allowed for the synthesis of various heterocycles through Liebeskind-Srogl desulfative coupling followed by Suzuki cross-coupling reactions

Finishing the euchromatic sequence of the human genome

The sequence of the human genome encodes the genetic instructions for human physiology, as well as rich information about human evolution. In 2001, the International Human Genome Sequencing Consortium reported a draft sequence of the euchromatic portion of the human genome. Since then, the international collaboration has worked to convert this draft into a genome sequence with high accuracy and nearly complete coverage. Here, we report the result of this finishing process. The current genome sequence (Build 35) contains 2.85 billion nucleotides interrupted by only 341 gaps. It covers ∼99% of the euchromatic genome and is accurate to an error rate of ∼1 event per 100,000 bases. Many of the remaining euchromatic gaps are associated with segmental duplications and will require focused work with new methods. The near-complete sequence, the first for a vertebrate, greatly improves the precision of biological analyses of the human genome including studies of gene number, birth and death. Notably, the human enome seems to encode only 20,000-25,000 protein-coding genes. The genome sequence reported here should serve as a firm foundation for biomedical research in the decades ahead