Polyfunctionalised pyrimidines and pyrazines from perhalogenated precursors

Chapter 1 introduces the modem pharmaceutical industry in terms of the drug discovery process leading into a discussion of the relevance of heterocyclic compounds with particular focus on the synthesis of multifunctional pyrimidines and pyrazines. An introduction into organofluorine chemistry is included followed by a review of the literature on 5-chloro-trifluoropyrimidine, tetrafluoropyrimidine and tetrafluoropyrazine. Chapter 2 describes a study of the reactivity of 5-chlorotrifluoropyrimidine with mono- and difunctional-nucleophiles. This research demonstrates the former are not selective and in the latter the 5-position chlorine atom is inert to nucleophilic aromatic substitution and cross-coupling methodologies. Chapter 3 explores the reactivity of tetrafluoropyrimidine with nitrogen, sulphur and oxygen containing nucleophiles and describes the development of a methodology for the synthesis of multisubstituted pyrimidines by establishing the regioselectivities of such processes. Chapter 4 investigates the reactivity of tetrafluoropyrimidine with difunctional nucleophiles. This study indicated it was not possible to synthesise [5,6]-ring fused systems and that in some cases dimers were formed owing to the 5-position fluorine atom being inactive substitution. Chapter 5 discusses the use of tetrafluoropyrazine in the syntheses of [5,6] ring-fused systems. The reactivity of the system towards MiV-dinucleophiles and C,0-dinucleophiles was investigated. Further functionalisations by nucleophilic aromatic substitution of the remaining fluorine atoms with nitrogen and oxygen nucleophiles are also discussed. Chapter 6 contains the experimental data for Chapters 2 to 5

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

Author correction : roadmap for naming uncultivated archaea and bacteria

Correction to: Nature Microbiology https://doi.org/10.1038/s41564-020-0733-x , published online 8 June 2020. In the version of this Consensus Statement originally published, Pablo Yarza was mistakenly not included in the author list. Also, in Supplementary Table 1, Alexander Jaffe was missing from the list of endorsees. These errors have now been corrected and the updated Supplementary Table 1 is available online

Roadmap for naming uncultivated Archaea and Bacteria

The assembly of single-amplified genomes (SAGs) and metagenome-assembled genomes (MAGs) has led to a surge in genome-based discoveries of members affiliated with Archaea and Bacteria, bringing with it a need to develop guidelines for nomenclature of uncultivated microorganisms. The International Code of Nomenclature of Prokaryotes (ICNP) only recognizes cultures as ‘type material’, thereby preventing the naming of uncultivated organisms. In this Consensus Statement, we propose two potential paths to solve this nomenclatural conundrum. One option is the adoption of previously proposed modifications to the ICNP to recognize DNA sequences as acceptable type material; the other option creates a nomenclatural code for uncultivated Archaea and Bacteria that could eventually be merged with the ICNP in the future. Regardless of the path taken, we believe that action is needed now within the scientific community to develop consistent rules for nomenclature of uncultivated taxa in order to provide clarity and stability, and to effectively communicate microbial diversity

Roadmap for naming uncultivated Archaea and Bacteria.

The assembly of single-amplified genomes (SAGs) and metagenome-assembled genomes (MAGs) has led to a surge in genome-based discoveries of members affiliated with Archaea and Bacteria, bringing with it a need to develop guidelines for nomenclature of uncultivated microorganisms. The International Code of Nomenclature of Prokaryotes (ICNP) only recognizes cultures as 'type material', thereby preventing the naming of uncultivated organisms. In this Consensus Statement, we propose two potential paths to solve this nomenclatural conundrum. One option is the adoption of previously proposed modifications to the ICNP to recognize DNA sequences as acceptable type material; the other option creates a nomenclatural code for uncultivated Archaea and Bacteria that could eventually be merged with the ICNP in the future. Regardless of the path taken, we believe that action is needed now within the scientific community to develop consistent rules for nomenclature of uncultivated taxa in order to provide clarity and stability, and to effectively communicate microbial diversity