DNA sequence information underpins genetic research, enabling discoveries of important biological or medical benefit. Sequencing projects have traditionally employed long (400–800 bp) reads, but the existence of reference sequences for the human and many other genomes makes it possible to develop new, fast approaches to re-sequencing, whereby shorter reads are compared to a reference to identify intra-species genetic variation. We report an approach that generates several billion bases of accurate nucleotide sequence per experiment at low cost. Single molecules of DNA are attached to a flat surface, amplified in situ and used as templates for synthetic sequencing with fluorescent reversible terminator deoxyribonucleotides. Images of the surface are analysed to generate high quality sequence. We demonstrate application of this approach to human genome sequencing on flow-sorted X chromosomes and then scale the approach to determine the genome sequence of a male Yoruba from Ibadan, Nigeria. We build an accurate consensus sequence from >30x average depth of paired 35-base reads. We characterise four million SNPs and four hundred thousand structural variants, many of which are previously unknown. Our approach is effective for accurate, rapid and economical whole genome re-sequencing and many other biomedical applications.

Alcohols have been employed as substrates for C-C bond-forming reactions which involve initial activation by the temporary removal of hydrogen to form an aldehyde. The intermediate aldehyde is converted into an alkene via a Horner-Wadsworth-Emmons reaction, nitroaldol and aldol reactions. The 'borrowed hydrogen' is then returned to the alkene to form a C-C bond.

The successful development of an indirect three‐step domino sequence for the formation of C–C bonds from alcohol substrates is described. An iridium‐catalysed dehydrogenation of alcohol 1 affords the intermediate aldehyde 2. The desired C–C bond can then be formed by a facile Wittig olefination, yielding the intermediate alkene 3. In the final step the alkene is hydrogenated to afford the indirect Wittig product, the alkane 4. The key to this process is the concept of borrowing hydrogen; hydrogen removed in the initial dehydrogenation step is simply borrowed by the iridium catalyst. Functioning as a hydrogen reservoir, the catalyst facilitates C–C bond formation before subsequently returning the borrowed hydrogen in the final step. Herein we present full details of our examination into both the substrate and reaction scope and the limitations of the catalytic cycle. (© Wiley‐VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, Germany, 2006)

No abstract

The 2,6-dibromoindole 5 underwent regioselective Sonogashira coupling at the 2 position with simple acetylenic partners. While, the imidazole-acetylene 16 failed to couple to 5, the cyclic carbonate 19 succeeded to give 20, which was further elaborated into the indole-imidazole 23. KeywordsChartelline C; securines; securamines; biogenetic; Sonogashira couplingThe chartelline marine alkaloids were isolated from the bryozoan Chartella papyracea and characterized in the 1980's. 1-3 A related bryozoan Securiflustra securifrons also produces the securines and securamines, 4,5 and they are plausible biogenetic precursors to the chartellines. It was reported that solutions of securine B 1 in DMSO-d 6 converted into securamine B 2, presumably via 1a , Scheme 1. 4 Redissolving 2 in CDCl 3 converted 2 back into 1. One could imagine that if this isomerization were carried out in the presence of an electropositive source of chlorine, 1 could be converted into chartelline C 3 through the intermediacy of 1b and 1c. The transformation of 1c into 3 can be written as a [1,5]-shift and is a key step in the recently reported biogenetically inspired strategy for the synthesis of 3 by Baran and Shenvi. 6,7 Several other groups have reported on synthetic approaches to chartelline C 6,8-11 as well as related alkaloids. 12,13 Our plan was also based on the supposition that the spiro-β-lactam in 3 could arise from a late stage oxidative cyclization of a suitable macrolactam. 14 The macrolactam precursor to 1c, namely 1, was envisioned as arising from macrolactamization, and to eventually achieve this a regioselective Sonogashira coupling at the 2-position of a 2-halo-6-bromoindole was required as a starting point. The only selective coupling of an acetylene at the 2-position of an indole that has a 6-bromo substituent was a 2-iodo-6-bromoindole, 7 and since this compound required a six step synthesis from 6-bromoindole, we were interested to see if a 2,6-dibromoindole exhibited any selectivity in a Sonogashira coupling reaction.Indole-3-acetonitrile 4 15,16 was regioselectively brominated using a known protocol 17 to give 5 (after t-butyl carbamate protection), Scheme 2. Exposure of 5 to standard Sonogashira © 2007 Elsevier Ltd. All rights reserved.Tel +1 512 471 3966: Fax +1 512 471 7839: p.magnus@mail.utexas.edu. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. coupling reaction conditions proceeded with complete regioselectivity to give the 2-coupled indoles 6, 7 and 8 respectively. It was found that the choice of protecting group on the indole nitrogen atom was essential to achieving r...