We present a comprehensive map of over 1 million polyadenylation sites and quantify their usage in major cancers and tumor cell lines using direct RNA sequencing. We built the Expression and Polyadenylation Database to enable the visualization of the polyadenylation maps in various cancers and to facilitate the discovery of novel genes and gene isoforms that are potentially important to tumorigenesis. Analyses of polyadenylation sites indicate that a large fraction (∼30%) of mRNAs contain alternative polyadenylation sites in their 3′ untranslated regions, independent of the cell type. The shortest 3′ untranslated region isoforms are preferentially upregulated in cancer tissues, genome-wide. Candidate targets of alternative polyadenylation-mediated upregulation of short isoforms include POLR2K, and signaling cascades of cell–cell and cell–extracellular matrix contact, particularly involving regulators of Rho GTPases. Polyadenylation maps also helped to improve 3′ untranslated region annotations and identify candidate regulatory marks such as sequence motifs, H3K36Me3 and Pabpc1 that are isoform dependent and occur in a position-specific manner. In summary, these results highlight the need to go beyond monitoring only the cumulative transcript levels for a gene, to separately analysing the expression of its RNA isoforms.

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Pharmaceuticals Division, Imperial Chemical Industries, Limited 1)uring the search for a more economical route to the broad spectrum anthelmintic, 6-pheny1-2,3,5,6-tetrahydroimidazo[2,1-b]thiazole (1) (a), the use of styrene as a possible starting material was investigated. Previous syntheses have involved the use of phmacyl bromide arid 2-aminothiazoline (3) and more recently, styrene oxide and ethyleneimine (4), as starting reagents. The formation of 1-arylsulphonylaziridines in high yield from olefins has been described by two of us (5). Utilizing this reaction, 2-phenyl-1Cp-toluenesulphony1)aziridine (11) can be generated in situ by reacting styrene with N,N-dichloro-ptoluenesulphonamide in toluene solution, followed by treatment with ammonium hydroxide to remove the labile chlorine and then with sodium hydroxide solution to effect cyclization. The potential of this activated aziridine (11) as a building block for the synthesis of I forms t h e subject of this paper. lkaction of 2-pheny l-1 -@toluenesulphony I) aziridine with ethanolamint: gave a mixture of the isomeric amines (111, X = OH) and IV. The ratio of the products obtained was found t o vary considerably with the solvent used. Aprotic solvents, in particular those containing the ether linkage, gave rise to predominantly the normal addition product (111, X = OH), whereas protic solvents such as 2-propanol favoured the abnormal addition product (IV).( )ptimum reaction conditions were obtained using dioxane as solvent, when 58% of (111, X = OM) was produced.Similar solvent effects have been reported by Parker & ltockett (6) for the reaction of styrene oxide with benzylamine. Excess ethanolamine t o two equivalents, enhanced the rate of reaction but hardly effected the yield of the normal addition product. However, a vast excess of ethanolamine gave a very poor yield of 111 (X = OH).The normal addition product was readily converted into the 2-iminothiazolidine (V) via the chloride (111, X = CI), by treatment first with thionyl chloride and then with ammonium thiocyanate. An 85% overall yield of V was obtained. The 2-iminothiazolidine could also be produced by reacting the aziridine (11) with 2-aminothiazoline. The yield of the normal addition isomer (V) was favoured as in the case of the ethanolamine reaction by the employment of aprotic solvents, but t h e variation between different aprotic solvents was marginal, the preferred solvent, xylene, giving a 41% yield of V. King closure of the 2-irninothiazolidine was readily effected, utilising concentrated sulphuric acid a t room temperature, to give the required 6 -phenyl-2,3,5,6 -tetrahydroimidazo [ 2,l -b It h iazole in 84% yield. Polyphosphoric acid also brought about this cyclization, but gave inferior results. Similar C-N fissions of sulphonamides rather than the normal N-S fissions in strong acid have been observed when it is possible to generate either a tertiary or a secondary aryl carbonium ion by such a fission (7). The ethanolamine (Ill, X = OH) also readily underwent an analogous cyclization ...

Meisenheimer rearrangement of the lob-vinylpyrroloi2,l-a]isoquinoline and Ilb-vinylbenzo[a]quinolizine N-oxide derivatives (4a,b) gave, in low yield, the first examples of the 3,7-epoxy-3-benzazonine and 2H-3,8-epoxy-3-benzazecine ring systems (5a) and (5b) respectively. Yasuda, N., and Williams, R. M., Tetrahedron Lett., 1989, 30, 3397.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

ChemInform is a weekly Abstracting Service, delivering concise information at a glance that was extracted from about 100 leading journals. To access a ChemInform Abstract of an article which was published elsewhere, please select a “Full Text” option. The original article is trackable via the “References” option.

Using a common 1-(1-phenylethenyl)-1,2,3,4-tetrahydroisoquinoline precursor to the required ylide or N-oxide intermediate, the Stevens [2,3] and analogous Meisenheimer [2,3] sigmatropic rearrangements have been applied to afford concise syntheses of phenyl -substituted representatives of each of the reduced 1H-3-benzazonine and 4,3-benzoxazonine systems, respectively. Single crystal X-ray structure determinations were employed to define the conformational characteristics for each ring type.

N-Methylation of 6,7-dimethoxy-1-(2�-phenylcyclopropyl)-3,4-dihydroisoquinoline (3b) with iodomethane in refluxing acetone gave the modified Cloke rearrangement product, 8,9-dimethoxy-4-methyl-3-phenyl-2,3,5,6-tetrahyropyrrolo[2,1-a] isoquinolinium iodide (5b), a new derivative of the pyrrolo [2,1-a] isoquinoline skeleton, together with the methiodide salt (4b) of (3b). The structure of (5b) was confirmed by X-ray crystallographic analysis.