Large germline deletions within the mismatch repair gene

oct-l-yl)ethyne, and 4-(dimethylamino)bicyclo[2.2.2]octane-lcarbaldehyde, are contained in supplementary pages following this article. carbonitrile, l-(trimethylsilyl)-2-(4-acetylbicyclo[2.2.2]oct-l-yl)ethyne, and 4-(dimethylamino)bicyclo[2.2.2]octane-l-carbaldehyde, and physical properties, elemental analytical data, and and 13C NMR parameters for the dichloroethenes (8, Y = CH=CC12), acetylenes (8, Y = CCH), and ethylenes (8, Y = CH=CH2) (14 pages). Ordering information is given on any current masthead page.

It was recently reported that base-promoted reaction of cyclobutanone with dialkyl (diazomethy1)phosphonates (DAMP) afforded cyclopentyne (eq l).'qz One part of that study involved I production of a [2 + 21 cycloaddition product 1 between the alkyne and dihydrofuran, a reaction first reported by Fitjer et al.4 The present report defines the stereochemistry of this type of cycloaddition.Reaction of cyclobutanone, the anion of DAMP (generated with KH at -78 "C), and cis-l-meth~xy-l-propene~*~ afforded a cycloadduct which was isolated by HPLC and characterized by standard spectroscopic methods as being 2.' Most relevant to J . Am. Chem. Soc.Foundation (F-815) for this research is gratefully acknowledged. We thank Dr. Steven Larson for the X-ray crystallographic results and Kevin Sweeney for GC-MS analyses.Supplementary Material Available: ORTEP structure, crystallographic data, and bond lengths and angles for adduct 5 (3 pages). Ordering information is given on any current masthead page.Ribonucleotide reductase (RDPR)' from E . coli catalyzes the conversion of nucleoside diphosphates to deoxynucleoside diphosphates.2 This enzyme is composed of two subunits: B, (a, a' M , 160000) binds NDP' substrates and contains redox active thiols and binding sites for the allosteric effectors; B2 (P,P M ,

The synthesis and biological evaluation of a new family of tricyclic indolodioxanes is described. These compounds all contain the 2,3-dihydro-7H-1,4-dioxino[2,3-e]indole nucleus and bear substituents at the 2 and/or 8 positions. Thirteen members of this class were prepared and shown to be potent ligands for the 5-HT1A receptor, with several compounds displaying subnanomolar inhibition constants. These compounds also bind to the dopamine D-2 receptor, but generally with higher inhibition constants than those for 5-HT1A. Certain members of this novel structural class show in vivo activity in the mouse hypothermia assay. One of these compounds, U-86192A, has been shown to have antihypertensive effects in the cat, completely eliminating sympathetic nerve discharge at 1 mg/kg iv and lowering mean arterial pressure to 50% pretreatment levels. These effects can be reversed by the administration of spiperone, indicating that U-86192A is acting via a central serotonergic mechanism.

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