Generation and carbonyl addition reactions of Z-dilithiohex-3-ene-1,5-diyne

The reaction of the title dilithio salt with carbonyl compounds leads to products bearing substructures found in recently discovered enediyne antibiotics. The bis condensation product with benzaldehyde undergoes a novel cycloaromatization reaction.     

Identification of the adduct between a 4-aza-3-ene-1,6-diyne and DNA using electrospray ionization mass spectrometry

The interactions between a novel enediyne [1-methyl-2-(phenylethynyl)-3-(3-phenylprop-2-ynyl)-3H-benzimidazolium] (1) and various cytosine-containing oligonucleotides were studied using electrospray ionization mass spectrometry (ESI-MS) in a flow injection analysis mode useful for small volumes. This enediyne ligand, developed as a potential alternative to the highly cytotoxic natural enediynes, some of which have been successfully used as anti-tumor agents, has previously been shown to interact with DNA through frank strand scission as well as via the formation of adducts that lead to 2'-deoxycytidine-specific cleavage. Through ESI-MS, the structures of these adducts were examined and a sequence dependence of the 2'-deoxycytidine-specific cleavage was noted. Collisionally activated dissociation of the observed adducts confirmed the strength of the interactions between the enediyne and DNA and supports a direct linkage between the enediyne and the cytosine nucleobase, likely the result of a nucleophilic attack of the phenylethynyl group by the cytosine amine.     

Isolation of a cyclopropane-containing product from the rearrangement of a 3-aza-3-ene-1,5-diyne under acid catalysis

A 3-aza-enediyne that undergoes rapid aza-Bergman rearrangement was treated with trifluoromethanesulfonic acid in the presence of 1,4-cyclohexadiene in an attempt to trap the putative 2,5-didehydropyridinium aza-Bergman intermediate. No pyridine products were detected; rather, a cyclopropane derivative of 1,4-cyclohexadiene derived from a 5-oxazolylcarbene was isolated.     

Preparation and spectroscopic properties of cyclodeca-1,6-diyne

The preparation of cyclodeca-1,6-diyne (=1) is reported. The PE results reveal a strong interaction between the in plane π molecular orbitals of {=1}.     

Synthesis and thermolysis of heterocyclic 3-aza-3-ene-1,5-diynes(1)

[reaction: see text] Simple, acyclic 3-aza-3-ene-1,5-diynes undergo an aza-Bergman rearrangement to a fleeting 2,5-didehydropyridine (2,5-ddp) intermediate that rapidly ring-opens to beta-alkynylacrylonitrile products. In an effort to access longer-lived 2,5-ddp intermediates, we have prepared heterocyclic 3-aza-3-ene-1,5-diynes. The thermolysis of one such heterocyclic aza-enediyne does not afford products derived from trapping a 2,5-ddp intermediate but rather cyclopropanes that appear to arise from a carbene intermediate and a product that appears to be a trapping product from a 2,3-ddp intermediate.     

Vibrational spectra and molecular conformations of 1,5-dichloro- and 1,5-dibromopentanes and 1,6-dichloro-and 1,6-dibromohexanes

The Raman and IR spectra of 1,5-dichloro- and 1,5-dibromopentanes and 1,6-dichloro-and 1,6-dibromohexanes have been measured. The normal coordinates have been calculated for these molecules using a consistent set of force constants and the molecular conformations studied by analysing the spectra with reference to the results of the calculations. In the crystalline solid state, 1,5-dichloropentane assumes the trans-trans-trans-gauche form and 1,5-dibromopentane, 1,6-dichloro- and 1,6-dibromohexanes assume the all-trans form. The normal coordinate treatment with the well-established force field was of great help in determining the whole molecular form of the relatively large chain molecules.     

Stereospecific syntheses of 3'-deuterated pyrimidine nucleosides and their site-specific incorporation into DNA

[reaction: see text] 2'-Deoxy-3'-deutero pyrimidines have been synthesized in high yields and incorporated into deoxyoligonucleotides using standard phosphoramidite chemistry. A key synthetic step is a stereospecific reduction of 3'-keto nucleosides using sodium triacetoxyborodeuteride to give 3'-deuterated thymidine and 2'-deoxy uridine nucleosides. Conversion of the corresponding phorphoramidites 7a and 7b to 4-triazolo derivatives has, for the first time, enabled incorporation of 2'-deoxy-3'-deutero cytidine and 2'-deoxy-3'-deutero-5-methyl cytidine into oligonucleotides.     

An extremely facile aza-Bergman rearrangement of sterically unencumbered acyclic 3-aza-3-ene-1,5-diynes

The factors that affect the kinetics of the aza-Bergman cyclization of aza-enediynes (C,N-dialkynyl imines) have not previously been elucidated. Here we report our kinetic studies of the aza-Bergman reactions of a series of 6-triisopropylsilyl and 6-unsubstituted 1-phenyl-4-aryl-3-aza-3-ene-1,4-diynes in which the aryl group is phenyl, o-(methoxy)phenyl, or p-(methoxy)phenyl. These aza-enediynes are prepared as single isomers in modest yield from the corresponding 1-aryl-3-(triisopropylsilyl)propynone oximes. These aza-enediynes undergo aza-Bergman reaction followed by a rapid retro-aza-Bergman cyclization to afford beta-alkynyl acrylonitrile products. In no case are products corresponding to trapping the intermediate 2,5-didehydropyridine diradical isolated. While the rate of aza-Bergman cyclization is not greatly affected by the nature of the 4-aryl substituent, the rate is very dependent on the nature of the 6-substituent. 1-Phenyl-4-aryl-3-aza-3-ene-1,5-diynes that lack a 6-substituent undergo aza-Bergman cyclization spontaneously at 20 degrees C with first-order half-lives of 36-78 min. The effect of solvent on the kinetics of aza-Bergman cyclization of 1,4-diphenyl-3-aza-3-ene-1,5-diyne was investigated. The rate of this cyclization is solvent dependent, proceeding more rapidly in less polar solvents.     

Stereospecific syntheses of coriolin,coriolin B and diketocoriolin B

Routes to the title compounds $\text{via}$ a fully stereospecific total synthesis of dihydrocoriolin are reported.     

Conformation and vibrational spectra of 1,5-hexadiyne (bipropargyl) and 1,5-hexadiyne-1,6-d2

The infrared spectra of 1,5-hexadiyne (bipropargyl) and 1,5-hexadiyne-1,6-d₂ as vapours, liquids, as solutes in various solvents and as crystalline solids at low temperatures and at high pressures have been recorded. Raman spectra were obtained for the liquids, including semiquantitative polarization measurements, and for the low temperature crystals.The data were interpreted in terms of two conformers, anti and gauche, in the vapour and liquid state and one, the anti, in the crystalline forms. A phase transition for 1,5-hexadiyne was observed at ca. 240 K. Both the high and low temperature crystals had molecules in the anti conformer.Interpretation of the spectra in terms of conformational equilibria was facilitated by a thorough vapour phase band contour analysis. With a few exceptions, all the vibrational fundamentals for both conformers were assigned and found to be in good agreement with results from normal coordinate calculations.     

Synthesis of (Z)- and (E)-3,4-Dimethyl-hex-3-ene-1,6-diols

(Z)- and (E)-3,4-dimethyl-hex-3-ene-1,6-diols (1 and 2) have been synthesized in 23% and 68% yields by a three step sequence requiring only one purification at the end. The steps are a) coupling of 2-lithio-1,3-dithiane with (Z)- or (E)-1,4-dibromo-2,3-dimethyl-but-2-ene (3 or 4), b) hydrolysis of the thioketals (8 and 9) with methyl iodide in a mixture of acetonitrile, acetone and water to give the 3,4-dimethyl-hex-3-ene-1,6-diols (10 and 11) and c) reduction with diisobutylaluminum hydride to provide the (Z)- and (E)-diols.