Synthesis of 1-deoxy-D-galactohomonojirimycin via enantiomerically pure allenylstannanes

1-Deoxy-D-galactohomonojirimycin was synthesized in seven steps from optically pure allenylstannane 4 and L-lactate-derived aldehyde 5 in 48% overall yield. The key step was the Lewis acid catalyzed reaction of 4 and 5 to give the syn-amino alcohol in excellent yield and very high diastereoselectivity.     

Electroorganic synthesis. Reductive alkylation of functionalized 1,2-dithiole-3-thiones

Two-electron reduction of some substituted 1,2-dithiole-3-thiones 1 followed by alkylation of the dianionic intermediates leads through electrosynthesis to mixture of Z and E isomers of the corresponding substituted alkyl-(3-thioalkyl)-2-propenedithioates 2, 3 in satisfactory yield. The structure of those products was established by ¹³C and ¹H nmr and mass spectroscopy. The isomers ratios were determined by nmr spectroscopy.     

Phage-display selection of a human single-chain fv antibody highly specific for melanoma and breast cancer cells using a chemoenzymatically synthesized G(M3)-carbohydrate antigen

Overexpression of the cell-surface glycosphingolipid G(M3) is associated with a number of different cancers, including those of the skin, colon, breast, and lung. Antibodies against the G(M3) epitope have potential application as therapeutic agents in the treatment of these cancers. We describe the chemoenzymatic synthesis of two G(M3)-derived reagents and their use in the panning of a phage-displayed human single-chain Fv (scFv) antibody library derived from the blood of cancer patients. Three scFv-phage clones, GM3A6, GM3A8, and GM3A15, were selected for recombinant expression and were characterized using BIAcore and flow cytometry. BIAcore measurements using the purified, soluble scFvs yielded dissociation constants (K(d)) ranging from 4.2 x 10(-7) to 2.1 x 10(-5) M. Flow cytometry was used to evaluate the ability of each scFv to discriminate between normal human cells (human dermal fibroblast, HDFa), melanoma cells (HMV-1, M21, and C-8161), and breast cancer cells (BCM-1, BCM-2, and BMS). GM3A6 displayed cross-reactivity with normal cells, as well as tumor cells, and GM3A15 possessed little or no binding activity toward any of the cell lines tested. However, GM3A8 bound to five of the six tumor cell lines and showed no measurable reactivity against the HDFa cells. Hence, we have demonstrated that a synthetic G(M3) panning reagent can be used to isolate a fully human scFv that is highly specific for native G(M3) on the surface of tumor cells. The result is a significant step toward effective immunotherapies for the treatment of cancer.     

Reversal of facial selectivity in complex Diels-Alder reactions

A complex Diels-Alder reaction between a semi-cyclic diene with allylic silyloxy substituents and a bromo enone presented an unusual diastereoselectivity: attack of the diene occured on its more hindered face, and this reversal of selectivity was shown to be induced by the presence of a bromo substituent in the dienophile.     

Modifications de la position C-8 de purines nucleosides par action de reactifs electrophiles sur leurs derives silyles et lithies

The alkylation of 8-lithiopurine trimethylsilyl nucleosides at carbon 8 can be carried out conveniently by reaction with various electrophilic reagents.     

A novel ethylene-bridged spiro[3.2]Hexane

3,3-Dichlorotricyclo[5.1.0.0^1,4]oct-5-en-2-one ($\text{1}$) was prepared by addition of dichloroketene to 1,3-cyclohexadiene followed by allylic bromination and dehydrobromination.     

Nature of the chemical bonds in HCN and C2N2

The function (M), which measures the effect of the bond formation on the electron density distribution, has been calculated for HCN and C₂N₂. The charge build up in the CN bonds is found to be quite the same in both molecules, which indicates that the outer bonds of C₂N₂ are practically unaffected by conjugation.

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Zusammenfassung Die Funktion (M), ein Maß für die Änderung der Elektronendichteverteilung durch Bildung von Bindungen, wurde für HCN und C₂N₂ berechnet. Danach ist die Ladungsanhäufung in den CN-Bindungen für beide Moleküle praktisch gleich, was darauf hinweist, daß die äußeren Bindungen im C₂N₂ durch die Konjugation kaum verändert werden.

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Résumé La fonction (M), qui mesure l'effet de la formation des liaisons sur la distribution de la densité électronique, a été calculée pour HCN et C₂N₂. D'après les calculs, l'accumulation de charge dans les liaisons CN est pratiquement la même dans les deux molécules, ce qui indique que les liaisons extérieures de C₂N₂ ne sont en fait pas affectées par la conjugaison.

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We are thankful to Miss Cl. Litt for programming the calculation of the function and to Mrs. M. Henseval for drawing the density contours.     

Sur les dérivés de la fluorénone VI Les acides bromo-3-fluorénonecarboxylique-2 et bromo-2-fluorénonecarboxylique-3 et la bromo-3-méthyl-4-fluorénone

Starting from 2-amino-3-bromo-9-oxofluorene and from 3-methylfluorene respectively the preparation of 3-bromo-9-oxofluorene-2-carboxylic acid and of 2-bromo-9-oxofluorene-3-carboxylic acid is described. A synthesis of 3-bromo-4-methyl-9-oxofluorene is also given.     

Bonding and redox properties of [Os(3)(CO)(9)(tmbp)(L)] (tmbp=4,4',5,5'-tetramethyl-2,2'-biphosphinine; L=CO, PPh(3)) clusters with an unprecedented electron-deficient metallic core and doubly bridging biphosphinine dianion

Herein we describe in detail the bonding properties and electrochemical behavior of the first known triosmium carbonyl clusters with a coordinated redox-active ligand 4,4',5,5'-tetramethyl-2,2'-biphosphinine (tmbp), the phosphorus derivative of 2,2'-bipyridine. The clusters investigated were [Os(3)(CO)(10)(tmbp)] (1) and its derivative [Os(3)(CO)(9)(PPh(3))(tmbp)] (2). The crystal structures of both clusters are compared with those of relevant compounds; they served as the basis for density functional theory (DFT and time-dependent DFT) calculations. The experimental and theoretical data reveal an unexpected and unprecedented bridging coordination mode of tmbp, with each P atom bridging two metal atoms. The tmbp ligand is formally reduced by transfer of two electrons from the triangular cluster core that consequently lacks one of the metal-metal bonds. Both 1 and 2 therefore represent 50e(-) clusters with a coordinated 8e(-) donor, [tmbp](2-). The HOMO and LUMO of 1 and 2 possess a predominant contribution from different pi*(tmbp) orbitals, implying that the lowest energy excited state possesses a significant intraligand character. This is in agreement with the photostability of these clusters. DFT calculations also predict the experimentally observed structure of 1 to be the most stable one in a series of several plausible structural isomers. Stepwise two-electron electrochemical reduction of 1 and 2 results in dissociation of CO and PPh(3), respectively, and formation of the [Os(3)(CO)(9)(tmbp)](2-) ion. The initially produced radical anions of the parent clusters, in which the odd electron is predominantly localized on the tmbp ligand, are sufficiently stable at low temperatures and can be observed with IR spectroelectrochemistry. The electron-deficiency of the cluster core in 1 permits facile electrocatalytic substitution of a CO ligand by tertiary phosphane and phosphite donors.