Asymmetric radical additions of trialkylboranes to 2H-azirine-3-carboxylates

Asymmetric additions of alkyl radicals, generated from R3B, to chiral 2H-azirine-3-carboxylates offer a new entry to enantio-enriched aziridines, and proceed with high diastereoselectivity when using 8-phenylmenthol as chiral auxiliary.     

Evaluation of (+)-sparteine-like diamines for asymmetric synthesis

Three new (+)-sparteine-like diamines were prepared from (-)-cytisine and evaluated as sparteine surrogates in the alpha-lithiation rearrangement of cyclooctene oxide and the palladium(II)/diamine catalyzed oxidative kinetic resolution of 1-indanol. The new diamines exhibited opposite enantioselectivity to that observed with (-)-sparteine but increasing the steric hindrance of the N-alkyl group beyond N-Et had a detrimental effect on enantioselectivity. The optimal N-Me diamine was evaluated with much success in five other (-)-sparteine-mediated processes involving different metals (lithium, magnesium, and copper) and different types of reaction mechanisms.     

Antiaromaticity in relation to 1,3,5,7-cyclooctatetraene structures

An isodesmic energy analysis has been carried out at the MP 2/6–31G *//HF /3–21G level for the nonplanar ground state ( 1 ) of 1,3,5,7-cyclooctateraene and for two planar forms, one having complete π delocalization ( 2 ) and the other having alternating single and double bonds ( 3 ). 1 is found to have a considerable degree of stabilization, which is attributed to limited π delocalization. The polyene 3 is the more stable of the two planar forms; it is a transition state in the inversion between two possible nonplanar structures. 2 is found to be a triplet at the Hartree–Fock level and is a critical point on an alternate pathway between the two possible arrangements of alternating single and double bonds in 3 . Both 2 and 3 have negative isodesmic energies, indicating the presence of stabilizing factors. Our results for 3 show that an “antiaromatic” system need not necessarily show a net destabilization. © 1994 John Wiley & Sons, Inc.     

Bildung tricyclischer Thietan-Derivate durch intramolekulare(2+2)-Cycloaddition

Formation of Thietane Derivatives via Intramolecular (2+2) Cycloaddition On irradiation, the two 4-vinyl-1,3-thiazole-5(4H)-thiones 1a, b , synthesized from thiobenzoic acid and the corresponding 3-amino-2H-azirines 2a , b , undergo an intramolecular (2+2)-cycloaddition reaction of the C?S and C?C bonds to give the tricyclic thietane derivatives 3a , b .     

Ganglioside analysis by thin-layer chromatography matrix-assisted laser desorption/ionization orthogonal time-of-flight mass spectrometry

Metastable decomposition of ions generated in matrix-assisted laser desorption/ionization (MALDI) mass spectrometers complicates analysis of biological samples that have labile bonds. Recently, several academic laboratories and manufacturers of commercial instruments have designed instruments that introduce a cooling gas into the ion source during the MALDI event and have shown that the resulting vibrational cooling stabilizes these labile bonds. In this study, we compared stabilization and detection of desorbed gangliosides on a commercial orthogonal time-of-flight (oTOF) instrument with results we reported previously that had been obtained on a home-built Fourier transform mass spectrometer. Decoupling of the desorption/ionization from the detection steps resulted in an opportunity for desorbing thin-layer chromatography (TLC)-separated gangliosides directly from a TLC plate without compromising mass spectral accuracy and resolution of the ganglioside analysis, thus coupling TLC and oTOF mass spectrometry. The application of a declustering potential allowed control of the matrix cluster and matrix adduct formation, and, thus, enhanced the detection of the gangliosides.     

Coleone C,D, I,I′ aus einer madegassischen Plectranthus sp. nov. Interkonversion von cis- und trans-A/B-6,7-Diketoditerpenen

Coleons C, D, I, I′, obtained from a Madagascan Plectranthus sp. nov.. Interconversion of cis- and trans-A/B-6,7-Diketoditerpenes. Fairly large amounts of Coleons C and D, as well as Coleons I and I′ (3-O-formyl derivative of Coleon I) can bc isolated from the orange glands of an unclassified North Madagascan Plectranthus sp. A reversible transformation of cis- and trans-A/B-6,7-dioxo-abietane via its diosphenol has been achieved for the first time. CD.-Spectra of these compounds are presented. Hydrogenolysis of Coleon D leads to 6β,16-dihydroxy-royleanone.     

Enantioselective monoreduction of 2-alkyl-1,3-diketones mediated by chiral ruthenium catalysts. dynamic kinetic resolution

The reduction of 2-alkyl-1,3-diketones using (R,R)- or (S,S)-RuCl[N-(tosyl)-1,2-diphenylethylenediamine](p-cymene) in the presence of formic acid and triethylamine affords syn-2-alkyl-3-hydroxy ketones as the major products with high enantioselectivity. [reaction: see text]     

Development of a formulation of Pirodavir using 2-hydroxypropyl-β-cyclodextrin

Pirodavir, 4-[2-[1-(6-Methyl-3-pyridazinyl)-4-piperidinyl]ethoxy]benzoic acid ethyl ester, is an antiviral compound which has low aqueous solubility (<0.01 mg/ml). The compound is a weak base (pKa 5.8) with high lipophicity (logP 4.44). Ionization of the compound increases the solubility in acidic medium to 2.3 mg/ml at pH 2.4. However, a low pH is not acceptable for nasal application as this would induce irritation. Extensive solubility studies were performed using different types of substituted cyclodextrins in order to select an appropriate derivate capable of increasing solubility to an acceptable level for formulations for nasal application. Aqueous solubility of pirodavir increased in a linear fashion with increasing concentration of most of the substituted cyclodextrins. However, using 2-hydropropyl-β-cyclodextrin (HPBCD) the solubility increased in a non-linear fashion. Based on these studies HPBCD was selected as the most appropriate excipient. To support a clinical study on the treatment of rhinovirus cold by intranasal Pirodavir formulations were developed containing up to 5 mg/ml of pirodavir and up to 10% of HPBCD. Stability of the formulations was studied and found to be acceptable.     

Diiodine complex of diferrocenyl(phenyl)phosphine sulfide: the structural and electrochemical behaviour of Fc2(Ph)PS · I2

The title compound, Fc₂(Ph)PS · I₂, has been prepared and characterised in both the solid state and solution. Single crystal X-ray crystallography reveals that the adduct adopts a molecular charge-transfer structure in the solid state. Mössbauer spectroscopy confirms the presence of low spin Fe²⁺ but also indicates the presence of ca. 24% of an Fe³⁺ species. The electrochemistry of Fc₂(Ph)PS · I₂, Fc₂(Ph)PS and Fc₂(Ph)P has been studied using a combination of cyclic voltammetry and differential pulse voltammetry. The data for Fc₂(Ph)PS · I₂ show two redox processes, consistent with the sequential oxidation of the ferrocenyl groups to ferrocenium species.     

A two-directional synthesis of (+/-)-perhydrohistrionicotoxin

An entirely two-directional synthesis of (+/-)-perhydrohistrionicotoxin is presented, utilizing a tandem oxime formation/Michael addition/[3 + 2] cycloaddition as the key step. This approach also constitutes formal syntheses of (+/-)-histrionicotoxin and (+/-)-histrionicotoxin 235A.