Assembly of the Entire Carbon Backbone of a Stereoisomer of the Antitumor Marine Natural Product Hemicalide

A strategy for the assembly of the entire carbon backbone of a stereoisomer of the antitumor marine natural product hemicalide has been investigated. The devised convergent approach relies on Horner–Wadsworth–Emmons and Julia–Kocienski olefination reactions for the construction of the C6=C7 and C34=C35 double bonds, respectively, an aldol reaction to create the C27−C28 bond, and a Suzuki–Miyaura cross-coupling as the endgame to form the C15−C16 bond.     

The Adamantane Rearrangement of Tricyclo[4.2.2.01,5]decane to Tricyclo[5.3.0.04,8]decane

Regioselective generation of the C(2)-carbocation a of tricyclo[4.2.2.0^1,5]decane ( 1 ) by treatment of both corresponding epimeric alcohols 5 and 6 with BF₃ and trapping the rearranged tricyclo[5.3.0.0^4,8]decan-7-yl carbocation b with Et₃SiH as hydride-ion donor (ionic hydrogenation) gives the corresponding hydrocarbon 3 as sole product in almost quantitative yield. The latter is a known intermediate in the Lewis-acid-catalyzed rearrangement of 1 to adamantane ( 4 ).     

AGGREGATION OF CHLOROPHYLL a SPECIES ABSORBING NEAR 700nm–1. THE INFRARED CARBONYL BANDS

Abstract— Amorphous chlorophyll a obtained by electrodeposition(Chl–678) undergoes a bathoch-romic shift upon solvation with gaseous alcohol at ambient temperatures. The process is reversible when the alcohol is removed. With 1-propanol, the red band of Chi a is displaced from 678 nm to 701 nm and a new aggregate is formed,Chl–701. To determine the nature of the new aggregate, the IR carbonyl bands of Chi are monitored. The free ketone massive band ofChl–678, situated at 1691 cm^-1, is decreased upon solvation to the profit of the associated ketone carbonyl massive band which absorbs at 1656 cm^-1. The bandwidths of the massive bands are much greater than the typical value of a carbonyl band of a ketone in solution. This is an indication that the massive bands are composed of overlapping bands. In order to determine the number and the position of the bands, the Fourier self-deconvolution technique has been used to enhance the spectral characteristics of the infrared spectra. The band fitting technique is then used on the original spectra to determine the difference in intensity between the bands ofChl–678 and those ofChl–701. The interpretation of the resolved IR spectra shows that the amorphous sample is composed of open dimers linked together by the CO-Mg coordinate bonds. When the solvated species are formed, these coordinate bonds are not ruptured and one molecule of alcohol for two molecules of chlorophyll is linked to these molecules by an hydrogen bond between the hydrogen of the alcohol and the available ketone and by a coordinate bond between the available Mg and the oxygen of the alcohol. Closed dimers are thus formed.     

Spontaneous Isomerization of Peptide Cation Radicals Following Electron Transfer Dissociation Revealed by UV-Vis Photodissociation Action Spectroscopy

Peptide cation radicals of the z-type were produced by electron transfer dissociation (ETD) of peptide dications and studied by UV-Vis photodissociation (UVPD) action spectroscopy. Cation radicals containing the Asp (D), Asn (N), Glu (E), and Gln (Q) residues were found to spontaneously isomerize by hydrogen atom migrations upon ETD. Canonical N-terminal [z₄ + H]^+● fragment ion-radicals of the R-C^●H-CONH- type, initially formed by N?C_α bond cleavage, were found to be minor components of the stable ion fraction. Vibronically broadened UV-Vis absorption spectra were calculated by time-dependent density functional theory for several [^●DAAR + H]⁺ isomers and used to assign structures to the action spectra. The potential energy surface of [^●DAAR + H]⁺ isomers was mapped by ab initio and density functional theory calculations that revealed multiple isomerization pathways by hydrogen atom migrations. The transition-state energies for the isomerizations were found to be lower than the dissociation thresholds, accounting for the isomerization in non-dissociating ions. The facile isomerization in [^●XAAR + H]⁺ ions (X = D, N, E, and Q) was attributed to low-energy intermediates having the radical defect in the side chain that can promote hydrogen migration along backbone C_α positions. A similar side-chain mediated mechanism is suggested for the facile intermolecular hydrogen migration between the c- and [z + H]^●-ETD fragments containing Asp, Asn, Glu, and Gln residues.

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2-Oxo-9C(3)-hydroxy- und 2-Oxo-9C(7)-hydroxy-bicyclo[3.3.1]nonan

A synthesis of the two C(9) epimers 14 and 15 of 2-oxo-9-hydroxy-bicyclo[3.3.1]nonane is described starting from the two C(2) epimers 3 and 4 of 2-hydroxy-9-oxo-bicyclo[3.3.1]nonane.     

Heterodiamantane und strukturell verwandte Verbindungen II. Pentacyclische Diäther der C10-Reihe: 5,12-Dioxapentacyclo-[6.4.0.02,6.04,9]dodecan und 4,12-Dioxapentacyclo[6.3.1.02,7.03,10.05,9]- dodecan

In connection with studies on heterodiamantanes and structurally related compounds the two novel pentacyclic diethers 9 and 10 were prepared starting from the photo-dimer 8 of cyclopentadienone. All three compounds have as common features a central carbocyclic 6membered ring with four axial alkyl substituents and two oxygen function in 1,4-position. The diether 9 was obtained on the one hand from the intermediate tetracyclic unsaturated alcohol 23 by intramolecular addition, catalyzed either by acid or base (scheme 3), and on the other hand from the tetracyclic diol 32 or the dibromoketones 34 (via 38 ) and 35 (via 39 ) by intramolecular substitution (schemes 4 and 5). The synthesis of the isomeric diether 10 was achieved by intramolecular substitution of the tetracyclic diol 33 (scheme 4). Diether 9 is thermodynamically more stable than 10 . The latter was easily isomerized to the former on treatment with concentrated sulfuric acid in benzene.     

Crystallographic and Spectroscopic Evidence for an Intramolecular (OH … π)-Interaction

Crystallographic and spectroscopic evidence for an intramolecular (OH … π)-interaction in anti^9,10-10endo-hydroxy, 10exo-butyltricyclo [4.2.1.1^2.5]deca-3, 7-dien-9-one ( 1 ) is presented.     

Inhibitors of prolyl endopeptidase: Characterization of the pharmacophoric pattern using conformational analysis and 3D-QSAR

Summary A structure-activity study has been carried out on several compounds known as inhibitors of the serine protease prolyl endopeptidase. Conformational analysis has been done using different molecular mechanics methods such as molecular dynamics, or a randomized conformational search method. The conformers obtained were classified using geometric and energetic criteria. A pattern recognition analysis was done in order to divide conformers according to families. The resulting dominant families, for all compounds investigated, showed very similar geometric features. Based on the lowest energy conformers obtained after randomized conformational analysis, a 3D-QSAR model was established using the CoMFA approach. The validity of this model was verified by prediciting correctly the activity of other molecules not used in the construction of this model.