The oxidative addition of diphenylphosphine and monophenylphosphine to the electron-rich rhenium-rhenium triple bond. The isolation and characterization of compounds that contain the four-center Re(μ-X)(μ-PR2)Re cluster (X=halide)

Diphenylphosphine oxidatively adds to the ReRe bonds of Re₂ X ₄(-dppm)₂ (X=Cl or Br; dppm=Ph₂PCH₂PPh₂) and Re₂Cl₄(-dpam)₂ (dpam=Ph₂AsCH₂AsPh₂) to afford the dirhenium(III) complexes Re₂(-X)(-PPh₂)HX ₃(-LL)₂. The dppm complexes have also been prepared from the reactions of Re₂(-O₂CCH₃)X ₄(-dppm)₂ with Ph₂PH, and a similar strategy has been used to prepare Re₂(-Cl)(-PPh₂)HCl₃(-dmpm)₂ (dmpm=Me₂PCH₂PMe₂) from Re₂(-O₂CCH₃)Cl₄(dmpm)₂. Phenylphosphine likewise reacts with Re₂ X ₄(-dppm)₂ to give Re₂(-X)(-PHPh)HX ₃(-dppm)₂. An X-ray crystal structure determination on Re₂(-Cl)(-PPh₂)HCl₃(-dppm)₂ confirms its edge-shared bioctahedral structure. This complex crystallizes in the space group (No. 148) witha=21.699(3) Å, =84.50(4)°,V=10084(5) ų, andZ=6. The structure was refined toR=0.049 (R _w 0.069) for 5770 data withI>3.0(I). The Re-Re distance is 2.5918(7) Å. Oxidation of the bromide complex Re₂(-Br)(-PPh₂)HBr₃(-dppm)₂ with NOPF₆ produces the unusual dirhenium(III, II) cation [Re₂(-H)(-Br)[P(O)Ph₂]Br₂(NO)(-dppm)₂]⁺ which has been structurally characterized as its perrhenate salt, [Re₂(-H)(-Br)[P(O)Ph₂]Br₂(NO)(-dppm)₂]ReO₄ · 2CH₂Cl₂. This complex crystallizes in the space group (No. 2) witha=14.187(7) Å,b=16.419(5) Å,c=16.729(5) Å, =98.76(2)°, =110.11(3)°, =104.66(3)°,V=3414(6) ų,Z=2. The structure was refined toR=0.040 (R _w =0.051) for 5736 data withI>3.0(I). The presence of a phosphorus-bound [P(O)Ph₂]^– ligand, a linear nitrosyl and a bridging hydrido ligand has been confirmed. The Re-Re distance is 2.6273(8) Å.     

Quantum capping potentials with point charges: a simple QM/MM approach for the calculation of large-molecule NMR shielding tensors

A simple quantum-mechanics/molecular-mechanics (QM/MM) approach for calculating NMR shielding tensors (sigma) is presented. The method involves capping the QM region with quantum capping potentials (QCPs) and representing the MM region with point charges. Test calculations on simple systems without MM charges show that calculated sigma values improve relative to the full QM results with increasing distance between the capped bond and chromophore. Calculations on the histidine amino acid and cytosine monophosphate (CMP) nucleic acid show that the use of QCPs with point charges result in mean errors in the isotropic component of sigma that are less than 1.6 ppm. The results also reveal that, contrary to previous work, the explicit effect of point charges on sigma through coupling with gauge factors, as in the gauge including atomic orbital approach, is minimal for the CMP molecule. The present QM/MM approach for calculating sigma is easy to apply and requires no code modification.     

Psymberin, a potent sponge-derived cytotoxin from Psammocinia distantly related to the pederin family

[structure: see text] Bioassay-guided fractionation of the sponge Psammocinia sp. afforded psymberin (1) possessing 5S,8S,9S,11R,13R,15S,16R,17R stereochemistry. Psymberin exhibits structural similarities to the pederin family metabolites. The potent cytotoxicty and unique structural features of 1 make it a promising lead for therapeutic development.     

Lipopeptides incorporated into supported phospholipid monolayers have high specific activity at low incorporation levels

The ability to present cell adhesion molecule (CAM) ligands in controlled amounts on a culture surface would greatly facilitate the control of cell growth and differentiation. Supported lipid monolayer/bilayer systems have previously been developed that allow for presentation of CAM ligands for cell interaction; however, these systems have employed peptide loadings much higher than those used in poly(ethylene glycol) (PEG)-based immobilization systems. We report the development of synthetic methods that can be used for the efficient and versatile creation of many linear and cyclic lipid-linked peptide moieties. Using RGD-based peptides for the alpha5beta1 integrin as a model system, we have demonstrated that these lipopeptides support efficient cell binding and spreading at CAM ligand loadings as low as 0.1 mol %, which is well below that previously reported for supported lipid systems. Engineered lipopeptide-based surfaces offer unique presentation options not possible with other immobilization systems, and the high activity at low loadings we have shown here may be extremely useful in presenting multiple CAM ligands for studying cell growth, differentiation, and signaling.     

A further study of the cytotoxic constituents of a milnamide-producing sponge

A reinvestigation of Auletta sp. yielded the novel compound milnamide C (3) plus the known compounds milnamide A (1), milnamide B (hemiasterlin) (2), jasplakinolide (5), and geodiamolides A (6), D (7), E (8), and G (9). The isolation work was guided by cytoskeletal bioactivity data. Compounds 2 and 3 were shown to cause microtubule depolymerization, and 6-9 were shown to cause microfilament disruption. This biological activity and the structural elucidation of 3, including X-ray analysis, are reported here. [structure: see text]     

The synthesis of symmetrical bis-1,2,5-thiadiazole ligands

We have been engaged in a search for coordination catalysts for the copolymerization of polar monomers (such as vinyl chloride and vinyl acetate) with ethylene. We have been investigating complexes of late transition metals with heterocyclic ligands. In this report we describe the synthesis of a symmetrical bis-thiadiazole. We have characterized one of the intermediates using single crystal X-ray diffraction. Several unsuccessful approaches toward 1 are also described, which shed light on some of the unique chemistry of thiadiazoles.     

Total Synthesis of d,l-Isospongiadiol: An Intramolecular Radical Cascade Approach to Furanoditerpenes

A stereoselective oxidative free-radical cyclization of beta-keto ester polyenes 7 and 19 has been accomplished as a one-step entry to the tricarbocyclic synthons 8and 21 which contain five and six stereogenic centers, respectively. These key synthons possessing an axial carboethoxy group at C-4 were ultimately converted to the spongian skeleton (8--> 14 and 21 --> 25 -->14). The synthesis of d,l-isospongiadiol (3) from the common intermediate 14 was realized after introduction of the 2alpha-hydroxy group in the spongian A-ring via epoxidation of silyl enol ether 28 and subsequent desilylation.     

Catalytic electronic activation as a tool for the addition of stabilised nucleophiles to allylic alcohols

This paper describes the activation of 2-cyclohexen-1-ol (1) and 2-cyclopenten-1-ol (11) through the use of aluminium-catalysed transfer hydrogenation. The electronically activated substrates are demonstrated to undergo facile conjugate addition and, when the alcohol functional group is subsequently restored in a one-pot procedure, this leads to an indirect addition of nucleophiles to allylic alcohols. This novel methodology has been termed catalytic electronic activation.The aluminium tert-butoxide catalysed conversion of 2-cyclohexen-1-ol (1) into 2-(3-hydroxycyclohexyl)-2-methylmalononitrile (18) and 2-cyclopenten-1-ol (11) into 2-(3-hydroxycyclopentyl)-2-methylmalononitrile (16) in 90 and 60% yield, respectively has been demonstrated through an efficient domino Oppenauer/Michael addition/Meerwein-Ponndorf-Verley process.