Total synthesis of (+)-4,5-deoxyneodolabelline

The first total synthesis of the marine dolabellane diterpene (+)-4,5-deoxyneodolabelline (1) has been accomplished. The highly efficient approach is characterized by the convergent assembly of dihydropyrans 2ab and cyclopentylsilanes 3ab. Allylic silane 3a was prepared from 2-methyl-2-cyclopentenone via a copper-catalyzed 1,4-addition followed by diastereoselective alkylation of the resulting enolate. A chemical resolution of racemic cyclopentanone 8 was effected by (S)-CBS-catalyzed borohydride reduction. Direct hydroxymethylation of the enantioenriched ketone 8 to form allylic alcohol 14 was achieved by a Stille palladium-catalyzed cross-coupling from the cyclopentenyl triflate 13. Treatment of the corresponding allylic phosphate 15 with trimethylsilylcopper reagent provided for displacement with allylic transposition yielding the exocyclic allylsilane 3a with excellent diastereoselectivity. Dihydropyrans 2a and 2b were prepared from optically pure acyclic acetals via ring-closing metathesis. Coupling of 3a and 2a or 2b via the carbon-Ferrier protocol gave trans-2,6-disubstituted dihydropyrans 30 and 35 with complete stereoselectivity. Vanadium-based pinacol coupling reactions were explored for closure of the medium-sized carbocycle to yield syn-diol 33. X-ray diffraction studies of the monobenzoate 34 have provided unambiguous stereochemical assignments. Substantial ring strain accounted for the lack of alkene products typical of reductive elimination using TiCl(3) and zinc-copper couple (McMurry) conditions leading to 37. Finally, the natural product 1 was obtained via Swern oxidation of the diol 37.     

The simplified technique of high resolution two-dimensional polyacrylamide gel electrophoresis: biomedical applications in health and disease

The application of our simplified technique of high resolution two-dimensional polyacrylamide gel electrophoresis (2-D PAGE) to human body fluids is reviewed. Serum/plasma protein changes associated with alcohol abuse, familial dyslipoproteinemia ("fish-eye" disease), and myocardial infarction are demonstrated. High resolution 2-D PAGE of amniotic fluid, cerebrospinal fluid, urine, and saliva is shown with reference to the work of others, and the detection of pink-violet staining "lumicarmines" in sweat and tear fluid is reported for the first time. General aspects relating to the methodology are discussed. These include sample preparation, the choice of electrophoresis conditions (denaturing or nondenaturing) and detection method (Coomassie Brilliant Blue or silver), and the effects of native protein pretreatment with sodium dodecyl sulfate prior to silver staining or isoelectric focusing gel shrinkage in glycerol prior to second-dimensional sodium dodecyl sulfate-polyacrylamide gel electrophoresis.     

New tetra-aryl and bi-aryl porphyrins bearing 5,15-related fluorenyl pendants: the influence of arylation on fluorescence

The new tetra-aryl trans-A₂B₂-porphyrin with two fluoren-2-yl and two phenyl groups at the meso-positions has been synthesized and characterized, together with the analogous bi-aryl trans-A₂-porphyrin incorporating only the fluorenyl groups. The photophysical properties of these new compounds in solution are reported. The two additional phenyl groups in the A₂B₂ porphyrin stabilize the first excited singlet state by approximately 500 cm⁻¹ compared to the A₂ system, as revealed by the red-shift of the absorption Q bands and of the fluorescence emission bands. Both compounds display enhanced emission quantum yields compared to tetraphenylporphyrin: the augmentation is higher for the tetra-aryl than for the bi-aryl system, although not as high as for tetrafluorenylporphyrin. Fluorescence lifetime measurements of the series of four compounds suggest that the trends can be interpreted in terms of the larger influence of fluorenyl over phenyl groups in increasing the fluorescence radiative rate constant of the porphyrin, k_f.     

Self-complementary

Three [3]catenanes with cavities large enough to accommodate aromatic guests have been designed and synthesized (yields = 5-20 %) by means of kinetically controlled self-assembly processes. The X-ray structural analysis of one of three [3]catenanes confirmed the presence of a rectangular cavity (dimensions = 7 x 11 A) lined by pi-electron-rich recognition sites and hydrogen-bond acceptor groups. In spite of their apparently ideal recognition features, none of these [3]catenanes bind guests incorporating a pi-electron-deficient bipyridinium unit. However, the template-directed syntheses of the [3]catenanes also produce, in yields of 2-23%, [2]catenanes incorporating a 1,5-dioxynaphtho[38]crown-10 interlocked with a bipyridinium-based tetracationic cyclophane. The X-ray structural analyses of two of these [2]catenanes revealed that a combination of [pi...pi] and [C-H...pi] interactions is responsible for the formation of supramolecular homodimers in the solid state. 1H NMR spectroscopic investigations of the four [2]catenanes demonstrated that supramolecular homodimers are also formed (Ka= 17-31M(-1), T= 185 K) in (CD3)2CO solutions. Dynamic 1H NMR spectroscopy revealed that the 1,5-dioxynaphtho[38]crown-10 and tetracationic cyclophane components in the four [2]catenanes and in the three [3]catenanes circumrotate (deltaGc(not equal to) = 9-14 kcal mol(-1)) through each other's cavity in (CD3)2CO. Similarly, the 1,5-dioxynaphthalene and the bipyridinium ring systems rotate (deltaGc(not equal to) =10-14 kcal mol(-1)) about their [O...O] and [N...N] axes, respectively, in solution.     

Application of Molecular Weight and Particle Growth Measurements in Continuously Uniform Latices to Kinetic Studies of Styrene Emulsion Polymerization

It is possible to generate, in specially formulated styrene emulsion polymerizations, latices in which the monomer—polymer particles are uniform through all stages of growth. These latices are kinetically similar to their polydispersed counterparts and can therefore be used as model systems in generalized kinetic studies of emulsion polymerization. The most important feature of these systems is the fact that the particles are uniform throughout the reaction with regard to all intrinsic properties and rate processes, and the particles can be characterized by this complete, continuous uniformity. Certain remarkably simple, but precise, relationships exist between the overall, measurable kinetic parameters and the individual particle kinetic parameters, thereby resulting in a heretofore unrealized analytic accessibility. Molecular weight kinetic analyses are an order of magnitude more accurate than in non-uniform systems. Application of these continuously uniform systems in actual kinetic studies indicates an inconsistency in the current concepts of emulsion polymerization, i.e., the generation of polymer at a constant molecular weight is predicted while an increase of several fold is observed. Before the situation can be clarified, further studies with continuously uniform systems are needed to evaluate molecular weight development, molecular weight distribution, and molecular structure and also to re-evaluate the rate and diffusion processes which control these structural features.     

Structural characterization of lipopeptide biomarkers isolated from Bacillus globigii

Spectra obtained using matrix-assisted laser desorption/ionization (MALDI) mass spectrometry of Bacillus globigii (Bacillus subtilis niger) spores, vegetative cells and the culture supernatant show a cluster of biomarkers centered at a molecular mass of 1478 Da. Three biomarkers were isolated from the cell-free culture supernatant by solid-phase extraction and reversed-phase high-performance liquid chromatography, and characterized using various kinds of mass spectrometry. A Fourier transform mass spectrometer with a MALDI source was used to determine the monoisotopic protonated masses at 1463.8, 1477.8, and 1505.8 Da in order of elution. The mass differences of 14 and 28 Da suggest that they are homologous molecules. Alkaline hydrolysis of each species showed that it contained a lactone linkage. Strong acid hydrolysis released a fatty acid from an amide bond, consistent with a lipopeptide. A quadrupole time-of-flight instrument with a nanospray source was used to sequence the hydrolyzed forms of the three biomarkers. The cyclic lipopeptides were found to have amino acid sequences identical with those in fengycins and plipastatins, antimicrobial compounds with phospholipase inhibitor activity, previously identified in related species of Bacillus subtilis and Bacillus cereus.     

On-line storage and retrieval of chemical information. II. Substructure and biological activity searching

An improved interactive system for searching substructure and biological activity data has been developed. Features of the system include a two-level substructure search (fragment screen and atom by atom) and an expanded biological activity data base. The system operates on a file of about 150 000 compounds.     

Direct conversion of macrocyclic furans into macrocyclic isothiazoles

The first calixhetarenes with more than one heteroatom in the constituent rings are prepared in one step by treatment of calix[4]furan 1a and calix[6]furan 1b with ethyl carbamate, thionyl chloride and pyridine to give 2, 3, 4 and 5, 6, 7 respectively; these products have been characterised by X-ray crystallography which reveals that in 2 all eight heteroatoms lie on one face of the macrocyle.     

Convenient Asymmetric Syntheses of anti-beta-Amino Alcohols

Condensation of allylborane reagents 9 and 12 with aldehydes gave anti-3-[(diphenylmethylene)amino]-1-alken-4-ols 10 and 13 with high relative and absolute stereocontrol. Subsequent deprotection gave the corresponding free anti-3-amino-1-alken-4-ols 11 and 14. Alternatively, reaction of imines 13a, 13f, and 13g with trifluoromethanesulfonic anhydride and acidic methanol gave, via rearrangement, double inversion, and hydrolysis, the isomeric anti-4-amino-1-alken-3-ols 22, 38a, and 38b in good yield. The stereochemistry of the rearrangement products has been established by a single crystal X-ray study of compound 37 and by chemical correlation.