Phenylsulfonyl ene-allenes as efficient precursors to bicyclic systems via intramolecular [2 + 2]-cycloaddition reactions

Various phenylsulfonyl allene derivatives were prepared with double bonds tethered either to the alpha-position or the gamma-position of the allene. These substrates underwent a highly regio- and stereospecific thermal [2 + 2]-cycloaddition across the nonactivated cumulene double bond, forming distal cycloadducts (i.e., 57) in the case of alpha-tethered allenes and proximal adducts (i.e., 25) in the case of gamma-tethered allenes. The mechanistic rationale for the observed stereospecificity involves initial diradical formation, followed by a rapid ring closure to the more stable cis-fused ring system. The tether may be equipped with heteroatoms, allowing for the formation of fused heterocycles (e.g., 61), and the cycloaddition can be facilitated by the introduction of sterically bulky groups and/or by conformational rigidity to the tether. Other modes of cyclization were observed in the presence of sodium benzenesulfinate or Lewis acids, in which cases polar mechanisms prevail. The chemoselectivity is reversed for [4 + 2]-cycloadditions, which prefer instead to engage the vinyl sulfone moiety, independent of whether the tether is attached to the alpha- or gamma-position of the allene.     

Rapid Aqueous Borohydride Reduction of Carbonyls Under Sealed-Tube Microwave Conditions

Ketones and aldehydes are conveniently and rapidly reduced to the corresponding alcohols in good yields using sodium borohydride under sealed-tube microwave conditions in either 95% ethanol or water. In purely aqueous systems, highly aliphatic substrates are sluggish, but this can be overcome by introducing sodium dodecyl sulfate (SDS) at the critical micelle concentration. With a 2:1 substrate/borohydride ratio and a reaction temperature of 100 °C, reduction is typically complete within 1 min in 95% ethanol and 5 min in water/SDS. The methodology is well suited for parallel and combinatorial synthetic approaches.     

A sulfone-based strategy for the preparation of 2,4-disubstituted furan derivatives

2,4-Disubstituted furans are prepared by treating 2,3-dibromo-1-phenylsulfonyl-1-propene (DBP, 2) with 1,3-diketones under basic conditions. The furan-forming step involves a deacetylation, and the selectivity of this process depends upon the steric demand of the R group. The substituent in position 4 is elaborated by reaction of sulfonyl carbanions with alkyl halides, acyl halides, and aldehydes. Oxidative or reductive desulfonylation produces the 2,4-disubstituted furans in 60-92% yield. This strategy has been used to prepare rabdoketone A (12) and the naturally occurring nematotoxic furoic acid 13.     

Rapid aerobic iodination of arenes mediated by hypervalent iodine in fluorinated solvents

Arenes are rapidly converted to the corresponding iodides by aerobic oxidative iodination at room temperature by treatment with iodine and catalytic quantities of nitrous acid in a fluorinated solvent. Dichloroiodic acid is proposed as the actual iodination reagent.     

Novel aerobic oxidation of primary sulfones to carboxylic acids

Primary alkyl aryl sulfones are converted to the corresponding carboxylic acids in fair to excellent yield through double deprotonation and exposure to atmospheric oxygen. The methodology allows for the convenient synthesis of (13)C labeled carboxylic acids.     

Observations of distortions of optical features in the UV auroraldistribution

Observations made by the Viking satellite have for the first time shown the development of multiple large-scale surge features. The longer time scale of the features is contrasted with smaller-scale vortex streets found along the poleward edge of the evening oval, which are generally observed to exist for less than 2 min. The ratio of wavelength-to-diameter of these features is shown to decrease with increasing wavelength. These observations support the view that the origin of the larger surge features are of the Kelvin-Helmholtz instability type, originating further out in the magnetosphere than their vortex-street counterparts. Observations of spiral features have been made at all local times and the spirals always have a counterclockwise sense (viewed in the direction of the magnetic field in the northern hemisphere). One interpretation of these events is that they are the result of an exponential growth along a field line of an initial upward field-aligned current perturbation     

2,3-Bis(phenylsulfonyl)-1,3-butadiene: Substrate for Michael Donor/Acceptors in a Novel Synthesis of Fused Cyclopentenes

The reaction of 2,3-bis(phenylsulfonyl)-1,3-butadiene with the anion of various 1-substituted dimethyl 1-pentenedioates has been investigated with the purpose of devising a tandem conjugate addition-[3 + 2]-anionic cyclization route for the synthesis of bicyclo[3.3.0]octenes. The reaction proceeds with complete stereospecificity as was evidenced by treating (E)- and (Z)-dimethyl (3-cyano-2-propenyl)propanedioate with NaH in the presence of the bis(phenylsulfonyl)diene. In both cases only a single cycloadduct was obtained with no detectable signs of the other diastereomer. The overall process involves a series of three sequential conjugate additions followed by benzenesulfinate ion ejection. The success of the method is dependent on the electrophilicity of the proximal pi-bond. When 2-((5-oxo-2,5-dihydrofuranyl)methyl)malonic acid dimethyl ester was used, a mixture of the tricyclic adduct as well as an allene was obtained. In this case, elimination of the benzenesulfinate group from the initially formed sulfone-stabilized carbanion is competitive with the intramolecular [3 + 2]-annulation process. The base-induced reaction of dimethyl 2-(methoxycarbonyl)-2-pentenedioate with the bis(phenylsulfonyl)diene was also studied. Even though the position of the acceptor moiety on the pi-bond was altered, the tandem Michael reaction sequence still occurs. The course of the reaction is dependent upon the length of the tether as well as the relative placement of the electron-withdrawing group on the olefin. Reaction with gamma-substituted beta,gamma-alkenyl derivatives leads to bicyclo[3.3.0]octenes, whereas beta-substituted beta,gamma-alkenyl reagents provide bicyclo[3.3.0]octenes derived from a novel alpha-elimination reaction.     

THE EVOLUTION OF PHOTODYNAMIC THERAPY TECHNIQUES IN THE TREATMENT OF INTRAOCULAR TUMORS

Abstract The techniques of photodynamic therapy (PDT) and the indications for its use in the treatment of intraocular tumors have evolved during the years in which it has been assessed in patients at our institution. It is now clear that transcorneal PDT delivered at a subthermal dose-rate to the surface of a pigmented lesion such as choroidal melanoma has little effect. In the absence of pigment, however, as in the case of retinoblastoma or amelanotic melanoma of the iris or choroid, the tumor kill attributed to PDT alone is significant. Data from animal tumor models in our institution and from patient studies elsewhere suggest that the addition of heat with the light delivery will predictably improve the outcome of the treatment of pigmented lesions. Ocular PDT delivered in conjunction with heat will be useful clinically as an adjunct to scleral plaque therapy by reducing the height of a lesion and concurrently the dose of radiation necessary at the base of the tumor for sterilization. Since the clinical tumoricidal effect of PDT is now known to be due at least in part to vascular damage, trans-scleral application of light to the base of melanomas and occlusion of its blood supply holds significant promise of efficacy with continued improvement of the light delivery system. Finally, a transpupillary approach to occlusion of the choroidal vascular supply to a melanoma by surrounding the tumor with photodynamic lesions may provide the best approach for ocular PDT as a primary therapy.     

THE INFLUENCE OF SODIUM PENTOBARBITAL ANESTHESIA ON in vivo PHOTODYNAMIC THERAPY

Abstract The use of sodium pentobarbital anesthesia 50 jig gm⁻¹ during localized photodynamic therapy (PDT) was examined in C57BL/6 mice transplanted with the pigmented B-16 melanoma. A 10 mg kg⁻¹ i.p. injection of Photofrin II was administered 24 h prior to light exposure (630 nm, 150 mW, cm⁻², 300-500 J cm⁻²). Separate groups of mice were utilized to monitor tumour temperature and PDT tumor response. Core tumor temperatures decreased by approx. 10^oC following sodium pentobarbital administration. Tumor responses were determined by documenting the percentage of treated animals without tumor recurrences for a period of 50 days following PDT. Superior PDT induced tumor responses were obtained in control (non-anesthetized) mice following light doses of 400 and 500 J cm⁻². The results of this study indicate that sodium pentobarbital can induce a protective effect on B-16 melanomas treated with PDT.     

Using molecules to measure nuclear spin-dependent parity violation

Nuclear spin-dependent parity violation arises from weak interactions between electrons and nucleons and from nuclear anapole moments. We outline a method to measure such effects, using a Stark-interference technique to determine the mixing between opposite-parity rotational/hyperfine levels of ground-state molecules. The technique is applicable to nuclei over a wide range of atomic number, in diatomic species that are theoretically tractable for interpretation. This should provide data on anapole moments of many nuclei and on previously unmeasured neutral weak couplings.