Stability of tin etiopurpurin

Formulations of the tin etiopurpurin (SnET2) have been observed to undergo a spectral change on storage in dimethylformamide solution. This results in an alteration in the action spectrum, with enhanced photodynamic activity at lower wavelengths and decreased activity at 660 nm. On the basis of structural considerations, a reduced analog of SnET2 was prepared with an absorbance maximum at 640 nm. Formation of this product, termed SnET2H(2) relieves steric strain inherent in the parent molecule. Nuclear magnetic resonance, spectral and photodynamic data are consistent with the formation of SnET2H(2) during SnET2 storage. Slight modifications in the original synthesis are also reported, resulting in improved yields of intermediate products.     

Radical amination with sulfonyl azides: a powerful method for the formation of C-N bonds

A novel reaction for the introduction of an azide moiety by means of a mild radical process is currently under development. Sulfonyl azides are suitable azidating agents for nucleophilic radicals, such as secondary and tertiary alkyl radicals. More electrophilic radicals, such as enolate radicals, do not react with sulfonyl azides. This feature allowed the development of efficient intra- and intermolecular carboazidations of olefins. Due to the versatility of the azido group, this reaction has an important synthetic potential, as already demonstrated by the preparation of the core of several alkaloids, particularly those containing an amino-substituted quaternary carbon center, such as FR901483.     

Partial-filling affinity capillary electrophoresis

Partial-filling affinity capillary electrophoresis (PFACE) is used to examine the binding interactions between two model biological systems: D-Ala-D-Ala terminus peptides to the glycopeptide antibiotic vancomycin (Van) from Streptomyces orientalis, and arylsulfonamides to carbonic anhydrase B (CAB, EC 4.2.1.1, bovine erythrocytes). Using these two systems, modifications in the PFACE technique are demonstrated including flow-through PFACE (FTPFACE), competitive flow-through PFACE (CFTPFACE), on-column ligand synthesis PFACE (OCLSPFACE), and multiple-step ligand injection PFACE (MSLIPFACE). In PFACE small plugs of sample are injected into the capillary column and an equilibrium is established between receptor and ligand during electrophoresis. Binding constants are then obtained by Scatchard analysis using changes in the migration time of the receptor/ligand on changing the concentration of the ligand/receptor. Data demonstrating the quantitative potential of these methods are presented. This review focuses on the unique capabilities of the different PFACE techniques as applied to two model biological systems.     

Carbon Participation in the Solvolysis of Tertiary Norbornyl Derivatives Norbornanes. Part 15. 6-substituted 2-methylnorbornyl 2-exo- and 2-endo-2,4-dinitrophenyl ethers

The solvolysis rates and products of the tertiary 2-methyl-2-exo- and -2-endo-norbornyl 2,4-dinitrophenyl ethers 1 and 2 , (X = 2,4-(NO₂)₂₂C₆H₃O) have been determined. The different sensitivities of the rates of these ethers to the inductive effect of substituents at C(6) indicate that graded bridging of C(2) by C(6) occurs in the ionization of the exo-ethers 1 , not, however, in the ionization of the endo-ethers 2. In both cases hydrolysis leads to 2-methyl-2-exo-norbornanols only. Consequently, substitution takes place with retention at C(2) in the exo-series 1 and with inversion at C(2) in the endo-series 2. It is concluded that stereoelectronic and polar effects, rather than steric bulk effects, determine the high exo/endo rate ratios of the parent norbornyl derivatives 1a and 2a .     

Die Synthese von 4-substituierten Bicyclo[2.2.2]oct-1-yl-p-nitrobenzolsulfonaten

Synthesis of 4-Substituted Bicyclo[2.2.2]oct-1-yl-p-Nitrobenzenesulfonates The syntheses of the 4-substituted bicyclo[2.2.2]oct-1-yl-p-nitrobenzenesulfonates 1a–2s are described.     

The diazo route to diazonamide A: studies on the tyrosine-derived fragment

Various approaches to the tyrosine-derived fragment of the marine secondary metabolite diazonamide A are described. Initial efforts were focused on the originally proposed structure of the natural product, and a feasibility study established that a model 4-aryltryptamine could be readily prepared. Protected 4-bromotryptamine underwent Pd0-catalyzed coupling with the boronic acid derived from 2-bromophenyl allyl ether by Claisen rearrangement, O-methylation and lithiation-boration. The resulting biaryl was elaborated into an alpha-diazo-beta-ketoester, dirhodium(II)-catalyzed reaction of which with N-Z-valinamide gave the desired tryptamine-oxazole following cyclodehydration of the intermediate ketoamide. A potential precursor to the benzofuran ring of the original structure of diazonamide A was prepared in eight steps from N-Z-tyrosine tert-butyl ester. Iodination, O-protection and Stille coupling gave the cinnamyl alcohol 25, converted via the bromide into the allyl aryl ether 27. Subsequent Claisen rearrangement and oxidative cleavage of the alkene gave the lactol 29, converted into the desired benzofuranone 31. The revision in the structure of diazonamide A to 2 resulted in the targeting of an alternative tyrosine-derived model benzofuranone 41 synthesized in four steps from N-Z-tyrosine methyl ester 36 by a route involving Claisen rearrangement of cinnamyl ether 37. Poor yields in this sequence prompted an investigation into the intramolecular Heck reaction as a route to benzofuranone 50. Coupling of 3-iodotyrosine 44 with 2-phenylbutenoic acid 48 gave ester 49 that readily underwent intramolecular Heck reaction to give benzofuranone 50, albeit with poor stereocontrol.     

From random to self-avoiding walks

A brief review will be given of the current situation in the theory of self-avoiding walks (SAWs). The Domb-Joyce model first introduced in 1972 consists of a random walk on a lattice in which eachN step configuration has a weighting factor Π _i=0 ^N?2 Π_j=i+2/N(1?ωδ_ij). Herei andj are the lattice sites occupied by the ith and jth points of the walk. When ω=0 the model reduces to a standard random walk, and when ω=1 it is a self-avoiding walk. The universality hypothesis of critical phenomena will be used to conjecture the behavior of the model as a function ofω for largeN. The implications for the theory of dilute polymer solutions will be indicated.     

Charge Dispersal in the Quinuclidine Radical Cation and in the Quinuclidinium Ion,as Revealed by PE and ICR Spectroscopy

The n ionization energies I and the gas-phase basicities GB of CH₃-, Cl-, or CN-substituted quinuclidines have been measured by PE and ICR spectroscopy. The dependence of the shifts ΔI and ΔGB (relative to the values of the parent molecule) allow conclusions about the charge dispersal accompanying the n ionization or the protonation of quinuclidine in the gas phase. The agreement with the results of a minimal basis set ab initio calculation is excellent. Comparison of the solution pK_a values with either I or GB reveals that 2-substituted quinuclidines exhibit sizeable solvent-induced proximity effects, i.e. that the corresponding quinuclidinium ions are more acidic in solution than expected on the basis of the gas-phase basicities. This agrees with earlier results concerning 2-substituted pyridines.     

A route to annulated indoles via a palladium-catalyzed tandem alkylation/direct arylation reaction

A norbornene-mediated palladium-catalyzed tandem alkylation/C-H functionalization sequence is described, in which an alkyl-aryl bond and a heteroaryl-aryl bond are formed in one pot. A variety of highly substituted six- and seven-membered ring annulated indoles were synthesized in good yields from bromoalkyl indoles and aryl iodides.     

Carbon Participation in the Solvolysis of 6- and 7-Substituted 2-Norbornyl p-Toluenesulfonates. Norbornanes,Part 11

The solvolysis rates and products of several 7-anti-substituted 2-endo-norbornyl p-toluenesulfonates 11 have been determined and compared with those of the previously reported 6-exo-substituted 2-exo-norbornyl p-toluenesulfonates 1. Although the number of bonds between the substituent and the reaction site is the same in the two series, the inductive effect of the substitutents is transmitted far more strongly in the 6-exo-2-exo-series 1 than in the 7-anti-2-endo-series 11 ; i.e. their inductivities differ widely. It is concluded that through space induction involves graded bridging of the substituent-bearing C-atom to the incipient cationic center at C(2) and that this involves differential bridging strain. The different reactivities of unsubstituted 2-exo- and 2-endo-norbornyl derivatives can then be ascribed to a stereoelectronic effect.