A. David Ward

The synthesis of dihematoporphyrin ether and related porphyrin dimers

Abstract Dihematoporphyrin ether (DHE) has been synthesised by two separate procedures; these routes also allow the synthesis of ether linked porphyrin dimers containing one or two vinyl groups rather than hydroxyethyl side chains. The latter dimers, but not DHE, have anti-cancer activity.

Synthesis of 4-methyl-5-arylpyrimidines and 4-arylpyrimidines: route specific markers for the Leuckardt preparation of amphetamine, 4-methoxyamphetamine, and 4-methylthioamphetamine

General synthetic routes to 4-methyl-5-arylpyrimidines and 5-arylpyrimidines are described. 4-Benzylpyrimidine, 4-methyl-5-phenylpyrimidine, 4-(4-methoxybenzyl)pyrimidine, and 4-methyl-5-(4-methoxyphenyl)pyrimidine have been positively identified as route-specific by-products in the Leuckardt preparations of amphetamine and 4-methoxyamphetamine. Using headspace solid phase microextraction (SPME) 4-(4-methoxybenzyl)pyrimidine and 4-methyl-5-(4-methoxyphenyl)pyrimidine have been identified in illicit tablets containing 4-methoxyamphetamine. This is an indication that illicit laboratories use the Leuckardt method for the preparation of 4-methoxyamphetamine. Flatliner tablets containing 4-methylthioamphetamine have been screened for the presence of 4-(4-methylthiobenzyl)pyrimidine and 4-methyl-5-(4-methylthiophenyl)pyrimidine using both headspace and aqueous phase SPME. As these pyrimidines were not detected it would appear likely that illicit laboratories are not using the Leuckardt method for the preparation of 4-methylthioamphetamine.

PHOTOPHYSICAL AND PHOTOBIOLOGICAL PROPERTIES OF DIPORPHYRIN ETHERS

Spectral properties of several diporphyrin ethers were assessed in different solvents and after accumulation by leukemia L1210 cells in vitro. To facilitate studies in a variety of solvents, both tetramethylesters of the diporphyrin ethers and free acids were employed. For comparison, studies on the corresponding porphyrin monomers were also carried out. The joining of two porphyrins by an ether linkage had several consequences. We observed a blue shift in the Soret band of the ethers, but not of the corresponding simple porphyrins, in protic solvents. This phenomenon is likely related to ether aggregation under conditions which promote H‐bonding. The presence of an ether linkage was associated with enhanced fluorescence at 630–640 nm and decreased fluorescence lifetimes and yields, especially in protic solvents. The ether linkage was unaffected by intracellular enzymes, but porphyrin esters were readily hydrolyzed upon accumulation by L1210 cells. The joining of two hematoporphyrin molecules by an ether linkage promoted dye accumulation by L1210 cells. In contrast, accumulation of mesoporphyrin and protoporphyrin was thereby retarded.

The cis chlorination of alkenes using selenium reagents

Abstract The phenylselenenyl chloride adduct from alkenes can be oxidised and the selenomoiety can be displaced by chloride to give high yields of dichlorides with cis geometry.

Complexation of alkali metal and alkaline earth ions by anthracene based fluorophores with one and two appended monoaza coronand receptorsElectronic supplementary information (ESI) available: figs. S1–S20: additional emission spectra. See http://www.rsc.org/suppdata/dt/b2/b210269b/

The complexation of alkali metal ions by 13-[2-(10-ethyl-9-anthryl)ethyl]-1,4,7,10-tetraoxa-13-azacyclopentadecane, 1, and 13-(2-{10-[2-(1,4,7,10-tetraoxa-13-azacyclopentadecanyl)ethyl]-9-anthryl}ethyl)-1,4,7,10-tetraoxa-13-azacyclopentadecane, 2, to form fluorescent complexes in acetonitrile is reported. The fluorescence quantum yields, ϕ, are 0.25 and 0.03 for 1 and 2, respectively. At 298.2 K and I = 0.05 mol dm−3 (NEt4ClO4) the [M1]+ complexes are characterised by complexation constants K1 = (1.28 ± 0.01) × 105 (ϕ1 = 0.71), (9.27 ± 0.04) × 104 (ϕ1 = 0.64), (1.73 ± 0.02) × 104 (ϕ1 = 0.60), (3.08 ± 0.05) × 103 (ϕ1 = 0.53) and (2.17 ± 0.04) × 103 (ϕ1 = 0.34) dm3 mol−1, respectively, as M+ changes from Li+ to Cs+. Fluorophore 2 forms weakly fluorescent [M2]+ and possibly the “sandwich” complex, [M2′]+, which are jointly characterised by complexation constants K1= (7.1 ± 0.03) × 105, (5.2 ± 0.3) × 105, (1.00 ± 0.03) × 104 and (1.8 ± 0.2) × 104 dm3 mol−1 for Li+, Na+, K+ and Rb+ and [M22]2+ characterised by K2 = (6.41 ± 0.01) × 104 (ϕ2 = 0.73), (4.84 ± 0.01) × 104 (ϕ2 = 0.53), (1.59 ± 0.06) × 103 (ϕ2 = 0.39) and (6.8 ± 0.1) × 102 dm3 mol−1 (ϕ2 = 0.15). (Cs+ induced insufficient fluorescence in 2 for quantitative study.) The alkaline earths form more stable complexes with 1 and 2 characterised by K1 and K2 ≥ 107 dm3 mol−1. The factors governing fluorescence and complex stability are discussed and the syntheses of 1 and 2 are described.

THE MOLECULAR WEIGHT OF HAEMATOPORPHYRIN DERIVATIVE, ITS GEL COLUMN FRACTIONS and SOME OF ITS COMPONENTS IN AQUEOUS SOLUTION

Abstract— The average molecular weights of haematoporphyrin derivative (HPD), the fractions of HPD that can he obtained by gel chromatography and of purified haematoporphyrin and protoporphyrin in aqueous solution have been determined by ultracentrifugation. The results show that HPD contains polymeric material with the excluded fraction from the gel column (HPD aggregate) having an average molecular weight of greater than 20000. The two remaining gel column fractions of HPD have lower molecular weights and their similarity indicates that these fractions do not separate because of molecular weight differences. Purified haematoporphyrin has a comparatively low molecular weight in aqueous solution but the data is not capable of discriminating between monomer, dimer or slightly higher oligomer. In contrast, protoporphyrin sediments to the bottom of the centrifuge tube under the conditions of sedimentation equilibrium indicating that it has an average molecular weight considerably greater than that of HPD aggregate.

SELENIUM INDUCED STEREOSELECTIVE CYCLIZATION OF N-SUBSTITUTED-4-HYDROXY-5-HEXENYLAMINES

The selenium induced cyclization of N-substituted 4-hydroxy-5-hexenylamines occurs regio- and stereoselectively to give N-substituted trans-2-(phenylselenomethyl)-3-hydroxypiperidines in moderate yield. Synthesis of the biologically active diol (8) was achieved via oxidation of the phenylseleno moiety to the phenylselenone and subsequent displacement with sodium hydroxide.

CIS 1,2-functionalization of cyclohexane using selenium intermediates

Abstract The trans 1,2-phenylseleno acetate, acetamide, alcohol and nitrile of cyclohexane may be oxidized at selenium by halogens and the phenylseleno moiety displaced by halide to give high yields of 1,2 halide-containing products with cis geometry.

Selenium induced stereoselective cyclization of N-protected 3-hydroxy-4-pentenylamines

Abstract The selenium induced cyclofunctionalization of N-protected 3-hydroxy-4-pentenylamine occurs regio- and steroselectively to give N-protected cis-2-(selenomethyl)-3-hydroxypyrrolidines in high yield. The rate of reaction and degree of stereoselectivity is shown to be dependent on the nature of the selenium reagent, reaction temperature and solvent.

The identification of a carbon linked oligomer in hematoporphyrin derivative and photofrin II

Abstract The presence of carbon linked oligomeric porphyrins in hematoporphyrin derivative and Photofrin II has been established by FAB mass spectrometry and hydrolysis studies. A dimer derived from this material has been isolated and characterized by nmr spectroscopy and mass spectrometry.