Mathew P. D. Mahindaratne

Novel asparagine-derived lipid enhances distearoylphosphatidylcholine bilayer resistance to acidic conditions

A novel asparagine-derived lipid analogue (ALA(11,17)) bearing a tetrahydropyrimidinone headgroup and two fatty chains (11 and 17 indicate the lengths of linear alkyl groups) was synthesized in high yield and purity. The thin film hydration of formulations containing 5 mol % or greater ALA(11,17) in distearoylphosphatidylcholine (DSPC) generated multilamellar vesicles (MLVs) that remained unaggregated according to optical microscopy, while those formed from DSPC only were highly clustered. The MLVs were processed into unilamellar liposomes via extrusion and were characterized by dynamic light scattering (DLS), zeta potential, turbidity, and scanning electron microscopy (SEM) analysis. Results show that the presence of ALA(11,17) in DSPC liposomes significantly alters the morphology, colloidal stability, and retention of encapsulated materials in both acidic and neutral conditions. The ability of ALA(11,17)-hybrid liposomes to encapsulate and retain inclusions under neutral and acidic conditions (pH < 2) was demonstrated by calcein dequenching experiments. DLS and SEM confirmed that ALA(11,17)/DSPC liposomes remained intact under these conditions. The bilayer integrity observed under neutral and acidic conditions and the likely biocompatibility of these fatty amino acid analogues suggest that ALA(11,17) is a promising additive for modulating phosphatidylcholine lipid bilayer properties.

Tandem Friedel-Crafts annulation to novel perylene analogues

Novel dialkyloxy- and dihydroxyoctahydroperylenes are regioselectively available via a new tandem Friedel-Crafts alkylation of tetrahydronaphthalene precursors followed by oxidative aromatization. Heating of 5-alkyloxy-1-tetralol with p-toluenesulfonic acid in sulfolane gave the corresponding octahydroperylenes in moderate yields. Studies with Lewis acids and tetralin-1,5-diol in acetonitrile at room temperature provided the 4,10-dihydroxy analogue cleanly, albeit in reduced yields. Examples of these new series of perylene analogues were partially oxidized to the corresponding contiguously aromatic, anthracene core products or fully aromatized to 3,9-dialkyloxyperylenes in good yields.

4,10-Diall-yloxy-1,2,3,6b,7,8,9,12b-octa-hydro-perylene.

In the title compound, C26H28O2, the central atoms are coplanar, with the –CH2—CH2– links of the cyclohexene groups lying to either side of the plane and with the diallyloxy residues twisted out of this plane [C—C—O—C torsion angles = 16.6 (3) and −13.9 (3)°]. In the crystal structure, molecules are connected into chains propagating in [100] via C—H⋯π interactions.

(2S,4S)-3-Acryloyl-6-oxo-2-phenyl­perhydro­pyrimidine-4-carboxylic acid

In the title compound, C14H14N2O4, the central six-membered ring adopts a twisted boat conformation with the phenyl substituent occupying an orthogonal position [dihedral angle = 86.88 (11)°]. In the crystal, molecules are linked by carboxylic acid–carbonyl O—H⋯O and amide–carbonyl N—H⋯O hydrogen bonds, forming a three-dimensional network.

Syntheses of cis- and trans-7-chloro-7,8,9,10-tetrahydrobenzo[a]pyren-8-ol: A remarkable solvent effect on epoxide hydrochlorination diastereoselectivity

Abstract Cis- or trans-7-chloro-7,8,9,10-tetrahydrobenzo[a]pyrene-8-ol were prepared from the corresponding epoxide in good selectivity and yield via LiCl hydrochlorination in different solvents. These preparations take advantage of a dramatic solvent effect on the hydrochlorination diastereoselectivity. Cis products strongly predominate in chlorinated hydrocarbons, and alternatively, trans chlorohydrin formation occurs in high selectivity in Et2O, THF, and acetone. This solvent effect was not significant for other halide salts.