Roger W. Read

Evidence that halogenated furanones from Delisea pulchra inhibit acylated homoserine lactone (AHL)-mediated gene expression by displacing the AHL signal from its receptor protein.

Acylated homoserine lactone (AHL)-mediated gene expression controls phenotypes involved in colonization, often specifically of higher organisms, in both marine and terrestrial environments. The marine red alga Delisea pulchra produces halogenated furanones which resemble AHLs structurally and show inhibitory activity at ecologically realistic concentrations in AHL bioassays. Evidence is presented that halogenated furanones displace tritiated OHHL [N-3-(oxohexanoyl)-L-homoserine lactone] from Escherichia coli cells overproducing LuxR with potencies corresponding to their respective inhibitory activities in an AHL-regulated bioluminescence assay, indicating that this is the mechanism by which furanones inhibit AHL-dependent phenotypes. Alternative mechanisms for this phenomenon are also addressed. General metabolic disruption was assessed with two-dimensional PAGE, revealing limited non-AHL-related effects. A direct chemical interaction between the algal compounds and AHLs, as monitored by 1H NMR spectroscopy, was shown not to occur in vitro. These results support the contention that furanones, at the concentrations produced by the alga, can control bacterial colonization of surfaces by specifically interfering with AHL-mediated gene expression at the level of the LuxR protein.

Reinvestigation of the sulfuric acid-catalysed cyclisation of brominated 2-alkyllevulinic acids to 3-alkyl-5-methylene-2(5H)-furanones

Abstract A synthesis of ethyl-, butyl-, hexyl- and dodecyl-substituted fimbrolides from alkyl-substituted levulinic acid derivatives through bromination and acid promoted lactonisation is described. The underlying reactions have been investigated using levulinic acid as a model, and the effects of varying the bromination conditions and changing acid concentration on product distribution are discussed. Dibromination proceeds best in CHCl 3 and proceeds in EtOH-free CHCl 3 without the complication of ester formation. Cyclisation occurs with concomitant oxidation in 98–100% H 2 SO 4 but gives highest yields of fimbrolides in 100% H 2 SO 4 . The formation of related beckerelide substances is also described.

Trifluoromethanesulfonic anhydride–4-(N,N-dimethylamino)pyridine as a reagent combination for effecting Bischler–Napieraiski cyclisation under mild conditions: application to total syntheses of the Amaryllidaceae alkaloids N-methylcrinasiadine, anhydrolycorinone, hippadine and oxoassoanine

A combination of triflic anhydride and 4-(N,N-dimethylamnino)pyridine effects Bischler–Napieraiski cyclisation of β-phenethytearbamates and β-phenethylamides under very mild conditions.

Direct (uncatalysed) formation of Meisenheimer complexes from primary, secondary and tertiary arylamines

Abstract Aniline, N -methylaniline and N , N -dimethylaniline react through their para positions with 4,6-dinitrobenzofurazan 1-oxide to form stable Meisenheimer complexes.

A major piperidine alkaloid from Microcos Philippinensis

Abstract Micropine, a major piperidine alkaloid, has been isolated from the leaves of Microcos philippinensis . Its structure has been determined by spectroscopic methods.

Benzisochromanquinones and an isofuranonaphthoquinone from Ventilago vitiensis (Rhamnaceae)

Abstract Three new quinones have been isolated from the root bark of Fijian Ventilago vitiensis . One, an isofuranonaphthoquinone, has been identified as 4,6,9-trihydroxy-3-methoxy-1-methylnaphtho[2,3- c ]furan-5,8- quinone (ventilone G), whereas the other two were benzisochromanquinones, 7,10-dihydroxy-1,3-dimethyl-1H- naphtho[2,3- c ]pyran-6,9-quinone (ventiloquinone L) and 7 or (8),10-dihydroxy-8 or (7)-methoxy-1,3-dimethyl-1H- naphtho[2,3- c ]pyran-6,9-quinone (ventiloquinone M).

Synthesis of fluorous acetal derivatives of aldehydes and ketones

Abstract The formation of acetals (and ketals) from polyfluoroalkylated 1,3-alkanediols and aldehydes and ketones is demonstrated for the first time. Four sets of reaction conditions are examined and the degree of conversion is shown to depend upon reaction conditions and the structure of the carbonyl substrate. Excellent yields are obtained, and wherever possible, diastereomeric products are observed.

TOTAL SYNTHESIS OF MICROPINE AND EPIMICROPINE

Abstract The enantioselective total synthesis of micropine, an unusual 2,6-disubstituted piperidine alkaloid, and epimicropine, through mercuric trifluoroacetate-catalysed intramolecular alkenylamide cyclisation is described. The synthesis proceeds from L -serine and affords material of the same positive sign of optical rotation as the natural product thereby confirming the absolute stereochemistry of micropine.

New N-acyl, N-alkyl, and N-bridged derivatives of rac-6,6', 7,7'-tetramethoxy-1,1', 2,2', 3,3', 4,4'-octahydro-1,1'-bisisoquinoline

Abstract The preparation of potential new ligand systems based on the rac-1,1′,2,2′,3,3′,4,4′-octahydro-6,6′,7,7′-tetramethoxy-1,1′-bisisoquinoline skeleton has been investigated. Syntheses of N-(2-bromobenzyl), N-(3-acetoxybenzyl), N-acetyl, N-chloroacetyl, N-chlorocarbonyl, N-ethoxycarbonyl and N-tert-butyloxycarbonyl derivatives and five macrocyclic, polyether containing derivatives are described.

Structural Studies of N-Acyl 1,1′-Bis(1,2,3,4-tetrahydroisoquinoline) Derivatives

The X-ray crystal structures of N-acyl substituted 1,1′-bis(1,2,3,4-tetrahydroisoquinolines) are disclosed for the first time and evidence is provided that the molecules reside in single preferred conformations in solution and solid states, with axial bonds bridging C1–C1′ that have no steric impediment to rotational freedom.