Peter Morand

Structure-activity studies of photoactivated antiviral and cytotoxic tricyclic thiophenes

The photoactivated antiviral and cytotoxic activities of the naturally occurring thiophene, α‐terthienyl (1), and 15 synthetic analogues were evaluated against murine cytomegalovirus and Sindbis virus, and murine mastocytoma cells. After irradiation with near UV light, α‐terthienyl and most of its analogues had significant toxicity, with minimum inhibitory concentrations in the range of 0.02–40 μM. In the absence of near UV irradiation, only one analogue had antiviral activity and five were cytotoxic. The most active analogues were those containing carboxylic acid, hydroxyl, or cyano substituents. Quantitative structure‐activity relationship analysis of thiophene phototoxicity suggested that the rate of singlet oxygen production is the primary determinant of antiviral and cytotoxic activities. For phototoxicity against murine cytomegalovirus, a significant role for hydrophobicity was also demonstrated. Tricyclic thiophenes show significant potential for photochemotherapy of viral infections and cancer. and further evaluation in animal models is recommended.

Light-mediated allelochemical effects of naturally occurring polyacetylenes and thiophenes from asteraceae on herbivorous insects.

Polyacetylenes and their thiophene derivatives, characteristic secondary metabolites of the Asteraceae, were examined for their effects on herbivorous insects. Three thiophenes (a monothiophene, a bithiophene, and α-terthienyl) and four polyacetylenes (phenylheptatriyne, phenylheptadiynene, phenylheptadiyene acetate, and matricaria lactone) were studied for their phototoxicity and light-independent toxicity to (1) a polyphagous lepidopteran,Ostrinia nubilalis, whose host range includes a number of phototoxic Asteraceae, (2) a polyphagous lepidoteran,Euxoa messoria, whose host range includes very few species of Asteraceae, and (3) an oligophagous lepidopteran,Manduca sexta, which is a specialist on Solanaceae. Several compounds were phototoxic toM. sexta andE. messoria even at very low irradiance levels, but behavioral adaptations, including spinning silk and boring into diet, allowedO. nubilalis to avoid photosensitization. Light-independent activity of the compounds to all three species involved feeding deterrence increasing in the orderO. nubilalis, E. messoria, andM. sexta, and longterm metabolic toxicity in the form of impaired nutrient utilization. The biosynthetically derived thiophenes were more toxic than their acetylenic precursors, and toxicity increased with increasing number of thiophene rings. The results are discussed in terms of plant-insect coevolution.

Phototoxicity of naturally occurring and synthetic thiophene and acetylene analogues to mosquito larvae

Abstract Naturally occurring and synthetic analogues and derivatives of polyacetylenes and thiophenes of the Asteraceae were investigated for their phototoxic effects on mosquito larvae, iodination, dimethylation in the 3′,4′-position or substitution of the middle ring of α-terthienyl reduced phototoxicity. Methylation at the 2′-position increased activity. In the acetylene series, retention of a triacetylene-furan chromophore was necessary for optimal activity.

Reduction of cyclic anhydrides. II. Factors affecting regioselectivity of attack on the carbonyl group by metal hydrides

The reduction of unsymmetrically substituted cyclic anhydrides with metal hydrides often leads to the preferential formation of one of the two possible lactones. In the light of recent experimental findings and theories concerning metal hydride addition to the carbonyl function, the electronic and steric factors influencing regioselectivity of cyclic anhydride reductions are discussed and an explanation for the observed patterns is proffered. Similar considerations may be extended to predict the major lactonic products in the reductions of various other unsymmetrical cyclic anhydrides.

Behavioral responses of western corn rootworm larvae to naturally occurring and synthetic hydroxamic acids

Hydroxamic acids have been shown to be toxic to many pest insects and pathogens. In this study, the behavioral responses of western corn rootworm larvae to naturally occurring and synthetic hydroxamic acids were investigated. In a choice test between corn roots treated with hydroxamic acids and roots treated with distilled water (control), western corn rootworm larvae chose to burrow into the control roots significantly more often than compoundtreated roots. In addition, when corn roots were treated with different hydroxamic acids in a designed searching-behavior test, neonate larvae of western corn rootworm responded by significantly reducing the number of turns, while the area searched and locomotor rate significantly increased. The responses were dependent on the concentrations of the test compounds. These results suggested that hydroxamic acids were acting as behavior-modifying and possibly feeding-deterrent chemicals.

Efficacy of the plant phototoxinα-terthienyl againstAedes intrudens and effects on nontarget organisms.

The botanical phototoxin, α-terthienyl (α-T) was spray applied to natural or artificial pools containing mosquito (Aedes intrudens) larvae and nontarget invertebrates (caddisfly, damselfly, midge, shrimp,Daphnia, snail) and one vertebrate (trout) at concentrations varying from 0.01 to 1 kg/hectare, under field and laboratory conditions. All field-treated nontarget invertebrates survived α-T treatment better thanA. intrudens which can be controlled at doses as low as 0.01 kg/hectare within one week. Under laboratory conditions, snails and trout survived α-T and UV treatments up to 10 kg/ hectare. These results compare favorably with organophosphates and pyrethroid insecticides currently used for mosquito control. The results confirm that α-T is a highly effective larvicide with acceptable nontarget effects.

Separation and quantitation of 1,4-benzoxazin-3-ones and benzoxazolin-2-ones in maize root extract by high-performance liquid chromatography

A high-performance liquid chromatography method is described for the separation and quantification of 1,4-benzoxazin-3-ones and benzoxazolin-2-ones in maize root extract. The four compounds, 2,4-dihydroxy-7-methoxy-1,4-benzoxazin-3-(4H)-one, 2,4-dihydroxy-7,8-dimethoxy-1,4-benzoxazin-3(4H)-one, 2-hydroxy-7-methoxy-1,4-benzoxazin-3(4H)-one and 6-methoxybenzoxazolinone, were separated and identified within 30 min on a C18 reversed-phase column using a gradient of methanol and phosphoric acid. The technique has useful applications in studies of the chemical ecology of plant root and subterranean pest interactions.

Highly regioselective reduction of unsymmetrical cyclic carboxylic acid anhydrides to γ-lactones

The highly regioselective partial reduction of an unsymmetrical carboxylic acid anhydride to the corresponding γ-lactone with LiAlH4 can be reversed by hydrogenation of the anhydride in the presence of [RuCl2(Ph3P)3] as catalyst.

Phototoxic substances from Flaveria trinervis and Simira salvadorensis

Abstract Phototoxic secondary metabolites are reported from Flaveria trinervis and Simira salvadorensis . A sensitive test for phototoxicity to Saccharomyces cereviceae was used to identify activity in plant material, crude extracts and purified compounds. This method led to the isolation and identification of α-terthienyl from tops of F. trinervis and harman from bark of S. salvadorensis .

Acid- and base-catalysed reactions of 4β,5β- and 4α,5α-epoxyandrostane-3,17,19-trione

The acid- and base-catalysed reactions of 4β, 5β- and 4α, 5α-epoxyandrostane-3,17,19-triones (2) and (7) have been examined to see if epoxide opening in these compounds would result in elimination of the C-10 substituent and the subsequent formation of estrone (25). However, the products obtained indicated that epoxide solvolysis or rearrangement concomitant with epoxide opening is the predominant mode of reaction under the conditions examined.