Richard H. Herbert

Identification and synthesis of the major sex pheromone of the olive fly (Dacus oleae)

The major component of the sex pheromone of the olive fly has been shown to be 1,7-dioxaspiro[5.5] undecane (1) and its structure has been confirmed by unambiguous synthesis; field studies have confirmed its biological activity.

Isolation and identification of the sex pheromone of the mediterranean fruit fly, Ceratitis capitata(Wied)

The volatile compounds emitted by sexually mature male mediterranean fruit flies (Ceratitis capitata) have been identified and the key component involved in the sexual attraction of virgin female flies to males demonstrated to be the novel sex pheromone 3,4-dihydro-2H-pyrrole (1).

Identification and synthesis of (Z)-(1′S,3′R,4′S)(–)-2-(3′,4′-epoxy-4′-methylcyclohexyl)-6-methylhepta-2,5-diene, the sex pheromone of the southern green stinkbug, Nezara viridula(L.)

The sex pheromone of the male green stinkbug, Nezara viridula(L.) has been shown to be a novel epoxybisabolene (Z)-(1′S,3′R,4′S)(–)-2-(3′,4′-epoxy-4′-methylcyclohexyl)-6-methylhepta-2,5-diene, whose structure has been confirmed by spectroscopic studies and synthesis of the eight possible stereoisomers.

3-benzyloxy-2-phenylpiperidine NK1 antagonists: The influence of alpha methyl substitution

Abstract In vitro metabolism studies on a series of 3,5-bis(trifluoromethyl)benzyl ethers have identified 3,5-bis(trifluoromethyl)benzoic acid as a significant metabolite possibly arising via oxidation of the benzylic position. A methyl group was introduced in an effort to suppress this route of metabolism. One diastereoisomer displayed an increase in affinity and a marked improvement in duration of action. In vitro metabolism studies on a series of 3,5-bis(trifluoromethyl)benzyl ethers have identified 3,5-bis(trifluoromethyl)benzoic acid as a significant metabolite possibly arising via oxidation at the benzylic position. A methyl group was introduced in an effort to suppress this route of metabolism. One diastereoisomer displayed an increase in affinity and a marked improvement in duration of action

Spirocyclic NK1 antagonists I:[4.5] and [5.5]-spiroketals

A series of novel spiroketal-based NK(1) antagonists is described. The effect of modifications to the spiroether ring and aromatic substituents are discussed, leading to the identification of compounds with high affinity and excellent CNS penetration.

3-(4-Piperidinyl)- and 3-(8-aza-bicyclo[3.2.1]oct-3-yl)-2-phenyl-1H-indoles as bioavailable h5-HT2A antagonists

A series of 3-(4-piperidinyl)- and 3-(8-aza-bicyclo[3.2.1]oct-3-yl)-2-phenyl-1H-indoles have been prepared and evaluated as ligands for the h5-HT2A receptor. 3-(8-Phenethyl-8-aza-bicyclo[3.2.1]oct-3-yl)-2-phenyl-1H-indole is a high-affinity (1.2nM), selective (>800 fold over h5-HT2C and hD2 receptors) antagonist at the h5-HT2A receptor with oral bioavailability in rats.

The solution conformation of 1-(3,5-dimethylphenyl)methyl-3(S)-(1H-indol-3-yl)methyl-6(S)-phenylmethyl-2,5-piperazinedione (1): An NMR and molecular modelling study

Abstract Comparison of NMR data with structures from molecular modelling of 1-(3,5-dimethylphenyl)methyl-3(S)-(1H-indol-3-yl)methyl-6-(S)-phenylmethyl-2,5-piperazinedione (1) showed it to have a specific solution conformation with the phenyl ring over the diketopiperazine ring and the tryptophan sidechain in the [G−o] rotamer.

Isolation and synthesis of 3- and 4-hydroxy-1,7-dioxaspiro[5.5]undecanes from the olive fly (Dacus oleae)

Two novel hydroxyspiroacetals, 3- and 4-hydroxy-1,7-dioxaspiro[5.5]undecane have been isolated from the rectal gland of the female olive fly (Dacus oleae) and a stereoselective synthesis of the latter developed.

Isolation and synthesis of 1,7-dioxaspiro[5.5]undecane and 1,7-dioxaspiro[5.5]undecan-3-and -4-ols from the olive fly (Dacus oleae)

The major component of the sex pheromone of the olive fly has been shown to be 1,7-dioxaspiro[5.5]undecane (16). Two hydroxyspiroacetals, 1,7-dioxaspiro[5.5]undecan-3- and -4-ols (17a) and (18a), have also been isolated from the rectal glands of the female olive fly, and stereoselective syntheses of these developed.

In Vitro Studies of the Oxidative Metabolism of L-737,415, A C5-Cycloalkylamine-1,4-Benzodiazepin-2-One CCKB Receptor Antagonist

Abstract In an effort to investigate and characterise the metabolism of the C5-cycloalkylamine-1,4-benzodiazepin-2-one CCKB receptor antagonist L-737,415 a study was undertaken using rat liver microsomes. A procedure is described in which the metabolism of the unlabelled compound is firstly investigated analytically under a controlled set of conditions, then scaled up to allow further metabolite elucidation. We also report the use of HPLC with diode array detection, and thermospray LC-MS and LC-MS-MS, to detect and characterise the observed metabolites. From the UV spectra obtained with diode array detection and fragmentation analysis from LC-MS-MS it is demonstrated that, contrary to other known benzodiazepinones such as diazepam or the CCKB antagonist L-365,260, metabolism seems to occur predominantly at the C5 substituent. Further work in which urine from rats dosed with L-737,415 was analysed indicated that the in vitro microsomal assay provides a good model for in vivo metabolism for this class of co...