James C. Anderson

Antifeedant effects of azadirachtin and structurally related compounds on lepidopterous larvae.

The antifeedant activity of azadirachtin, azadirachtin‐derivatives and related limonoids was assessed in choice and no‐choice bioassays against four species of Lepidoptera: Spodoptera littoralis, Spodoptera frugiperda, Heliothis virescens and Heliothis armigera. The choice bioassay showed that the feeding behaviour of S. littoralis was affected by more of the compounds than that of either S. frugiperda or H. virescens. H. armigera was the least affected. Azadirachtin and dihydroazadirachtin were the most potent of the 40 compounds tested. The results showed that hydrogenation of the C‐22,23 double bond did not decrease antifeedant activity and the nature of the substitutes at C‐1, C‐3 and C‐11 were important. Molecules with bulky substitutes at either C‐22 or C‐23 were usually ineffective antifeedants as were compounds lacking an epoxide. Compounds recorded as active antifeedants in the choice bioassay were not always as active in the no‐choice test. The value of the bioassays in assessing the mode of action of the compounds is discussed.

Neo-clerodane insect antifeedants from Scutellaria galericulata

Abstract Four neo-clerodane diterpenoids have been isolated from aerial material of Scutellaria galericulata . Three compounds, jodrellin T, 14,15-dihydrojodrellin T and galericulin, are novel structures. The fourth, jodrellin B has been previously isolated from Scutellaria woronowii . Jodrellin B is amongst the most potent neo-clerodane antifeedants so far described, 14,15-dihydrojodrellin T is also active. Chemical structures were rigorously determined by spectroscopic methods.

Developmental inhibition ofSpodoptera litura (Fab.) larvae by a novel caffeoylquinic acid from the wild groundnut,Arachis paraguariensis (Chod et Hassl.).

A novel compound, 1-caffeoyl-4-deoxyquinic acid (1-CdQA) has been identified along with 3-caffeoylquinic acid (3-CQA) and 5-caffeoylquinic acid (5-CQA) (syn. chlorogenic acid) in the foliage ofArachis paraguariensis, a wild species of groundnut that is highly resistant to attack by the larvae ofSpodoptera litura. When neonate larvae were fed on diets treated with 3-CQA or 1-CdQA, their development was severely inhibited compared to larvae on untreated diets, and the effects were similar in nature and magnitude to those observed for larvae feeding on diets treated with 5-CQA, rutin, and quercetin. The effects of all the compounds were dose related, and their optimal concentration was approximately 3 mM, which corresponds to the total foliar concentration of both caffeoylquinic acids and quercetin diglycosides inA. paraguariensis. After 24 h, the development of third stadium larvae feeding on diets treated with 5-CQA, rutin and 1-CdQA was promoted compared to larvae on control diets, but after 96 hr larvae feeding on treated diets had gained significantly less weight than those on the control diets. 1-CdQA, 3-CQA, and quercetin dyglycosides (previously identified in the foliage ofA. paraguariensis) are considered to be valuable components in resistance of groundnuts toS. litura and may provide useful genetic markers in future breeding for resistance to this pest.

Azadirachtin: structural requirements for reducing growth and increasing mortality in lepidopterous larvae

Spodoptera littoralis, Spodoptera frugiperda and Heliothis virescens were exposed to azadirachtin and 23 other related compounds in three bioassays: oral cannulation, haemolymph injection and topical application. Spodoptera littoralis was susceptible to a larger proportion of the compounds than either of the other species. Overall, azadirachtin, 22,23‐dihydroazadirachtin and 1‐detigloyl‐22,23‐dihydroazadirachtin were the most active compounds. The nature of the substitutes at C‐1 and C‐3 of the decalin ring affects the potency of the compounds, as does the addition of substitutes to C‐22,23. Generally, larvae were less sensitive to compounds when they were topically applied than when they were cannulated into the gut or injected into the haemolymph.

The structure of two new clerodane diterpenoid potent insect antifeedants from Scutellaria woronowii (Juz); Jodrellin A & B

Abstract Two new clerodane diterpenoids isolated from Scutellaria woronowii (Juz) were shown to be the most potent clerodane antifeedants yet discovered. Their structures were rigorously determined by 1 H, 13 C, nuclear Overhauser difference 1-D, 1 H COSY 2-D n.m.r. and mass spectroscopy.

Insect antifeedants from azadirachta indica (part 5): Chemical modification and structure-activity relationships of azadirachtin and some related limonoids

Abstract Chemical modification of the potent insect antifeedant and growth-disruption agent azadirachtin (1) and the related limonoids 3-tigloyl azadirachtol (6) and salannin (27) have permitted an exploration of the biological activity of these compounds. General comments are made regarding the structural dependency of the antifeedant effect.

Total Synthesis of Rapamycin

For over 30 years, rapamycin has generated a sustained and intense interest from the scientific community as a result of its exceptional pharmacological properties and challenging structural features. In addition to its well known therapeutic value as a potent immunosuppressive agent, rapamycin and its derivatives have recently gained prominence for the treatment of a wide variety of other human malignancies. Herein we disclose full details of our extensive investigation into the synthesis of rapamycin that culminated in a new and convergent preparation featuring a macro-etherification/catechol-templating strategy for construction of the macrocyclic core of this natural product.

Antifungal activity of Neo-clerodane diterpenoids from Scutellaria

Abstract Three neo -clerodane diterpenoids, jodrellin A, jodrellin B and clerodin have been isolated from Scutellaria spp. assayed for antifungal activity against the plant pathogenic fungi Fusarium oxysporum f. sp. lycopersici and Verticillium tricorpus . Spore germination of V. tricorpus was delayed by clerodin and jodrellin B. Growth of F. oxysporum and V. tricorpus was inhibited by the clerodanes in a dose dependent manner. Ecological implications are discussed.

Studies towards the total synthesis of rapamycin: A convergent and stereoselective synthesis of the C22C32 carbon framework

Abstract A convergent synthesis of the C22C32 portion of rapamycin has been achieved by way of a Nozaki-Kishi coupling of vinyl iodide 14 with aldehyde 13. This aldehyde is available by the stereoselective addition of organometallic reagents to aldehyde 5, synthesised by either of two selenium mediated electrophilic cyclisations. Optically active starting materials for this synthesis are prepared by an enzymatic acylation of meso-diol 6.

Investigation of the importance of nitrogen substituents in a N–P chiral ligand for enantioselective allylic alkylation

The synthesis of three chiral chelate nitrogen-phosphorus (S)-valine derived ligands with the potential fur stereogenic nitrogen donation is described. In palladium catalysed allylic substitution reactions the ligands induced varying enantioselectivities ranging From 92%, e.e. of the (R)-enantiomer to 83% e.e. of the (S)-enantiomer. Structural and spectroscopic investigations into the origin of this effect were conducted, but were inconclusive. However, the importance of the consideration of N-substituents in such systems is highlighted