Howard B. Broughton

An x-ray crystallographic, mass spectroscopic, and NMR study of the limonoid insect antifeedant azadirachtin and related derivatives

Abstract The limonoid insect antifeedant azadirachtin (1) may be partially hydrogenated at the C22-C23 position and subsequently treated with an excess of sodium periodate and potassium permanganate in the presence of a base to give detigloyldihydroazadirachtin (4). This compound was examined by X-ray crystallographic techniques which revealed key structural fragments and together with detailed n.m.r. and mass spectroscopic studies allowed the complete unambiguous structure assignment to the parent azadirachtin molecule. Two further compounds, 3-deacetyl-11-desoxyazadirachtin (2), and 3-acetoxy-7-tigloyl-vilasinin lactone (3) were also isolated and characterised from a Senegal sample of neem seed.

X-Ray crystallographic structure determination of detigloyldihydroazadirachtin and reassignment of the structure of the limonoid insect antifeedant azadirachtin

The structure of detigloyldihydroazadirachtin (tigloyl = 2-methylcrotonoyl) has been determined by single-crystal X-ray diffraction methods and for the first time permits unambiguous structure assignment of the limonoid insect antifeedant azadirachtin.

Chemistry of insect antifeedants from azadirachta indica (part 4): synthesis towards the limonoid azadirachtin; preparation of a functionalised decalin fragment

Abstract Synthetic studies are described towards the functionalised decalin (2). This represents an advanced intermediate in a proposed total synthesis of the naturally occurring insect antifeedant azadirachtin (1) involving a late coupling reaction to form the C-8 – C-14 bond. The final route to (2) involved an intramolecular Diels-Alder reaction of (13) and subsequent internal Michael addition to construct the trans -decalin (26). A series of stereoselective functional group interconversions were used to transform this compound into (2) in good overall yield.

The Synthesis of Azadirachtin: A Potent Insect Antifeedant

We describe in full the first synthesis of the potent insect antifeedant azadirachtin through a highly convergent approach. An O-alkylation reaction is used to unite decalin ketone and propargylic mesylate fragments, after which a Claisen rearrangement constructs the central C8-C14 bond in a stereoselective fashion. The allene which results from this sequence then enables a second critical carbon-carbon bond forming event whereby the [3.2.1] bicyclic system, present in the natural product, is generated via a 5-exo-radical cyclisation process. Finally, using knowledge gained through our early studies into the reactivity of the natural product, a series of carefully designed steps completes the synthesis of this challenging molecule.

Chemistry of insect antifeedants from azadirachta indica (part 2): Synthesis of a polyoxygenated decalin with limonoid structural homology.

Abstract The synthesis of a polyoxygenated decalin (2) with limonoid structural homology, common to salannin and azadirachtin, has been completed using an efficient intramolecular Diels- Alder cycloaddition.

Chemistry of labdanediol from Cistus ladaniferus, L. synthesis of 12-Nor-ambreinolide and α and β-levantenolides

Abstract Labdanediol, 2 , the major component of the neutral part of Cistus ladaniferus L, was transformed into 12- nor -ambreinolide, precursor of ambrox ® , in three steps with an overall yield of 70%. Molecular modelling techniques have been used to determine the stereochemistry of the byproducts of these reactions. The selenylation and elimination reactions of α and βlevantanolides, obtained from labdanediol, 2 , were used to synthetise α and β-levantenolides.

Preparation of β-ketomacrolactones and β-ketodiolides using S-t-butyl 3-oxobutanethioate and S-t-butyl 4-diethylphosphono-3-oxobutanethioate

Using S-t-butyl-3-oxobutanethioate (1) and S-t-butyl 4-diethylphosphono-3-oxobutanethioate (2) various homologation reactions with t-butyldimethylsilyl protected hydroxy-iodides and aldehydes are reported. The products of these reactions after deprotection may be treated with copper(I) trifluoroacetate to afford β-ketomacrolide or β-ketomacrodiolides ranging in ring size from 13 to 32 depending upon the linking carbon atom chains and the reaction conditions. Several of the macrocyclic structures have been studied by X-ray crystallographic methods to determine their solid state conformations

Electrostatic vs. orbital control in π-facial diasteroselection: a PM3 SCF-MO study of electrophilic reactivity in 7-methylenenorbornanes

PM3 calculations indicate that π-facial diastereoselection in the reaction between 2,3-endo-substituted 7-methylenenorbornanes and electrophiles such as Hg(OR)2 or I+ is determined by electrostatic asymmetry whereas the reaction with BH3 is controlled by orbital interactions.

Structural reappraisal of the limonoid insect antifeedant azadirachtin

Based upon a detailed 250 MHz 1H n.m.r. study an alternative structure for the limonoid antifeedant azadirachtin has been determined.

A semiempirical SCF-MO study of the tautomeric forms of 3-acetyl tetronic- and tetramic acids

SummaryA number of tautomeric geometries of 3-acetyl tetramic acid and 3-acetyl tetronic acid were examined using the AM1 and PM3 methods. The results are compared with experimental data and with studies using MNDO and older methods, with the conclusion that both AM1 and PM3 provide satisfactory models of the behaviour of these species.