Ian Holden

9, 21-Didehydroryanodine: a new principal toxic constituent of the botanical insecticide Ryania

A major insecticidal constituent of Ryania speciosa is isolated and characterized by n.m.r. and mass spectroscopy as the new alkaloid 9, 21-didehydroryanodine (2); reduction of (2) with hydrogen (or tritium)gas yields both ryanodine (1) and 9-epiryanodine (3)(or their 9,21-3H analogues) in a 1:9 ratio.

Peracid-mediated n-oxidation and rearrangement of dimethylphosphoramides: plausible model for oxidative bioactivation of the carcinogen hexamethylphosphoramide (HMPA)

Abstract Dimethylphosphoramides react with m -chloroperoxybenzoic acid (MCPBA) in anhydrous acetone to yield the previously unknown P -dimdethylamino-oxyphosphonous derivatives via N -oxidation and rearrangement. Further MCPBA oxidation yields formaldehyde and nitrosomethane, isolated as its trans -dimer. These reactions provide a possible biomimetic model for the metabolic activation of hexamethylphosphoramide as a mutagen and carcinogen.

Phosphinyliminodithiolane insecticides: Oxidative bioactivation of phosfolan and mephosfolan

Abstract 2-(Diethoxyphosphinylimino)-1,3-dithiolane (phosfolan) and its 4-methyl analog (mephosfolan) are proinsecticides as determined by microsomal mixed-function oxidase (MFO) activation to potent acetylcholinesterase (AChE) inhibitors. They are similarly activated by peracid oxidation which yields the sulfoxide and sulfone derivatives. The hydrolytically unstable S -oxides are irreversible AChE inhibitors that are 160- to 47,000-fold more potent than phosfolan and mephosfolan. MFO S -oxidation is indicated for both proinsecticides by (a) NADPH-dependent increases in potency as AChE inhibitors to an extent expected of sulfoxides, and (b) formation of the S -oxide hydrolysis product diethyl phosphoramidate.

Direct n.m.r. detection of an epoxyfuran intermediate in peracid oxidation of the fungicide methfuroxam

A 4,5-epoxyfuran intermediate has been detected by 1H and 13C n.m.r. spectroscopy in the oxidative conversion of 2,4,5-trimethyl-N-phenylfuran-3-carboxamide (the fungicide Methfuroxam) into 3-(N-phenylcarbamoyl)-4-methylhex-3-ene-2,5-dione.

[]-azoxybis(methylene) bis(3-chlorobenzoate): potent mutagen from reaction of hexamethylphosphoramide, -methylhydroxylamine and []-nitrosomethane dimer with 3-chloroperoxybenzoic acid

Abstract [ E ]-Azoxybis(methylene) bis(3-chlorobenzoate), an exceptionally potent mutagen (3050 revertants/nmol) in the Salmonella typhimurium (strain TA100) assay, is formed in trace ( E ]-nitrosomethane dimer on treatment of hexamethylphosphoramide or N -methylhydroxylamine with 3-chloroperoxybenzoic acid.

Phosphinyliminodithiolane insecticides: Novel addition reactions of phosfolan and mephosfolan sulfoxides and sulfones

Abstract The sulfoxides and sulfones of phosfolan [2-(diethoxyphosphinylimino)-1,3-dithiolane] and mephosfolan (its 4-methyl analog) react by nucleophilic attack of water, methanol, and thiols at the imino carbon rather than at the phosphorus. Some of the addition products are in turn reactive. Thiolcarbamates formed on hydrolysis of the sulfoxides and sulfones further react with water at physiological pH giving diethyl phosphoramidate via a carbamic acid and with methanol yielding a methyl carbamate. Sulfenic acids from sulfoxide addition reactions readily condense with thiols, e.g., phosfolan sulfoxide readily forms a bis conjugate from addition of two molecules of glutathione. These addition reactions may serve as models for inhibition of acetylcholinesterase, detoxification, and tissue binding.

Formation and dehydration of a prochiral 2-hydroxyisopropyl centre during biosynthesis: the rot-2′-enonic acid–rotenone transformation in Amorpha fruticosa

Rot-2′-enonic acid (2), dalpanol (4), and rotenone (5) are formed during the conversion of 9-demethylmunduserone (1) into amorphigenin (6) by Amorpha fruticosa seedlings: the 4′-E-methyl of (2) becomes predominantly the 7′-methylene of (5), leading to stereochemical proposals for a formation scheme.

Synthesis of [7′-14C]- and [7′-13C]-rotenone, and [4′-14C]- and [4′-13C]-rot-2′-enonic acid: 1,4-allylic hydrogenolysis showing substantial stereoselectivity

C-Trimethylsilyloxy protection of the B/C-ring junction allows regenerative synthesis of (–)-rotenone isotopically labelled at the C-7′-methylene, without loss of chirality; 1,4-hydrogenolysis of (–)-rotenone labelled in this way proceeds stereoselectively with transference of 88% of the label to the 4′-E-methyl of (–)-rot-2′-enonic acid.

Hydroxylation of rotenone to amorphigenin in Amorpha fruticosa seedlings

Rotenone (2), but neither of the 6′-epimers of amorphigenol (3), is an excellent precursor for amorphigenin (1) in Amorpha fruticosa; using [7′-14C]rotenone and three different work-up techniques, the 14C-label was found to be equivalently distributed between the 7′-methylene and 8′-hydroxymethylene of amorphigenin.