Spyros V. Serves

REACTION OF ARSENIC(III) OXIDE, ARSENOUS AND ARSENIC ACIDS WITH THIOLS

Abstract Arsenic(III) oxide and arsenous acid in water or aqueous ethanolic solutions react, at room temperature, with a variety of lipophilic and hydrophilic thiols giving quantitatively triaryl and trialkyl trithioarsenites, (ArS)3As and (RS)3As. Aqueous solutions of arsenic acid react with certain thiols giving quantitatively mixtures of trithioarsenites and disulfides, RSSR. These reactions may help towards the elucidation of the biochemistry of arsenous and arsenic acids.

ONE POT SYNTHESIS OF ARSONOLIPIDS VIA THIOARSENITE PRECURSORS

Abstract Reduction of the racemic and optically active 1,2-dihydroxypropyl-3-arsonic acids by thiophenol gives the chloroform soluble phenyl esters of rac-, (R-, and (S)-1,2-dihydroxypropyl thioarsonous acids which are acylated by fatty acid chlorides/pyridine to give the racemic and optically active arsonolipids (1,2-diacyloxypropyl-3-arsonic acids). The yields of long chain arsonolipids are significantly higher than those reported from the acylation of salts of 1,2-dihydroxypropyl-3-arsonic acid. The yield of short chain arsonolipids are lower, partly because of difficulties in removing traces of coprecipitated fatty acids. The esters of alkylthioarsonous acids are decomposed by carboxylic acids and on silica gel and a mechanism for their acylation is proposed. The melting points of arsonolipids [(R) = (S) > rac] increase smoothly with the fatty chain length while the enthalpies of fussion [(R) > (S) > rac] show a maximum at 1,2-dimyristoyloxypropyl-3-arsonic acid. The thermal behaviour of the aqueous d...

SYNTHESIS OF (R)- AND (S)-1,2-DIACYLOXYPROPYL-3-ARSONIC ACIDS: OPTICALLY ACTIVE ARSONOLIPIDS

Abstract Reaction of trisodium arsenite with (R)- and (S)-glycidol affords in good yields the (R)- and (S)-1,2-dihydroxypropyl-3-arsonic acid, the tetrabutylammonium salt of which upon acylation with myristic, palmitic and stearic anhydrides in the presence of pyridine gives, in moderate to low yields, optically active arsonolipids, i.e., (R)- and (S)-1,2-diacyloxypropyl-3-arsonic acids. The thermotropic phase transitions of these arsonolipids are characterized. Results show that the transition temperatures and enthalpies of fusion of the racemates are lower than those of the enantiomers in the powder form presumably because of conglomerate formation. The thermotropic transition characteristics of the aqueous dispersions of the arsonolipids change with the acyl chain lengths, and the overall behaviour is similar to that of the aqueous dispersions of phospholipids.

Carbonic anhydrase inhibitors—Part 33.1 isozyme II inhibition with 2,3-dihydroxypropylarsonic acids and arsonolipids

Abstract The inhibition of bovine carbonic anhydrase (CA), isozyme II was investigated with ( R )- and ( S )-2,3-dihydroxypropylarsonic acids, and with some of their acylated derivatives (arsonolipids) containing long aliphatic chains. Dose response, and kinetic experiments showed the ( S )-derivatives to be more active than the corresponding ( R ) ones, and the longer the acyl chain the more potent noncompetitive inhibitors the arsonolipids were. The mechanism of inhibition probably involves binding of the inhibitor in ionized state to the Zn(II) ion within the enzyme active site.

On the Mechanism of the Meyer Reaction With Epoxides and 2-Haloalcohols As Substrates†

Abstract The Meyer reaction of alkaline arsenious acid with glycidol is first order in As(III) and first order in glycidol. The kinetic and stereochemical evidence shows that the reaction follows an SN2 mechanism. The uncertainty in the pK 2 and, especially, pK 3 values for H3AsO3 does not distinguish between HAsO3 2- and AsO3 3- as the actual nucleophile in the Meyer reaction with glycidol as substrate. Kinetic runs and synthetic experiments point towards AsO3 3- as the most probable nucleophile. The Meyer reaction with 3-chloropropane-1,2-diol, proceeds either via glycidol or by direct displacement of chloride, in a ratio determined by the starting stoichiometry. HAsO3 2- does not react with the chlorodiol, thus leaving AsO3 3- as the nucleophile in the Meyer reaction.

rac-3,4-DIHYDROXYBUTYLARSONIC ACID: A KEY INTERMEDIATE FOR ISOSTERIC ARSONOLIPIDS

Abstract Synthetic routes starting from 4-bromobut-1-ene and leading to rac-3,4-dihydroxybutylarsonic acid and diphenyl rac-3,4-dihydroxybutyldithioarsonite were explored. All of them gave overall yields 5–16%. Some properties of the free acid and its dilithium salt are described.

SYNTHESIS OF ISOSTERIC ARSONOLIPIDS: RAC-3,4-DIACYLOXYBUTYLARSONIC ACIDS

Abstract Acylation of diphenyl rac-3,4-dihydroxybutyldithioarsonite with acyl chlorides and oxidation by hydrogen peroxide gave in low yields (7–14%) a new class of isosteric arsonolipids, rac-3,4-diacyloxybutylarsonic acids. The low yields are partially due to carbon-arsenic bond cleavage.

Reaction of Tris(Trimethylsilyl) Phosphite with Epihalohydrins

Abstract The reaction of tris(trimethylsilyl) phosphite with halohydrins does not lead to an Arbuzov product but to bis(trimethylsilyl) esters of 3-halo-2-trimethylsiloxypropylphosphonic acids. Methanolysis and neutralization affords the 3-halo-2-hydroxypropylphosphonic acids and their salts.

REACTION OF TRIS(TRIMETHYLSILYL) PHOSPHITE WITH EPOXIDES AND GLYCIDOL DERIVATIVES

Abstract Tris(trimethylsilyl) phosphite deoxygenates styrene epoxide and tritylglycidol. The same phosphite with glycidyl mesylate gave bis(trimethylsilyl) ester of 3-mesyl-2-trimethylsiloxypropylphosphonic acid by attack at the epoxide methylene carbon. The ester was not stable and reacted further intrarnolecularly. With glycidyl tosylate and glycidyl 3-nitrobenzenesulfonate, however, the reaction was more complicated and glyceryl 1,3-bis(arenesulfonate) was one of the products. With these activated glycidols deoxygenation and reduction of the nitro group were also observed.

Reactions of cis-3,5-dibromo-4-oxo-2,2,6,6-tetramethylpiperidin-1-yloxy with nitrogen and phosphorus nucleophiles

Abstract The title free radical can be used to spin label biochemically important amines, but not those which it oxidizes, e.g., epinephrine (adrenaline), and diamines. Product analysis of the reaction between the radical and triethyl phosphite gives evidence that the first step in the Perkow reaction may occur via halogen attack giving enolate bromophosphonium ion pair as the common intermediate.