R. P. Sharma

Stereospecific synthesis of α-aminoacyl aldehydes and their interaction with α-chymotrypsin

A general procedure for the synthesis of optically pure α-aminoacyl aldehydes is described; these aldehyde analogues have been used to explore the nature of the various P–S interactions in α-chymotrypsin (from bovine pancreas).

Fusicoccin. Part III. The structure of fusicoccin H

The structure (IIa) of fusicoccin H, a minor phytotoxic glycoside produced by Fusicoccum amydali, has been determined by degradative studies and by chemical correlation with the known fusicoccin series. Feeding experiments have shown that fusicoccin H can act as a precursor of fusicoccin. This strongly suggests that fusicoccin is a diterpenoid and not a degraded sesterterpenoid.

Formation and thermal cleavage reactions of the cycloadduct of 9,10-dimethylanthracene and nitrosyl cyanide

Nitrosyl cyanide and 9,10-dimethylanthracene (DMA)(2) reacted at –25 °C to form the crystalline cycloadduct, 9,10-dihydro-9,10-(N-cyanoepoxyimino)-9,10-dimethylanthracene (1). The adduct (1) decomposed in the presence of the conjugated diene thebaine (3), to form DMA (2) and the adduct (4) of nitrosyl cyanide and thebaine. First-order kinetics, k= 6.9 × 10–5s–1, were observed for the release of DMA in benzene at 40 °C, consistent with slow dissociation of the adduct (1) followed by rapid capture of nitrosyl cyanide by thebaine. A similar first-order rate, k= 6.8 × 10–5s–1, was observed for the reaction of the adduct (1) and triphenylphosphine (2 mol equiv.) under the same conditions, the products being DMA, triphenylphosphine oxide, and triphenylphosphine N-cyanoimide (5). The reactions of nitrosyl cyanide, generated thermally from the adduct (1), were studied with a range of dienes. The conjugated dienes, N-cyanomethyl-N-northebaine (3; NCH2CN replacing NMe), trans,trans-1,4-diphenylbuta-1,3-diene (6; R = H), and ergosteryl acetate (11) all gave the expected cycloadducts (3,6-dihydro-2H-1,2-oxazines). Norbornadiene gave the tetracyclic adduct (10) arising from 1,4-conjugate addition of nitrosyl cyanide. The reactions of the adduct (1) with tetraphenylcyclopentadienone (14), 1,3-diphenylisobenzofuran (18), 2-methyl-1,3-diphenylisoindole (23), diazofluorene (24), and diphenyldiazomethane all took a more complex course leading in each case to the formation of an N-cyano-ketimine (alkylidene-cyanamide)

Formation and reactions of C-nitrosoformate esters, a new class of transient dienophiles

Oxidation of N-hydroxycarbamic esters, ROCONHOH, with tetraethylammonium or sodium periodate in the presence of conjugated dienes gave N-alkoxycarbonyl-3,6-dihydro-2H-1,2-oxazines, formed apparently by cycloaddition of transient C-nitrosoformate esters, ROCONO, with the dienes. Cleavage of various N-alkoxycarbonyl derivatives under mild conditions is exemplified. The cycloadduct (10a) of benzyl nitrosoformate and 9,10-dimethylanthracene decomposed in benzene at 80 °C in the presence of thebaine (3) to give the corresponding adduct (4a) of thebaine, together with 9,10-dimethylanthracene. Similarly, the adduct (6b) of 2,2,2-trichloroethyl nitrosoformate and cyclopentadiene, when heated with ergosteryl acetate, gave the corresponding adduct (8b) of the steroid. Benzyl and t-butyl azidoformates decomposed in dimethyl sulphoxide at 115–130 °C in the presence of thebaine to give the adducts (4a) and (4c) of benzyl and t-butyl nitrosoformate and the alkaloid. The other, major products were the sulphoximides (20a) and (20c). Alkoxycarbonylnitrenes, therefore, attack dimethyl sulphoxide either on sulphur, to give sulphoximides, or on oxygen, to give nitrosoformates. Benzyl nitrosoformate, generated thermally from either the adduct (10a) or (6a), reacted with triphenylphosphine to give, apparently, benzyloxycarbonylnitrene which attacked the solvent, benzene, to form N-benzyloxycarbonylazepine (24a). The adduct (6c) of t-butyl nitrosoformate and cyclopentadiene behaved likewise to give the azepine (24c). The reaction of (6c) with triphenylphosphine in benzene or dichloromethane gave a small quantity of 5,5-dimethyloxazolidin-2-one (26), a known cyclisation product of t-butyloxy-carbonylnitrene.

Aryne chemistry. Part XXX. Approaches to the synthesis of 9-alkyl- and 9,10-dialkyl-1,2,3,4,5,6,7,8-octafluoro-9,10-dihydro-9,10-o-benzeno-anthracenes (9-alkyl- and 9,10-dialkyl-1,2,3,4,5,6,7,8-octafluorotriptycenes)

Two routes for the preparation of 2-methyl-5-t-butylfuran have been investigated; the reactions of tetrafluoro-benzyne with this furan and with 2-methyl- and 2,5-dimethyl-furan afforded the anticipated derivatives of 1,4-epoxy-5,6,7,8-tetrafluoro-1,4-dihydronaphthalene. The methyl-substituted adducts were elaborated, with butadiene, to give 9-methyl- and 9,10-dimethyl-1,2,3,4-tetrafluoro-5,6,7,8-tetrahydroanthracenes. Further reactions with tetrafluorobenzyne, followed by dehydrogenation, afforded the title compounds.

Aryne chemistry. Part XXXIII. Reactions of tetrahalogenobenzynes with methoxyarenes and the photolysis and thermolysis of some of the products

The reactions of tetrahalogenobenzynes with methoxyarenes afford good yields of both 1,4-dihydro-1-methoxy-1,4-ethenonaphthalene derivatives and, in certain cases, 3,4-dihydro-1,4-ethenonaphthalen-2(1H)-ones. Thermolysis or photolysis of these compounds leads to naphthalene derivatives in high yield.

Formation of isocyanates by deoxygenation of C-nitrosocarbonyl compounds

The cycloadduct (1a) of 9,10-dimethylanthracene (2)(hereinafter referred to as DMA) and nitrosocarbonylbenzene decomposed in benzene at 80 °C in the presence of triphenylphosphine to give DMA, triphenylphosphine oxide, and phenyl isocyanate in high yield. The corresponding adducts of 4-chloro-(1b), 4-methoxy-(1c), and 4-nitro-nitrosocarbonylbenzene (1d) behaved likewise. The cycloadduct of DMA and 4-methoxybenzylnitrosocarbonylmethane (1e) and of DMA and 1-(4-methoxyphenyl)-2-nitrosocarbonylethane (1f) gave lower (20–30%) yields of isocyanates. The rates of decomposition of the adduct (1a) in the presence of either the conjugated diene thebaine (3) or various phosphorus(III) derivatives were the same within experimental error. A similar observation was made for compound (1d). The formation of isocyanates is believed to involve slow dissociation of the cycloadducts followed by rapid deoxygenation of the transient nitrosocarbonyl compounds by triphenylphosphine. Stable complexes (8) of triphenylphosphine oxide with N-(4-nitrophenyl)-N′-propylurea and N-(4-nitrophenyl)-N′-phenylurea are described.

Formation of aryl isocyanates by deoxygenation of nitrosocarbonylarenes

The adducts of nitrosocarbonylarenes and 9,10-dimethylanthracene decompose in the presence of triphenylphosphine to give aryl isocyanates in high yield; kinetic evidence supporting the involvement of free nitrosocarbonylarenes in this process is presented.

Rearrangement reactions of bicyclic systems. Part I. Synthesis of a model compound related to flavothebaone trimethyl ether. The abnormal ultraviolet absorption spectrum of flavothebaone and its trimethyl ether

3,6-Dimethoxybenzenediazonium-2-carboxylate decomposed to 3,6-dimethoxybenzyne (8), which reacted with veratrole to form 1,5,8-trimethoxy-1.4-etheno-2-tetralone (9) in 40% yield. Reduction, and acid-catalysed rearrangement of the resulting exo-alcohol (10). afforded 5,9-dihydro-1,4-dimethoxy-5,9-methanobenzocyclo-hepten-6-one (7). The u.v. spectrum of compound (7) is entirely analogous to that of flavothebaone trimethyl ether (3).