Dithiophosphorylation of quinine

Abstract

SHORT COMMUNICATIONSNatural compounds with asymmetric carbon atoms, in particular alkaloids, can be used as a source of chiral centers in their functionalization products. Promising synthons in the design of biologically active compounds are hydroxy-containing chiral alkaloids, such as quinine and cinchonine. Accessibility of these alkaloids has underlain their use as chiral P,N-bidentate ligands for metal complexes, catalysts for asymmetric syntheses, chromatographic selectors, and chiral NMR reagents [1][2][3][4]. Wide potential of their application for various purposes is determined by specific features of the molecular structure of quinine and cinchonine as major components of cinchona alkaloids, which consist of a quinoline fragment and vinyl-substituted bicyclic quinuclidine moiety with a tertiary nitrogen atom. Their molecules possess four chiral carbon atoms and one stereogenic nitrogen atom. Quinine alkaloids are represented by diastereoisomeric 8R,9S-quinidine and 8S,9R-quinine. Dithiophosphorylation products of quinine derivatives have not been reported so far. Dithiophosphates with quinine and cinchonidine fragments linked to the phosphorus through a sulfur atom have recently been synthesized by stereoselective functionalization of the corresponding O-methanesulfonyl derivatives with O,O-diethyl hydrogen phoshorodithioate in the presence of triethylamine [1]. In this work we used tetraphosphorus decasulfide P 4 S 10 as dithiophosphorylating agent whose reaction with alcohols is a traditional method of synthesis of dithiophosphoric acid derivatives [5]. By reaction of P 4 S 10 with quinine in benzene at 60°C (10 h) we obtained O,O-bis[(8S,9S)-quinin-9-yl] phosphorodithioate (2) which was isolated as inner ammonium salt.The 31 P-{ 1 H} NMR spectrum of 2 in benzene contained two signals at δ P 105.5 and 106.2 ppm at a ratio of 1 : 1. The downfield shift of the phosphorus signal from the region typical of dithiophosphoric acid derivatives (δ P 83-86 ppm [6]) is likely to result from migration of the SH proton to the tertiary nitrogen atom of the quinuclidine fragment with formation of inner salt. In fact, compound 2 displayed in the IR spectrum (KBr) a broad absorption band at 3358 cm -1 due to stretching vibrations of the N + -H bond. In the

α‐d‐Glucofuranose and α‐d‐allofuranose diacetonides and silyl ether of α‐d‐glucofuranose diacetonide in dithiophosphorylation reactions

“…We have been involved in developing new synthetic routes for biologically active dithiophosphates‐ and dithiophosphonates‐bearing pharmacophoric O ‐organyl groups on the basis of natural chiral alcohols and diols. We have recently obtained optically active dithiophosphates and dithiophosphonates, their ammonium salts and S ‐esters by the reactions of tetraphosphorus decasulfide and 2,4‐diaryl 1,3,2,4‐dithiadiphosphetane‐2,4‐disulfides with (1 R ,2 S ,5 R )‐(−)‐menthol and (1 S ,2 R ,5 S )‐(+)‐menthol, (1 S )‐endo‐(−)‐borneol, (1 R )‐endo‐(+)‐fenchyl alcohol, (1 S ,2 S ,3 S ,5 R )‐(+)‐isopinocampheol, quinine, and (+)‐dimethyl tartrate . We have assumed that the reactions of unprotected α‐ d ‐allofuranose and α‐ d ‐glucofuranose with 2,4‐diorganyl 1,3,2,4‐dithiadiphosphetane‐2,4‐disulfides can lead to mixtures of organothiophosphorus products.…”

Nematicidal activity of menthol and its dithiophosphoric derivatives

“…Our research group curries out systematic research on the creation of biologically active drugs based on dithiophosphoric acids and their salts using nitrogenous organic compounds [21][22][23][24], many of these acids were obtained from monoterpene alcohols. We assumed that dithiophosphoric acids obtained from enantiomerically pure menthols and their salts can be of interest for studying nematicidal activity.…”

Cinchona Alkaloids in the Synthesis of Chiral Salts of Phosphorus Dithioacids on the Basis of 1,2:3,4‐Di‐O‐isopropylidene‐α‐D‐galactopyranose

“…The stereochemical features of cinchona alkaloids and their derivatives are determined by configuration at the C 8 /C 9 stereogenic centres . We have recently obtained O,O ‐di(8 S ,9 S ‐quinin‐8‐yl)dithiophosphate as the zwitter ion by the reaction of 8 S ,9 R ‐quinine with tetraphosphorus decasulfide . We deemed it to be necessary to prepare new types of ionic liquids on the basis of cinchona alkaloids and chiral dithiophosphoric acids to get new antimicrobials.…”