Jacek Thiel

An NMR and molecular mechanics structural study on some ethereal and Δ3,10 isomers of cinchona alkaloids

Abstract Z configurations have been ascribed to the ethylidene side chains of apocinchonine 2a and apoepiquinidine 2b . Unknown absolute configurations around C10 atoms, R for α-isocinchonine 4a and α-isoquinidine 4b and S for γ-isoquinidine 5 were determined. The C10 S arrangement for isoepiquinidine 6 and the C9 S for α-isocinchonine were confirmed. All the ethereal derivatives showed—in contrast with the parent alkaloids—the left-handed twist of their quinuclidine rings. The seven-membered intramolecular ethereal rings of the α and γ isomers adopt predominantly the ‘twist-chair’ conformation while in isoepiquinidine the ‘twist-boat’ form dominates. These conformations, deduced from NMR data, were confirmed by MM calculations. Both these methods allowed indication of the energetically most favourable positioning of the quinuclidine moiety in respect of the quinoline ring for the alkaloids investigated. ‘Anti-closed’ conformation I was found for isoepiquinidine whereas the remaining C10OC9 isomers prefer ‘anti-open’ forms VI, X, XIV . Minimum energy conformers ‘anti-closed’ XIX and ‘anti-open’ XVIII were found for Z -apocinchonine while Z -apoepiquinidine exists in prevailing ‘syn-open’ conformation XXV .

1H and 13C n.m.r. spectral characteristics of aliphatic component of coal extracts

Abstract 13 C and 1 H n.m.r. spectroscopy have been applied to benzene extracts of Polish coals to obtain additional information on their molecular structure. The data have shown that a considerable amount of the material can occur in the form of aliphatic carbon chains as paraffins and/or n-alkyl substituents on aromatic and hydroaromatic rings. Different types of branching both of alkane and alkyl groups were also indicated.

Conformation of some sparteine N-16 oxides revisited

Sparteine N-16 oxides were thought to occur in all chair conformations with cis fusion between their C and D rings. NMR spectral analysis made possible indication of the chair – chair – boat– chair form with cis fussion of C, D rings for sparteine, 2phenyl- and 2-methylsparteine N-16 oxides. Molecular energy found by means of DFT, Hartree– Fock, AM1, PM3 methods supported this new shape of bisquinolizidine skeleton. q 2002 Elsevier Science B.V. All rights reserved.

The steric structure of multiflorine methylation products

SummaryMultiflorine (1) — a minor lupine alkaloid — treated by methyl lithium or methyl magnesium iodide affords 4S-4-hydroxy-4-methyl-2,3-didehydrosparteine (2) and 2S-2-methyl-4-oxosparteine (3), respectively, as the dominating products. Their steric structure, determined by1H and13C NMR techniques, points to stereospecific preferences of these reactions. The observed nucleophilic 1,2- and 1,4-additions indicate that regiospecificity of the action of MeLi or MeMgI on multiflorine is different from that of the so far known similar alkylation of other enamino ketones.ZusammenfassungMultiflorin (1), ein Lupin-Nebenalkaloid, ergibt bei Umsetzung mit Methyllithium oder Methylmagnesiumiodid 4S-4-Hydroxy-4-methyl-2,3-didehydrospartein (2) und 2S-2-Methyl-4-oxospartein (3) als Hauptprodukte. Ihre NMR-spektroskopisch (1H und13C) aufgeklärte räumliche Struktur weist auf eine Stereoselektivität der erwähnten Reaktionen hin. Die beobachteten nucleophilen 1,2- und 1,4-Additionen zeigen, daß sich die Regiospezifität der Einwirkung von MeLi oder MeMgl auf Multiflorin von jener bis jetzt bekannter Alkylierungen von Enaminoketonen unterscheidet.

Cinchona alkaloids: the structure of β-isocinchonicine revisited

Abstract Analysis of β-isocinchonicine — the enolo-ethereal derivative of cinchonine — by NMR, AM1 calculations, and X-ray diffraction resulted in the assignment of its structure as 1( S )-ethyl-3-(quinol-4-yl)-2-oxa-6( S )-9-azabicyclo[4.4.0]dec-3-ene contrary to the structure with seven-membered enolo-ethereal ring reported in the literature. The AM1 calculations also showed several energetically favorable conformations with the ethyl group equatorial in relation to the piperidine fragment. Four of these forms ( II , V , VIII , XI ), supported by NOEs and being the rotamers of the quinolyl and ethyl substituents, are most probable components of the conformational equilibrium mixture of β-isocinchonicine. Three of the rotamers have been observed by X-ray diffraction: two in the crystals of β-isocinchonicine hydroiodide monohydrate ( 7 ·HI·H 2 O) are linked into an asymmetric dimer by a pair of N–HN + hydrogen bonds and another rotamer in its hydroiodide dihydrate ( 7 ·HI·2H 2 O) where the cations are linked by N–HN + hydrogen bond into helices.

The structure of cinchonhydrines — the derivatives of cinchonine

Abstract Cinchonhydrines, to which formulae 5 had been previously ascribed, appeared to be the analogs of known niquidine/niquine derivatives of cinchona alkaloids. Their structures 6 and 7 , determined mainly by means of NMR techniques, point to a formal loss of the C2 carbon atom from the quinuclidine moiety of the parent cinchonine ( 1c ).

THE STRUCTURE OF INTERMEDIATE PRODUCTS OF 'FRAGMENTATION' OF 10-BROMODIHYDROCINCHONINE

Abstract 10-Bromodihydrocinchonine 1d , similarly to analogical derivatives of other main cinchona alkaloids, transforms into nicinquine and isonicinquine 2d formally loosing its C2 carbon atom in a form of formaldehyde. This reaction was found to proceed via the so-far unstudied intermediate compounds ( 5a ) 4- S -( Z -propenyl)- and ( 5 4- S -( E -propenyl)-6- R -7- S -(quinolyl-4)-8-oxa-1- R -azabicyclo[4.3.0]nonane which at the same time are products of a novel rearrangement of the parent cinchonine. The stereostructure of these compounds was determined using, mainly, NMR techniques. The energy minima of conformers 5 and 5a were supported by molecular mechanics calculations. The mechanisms for the 1d → 5 → 2d sequence have been discussed. The alkaloid 5 is sterically preferred to its Z -isomer. The accompanying nucleophilic substitution ( 1d → 6 ) and elimination ( 1d → 7 ) are also stereospecific.

Structural studies of coal extracts

Abstract The reductive alkylation of a medium-volatile bituminous coal was carried out using potassium and naphthalene in tetrahydrofuran, and using methyl, ethyl and butyl iodides to alkylate the resultant polyanion. The soluble products of the reductive alkylation reaction were isolated by extraction with n-pentane and benzene. The extracts were characterized by i.r. and 1 H n.m.r. spectroscopy, molecular mass and ultimate analyses.

Asymmetric conversions of 10-bromo-10,11-dihydroquinines into 8-oxa-1-azabicyclo[4.3.0]nonane derivatives and related compounds

Abstract Some transformations of (10 R )- and (10 S )-bromo-10,11-dihydroquinine 2a and 2b have been investigated in order to obtain insights into their unexplored chirality. The (10 R )-diastereomer 2a converts stereoselectively into (4 S )-( E -propenyl)-(6 S ,7 R )-(6-methoxy-quinol-4-yl)-8-oxa-(1 R )-azabicyclo[4.3.0]nonane 10 , which is the product of a novel rearrangement of the parent quinine 1 and displays the N(1)-( S )-configuration ( 10a ) in the solid state. The (10 S )-diastereomer 2b afforded 10 and its ( Z )-propenyl isomer 15 (in the ratio 55:45), as well as ( Z )-3,10-didehydro-10,11-dihydro-quinine 19 . On treatment with acid the alkaloid 10 yields [(4 S )-( E )-propenyl)-(2 S )-piperidinyl]-6-methoxyquinoline-(α R )-methanol 12 . Closure of the oxazolidine ring in 12 gives 14 , the 9,9-dimethyl-derivative of 10 , with the N(1) configuration inverted. The molecular structures of 10a and 14 , determined by X-ray diffraction, show their similar conformations except for the axial ( E )-propenyl substituent, disordered in two orientations in 10a and ordered in another position in 14 .

Mass spectra of iso-cinchona- and halogenated cinchona alkaloids

The electron impact ionisation (EI) and electrospray ionisation (ESI) mass spectra using in-source collision-induced dissociation of nine different cinchona alkaloid derivatives [iso-cinchona alkaloids (ethereal isomers) and 10-Br(Cl) containing cinchona compounds] have been studied. In the case of the EI method for iso-cinchona alkaloids the observed fragmentation directions are as follows: isomerisation of the cyclic ethers to the corresponding C9 ketone, the formation of [M − 15]+, [M − 29]+ and [M − 57]+ fragments as a result of the loss of methyl, ethyl and butyl radicals, and the cleavage of the C8–C9 bond. The fragmentation of the compounds containing C10–Br(Cl) bonds started with the scission of this bond. The primary bond rupture is followed by the fragmentation of the primary product into two parts across the C8–C9 bond. In the case of the ESI method at low capillary exit voltage only the peak of the protonated molecule ([M + H]+), and in a significantly lower abundance, the peak of the [M + 2H]2+ ion can be observed. Increasing the capillary exit voltage causes fragmentation to occur. For iso-cinchona alkaloids the main direction is the cleavage of C8–C9 bond. For the C10–Br(Cl) compounds, the primary fragmentations are the cleavage of the C9–O and C10–Br(Cl) bonds. Fragmentation pathways are discussed.