Klaus K. Mayer

A NOVEL APPROACH TO 4-BENZYLISOQUINOLINES

Abstract The reaction of quinone methides with 3.4-dihydroisoquinoline or isoquinoline leads to benzylisoquinoline derivatives. NMR and ms investigations as well as chemical degradation prove that benzylation takes place at C-4 of the isoquinoline nucleus. Spectroscopic data are given for all new compounds.

Modification of DNA bases by anthralin and related compounds

Modification of bases in calf thymus DNA by treatment with the antipsoriatic drug anthralin was studied. The products of DNA bases were identified and their yields measured by gas chromatography-mass spectrometry with selected ion monitoring. Treatment of calf thymus DNA with anthralin significantly enhanced the amount of modified bases above control levels. Purine bases were modified to products identical with those known to be typical of DNA damage induced by hydroxyl radicals. The yields of Fapy-adenine, 8-hydroxyadenine, Fapy-guanine, and 8-hydroxyguanine were maximally increased at an anthralin concentration of 75 microM. A variety of structural analogues of anthralin were also tested at 75 microM were either weaker or stronger hydroxylating agents. It is likely that damage to DNA bases induced by anthrones contributes to their antiproliferative activity. The pharmacological implications of these characteristics of the action of anthralin on DNA bases are discussed.

Elektronenstoß-induzierte Spaltung der Stilben-Doppelbindung

Syntheses ofo-(β-aminoethyl)-stilbene-urethanes (types1, 2 and3) ando-(β-phenethyl)-stilbenes4 are described. The urethanes are obtained by degradation of 1-benzyl-1,2,3,4-tetrahydroisoquinolines with ethylchloroformate;4 is synthesized by reduction of desoxybenzoines, followed byo-formylation andWittig-reaction. The deuteriated isotopomers were obtained via the corresponding deuteriated precursors.

ELECTRON IMPACT INDUCED FRAGMENTATION OF 4-ARYL-4,6,7,8-TETRAHYDRO-1H, 3H-QUINAZOLINE-2,5-DIONES

The mol. ions (M+×) of 4-substituted aryl-4,6,7,8-tetrahydro-1H,3H-quinazoline-2,5-diones (Biginelli compds.) (2 - 18) decomp. by loss of the substituents X of the Ph group (X = o-F; o-, m-, p-Cl, Br, OCH3, CH3; 2,3-, 2,4-, 2,6-, 3,4-dichloro) giving rise to prominent (M - ×X)+ ions at 70 and 12 eV, resp. In the cases of o-Cl and o-Br substitution, the M+× is extremely unstable. In general, metastable M+× (1st ffr) eliminates preferably H×, that of 15 (2,6-dichloro), however, exclusively a chlorine atom. As corroborated by 2H-labeling, reversible H-migration from C-4 to the Ph group takes place. The collisional activation spectra of the (M - ×X)+ ions of 3 (o-Cl) and 6 (o-Br) are identical but different from the indistinguishable spectra of the (M - ×X)+ ions of 4 (m-Cl), 5 (p-Cl), 9 (o-OCH3), 11 (p-OCH3), and 14 (p-CH3). Semiempirical MO calcns. (MOPAC 6.0, PM 3 Hamiltonian) of the M+× of all ortho-substituted derivs. support a close interaction of o-Cl and o-Br with the carbonyl oxygen, leading to elimination of these substituents and affording cyclic oxonium ions. In the other cases loss of X× is explained as a consequence of 4-H migration to the Ph group.

Elektronensto-induzierte Spaltung der Stilben-Doppelbindung@@@Electron-impact induced fission of the stilbene double bond: 2. Teil: Untersuchungen zum Mechanismus

Electron impact ionization succeeded by a twofold 1,5-H-shift causes fission of the double bond in stilbenes with a β-aminoethyl-(1) or a β-phenylethyl-(4) sidechain ino-position leading to ions atm/z 278 andm/z 253, respectively. Deuteriation and analysis of metastable ions reveal formation of indene cations atm/z 175 after benzylic cleavage of the side chains in1 and4. TheMcLafferty fragment of1 cyclizes to an indanyl radial-cation which is the precursor of the dimethoxybenzyl cation atm/z 151.

Functional group migration in benzaldoxime-O-n-propyl ether radical cation

The mechanism of the elimination of CH2O and C2H4O from the molecular ions of benzaldoxime-O-n-propyl ether (1) was studied using specifically deuterated derivatives, methods of tandem mass spectrometry, and ab initio calculation of the minimum energy reaction path (MERP) at the B3LYP/6-311G*//UHF/3-21G* level of theory. The results show that the eliminated CH2O (major) and C2H4O (minor) contain specifically the alpha- and beta-CH2 groups, respectively, of the propoxy chain of 1, requiring a rearrangement of the molecular ion of 1 by a 1,5-shift of the benzaldimine moiety along the propoxy chain. This rearrangement reaction follows the general Longevialle mechanism of functional group transposition along an aliphatic chain by rearrangement of distonic ions. In the case of 1(.+) the initial delta-distonic ion 1dist is generated by a 1,5-H shift from the terminal CH3 group to the N-atom of the oxime group. The compound 1dist is converted to the alpha-distonic isomer 5dist by cyclization of the molecular ion of N-benzyl-1,2-oxazolidine (5) and by subsequent ring opening into the 8-distonic isomer 2dist of N-(3-hydroxypropyl)benzaldimine (2) (see Scheme 4). Eventually the distonic ion 2dist fragments by loss of CH2O and C2H4O. The possibility that the distonic isomers of 1(.+) and 2(.+) interconvert with their cyclic isomers 2H-3,4,5,6-tetrahydro-3-phenyl-1,2-oxazine radical cation (3(.+)) and 2H-3,4,5,6-tetrahydro-3-phenyl-1,3-oxazine radical cation (4(.+)) was also examined by comparing the EI- and MIKE-spectra and the CID of the molecular ions of the isomers and by ab initio calculation. (Int J Mass Spectrom 217 (2002) 153-168)

Electron impact induced fragmentation of aromatic N-alkoxy-imines I. Ring closure in (M-CH2O)+• ions by intramolecular aromatic substitution

SummaryN-Butoxy- and N-propoxy-imines derived fromo-,m-, andp-substituted benzaldehydes (X = F, Cl, Br, I) decompose upon electron impact to the respective aldoximes by loss of CnH2n and competitivelyvia 1,5-distonic radical cations by loss of CH2O to 1,3-distonic ions which eliminate H• and/or a halogen atom in the course of homolytic aromatic substitution, giving rise to cyclic (M-CH2O-H•)+ or (M-CH2O-X•)+ ions.ZusammenfassungN-Butoxy- und N-Propoxy-imine auso-,m-, undp-substituierten Benzaldehyden (X=F, Cl, Br, I) zersetzen sich unter Elektronenbeschuß durch Verlust von CnH2n zu den entsprechenden Aldoximen. In einer Konkurrenzreaktion entstehen über 1,5-distonische Radikalkationen durch Abspaltung von CH2O 1,3-distonische Ionen, die im Verlauf einer homolytischen aromatischen Substitution H2022 und/oder ein Halogenatom eliminieren, wodurch cyclische (M-CH2O-H•)+-oder (M-CH2O-X•)+-Ionen gebildet werden.

Crystalloid Lumps from the Skin of a Patient with Lupus Erythematosus Panniculitis: Chemical Analysis

Summary. Analysis of the lumps mentioned in the title revealed calcium, phosphate, and carbonate besides minor quantities of other inorganic ions. Moreover, saturated, unsaturated, and odd numbered fatty acids as well as extractable proteins of about 29, 45, and 66 kD were identified.Zusammenfassung. Die Analyse der im Titel genannten Ablagerungen ergab Calcium, Carbonat und Phosphat neben geringen Mengen anderer anorganischer Ionen. Außerdem wurden gesättigte, ungesättigte und ungeradzahlige Fettsäuren neben extrahierbaren Proteinen von ca. 29, 45 und 66 kD nachgewiesen.