TY  - JOUR
A1  - Tacke, Reinhold
A1  - Linoh, H.
A1  - Ernst, L.
A1  - Moser, U.
A1  - Mutschler, E.
A1  - Sarge, S.
A1  - Cammenga, H. K.
A1  - Lambrecht, G.
T1  - Darstellung und Eigenschaften der Enantiomere der Antimuskarinika Sila-Procyclidin und Sila-Tricyclamol-iodid: Optisch aktive Silanole mit Silicium als Chiralitätszentrum
N2  - Durch Racematspaltung mit L-( + )- bzw. o-(-}-Weinsäure wurden die Enantiomere des Sila-Procyclidins (R}-1 b und (S}-1 b erhalten (>97% ce (NMR), 99.7% ee {DSC)]. Daraus wurden die Hydrochloride (R}-2b und (S)-lb und durch Umsetzung mit CH31 die Enantiomerc des Sila-Tricyclamol-iodids (R)-3b und (S}-3b [>96% ee (NMR)] hergestelll Die optisch aktiven Silanoie sind in k:ristalliner Form und in inerten Lösungsmitteln konfigurationsstabil. während sie in wässeriger Lösung raoemisieren (3 b schneller als 111). In. Analogie zur Stereoselektivität der antimuskarin. iscben Wirkung der Enantiomere der Kohlenstoff-Analoga Procyclidin (la) und Tricyclamol-iodid (3a) besitzen die (R)Enantiomere von 1 b und 311 eine größere Affinität zu den ilealen M2&- und atrialen M2ar-Muskarinrezeptorcn des Meerschwein,;, cbens als die (S)-Antipoden. Alle Silicium-Verbindungen sind stärker antiinuskarinisch wirksam als ihre Kohlenstoff-Analoga, deren Stereoselektivität jedoch stärker ausgeprägt ist. Die Unterschiede in der A1Tmität von (R}-1 b und (S)-1 b zu den ilealen und atrialen Muskarinrezeptoren bestätigen das Konzept der Heterogenität musk:arinis.cher M 2-Rezeptoren (M 2\(_\alpha\): atrialer Typ; M2\(_\beta\): ilealer Typ).
N2  - The enantiomers of sila-procyclidine (R}-1 band (S)-1 b [ > 97% ee (NMR~ 99.7% ee (DSC}] were obtained by resolution with L( + )· and o-(-)-tartaric acid. rcspectively. Starting from (R}-1 b and (S)-1 b. the hydrochlorides (R)-lla and (S)-lb wcre ptepared and thc enantiomcrs of sila-tricyclamol iodide {R)-311 and (S}-3b [>96% ee (NMR)] were syothesized by reaction witb CH31. Tbe optically active silanols show configurational stabiUty in the crystalline state and in inert solvents. whereas they racemizc in aqucous solution (3b faster tban 1 b). By analogy with the stereoselectivity of antimuscarinic action of the enantiomers of tbe carbon analogues procyclidine (la) and tricyclamol iodide (Ja), tbe t.R) enantiomers of 1b and 3b show a greater aftinity for the ileal M211 and atrial M2a _muscarinic reoeptors of the guinea pig than the corresponding (S) antipodes. AU silicon compounds e:xhibit a greater antimuscarinic potency than their carbon analogues, whercas the stereoselectivity of action is more pronounced for the carbon compounds. The difTerences in affmity for (R}-1 b and (S}l b for ileal and atrial muscarinic receptors confirm the present concept of heterogencity in muscarinic M2 rccepton (M 2\(_\alpha\): atrial type; M 2\(_beta\): ileal type).
KW  - Anorganische Chemie
Y1  - 1987
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63822
ER  - 
TY  - JOUR
A1  - Tacke, Reinhold
A1  - Strohmann, C.
A1  - Sarge, S.
A1  - Cammenga, H. K.
A1  - Schomburg, D.
A1  - Mutschler, E.
A1  - Lambrecht, G.
T1  - Darstellung und Eigenschaften der Enantiomere des selektiven Antimuscarinikums 1-Cyclohexyl-1-phenyl-4-piperidino-1-butanol (Hexahydro-Difenidol)
N2  - No abstract available
KW  - Anorganische Chemie
KW  - Difenidol
KW  - (R)- and (S)-hexahydro- / Antimuscarinic properties / Muscarinic receptor subtypes
Y1  - 1989
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63950
ER  - 
TY  - JOUR
A1  - Strohmann, C.
A1  - Bauerecker, S.
A1  - Cammenga, H. K.
A1  - Jones, P. G.
A1  - Mutschler, E.
A1  - Lambrecht, G.
A1  - Tacke, Reinhold
T1  - Enantiomers of the muscarinic antagonist 1-cyclohexyl-1-(4-fluorophenyl)-4-piperidino-1-butanol (p-fluoro-hexahydro-difenidol): synthesis, absolute configuration, and enantiomeric purity
N2  - The enantiomers of the antimuscarinic agent 1-cyclohexyl-1- (4-fluorophenyl)-4-piperidino-1-butanol [(R)- and (S)-p-fluorohexahydro- difenidol] ((R)- and (S)-2a] and their methiodides (R)- 3 and (S)-3 were prepared with high enantiomeric purity. (R)- 2a and (S)-2a (isolated as hydrochlorides) were obtained by catalytic hydrogenation (Pd/C contact) of the corresponding enantiomers of 1-cyclohexyl-1-( 4-fl uorophen yl)-4-piperidino- 2-butyn-1-ol [(R)- and (S)-4]. Reaction of (R)-2a and (S)-2a with rnethyl iodide led to (R)-3 and (S)-3, respectively. The unsaturated precursors (R)- and (S}-4 (enantiorneric purity ~ 99.80 and ~99.94% e.e.; calorimetric analysis) were prepared by res-sepaolution of rac-4 [available from 4-FC\(_6\)H\(_4\)C(O)C\(_6\)H\(_{11}\) by reaction with LiC ~ CCH\(_2\)NC\(_5\)H\(_{10}\)] using (R)- and (S)-mandelic acid as resolving agents. The absolute configurations of the (R) and (S) enantiomers of 2a, 3, and 4 were determined by an X-ray crystal-structure analysis of (S)-5, the methiodide of (S)-4. (R)- 2a and (R)-3 exhibit a higher affinity for muscarinic M1, M2, M3, and M4 receptors (by up to two orders of magnitude) than their corresponding antipodes (S)-2a and (S)-3, the degree of stereoselectivity depending on the receptor subtype involved. (R)-2a represents a useful tool for rnuscarinic receptor research (affinity profile: M1 ~ M3 ~ M4 > M2).
KW  - Anorganische Chemie
KW  - Difenidol
KW  - p-fluoro-hexahydro-
KW  - enantiomers of / Muscarinic receptors
KW  - subtypes of
Y1  - 1991
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64144
ER  - 
TY  - JOUR
A1  - Sarge, S.
A1  - Cammenga, H. K.
A1  - Becker, B.
A1  - Rohr-Aehle, R.
A1  - Tacke, Reinhold
T1  - Energetic and kinetic investigation of thermally induced molecular rearrangements of esters of (hydroxymethyl)hydridosilanes by DSC
N2  - No abstract available
KW  - Anorganische Chemie
Y1  - 1988
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-63850
ER  - 
TY  - JOUR
A1  - Tacke, Reinhold
A1  - Wiesenberger, F.
A1  - Becker, B.
A1  - Rohr-Aehle, R.
A1  - Schneider, P. B.
A1  - Ulbrich, U.
A1  - Sarge, S. M.
A1  - Cammenga, H. K.
A1  - Koslowski, T.
A1  - Niessen, W. von
T1  - Ester von (Hydroxymethyl)diorganylsilanen: Synthese und thermisch induzierte Umlagerung
T1  - Esters of (Hydroxymethyl)diorganylsllanes: Synthesis and Thermally Induced Rearrangement
N2  - Twenty silanes of the type R\(^1\)R\(^2\)Si(H)CH\(_2\)OR\(^3\) (A) were syn- and entropy of activation) of these reactions were studied by thesized {R\(^1\), R\(^2\) = Me, Ph, 1-naphthyl, PhCH\(_2\), Me\(_3\)SiCH\(_2\); OR\(^3\) means of düferential scanning calorimetry (DSC). In addition, = OC(O)Me, OC(O)Ph, OC(O)CF\(_3\) , OS(0)\(_2\)CF\(_3\), OP(O)Ph\(_2\), the kinetics of all reactions were investigated by 1H-NMR OC(O)Cl, and studied for their thermal behaviour. The silanes spectroscopy. The transition state of the rearrangement was A undergo a thermally induced rearrangement to give the investigated by an ab initio study based on the model comcorresponding silanes R\(^1\)R\(^2\)Si(OR\(^3\))Me (B). For compounds with pound H\(_3\)SiCH\(_2\)OC(O)H (-> MeH\(_2\)SiOC(O)H]. The theoretical OR3 = OC(O)Cl, an additional decarboxylation takes place to data and the experimentally obtained energetic and kinetic yield the chlorosilanes R1R2Si(Cl)Me. Except for the deriva- data are discussed in terms of mechanistic aspects of the retives with OR\(^3\) = OC(O)Cl, the energetic (reaction enthalpy) arrangement reaction A -> B. and kinetic data (reaction order, frequency factor, enthalpy ...
KW  - Anorganische Chemie
Y1  - 1992
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-64188
ER  -