Reaktionen an Indolderivaten, LIII. Enantioselektive Totalsynthese von (+)‐Geissoschizin und (−)‐Geissoschizol

Abstract

uber einen diastereoselektiven Schlusselschrilt mit optisch aktiven vinylogen Urethanen werden enantiomerenreine exo-Ethyliden-lactame 2 gewonnen, aus denen Geissoschizin (3)und Geissoschizol (4) unter Nutzung bekannter Syntheseschritte hervorgehen. Reactions with Indole Derivatives, LIII I). -Enantioselective Total Synthesis of (+)-Geissoschizine and (-)-GeissoschizolEnantiomerically pure exo-ethylidenelactams 2 are obtained via a diastereoselective key reaction using optically active vinylogous urethanes and arc transformed into geissoschizine as well as geissoschizol in a well-established synthetic scqucnce.Vor einigen Jahren zeigten wir, daB die fur die Totalsynthese von CorynantheAlkaloiden auBerst nutzliche Methylen-Lactam-Umlagerung bei 12b,2-truns-konfigurierten Verbindungen wie 1 wegen geringerer sterischer Hinderung mit hoherer Effzienz und unter milderen Bedingungen durchgefuhrt werden kann als an den Stereoisomeren mit cis-standigen Wasserstoffatomen an diesen beiden Zentren ''.Dariiber hinaus bildet sich bei kinetisch kontrollierter Reaktion -unabhangig von der Konfiguration der Carboxygruppe (Aquilibrierung im gemischten Anhydrid) -die thermodynamisch instabile Z-Konfiguration der exocyclischen Doppelbindung (s. 2). Verursacht wird diese Selektivitat, wie wir friiher schon festgestellt haben 'I, durch sterische Kompression zwischen der Methylgruppe an der Doppelbindung und der Essigester-Seitenkette im zum E-lsomeren fuhrenden Ubergangszustand. Da die in 1 und 2 angegebene 12b,2-anti-Konfiguration der sp3-hybridisierten Zentren in der Reihe der lndolochinolizidine ebenfalls die thermodynamisch instabilere Konfiguration reprasenticrt, besteht die giinstige Gelegenheit, im kinetisch kontrollierten Reaktionsakt das thermodynamisch instabilste Stereoisomere einer groaen Naturstoflklasse zu generieren. Aus diesem sollten alle anderen Stereoisomeren durch Epimerisierungsreaktionen erreichbar sein, so daD die gesamte Hierarchie der stereoisomeren Corynunthe-Alkaloide auf diese Weise zuganglich wird, inklusive derjenigen mit der in der Natur relativ seltenen 8 VCH Verlagsgesellschaft mbH, D

Synthesais of Corynanthe Alkaloids Corynantheine, Hirsuteine, and the Isositsirkines

“…I . Furthermore, comparison of the spectrum of 6 with that of I shows that signals due to 17-methylene protons in 6 having 1 6~* configuration appeared at higher field than those in I having 16~*-configuration while signals due to the ester methyl group in I appeared at higher field than that in 6 bath due to the anisotropic effect of the ethylidene group at C-20. These spectral data suggest that these four compounds exist in the conformation with an axially oriented 15-substituent group and an anti relationship between 15and 16-hydrogens as shown in Figure 2.…”

“…6. He probably was right with his suspicion that failure of this reaction may be due to thc formation of the corresponding mcthyl kctone instead of the en01 cther, at least when we, using 38 geissoschizine ( 4 1 ) as a model system, trcated this aldehyde with diazomethane in methylerle dichloride nonc of the corresponding en01 cther was Cormed, but the main reaction product (51%) turned out to be a mixture of the epimcric B k e t o ester 56 which is very probably formed by nucleophilic attack to aldehyde and subsequent hydride shift.…”

“…The Crystal Structure of ii[1][2][3][4][5][6] L'ext, total synthesis of isositsirikines 4 and 5 with 3 0 -H : I 5 1 corrfiguration was accomplished by aliplying the known inversion reaction from 6 to a of the configuration at C-3 in the lactam 1 4 6 (Scheme 1 6 ) . Thus.…”

“…0.5 Hz,[2][3][4][5][6] 7.23 (3H, and 5 5.11 (lH,, 4.85 (1H, br dd, J=10.3, 4.5 Hz, 3-HI, 4.21 ( I H , qd, J=7, 3.5 Hz, 19-H), 2.80 (lH, m , 15-H), 2.43 (lH, br t, 5.3.5 Hz, 20-HI, 2.30 -i3H, m , 16-HZ and 14-Heq), 1.99 (lH, ddd, 5=13.9, 10.3, 4.5 Hz, 14-Hax), 1.17 (3H. Calcd C.,HneNzOs: C , 72.60: H , 7.42:N. 7.37.…”

Development of New Synthetic Reactions for Nitrogen-Containing Compounds and Their Application

“…113) Thus we provided all four stereoisomers of the intermediates total synthesis of eight possible stereoisomers of isositsirikines via the route involving transformations of the functional group, selective reduction of the lactam carbonyl group, introduction of the formyl group, and NaBH 4 reduction. Among them, isositsirikine, 16-epi-isositsirikine, (16R)-19-20-(Z)-isositsirikine, and 16-epi-(Z)-isositsirikine, were identical to the respective natural products but the final products derived from 3,15-anti-19E 125 were not identical to natural rhazimanine and bhimberine, and thus the structural elucidation requires reinvestigation.…”