Synthetische Arbeiten in der Reihe der aromatischen Erythrina‐Alkaloide, XI Anwendungen der Glyoxylester‐Synthese

Abstract

Zum Aufbau neuer Erythrinane wird die Glyoxylester-Synthese auf C-4-substituierte Cyclohexanone ubertragen. Der RingschluD der Enamin-Vorstufen 1 b, c und d fuhrt glatt zu den Erythrinan-Derivaten 2b, c und d, waihrend die Vorstufe 33 zum Isatin-Derivat 37 aromatisiert und dehydriert wird. Im Mittelpunkt der Arbeit steht der cyclische Ather 10 mit fixierter cis-Verkniipfung des Ringsystems. Seine Aufspaltungsprodukte 12a und 13a, dcren Struktur durch Hilfssynthesen bewiesen wurde, ermoglichten die Losung des gesamten Stereoproblems der gesattigten Erythrinane. Die Enamin-Vorstufen liefern mit Siuren ticffarbige Kationen, deren Chromophor dem des Bisnor-hexahydrocurarins ahnelt. Syntheses of Aromatic Erythrina Alkaloids, XI Applications of the Glyoxylic Ester SynthesisThe glyoxylic ester synthesis of erythrinanes has been further developed and transferred to C-4-substituted cyclohexdnones. Cyclisation of the precursors 1 b, c and d, stabilized by enamine formation, leads smoothly to the erythrinane derivatives 2b, c and d, whereas 33 yields the isatin 37 by aromatisation and dehydrogenation. The key compound is thecyclic ether 10 with fixed cis-arrangement of the ring system. Its cleveage products 12a and 13a, the structures of which have been proved by independent syntheses, were used to solve all stereoche-mica1 problems of the saturated erythrinanes. The enamine type precursors react with acids to yield deeply coloured cations, the chromophore of which is very similar to that of bisnor-hcxahydrocurarine.Die im Jahre 1958 entdeckte Glyoxylester-Synthese zum Aufbau von Erythrinanen mit funktionellen Gruppen im Fiinfring hat sich vorzuglich bewahrt 2). Ihr weiterer Ausbau hat in den folgenden Jahren die gesamte Entwicklung auf dem Arbeitsgebiet entscheidend beeinflu&. Bei der grundlegenden Reaktion wird Cyclohexanon-2glyoxylester mit Homoveratrylamin zur Enamin-Vorstufe 1 a kondensiert und diese rnit verdiinnter Phosphorsaure m m Keto/Enol-lactam 2a cyclisiert ; beide Stufen verlaufen mit hohen Ausbeuten.

Domino reactions of rhodium(ii) carbenoids for alkaloid synthesis

“…When the cycloadducts were exposed to BF 3 ÁOEt 2 in CH 2 Cl 2 at 0 1C, the cyclized product 24 was isolated as a single diastereomer (Scheme 7). The cis stereochemistry of the A/B ring junction was assigned by analogy to similar erythrinane products obtained via a Mondon-enamide type cyclization 12 and was unequivocally verified by X-ray crystal analysis of the final product. The anti stereochemical relationship is still maintained between the hydroxyl stereocenter (from the oxygen bridge) and the bridgehead proton (R 2 = H) or methyl (R 2 = CH 3 ) group.…”

The domino cycloaddition/N-acyliminium ion cyclization cascade

“…18,19 Indeed, cyclization of the aromatic ring onto the N-acyliminium ion center readily occurred from the axial position. 20 The rearranged product 9 was then converted into the key intermediate previously used by Stork for the synthesis of (±)-lycopodine 11. 18 Application of the domino cyclization/cycloaddition sequence to the pentacyclic skeleton of the aspidosperma ring system Prompted by our work dealing with the internal [4 + 2]-cycloaddition reaction of mesoionic oxazolium ylides, 10 we became interested in the rhodium(ii)-catalyzed reactions of diazo ketoamides such as 12.…”

Use of nitrogen and oxygen dipole ylides for alkaloid synthesis

“…[61][62][63] Indeed, cyclization of the aromatic ring onto the N-acyliminium ion center readily occurred from the axial position. [64][65][66] The rearranged product 127 was then converted into the key intermediate 128 previously used by Stork for the synthesis of (±)-lycopodine 129. 61,62 Scheme 25…”