On the construction of the C/D ring systems of chasmanine and napelline by diene addition

Abstract

. Can. J. Chem. 56, 1102 (1978). The construction of the C / D ring system of the alkaloids chasmanine and napelline by modification and rearrangement of a common intermediate is explored o n model compounds.The phenolic acid 9 was oxidized to the spirolactone 10. Addition of benzyl vinyl ether to this material gave the adduct 28 in high yield. This central 'nordenudatine' type intermediate was then modified (in a very few stereospecific steps) to the 'napelline' model compound 47 and to the keto acetal38. Con~pound 38 is an intermediate of our photochemical route and we have already described its conversion to a chasmanine model derivative.The new syntheses of chasmanine and napelline foreshadowed by the present niodel studies are expected to be completely stereo-and regiospecific, alniost 10 steps shorter and a n order of magnitude more efficient than the total syntheses of these two alkaloids which we have reported in the recent past.Incidentally, with these ~ilodel studies, the methoxy ketone 20 was prepared. The methoxyl in this compound is epinieric to the corresponding (C16) niethoxyl of the aconite alkaloids. Some relevant observations on the nmr spectra and allylic rearrangement (pyro-isopyro rearrangement) of this material are also reported. On etudie, sur des composts modeles, la possibilitt de construire les systtmes des cycles C/D des alcaloides chasmanine et napelline par une modification et une transposition d'un intermtdiaire commun.On a oxydt I'acide phenolique 9 en spirolactone 10. L'addition d'ether benzylvinylique ce compose conduit a I'adduit 28 avec un bon rendenlent. On a alors modifit cet intermediaire central de type "nordenudatine" (a I'aide de quelques etapes tres stertospCcifiques) pour conduire au conipose niodele 47 "napelline" et au ceto-acktal 38. Le conipose 38 est u n intermediaire dans notre voie photochimique et nous avons deja decrit sa transformation en un dtrivt modele de chasmanine.On prevoit que les nouvelles syntheses de la chasmanine et de la napelline preconistes par les presentes etudes modeles seront conipletement stereo-et regiospecifique, qu'elles comporteront dix etapes de nioins et seront au noi ins 10 fois plus efficaces que les syntheses totales de ces deux alcaloi'des qui ont ete rapportis recemment.Incidemment, avec ces etudes modeles, on a prepare la methoxy cetone 20. Le groupe nlethoxy de ce compose est en position epimtre par rapport au groupement methoxy correspondant (C16) des alcaloi'des de I'aconite. On rapporte aussi quelques observations appropriees concernant les spectres rlnn et la transposition allylique (transposition pyro-isopyro) de ce conipost.[Traduit par le journal] Introduction We have shown (1) that a route proceeding via denudatine-type intermediates is very advantageous for the construction of polysubstituted C19 aconite alkaloids and very recently we have successfully completed a stereospecific total synthesis of the alkaloid chasmanine I using such a route (2). In this synthesis the denudatine-type intermediate 11 was constructed by a...

Total synthesis of delphinine-type alkaloids by simple, fourth generation methods

“…This intention was well supported by preliminary studies which as usual were conducted on a model benzobicyclopentene system (12). The phenol (39) was alkylated with methyl bromoacetate in dry acetone in the presence of-potassium carbonate and 18-crown-6 ether.…”

“…Pyrolytic elimination of methanol from the dimethylacetal in refluxing o-xylene completed the preparation of the enol ether (11). Brought to you by | New York University Bobst Library Technical Services Authenticated Download Date | 6/13/15 11:11 AM Compound (11) was now carboxylated in tetrahydrofuran at -70°C with n-butyl lithium an~carbon dioxide gas; hydrolysis of the enol ether group on work up gave the crystalline keto acid (12). The keto group of (12) was reduced with sodium borohydride and the product (13) was heated underreflux with phosphoric acid in dioxane.…”

“…The product (40) was obtained in a yield of 90% and it was quantitatively hydrolyzed with hydrochloric acid in tetrahydrofuran to the phenolic acid (41). Oxidation of this material with N-bromosuccinimide (11,12) in-methylene Chloride and aqueous sodium acetate in a two-phase system yielded a crude spirolactone, presumably (42) but actually a mixture of (42) and (43), which was isolated and immediately allowed to react with an excess of~enzyl vinyl ether at room temperature for 24 hours.…”

(+)-Podocarpic Acid as Chiral Template in the Synthesis of Aphidicolane, Stemodane and Stemarane Diterpenoids †

“…This choice would permit adoption of (+)-podocarpic acid (4) as starting material. [24][25][26]. The end of this fruitful and exciting experience coincided with the disclosure of the first two syntheses of (±)-aphidicolin (1) [7,8].…”

“…Between 1976 and 1978 one of us (RMB) had been involved, as a member of the Wiesner group at the University of New Brunswick (Fredericton, NB, Canada), in the synthesis of some diterpene alkaloids whose C/D ring system, constituted by a bicyclo [ [24][25][26]. The end of this fruitful and exciting experience coincided with the disclosure of the first two syntheses of (±)-aphidicolin (1) [7,8].…”