Deplancheine

Further elaboration of 152 resulted in the synthesis of (derived from the reduction of pyridinium salt 150b with excess of LiAlFt4 in THE Acid-catalyzed cyclization of 154 led to indoloquino-lizidine 155 (25% yield from 150b), a precursor of deplancheine (80TL2341) (Scheme 5). 

Deplancheine (7) was isolated first from the stem and bark of Alstonia deplanchei van Heurck and Muell. Arg. by Husson et al. (14). The structure of this novel type of alkaloid has been established from spectral evidence the trans annellation of rings C and D is supported by the presence of characteristic Bohlmann bands in the IR spectrum and also by the chemical shift of the C-3 proton below 3.7 ppm. The ethylidene side chain was also indicated by the H-NMR spectrum [8 1.52 (3H, d, J =6 Hz), 5.30 (1H, q, J = 6 Hz)] and its E configuration was confirmed by regio- and stereospecific total synthesis (14). 10-Methoxydeplancheine (8) has been found in the leaves of Alstonia lanceolifera... 

Interestingly enough, racemic deplancheine (7) had been synthesized 6 years before the isolation of the alkaloid from the stem bark of Alstonia deplanchei van Heurck and Mull. Arg. (14). Winterfeldt and co-workers (112) treated enamine... 

After its isolation, the structure of alkaloid deplancheine (7) was unambiguously proved by several total syntheses. In one of the first approaches (14), 1,4-dihydropyridine derivative 161, obtained by sodium dithionite reduction of A-[2-(indol-3-yl)ethyl]pyridinium salt 160, was cyclized in acidic medium to yield quinolizidine derivative 162. Upon refluxing 162 with hydrochloric acid, hydrolysis and decarboxylation took place. In the final step of the synthesis, the conjugated iminium salt 163 was selectively reduced to racemic deplancheine. 

Deplancheine has also been achieved (175) from the easily available pyridinium salt 164, utilizing a Wittig reaction to establish the desired ethylidene side chain at C-20. 

Ketone 166, the key intermediate of deplancheine was obtained in 63% overall yield by the reaction of harmalane (150) with l-bromo-2,3-epoxypropane, followed by sodium borohydride reduction and Moffat oxidation (116). Methods for the elaboration of the exocyclic, -configurated double bond are reviewed (117). 

An alternative total synthesis of ( )-deplancheine, applying stereocontrolled formation of the exocyclic double bond, has also been reported (118). The final ring closure was reached in this case by an acid-catalyzed iminium ion-vinylsi-lane cyclization (170—>7). 

A short synthesis of ( )-deplancheine has been reported by Hameila and Lounasmaa (119) by lithium aluminum hydride reduction of 3-acetylin-dolo[2,3-a]quinolizine derivative 171. 

Two new approaches to achieve ( )-deplancheine have been developed by... 

In the other approach, again harmalane (150) was treated with methyl 2-(di-ethylphosphono)acrylate (174), resulting in iminophosphonate 175. By its sodium borohydride reduction and subsequent lactonization, the amidophospho-nate 176 has been obtained, Wittig-Homer reaction of 176 with acetaldehyde followed by selective reduction of the carbonyl group of the enamide function supplied ( )-deplancheine in good yield (116). 

Recently, a multistep synthesis of ( )-deplancheine was developed by Rosen-mund and Casutt (120), starting from tryptamine and coumalic ester. In the key step of this approach, 1,4-addition of hydrogen to diene 179 was achieved with full stereoselectivity by means of hydrogen in the presence of toluenetricarbonyl-chromium catalyst. 

A highly stereoselective synthesis of ( )-deplancheine has been developed (121), utilizing a photocyclization process for the preparation of enelactam 181, which was reduced by zinc in acetic acid to lactam 182. In the latter, the double bond was shifted to the 19,20 position stereoselectively with an E geometry by the use of nonacarbonyldiiron catalyst to supply 159, previously synthesized and transformed to ( )-7 by Winterfeldt et al. (112). 

Although the reaction of dihydropyridinium ions produced by the electrophilic attack of dihydropyridines has promise in organic synthesis, this reaction has not been extensively exploited. Some examples of their potential are provided by the acid-catalyzed reactions with indoles (80TL2341). An application of this reaction for an efficient synthesis of ( )-deplancheine is shown in Scheme 25. An interesting feature of this reaction was the use of the alkoxy-substituted dihydropyridine as a carbonyl precursor. 

In an extension of this work, unnatural (—)-(S)-deplancheine was synthesized from 3. Thus, the configuration of the natural product was corrected to R 6. 

Iminium ion-vinylsUane cyclization. This reaction can be used to control the configuration of exocyclic double bonds /i to the nitrogen function of alkaloids. Thus, reaction of the (Z)- and (E)-vinylsilanes 1 and 2 with paraformaldehyde (excess) and tf-camphor-10-sulfonic acid proceeds with >98% retention of configuration to give 3 and 4, respectively. The latter product is identical with the natural indoloquinolizidine alkaloid deplancheine. ... 

Deoxyribonolactone, 333 Deoxy sugars, 550 Deplancheine, 240, 241 Desamylhistrionicotoxin, 272 Desepoxy-4,5-didehydromethylenomycin, 4 Desilylbrominalion, 75... 

Deplancheine (82), from the stem bark of Alstonia deplanchei van Heurck et Miill.-Arg., is an indoloquinolizidine alkaloid of a novel type in which the three-carbon unit that is normally attached to C-15 is missing.620 The structure (82) was deduced from its spectroscopic properties, and has been confirmed by two independent syntheses (Scheme 10).62° 6 It is of some interest that racemic (82) had been prepared,62c and its configuration established, some six years before its isolation from natural sources. 

This reduetion is useful for stereoselective preparation of exocyclic alkenes. Thus the alkaloid deplancheine (2) is obtained in essentially quantitative yield by hydrogenation of the diene 1 catalyzed by (toluenelCrfCO),. ... 

The synthesis of the indoloquinolizadine alkaloid deplancheine (52 Scheme 24), using an exocyclic variant of an iminium ion initiated vinylsilane cyclization, has been reported by Malone and Ovemuui. Thus, treatment of vinylsilane (51) with formaldehyde resulted in the generation of an intermediate im-... 

The asymmetric alkylation of the p-carboline formamidine was also used in the asymmetric synthesis of deplancheine in 96% ee (Scheme 31), a synthesis which served to correct the previously assigned absolute configuration of the natural product. ... 

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