Deplancheines, synthesis

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... 

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. 

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. 

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. 

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. ... 

An imine-enamine annulation has been used in the synthesis of the indoloquinolizidine alkaloid ( )-deplancheine.52 The annulation of dialkyl (1-alkoxycarbonyl)vinylphosphonates via a Horner-Wadsworth-Emmons reaction has been developed in the synthesis of [3.3.0] fused pyrazolid-inones from monocyclic pyrazolidinones. - Treannent of diethyl l-(ethoxycarbonyl)vinylphos-phonate in excess (2 eq) with imide anions such as phthalimide, maleimide, and succinimide successfully produces the corresponding six-membered fused heterocycles. Similarly, synthesis of functionalized cyclohexenylphosphonates is achieved by condensation of diethyl l-(ethoxycar-bonyl)vinylphosphonate (2 eq) with cyclopentanone enolates (Scheme 8.29). - ... 

Allin, S.M., Thomas, C.I., Doyle, K. and Elsegood, M.R.J. (2005) An asymmetric synthesis of both enantiomers of the indole alkaloid deplancheine. The Journal of Organic Chemistry, 70, 357-359. 

Deplancheine As illustrated in Scheme 12.95, the synthesis of deplancheine 373 began with an identical approach as tangutorine, with the divergent point being reaction of the free amine with 4-methoxy-3-buten-2-one 376. 

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