Ester Zulaica

Total Synthesis of the Bridged Indole Alkaloid Apparicine

An indole-templated ring-closing metathesis or a 2-indolylacyl radical cyclization constitute the central steps of two alternative approaches developed to assemble the tricyclic ABC substructure of the indole alkaloid apparicine. From this key intermediate, an intramolecular vinyl halide Heck reaction accomplished the closure of the strained 1-azabicyclo[4.2.2]decane framework of the alkaloid with concomitant incorporation of the exocyclic alkylidene substituents.

A straightforward synthetic entry to cleavamine-type indole alkaloids by a ring-closing metathesis-vinyl halide Heck cyclization strategy.

An indole-templated ring-closing metathesis has been used to create the central nine-membered ring of the cleavamine-type alkaloids. A subsequent intramolecular vinyl halide Heck reaction upon the resulting azacyclononene ring completes the assembly of the strained 1-azabicyclo[6.3.1]dodecane framework of the alkaloids. The usefulness of the approach is illustrated with the synthesis of (±)-cleavamine and (±)-dihydrocleavamine.

Studies on the synthesis of akuammiline-type alkaloids. Construction of the hexahydro-1,5-methanoazocino[3,4-b)indole fragment

Abstract A three step route to the title tetracyclic substructure of akuammiline-type alkaloids consisting in the nucleophilic addition of an ester α-anion to an N -alkylpyridinium salt, acid-induced cyclization of the resultant 1,4-dihydropyridine, and stereoselective elaboration of the ethylidene substituent is reported.

Studies on the synthesis of akuammiline alkaloids. Access to 3,4-secoakuammilan derivatives

Abstract Cleavage of the C-3/N-4 bond of tetracycles 1 and 6 with chloroformates or acyl chlorides, followed by reduction, led to tetrahydrocarbazoles 4a,b and 8b-d, from which dithioacetal 12 and sulfoxides 5a,b, 11, and 17 were prepared. Whereas attempts to construct the quaternary C-7 centre of akuammiline alkaloids either by DMTSF-promoted cyclization of 12 or by Pummerer cyclization of sulfoxides 5a,b and 11 resulted in failure, sulfoxide 17 underwent cyclization on the indole 3-position to give the tetracyclic 3,4-secoakuammilan-type derivative 18.

Construction of the pentacyclic ring system of apogeissoschizine

Abstract The synthesis of pentacyclic apogeissoschizine-type compounds is reported. It involves the construction of the seven-membered E ring by addition of the enolate derived from methyl 1-indolepropionate to the γ-position of a pyridinium salt, with subsequent acid-promoted cyclization of the resulting 1,4-dihydropyridine, and the closure of the C ring by cyclization on the indole 3-position in the last synthetic step.

Total synthesis of the indole alkaloids ngouniensine and epingouniensine

Abstract The first total synthesis of ngouniensine and epingouniensine, by cyclization of a suitable 1-(3-indolylethyl)piperidine-2-carboxylic acid followed by the elaboration of the exocyclic methylene group, is reported.

Total synthesis and stereochemical reassignment of the indole alkaloid vinoxine

Abstract The first total synthesis of the indole alkaloid vinoxine and the reassignment of the relative configuration at carbon-16 in this alkaloid is reported.

A synthetic entry to 3,5-disubstituted pyridines

Abstract A straightforward entry to 3,5-disubstituted pyridines from 3-substituted pyridines, based on the acylation of N -alkyl-1,4-dihydropyridine derivatives followed by a tandem N -dealkylation–oxidation sequence is reported.

Nucleophilic addition to chiral pyridinium salts: stereoselective synthesis of (−)-Na-methylervitsine

Abstract Chiral non-racemic 4-substituted 3,5-diacyl-1,4-dihydropyridines 8 are prepared by the regio- and diastereoselective addition of organocopper reagents to chiral pyridinium salt 2 , followed by acylation with trichloroacetic anhydride and subsequent haloform reaction. Additionally, (−)- N a -methylervitsine is synthesized by reaction of the enolate derived from 2-acetylindole 9 with pyridinium salt 2 , followed by electrophile (Me 2 N + CH 2 I − )-induced cyclization and subsequent elaboration of the 16-methylene and (20 E )-ethylidene substituents.

Addition of chiral enolates to N-alkyl-3-acylpyridinium salts. Total synthesis of (+)-16-epivinoxine and (−)-vinoxine

Abstract Chiral enolates of indolylacetyl derivatives 6a–f undergo addition to pyridinium salt 7 with complete trans-selectivity and varied diastereofacial selectivities to give, after acid-induced cyclization of the intermediate 1,4-dihydropyridines, the vinoxine-related tetracycles 8a–f. Starting from (S)-prolinol indolylacetamide 6e, subsequent elaboration of the ethylidene substituent from tetracycle 8e and removal of the chiral auxiliary has resulted in a straightforward synthesis of (+)-16-epivinoxine and (−)-vinoxine.