The illustrated azomethine ylide, produced through a Schiff base condensation of the corresponding aldehyde-containing C3a-arylhexahydroindole with ethyl l-leucinate, engages in a stereoselective intramolecular cycloaddition reaction to give adduct 23 that has been elaborated, over eight steps, into the racemic modification of the alkaloid derivative gracilamine (1). The formation of this ylide and its conversion into isomer 23 mimics the proposed biogenesis of the pentacyclic framework of compound 1.

A total synthesis of the racemic modification, (±)-2, of the tazettine-type alkaloid 3-O-demethylmacronine is described. The key steps are an intramolecular Alder-ene (IMAE) reaction and a lactam-to-lactone rearrangement of tetracycle 13, a compound that embodies the haemanthidine alkaloid framework.

The total syntheses of a wide range of terrestrially derived alkaloids, especially ones isolated from members of the Amaryllidaceae family, are described. Two recurring themes associated with these syntheses are the use of two types of building blocks, namely ring-fused cyclopropanes, especially geminally-dihalogenated ones, and enzymatically derived cis-1,2-dihydrocatechols. These have often served as precursors to 2- or 3-halogenated 2-cyclohexen-1-ols that are themselves engaged in cross-coupling reactions, radical addition-elimination processes and/or Claisen- or Overman-type rearrangements so as to construct the highly functionalized six-membered rings associated with the target alkaloids.

The application of the title building blocks, the 6,6-dibromobicyclo[3.1.0]hexanes and the cis-1,2-dihydrocatechols, to the total synthesis of crinine and lycorinine alkaloids is described.

Review: 43 refs.