ABSTRACT
[structures: see text] The total syntheses of the amaryllidaceae alkaloids haemanthidine, pretazettine, and tazettine as optically pure enantiomers are reported. Using D-mannose as the starting material, the critical relative stereochemical relationships are established with an intramolecular nitrone-alkene cycloaddition reaction. The synthetic route leads successively to (-)-haemanthidine and then to (+)-pretazettine and (+)-tazettine, taking advantage of the well-established complex relationships among these three alkaloids.
Subject(s)
Alkaloids/chemical synthesis , Amaryllidaceae Alkaloids , Antineoplastic Agents, Phytogenic/chemical synthesis , Phenanthridines , Plant Extracts/chemical synthesis , StereoisomerismABSTRACT
The tetrachlorophthaloyl (TCP) group can be utilized when imidic protection of an amine is desired and durability of the protecting group to conditions ranging from mildly basic to harshly acidic is required. Installation can be accomplished in two steps by treating the free base with the commercially available TCP anhydride, and then closing the imidic ring with acetic anhydride and pyridine. Cleavage is effected by 2-4 eq of ethylenediamine under very mild conditions under which esters and glycopeptides have been shown to be stable, and racemization of amino acid residues does not occur. Unsubstituted phthalimides, even within the same molecule, are also unaffected during TCP cleavage. TCP protecting groups serve as beta-directors on donors and can also be present on acceptor species during electrophilic couplings in oligosaccharide synthesis.
