The First Total Synthesis of Amphorogynine

Although two syntheses of amphorogynine A (of 17 and 21 steps with 3% and 5% overall yields) [81,82] and one synthesis of amphorogynine D [83] have been reported, the preparation of amphorogynine C was not described up to our work [28]. 

FIGURE 14.5 Examples of peptide-carbohydrate hybrids synthesized in our group. 

FIGURE 14.6 Strategy for the use of the sequential intramolecular azide-aUcene cycloaddi-tion/nitrogen extrusion/unine-enamine isomerization/nucleophilic addition. 

FIGURE 14.8 Structures of the pyrrolizidine alkaloids isolated from Amphowgyne spicata. 

With a convenient route to azide-alkene 17 in hand, we tested the key intramolecular 1,3-cycloaddition/nitrogen extrusion to obtain the fused pyrano[4,3-fc]pyrrole 16, which was attained along with the expected tricyclic aziridine 18, as a minor product. The experiments were realized by heating a solution of 17 in either a polar solvent [dimethylformamide (DMF)] or an apolar solvent (toluene) in both sealed tubes (at 140°C for both solvents) or under microwave radiation (at 140°C in DMF and at 120°C in toluene). In the four experiments, the ratio between the pyrroline and the aziridine is approximately the same (4.3 1), which indicates that the observed ratio 

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