Total Synthesis of (–)-Flueggine A and (+)-Virosaine B

Key words

dipolar cycloaddition - relay ring-closing metathesis - [1,3]-sigmatropic rearrangement - Meisenheimer rearrangement

Significance

Securinega alkaloids have been used for a long time in traditional Chinese medicine. Two recently isolated members of this family, (–)-flueggine A and (+)-virosaine B, have now been synthesized for the first time. The concise route to access the two natural products involves a [1,3]-dipolar cycloaddition. The precursors for this key step are synthesized by a sequence including a relay ring-closing metathesis followed by a Meisenheimer rearrangement.

Comment

The route starts with the synthesis of the two natural products (–)-norsecurinine (E) and (+)-allonorsecurinine (F) by a relay ring-closing metathesis, whereby the order of ring-closing events can be carefully controlled. The route then follows a previously described strategy (Tetrahedron 1993, 49, 8059) to access the two O-alkylhydroxylamines H and K. Finally, heterodimeric (–)-flueggine A is accessed by allowing nitrone I to react with E, whereas (+)-virosaine B results from an intramolecular cycloadditon of nitrone L.