Acid-Catalyzed Aza-Diels−Alder Reactions for the Total Synthesis of (±)-Lapatin B

Abstract

A 5-step total synthesis of microfungal alkaloid (+/-)-lapatin B has been accomplished via a key 2-aza-Diels-Alder reaction. Brønsted acids catalyze the cycloaddition step and provide improved exo selectivity. This synthetic route has been applied to the construction of related spiro-quinazoline structures.

Simple indole alkaloids and those with a nonrearranged monoterpenoid unit

“…The exo adduct 290b was transformed to 284 (Scheme 51). 105 A total synthesis of unnatural (À)-serantrypinone (292) from L-tryptophan has been reported. The key step involved the transformation of selenoxide 293 to acetate 294 via trapping of a presumed intermediate in a seleno-Pummerer reaction.…”

Control of Hetero-Diels-Alder Stereoselectivity through Solvent Polarity and Brønsted or Lewis Acid Catalysis; Theory and Experiment

“…In an earlier communication, 5 we reported the synthesis of (±)-lapatin B by implementing Kende's elegant approach to the synthesis of (±)-alantrypinone. 3 Lapatin B and alantrypinone arise from an exo orientation of dienophile 6 in the Diels-Alder cycloaddition with dienes 4 and 5, respectively (Scheme 1).…”

The spiroquinazoline family of alkaloids: a review

“…37,38 The first synthesis, from the Syntenta group in Switzerland, followed the Kende approach to alantrypinone and gave racemic material. The second synthesis followed the aforementioned routes to ent-alantrypinone and ent-serantrypinone and confirmed that the absolute configuration of lapatin B 9 is pseudoenantiomeric with alantrypinone 7 and serantrypinone 8.…”