Identification of an unexpected 2-oxonia[3,3]sigmatropic rearrangement/aldol pathway in the formation of oxacyclic rings. Total synthesis of (+)-aspergillin PZ

This paper reports the first unambiguous evidence that the cascade synthesis of tetrahydrofuran-containing oxacyclic molecules depicted in can take place by a 2-oxonia[3,3]sigmatropic/aldol mechanism rather than by a Prins cyclization/pinacol rearrangement sequence. The 8-oxabicyclo[3.2.1]octyl aldehyde products of this reaction, 20 and 29, were employed to complete the first total synthesis of the structurally remarkable isoindolone alkaloid (+)-aspergillin PZ (1). The lack of activity seen in two tumor cell lines for synthetic (+)-aspergillin PZ calls into question the suggestion that aspergillin PZ, like many aspochalasin diterpenes, might exhibit useful antitumor properties.