Concise Total Synthesis of (+)-Lanceolactone A: Revision of Absolute Stereochemistry

J Org Chem. 2022 Oct 7;87(19):12867-12876. doi: 10.1021/acs.joc.2c01450. Epub 2022 Sep 28.

Abstract

A chiral-pool protecting-group-free five-step total synthesis of tetranorsesquiterpenoide (+)-lanceolactone A and all of its four stereoisomers using (S)-(+)-, and (R)-(-)-linalool (coriandrol) as building blocks is disclosed. The key steps involved in this synthetic route are regioselective ozonolysis, Au(I)-catalyzed cycloisomerization-induced construction of furan from alleneone, and dye-sensitized photo-oxidation (through 1O2; singlet oxygen) of hydroxyalkyl-tethered furan to access oxaspirolactone. After a thorough evaluation of electronic circular dichroism (ECD) and optical rotation data of all possible stereoisomers, the absolute configuration of natural lanceolactone A at the C4 and C7 positions has been assigned as (+)-(4S,7S), which is an enantiomer to the initially proposed structure (+)-(4R,7R). Further, these investigations led us to extend Feringa and Gawronski's CD correlation method to [5,5]- and [6,5]-oxaspirolactones.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Circular Dichroism
  • Furans
  • Ozone*
  • Singlet Oxygen*
  • Stereoisomerism

Substances

  • Furans
  • Singlet Oxygen
  • Ozone