Synthesis of the ABC-ring models of goniodomin A: preference for the unnatural configuration at C11 of the BC-ring in a non-macrocyclic model system

Abstract

To confirm the natural relative stereochemistry of the ABC-ring of goniodomin A ( 1), the corresponding three stereoisomeric compounds, (2 R,5 S,6 S,7 S,9 S,11 R,15 S)-, (2 R,5 S,6 S,7 R,9 R,11 S,15 R)-, and (2 R,5 S,6 S,7 R,9 R,11 R,15 S)-isomers ( 2, 3, and 5, respectively), were stereoselectively synthesized using a Nozaki–Hiyama–Kishi reaction as a key step. It was also found that a (2 R,5 S,6 S,7 R,9 R,11 S,15 S)-isomer ( 4), corresponding to the absolute configuration of 1 recently proposed by Sasaki, was not detected during the formation of 5 from a common ketodiol substrate under acid-catalyzed spiroacetalization conditions. This would be attributable to the absence of a macrocyclic framework.