iso-epoxy-amphidinolide N Pt. I
Two papers in OBC this week from the Nicolaou labs, concerning the synthesis of the related structures iso-epoxy-amphidinolide N and des-epoxy-caribenolide I. In another two part discussion, we’ll consider their initial strategy, and a further, more successful attempt.
Their initial synthesis relied upon a late-stage epoxidation, as the allylic epoxide was deemed too sensitive to survive even a standard deprotection. Thus, taking that back to the exocyclic alkene, they were left with a possible enyne metathesis – either ring-closing or in a acyclic cross-metathesis fashion. The other obvious disconnection is the ester, which, again, could be ring-closing in a yamaguichi sense.
Disconnection of the pyran moiety to a masked 1,3-dihydroxyketone was then proposed, used technology developed by Enders:
They then tried to couple this advanced fragment in a cross-metathesis, but were unable to perform this as either an alkene or enyne metathesis. Thus, they performed the esterifcation mentioned above, and then attempted an enyne RCM, which, unfortunately, again failed.
A second synthesis, aiming at inserting this diene moiety via a either a Sonagashira or Stille coupling also failed. However, much was learnt in these routes, and a synthesis of the related iso-epoxy-amphidinolide N was successful, and will be discussed tomorrow.