Heterocyclic Mechanisms – Isopyrodysinoic acid

Every Thursday morning at Sydney we have a problem session attended by all organic chemistry staff, PhD and Honours students. Part of these sessions always involves running through mechanisms and syntheses on our perpetually spotless blackboards. This is a useful exercise, and usually the simplest questions bring up the most interesting points for discussion.

Recently, one of our graduate students, Kaitlin, challenged the other teams to devise a synthesis of a recently-isolated natural product isopyrodysinoic acid. (One of the reasons Kaitlin chose a “new” molecule is that the question circumvents the repetition of a literature answer. Incredibly “isopyrodysinoic” is a one-word Googlewhack, or at least it was until this post.)

Isopyrodysinoic acid synthesis and mechanism

Another of our students, Fargol, wrote up a synthesis on the board for about an hour, and towards the end got to a molecule containing fragment 1. She suggested that in the presence of heat and acid this molecule would cyclise to 2, which is probably true. There was some discussion of how this transformation is possible – Fargol drew the direct displacement of the protonated alcohol by the amide, which probably would not happen. This is quite an interesting step, requiring a different mechanism. I know how I would do it. Suggestions? This would make a good advanced chem question for next year.