Level 1 – Case 1
A Surprise in the Synthesis of Guanacastepene A
Key point: Unexpected result in a well-known reaction
H
OH
O
O
O
O
EtO
O
O
O
EtO
O
Guanacastepene A
A Surprise in the Synthesis of Guanacastepene A
Sometimes a reaction with a well-established mechanism does not work as expected. In these cases the mechanism has to be reinvestigated and the careful analysis
of the reaction products usually gives the key of the mechanistic pathway. This
situation can be found in multistep synthetic sequences that have been designed to
achieve a target molecule and that are based on the predictable outcome of each
step. We have an example in the synthesis of guanacastepene A 1, the parent
member of a family of diterpene natural products obtained from a fungus. This
compound is a synthetic target of current interest due to its novel structure and the
possibility of exploring its activity against antibiotic-resistant bacteria.
O
H
OH
O
O
O
1
One of the diverse approaches to the synthesis of 1 is based on the formation of
the tricyclic core of guanacastepene 3 by means of a direct Knoevenagel cyclization of E-keto ester precursor 2 (Scheme 1.1).