Conformational Locking through Allylic Strain as a Device for Stereocontrol—Total Synthesis of Grandisine A

Controlled fusion: The use of a seco ring D precursor to control both the stereochemistry of a critical cycloaddition with acetaldehyde and the direction of protonation of the resultant silyl enol ether cycloadduct has led to the total synthesis of grandisine A, which shows promising selectivity for binding to the δ-opioid receptor. The D ring is installed in the final stages of the synthesis (see scheme, LA=Lewis acid).