Total Syntheses of Herqulines B and C

An approach for the syntheses of
herqulines B and C is reported
that takes advantage of an l-tyrosine-derived diketopiperazine,
a mycocyclosin analogue, as a synthetic precursor. The strategy relies
on a series of consecutive reductions to adjust the mycocyclosin oxidation
state to that observed in the herquline class of natural products.
The strained and distorted l-tyrosine-based biaryl system
characteristic for mycocyclosin is selectively converted to the 1,4-diketone
structural motif common to the herqulines via initial hypervalent
iodine-mediated dearomatization and a subsequent directed Birch reduction,
enabled by an intramolecular H-source. Additionally, the piperazine
oxidation state is accessible via an iron-catalyzed reduction of a
diketopiperazine intermediate.