Application of two direct C(sp3)-H functionalizations for total synthesis of (+)-lactacystin.

Herein, we report a new synthetic route from (S)-pyroglutaminol to (+)-lactacystin, a potent inhibitor of the 20S proteasome. The photoinduced intermolecular C(sp(3))-H alkynylation and intramolecular C(sp(3))-H acylation chemo- and stereoselectively constructed the tetra- and trisubstituted carbon centers, respectively. The obtained bicycle was transformed into the target compound in a concise manner. The present total synthesis demonstrates the power of the direct C(sp(3))-H functionalizations for the assembly of multiple functionalized structures of natural products.