Application of two direct C(sp3)-H functionalizations for total synthesis of (+)-lactacystin
Shun Yoshioka1, Masanori Nagatomo, Masayuki Inoue
1Graduate School of Pharmaceutical Science, The University of Tokyo , Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Abstract:
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.
Related Concept Videos
Production of Organic Acids
Alkylation of β-Diester Enolates: Malonic Ester Synthesis
Alkylation of β-Ketoester Enolates: Acetoacetic Ester Synthesis
Synthesis of α-Substituted Carbonyl Compounds: The Stork Enamine Reaction
Diels–Alder Reaction Forming Cyclic Products: Stereochemistry
Preparation of Carboxylic Acids: Overview


