title: Application of two direct C(sp3)-H functionalizations for total synthesis of (+)-lactacystin.
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.
authors.affiliation: Graduate School of Pharmaceutical Science, The University of Tokyo , Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
authors.forename: Shun
authors.initials: S
authors.lastname: Yoshioka
authors.forename: Masanori
authors.initials: M
authors.lastname: Nagatomo
authors.forename: Masayuki
authors.initials: M
authors.lastname: Inoue
mesh_terms: D000111:Acetylcysteine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000215:Acylation; D001688:Biological Products / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D015394:Molecular Structure; D046988:Proteasome Endopeptidase Complex / Q000187:drug effects*; D061988:Proteasome Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D011758:Pyrroles / Q000737:chemistry*; D013237:Stereoisomerism
chemical_list: D001688:Biological Products; D061988:Proteasome Inhibitors; D011758:Pyrroles; C431590:pyroglutaminol; C067713:lactacystin; D046988:Proteasome Endopeptidase Complex; D000111:Acetylcysteine