Evolution of the total synthesis of (-)-okilactomycin exploiting a tandem oxy-cope rearrangement/oxidation, a Petasis-Ferrier union/rearrangement, and ring-closing metathesis.
An effective, asymmetric total synthesis of the antitumor antibiotic (-)-okilactomycin (1), as well as assignment of the absolute configuration, has been achieved exploiting a convergent strategy. Highlights of the synthesis include a diastereoselective oxy-Cope rearrangement/oxidation sequence to install the C(1) and C(13) stereogenic centers, a Petasis-Ferrier union/rearrangement to construct the highly functionalized tetrahydropyranone inscribed within the 13-membered macrocycle ring, employing for the first time a sterically demanding acetal, an intramolecular chemoselective acylation to access an embedded bicyclic lactone, and an efficient ring-closing metathesis (RCM) reaction to generate the macrocyclic ring.
Smith
Amos B
AB
Department of Chemistry, Penn Center for Molecular Discovery, and Monell Chemical Senses Center, University of Pennsylvania, Philadelphia, Pennsylvania 19104, USA.
Bosanac
Todd
T
Basu
Kallol
K
D000080:Acetals / Q000737:chemistry; D000447:Aldehydes / Q000138:chemical synthesis / Q000737:chemistry; D003500:Cyclization; D007783:Lactones / Q000138:chemical synthesis; D047028:Macrocyclic Compounds / Q000138:chemical synthesis; D010084:Oxidation-Reduction; D011714:Pyrans / Q000138:chemical synthesis / Q000737:chemistry; D013237:Stereoisomerism; D013302:Streptomyces / Q000737:chemistry
D000080:Acetals; D000447:Aldehydes; D007783:Lactones; D047028:Macrocyclic Compounds; D011714:Pyrans; C054471:okilactomycin