Total synthesis, structure revision, and absolute configuration of (+)-yatakemycin.
The total synthesis of the reported structure 2 for yatakemycin, an exceptionally potent, naturally occurring antitumor agent disclosed in 2003, and its lack of correlation with the natural product are detailed. On the basis of spectroscopic distinctions between 2 and yatakemycin, the natural product structure was reformulated as 3, now bearing a thiomethyl ester versus thioacetate in the left-hand subunit. Total synthesis of 3 provided a compound nearly identical to but still subtly distinct from the natural product. A second reformulation of the yatakemycin structure as 1, incorporating the alternatively substituted right-hand subunit as well as the initial thiomethyl ester reformulation, was confirmed by total synthesis of both (+)- and ent-(-)-1 in studies that also unambiguously established the absolute configuration of the natural product.
Tichenor
Mark S
MS
Department of Chemistry and the Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Kastrinsky
David B
DB
Boger
Dale L
DL
D000080890:Duocarmycins; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry*; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism; D013302:Streptomyces / Q000737:chemistry
D000080890:Duocarmycins; D007211:Indoles; D011758:Pyrroles; C474180:yatakemycin