Total synthesis of (+)-yatakemycin.
A convergent total synthesis of (+)-yatakemycin was accomplished by a 20-step sequence in 13% overall yield. The regioselective ring opening of (S)-epichlorohydrin with a 2,6-dibromophenyllithium derivative enabled us to introduce a chiral carbon center, which was required for the stereoselective construction of the cyclopropane ring. The five aryl-nitrogen bonds in (+)-yatakemycin were constructed by a mild copper-mediated aryl amination that utilized the combination of CuI with CsOAc. The efficient and chemoselective debenzylation of aryl benzyl ether with BCl3 in the presence of pentamethylbenzene was developed. With these new methodologies, the subgram-scale synthesis of (+)-yatakemycin was achieved.
Okano
Kentaro
K
Graduate School of Pharmaceutical Sciences, University of Tokyo, Hongo, Bunkyo-ku, Tokyo 113-0033, Japan.
Tokuyama
Hidetoshi
H
Fukuyama
Tohru
T
D000586:Amination; D001593:Benzyl Compounds / Q000737:chemistry; D000080890:Duocarmycins; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry; D008024:Ligands; D015394:Molecular Structure; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry; D013141:Spiro Compounds / Q000737:chemistry
D001593:Benzyl Compounds; D000080890:Duocarmycins; D007211:Indoles; D008024:Ligands; D011758:Pyrroles; D013141:Spiro Compounds; C474180:yatakemycin