TY - JOUR
T1 - Total Synthesis of the Broad-Spectrum Antibiotic Amycolamicin
AU - Meguro, Yasuhiro
AU - Ito, Junya
AU - Nakagawa, Kiyotaka
AU - Kuwahara, Shigefumi
N1 - Funding Information:
This work was financially supported by JSPS Kakenhi (20H02920 and 21K20566) and AMED (JP20am010100). Thanks are due to Drs. Hayamitsu Adachi and Masayuki Igarashi (BIKAKEN) for valuable discussions and to Ms. Yuka Taguchi (Tohoku University) for help with NMR and MS measurements.
Publisher Copyright:
© 2022 American Chemical Society.
PY - 2022/3/30
Y1 - 2022/3/30
N2 - The total synthesis of the antibiotic amycolamicin with a hybrid molecular architecture composed of five ring systems, which exhibits potent antibacterial activity against a wide range of drug-resistant bacteria, has been achieved in a convergent manner. A protecting-group-free intramolecular Diels-Alder reaction of a hydroxy tetraenal intermediate promoted by two equivalents of Et2AlCl, which proceeds highly diastereoselectively via an endo-equatorial transition state, has been utilized to construct the trans-decalin moiety of the molecule. The full structure of amycolamicin was assembled by a completely stereoconvergent N-acylation of a northern N-glycoside unit (α-anomer/β-anomer = 1:1.1) with a southern β-keto thioester segment followed by installation of the central tetramic acid moiety.
AB - The total synthesis of the antibiotic amycolamicin with a hybrid molecular architecture composed of five ring systems, which exhibits potent antibacterial activity against a wide range of drug-resistant bacteria, has been achieved in a convergent manner. A protecting-group-free intramolecular Diels-Alder reaction of a hydroxy tetraenal intermediate promoted by two equivalents of Et2AlCl, which proceeds highly diastereoselectively via an endo-equatorial transition state, has been utilized to construct the trans-decalin moiety of the molecule. The full structure of amycolamicin was assembled by a completely stereoconvergent N-acylation of a northern N-glycoside unit (α-anomer/β-anomer = 1:1.1) with a southern β-keto thioester segment followed by installation of the central tetramic acid moiety.
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U2 - 10.1021/jacs.2c00647
DO - 10.1021/jacs.2c00647
M3 - Article
C2 - 35297637
AN - SCOPUS:85127245519
SN - 0002-7863
VL - 144
SP - 5253
EP - 5257
JO - Journal of the American Chemical Society
JF - Journal of the American Chemical Society
IS - 12
ER -