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Pactamycin and Its Derivatives: Improved Synthesis Route
Author(s) -
Ohmi Kohki,
Miura Yusuke,
Nakao Yuta,
Goto Atsumi,
Yoshimura Satoshi,
Ouchi Hitoshi,
Inai Makoto,
Asakawa Tomohiro,
Yoshimura Fumihiko,
Kondo Mitsuru,
Kan Toshiyuki
Publication year - 2020
Publication title -
european journal of organic chemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.825
H-Index - 155
eISSN - 1099-0690
pISSN - 1434-193X
DOI - 10.1002/ejoc.201901747
Subject(s) - chemistry , cyclopentane , aldol reaction , stereoselectivity , enamine , moiety , ozonolysis , stereochemistry , cyclopropanation , total synthesis , annulation , enantioselective synthesis , organocatalysis , medicinal chemistry , intramolecular force , cyclohexene , catalysis , organic chemistry
Stereoselective construction of the cyclopentane core 21 of pactamycin ( 1 ) was achieved from symmetric cyclohexadiene 7 . Our synthetic strategy features catalytic Rh‐mediated desymmetric aziridination of the cyclohexadiene derivative, selective ring‐opening reaction at the C2 position of sulfonylaziridine with NaN 3 , ring‐contraction of cyclohexene 9 by ozonolysis followed by intramolecular aldol reaction via enamine intermediate 11 , and construction of the two consecutive tetra‐substituted carbon centers by stereoselective epoxidation of the exo ‐methylene moiety of 14c with DMDO, followed by methylation reaction. Introduction of the urea unit on tetra‐substituted carbon of 16 was achieved by amidation and subsequent Hofmann rearrangement.