Second-generation total synthesis of aplyronine A featuring Ni/Cr-mediated coupling reactions.
Second-generation total synthesis of aplyronine A, a potent antitumor marine macrolide, was achieved using Ni/Cr-mediated coupling reactions as key steps. The overall yield of the second-generation synthetic pathway of aplyronine A was 1.4%, obtained in 38 steps based on the longest linear sequence. Compared to our first-generation synthetic pathway of aplyronine A, the second-generation synthesis greatly improved both the yield and number of steps. In particular, we improved the stereoselectivity in the construction of the C13 stereogenic center and the C14-C15 (E)-trisubstituted double bond using the asymmetric Ni/Cr-mediated coupling reaction. Furthermore, we established efficient reaction conditions for the asymmetric Ni/Cr-mediated coupling reaction between the C21-C28 segment and C29-C34 segment. Thus, this coupling reaction proceeded with an equimolar ratio of each segment.
Division of Applied Chemistry, Graduate School of Natural Science and Technology, Okayama University, 3-1-1 Tsushima-naka, Kita-ku, Okayama 700-8530, Japan. ichiro.hayakawa@okayama-u.ac.jp.
Ichiro
I
Hayakawa
Department of Chemistry, Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8571, Japan. kigoshi@chem.tsukuba.ac.jp.
Keita
K
Saito
Department of Chemistry, Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8571, Japan. kigoshi@chem.tsukuba.ac.jp.
Sachiko
S
Matsumoto
Department of Chemistry, Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8571, Japan. kigoshi@chem.tsukuba.ac.jp.
Shinichi
S
Kobayashi
Department of Chemistry, Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8571, Japan. kigoshi@chem.tsukuba.ac.jp.
Ayaka
A
Taniguchi
Department of Chemistry, Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8571, Japan. kigoshi@chem.tsukuba.ac.jp.
Kenichi
K
Kobayashi
Department of Chemistry, Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8571, Japan. kigoshi@chem.tsukuba.ac.jp.
Yusuke
Y
Fujii
Department of Chemistry, Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8571, Japan. kigoshi@chem.tsukuba.ac.jp.
Takahiro
T
Kaneko
Department of Chemistry, Graduate School of Pure and Applied Sciences, University of Tsukuba, 1-1-1 Tennodai, Tsukuba 305-8571, Japan. kigoshi@chem.tsukuba.ac.jp.
Hideo
H
Kigoshi
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D001048:Aplysia / Q000737:chemistry; D002384:Catalysis; D002857:Chromium / Q000737:chemistry*; D018942:Macrolides / Q000138:chemical synthesis*; D009532:Nickel / Q000737:chemistry*; D013237:Stereoisomerism
D000970:Antineoplastic Agents; D018942:Macrolides; D002857:Chromium; C104057:aplyronine A; D009532:Nickel