TY - JOUR
T1 - Second-generation total synthesis of aplyronine A featuring Ni/Cr-mediated coupling reactions
AU - Hayakawa, Ichiro
AU - Saito, Keita
AU - Matsumoto, Sachiko
AU - Kobayashi, Shinichi
AU - Taniguchi, Ayaka
AU - Kobayashi, Kenichi
AU - Fujii, Yusuke
AU - Kaneko, Takahiro
AU - Kigoshi, Hideo
N1 - Funding Information:
This work was supported by Grants-in-Aid for Scientific Research on Innovative Areas 'Chemical Biology of Natural Products'(Grant Number JP23102014) and for Scientific Research (Grant Number JP26242073) from the Ministry of Education, Culture, Sports, Science and Technology (MEXT)/Japanese Society for the Promotion of Science (JSPS). I. H. thanks the Okayama Foundation for Science and Technology, the Naito Foundation, the Kurata Grant awarded by the Kurata Memorial Hitachi Science and Technology Foundation, the NOVARTIS Foundation (Japan) for the Promotion of Science, and the Suzuken Memorial Foundation for their financial support.
Publisher Copyright:
© The Royal Society of Chemistry.
PY - 2017
Y1 - 2017
N2 - 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.
AB - 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.
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U2 - 10.1039/c6ob02241c
DO - 10.1039/c6ob02241c
M3 - Article
C2 - 27824201
AN - SCOPUS:85006910789
SN - 1477-0520
VL - 15
SP - 124
EP - 131
JO - Organic and Biomolecular Chemistry
JF - Organic and Biomolecular Chemistry
IS - 1
ER -
