TY - JOUR
T1 - Biomimetic Syntheses of (±)-Isopalhinine A, (±)-Palhinine A, and (±)-Palhinine D
AU - Chen, Chih Ming
AU - Shiao, Hui Yi
AU - Uang, Biing Jiun
AU - Hsieh, Hsing Pang
N1 - Funding Information:
The authors acknowledge the financial support by National Health Research Institutes and Ministry of Science and Technology, Taiwan (MOST-106-2113-M-400-001). We thank Prof. Chun-Chen Liao (National Tsing Hua University, Taiwan) for valuable comments regarding masked ortho-benzoquinones and their corresponding Diels–Alder adducts, and Dr. Kak-Shan Shia (National Health Research Institutes, Taiwan) and Dr. Yung Chang-Hsu (National Health Research Institutes, Taiwan) for valuable comments regarding radical cyclizations. Special thanks to Dr. Lun Kelvin Tsou (National Health Research Institutes, Taiwan) for critical comments and manuscript editing. We also thank Ting-Shen Kuo (National Taiwan Normal University, Taiwan) for assistance with X-ray crystallographic analysis, and Ju-Lan Peng (National Tsing Hua University, Taiwan) for assistance with 600 MHz NMR spectroscopy. Special thanks to Dr. Richard Guy for English proofreading and editing.
Publisher Copyright:
© 2018 Wiley-VCH Verlag GmbH & Co. KGaA, Weinheim
PY - 2018/11/19
Y1 - 2018/11/19
N2 - The first total synthesis of isopalhinine A, as well as unified syntheses of palhinine A and palhinine D, were successfully accomplished by means of a biomimetic strategy that proceeds through a bioinspired 5/6/6/9 tetracyclic intermediate, which mimics the amino ketone form of palhinine D. An early-stage direct SN2 cyclization to construct the nine-membered azonane ring minimized the transannular strain that would otherwise be increased by the twisted nature of the isotwistane skeleton. Then, a diastereoselective Diels–Alder reaction of a masked ortho-benzoquinone using the nine-membered ring as a steric shielding group furnished a functionalized 6/6/9 tricyclic skeleton and established the desired stereochemistry at the C3, C7, C12, and C15 positions in one step. A thiol-mediated acyl radical cyclization gave the bioinspired intermediate bearing three differentiated oxygen-containing functional groups, from which all three total syntheses could be completed in either two or three additional steps.
AB - The first total synthesis of isopalhinine A, as well as unified syntheses of palhinine A and palhinine D, were successfully accomplished by means of a biomimetic strategy that proceeds through a bioinspired 5/6/6/9 tetracyclic intermediate, which mimics the amino ketone form of palhinine D. An early-stage direct SN2 cyclization to construct the nine-membered azonane ring minimized the transannular strain that would otherwise be increased by the twisted nature of the isotwistane skeleton. Then, a diastereoselective Diels–Alder reaction of a masked ortho-benzoquinone using the nine-membered ring as a steric shielding group furnished a functionalized 6/6/9 tricyclic skeleton and established the desired stereochemistry at the C3, C7, C12, and C15 positions in one step. A thiol-mediated acyl radical cyclization gave the bioinspired intermediate bearing three differentiated oxygen-containing functional groups, from which all three total syntheses could be completed in either two or three additional steps.
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U2 - 10.1002/anie.201809130
DO - 10.1002/anie.201809130
M3 - Article
C2 - 30284752
AN - SCOPUS:85055931709
VL - 57
SP - 15572
EP - 15576
JO - Angewandte Chemie - International Edition
JF - Angewandte Chemie - International Edition
SN - 1433-7851
IS - 47
ER -