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Biomimetic Syntheses of (±)‐Isopalhinine A, (±)‐Palhinine A, and (±)‐Palhinine D
Author(s) -
Chen ChihMing,
Shiao HuiYi,
Uang BiingJiun,
Hsieh HsingPang
Publication year - 2018
Publication title -
angewandte chemie
Language(s) - English
Resource type - Journals
eISSN - 1521-3757
pISSN - 0044-8249
DOI - 10.1002/ange.201809130
Subject(s) - chemistry , ketone , stereochemistry , ring (chemistry) , steric effects , total synthesis , benzoquinone , radical cyclization , biomimetic synthesis , organic chemistry
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 S N 2 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.