Selectivity in the Aerobic Dearomatization of Phenols: Total Synthesis of Dehydronornuciferine by Chemo- and Regioselective Oxidation

2018 ◽  
Vol 57 (6) ◽  
pp. 1514-1518 ◽  
Author(s):  
Kenneth Virgel N. Esguerra ◽  
Jean-Philip Lumb
Keyword(s):  
Total Synthesis ◽  
Regioselective Oxidation

scholarly journals Synthesis and Mechanistic Interrogation of Ginkgo biloba Chemical Space en route to (–)-Bilobalide

2020 ◽  
Author(s):  
Robert Demoret ◽  
Meghan Baker ◽  
Masaki Ohtawa ◽  
Shuming Chen ◽  
Ching-Ching Lam ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Isotope Labeling ◽  
Driving Forces ◽  
Chemical Space ◽  
Lone Pair ◽  
Mineral Acid ◽  
Reformatsky Reaction ◽  
Asymmetric Allylation ◽  
Regioselective Oxidation ◽  
High Information

Here we interrogate the structurally dense (1.63 mcbits/Å<sup>3</sup>) GABA<sub>A</sub> receptor antagonist bilobalide, intermediates en route to its synthesis and related mechanistic questions. <sup>13</sup>C isotope labeling identified an unexpected bromine migration en route to an α-selective, catalytic asymmetric Reformatsky reaction, ruling out an asymmetric allylation pathway. Experiment and computation converge on the driving forces behind two surprising observations. First, an oxetane acetal is shown to persist in concentrated mineral acid (1.5 M DCl in THF-d<sub>8</sub>/D<sub>2</sub>O), and its longevity is correlated to destabilizing steric clashes between substituents. Second, a regioselective oxidation of <i>des</i>-hydroxybilobalide is found to rely on lactone acidification through lone-pair delocalization, which leads to extremely rapid intermolecular enolate equilibration. In addition, we describe multiple pitfalls, puzzles and unexpected reactions that ultimately uncovered a concise total synthesis. These problems arose from the high information density of bilobalide that distinguishes it from other scaffolds and may characterize natural product (NP) space more generally. Therefore, we also include a Python script to quickly (<i>ca.</i> 132,000 molecules/ minute) calculate information content (Böttcher scores), which may be helpful to identify important features of NP space.

scholarly journals Synthesis and Mechanistic Interrogation of Ginkgo biloba Chemical Space en route to (–)-Bilobalide

2020 ◽  
Author(s):  
Robert Demoret ◽  
Meghan Baker ◽  
Masaki Ohtawa ◽  
Shuming Chen ◽  
Ching-Ching Lam ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Isotope Labeling ◽  
Driving Forces ◽  
Chemical Space ◽  
Lone Pair ◽  
Mineral Acid ◽  
Reformatsky Reaction ◽  
Asymmetric Allylation ◽  
Regioselective Oxidation ◽  
High Information

Here we interrogate the structurally dense (1.63 mcbits/Å<sup>3</sup>) GABA<sub>A</sub> receptor antagonist bilobalide, intermediates en route to its synthesis and related mechanistic questions. <sup>13</sup>C isotope labeling identified an unexpected bromine migration en route to an α-selective, catalytic asymmetric Reformatsky reaction, ruling out an asymmetric allylation pathway. Experiment and computation converge on the driving forces behind two surprising observations. First, an oxetane acetal is shown to persist in concentrated mineral acid (1.5 M DCl in THF-d<sub>8</sub>/D<sub>2</sub>O), and its longevity is correlated to destabilizing steric clashes between substituents. Second, a regioselective oxidation of <i>des</i>-hydroxybilobalide is found to rely on lactone acidification through lone-pair delocalization, which leads to extremely rapid intermolecular enolate equilibration. In addition, we describe multiple pitfalls, puzzles and unexpected reactions that ultimately uncovered a concise total synthesis. These problems arose from the high information density of bilobalide that distinguishes it from other scaffolds and may characterize natural product (NP) space more generally. Therefore, we also include a Python script to quickly (<i>ca.</i> 132,000 molecules/ minute) calculate information content (Böttcher scores), which may be helpful to identify important features of NP space.

scholarly journals Synthesis and Mechanistic Interrogation of Ginkgo biloba Chemical Space en route to (–)-Bilobalide

2020 ◽  
Author(s):  
Robert Demoret ◽  
Meghan Baker ◽  
Masaki Ohtawa ◽  
Shuming Chen ◽  
Ching-Ching Lam ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Isotope Labeling ◽  
Driving Forces ◽  
Chemical Space ◽  
Lone Pair ◽  
Mineral Acid ◽  
Reformatsky Reaction ◽  
Asymmetric Allylation ◽  
Regioselective Oxidation ◽  
High Information

Here we interrogate the structurally dense (1.63 mcbits/Å<sup>3</sup>) GABA<sub>A</sub> receptor antagonist bilobalide, intermediates en route to its synthesis and related mechanistic questions. <sup>13</sup>C isotope labeling identified an unexpected bromine migration en route to an α-selective, catalytic asymmetric Reformatsky reaction, ruling out an asymmetric allylation pathway. Experiment and computation converge on the driving forces behind two surprising observations. First, an oxetane acetal is shown to persist in concentrated mineral acid (1.5 M DCl in THF-d<sub>8</sub>/D<sub>2</sub>O), and its longevity is correlated to destabilizing steric clashes between substituents. Second, a regioselective oxidation of <i>des</i>-hydroxybilobalide is found to rely on lactone acidification through lone-pair delocalization, which leads to extremely rapid intermolecular enolate equilibration. In addition, we describe multiple pitfalls, puzzles and unexpected reactions that ultimately uncovered a concise total synthesis. These problems arose from the high information density of bilobalide that distinguishes it from other scaffolds and may characterize natural product (NP) space more generally. Therefore, we also include a Python script to quickly (<i>ca.</i> 132,000 molecules/ minute) calculate information content (Böttcher scores), which may be helpful to identify important features of NP space.

scholarly journals Copper(ii)-catalyzed and acid-promoted highly regioselective oxidation of tautomerizable C(sp3)–H bonds adjacent to 3,4-dihydroisoquinolines using air (O2) as a clean oxidant

RSC Advances ◽  
2021 ◽  
Vol 11 (47) ◽  
pp. 29702-29710
Author(s):  
Yun-Gang He ◽  
Yong-Kang Huang ◽  
Qi-Qi Fan ◽  
Bo Zheng ◽  
Yong-Qiang Luo ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Regioselective Oxidation

A novel Cu(ii)-catalyzed and acid-promoted highly regioselective oxidation of tautomerizable C(sp3)–H bonds adjacent to 1-Bn-DHIQs was developed. This method was successfully applied in the first total synthesis of canelillinoxine.

Total synthesis of Δ9(12)-capnellene-8α,10α-diol

1982 ◽  
Vol 23 (52) ◽  
pp. 5471-5474
Author(s):  
G Pattenden
Keyword(s):  
Total Synthesis

Total synthesis of melleumins A and B and their analogs: Determination of stereochemistry and Wnt signal inhibitory activity

Planta Medica ◽  
2008 ◽  
Vol 74 (09) ◽  
Author(s):  
M Ishibashi ◽  
S Hanazawa ◽  
Y Uchino ◽  
X Li ◽  
MA Arai
Keyword(s):  
Total Synthesis ◽  
Inhibitory Activity ◽  
Wnt Signal

Progress Toward The Total Synthesis Of The Marine Natural Product Karlotoxin 5

Planta Medica ◽  
2013 ◽  
Vol 79 (10) ◽  
Author(s):  
M Albadry ◽  
Y Zou ◽  
Y Takahashi ◽  
A Waters ◽  
M Hossein ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Natural Product ◽  
Marine Natural Product
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