scholarly journals Total Syntheses of the C19 Diterpenoid Alkaloids (–)-Talatisamine, (–)-Liljestrandisine, and (–)-Liljestrandinine by a Fragment Coupling Approach

2021 ◽  
Author(s):  
Alice Wong ◽  
Nicholas Fastuca ◽  
Victor Mak ◽  
Jeff Kerkovius ◽  
Susan Stevenson ◽  
...  
Keyword(s):  
Original Structure ◽  
Synthetic Approach ◽  
Diterpenoid Alkaloids ◽  
Total Syntheses ◽  
Pinacol Rearrangement ◽  
Coupling Approach ◽  
Structure Assignment

<p>The C19 aconitine-type diterpenoid alkaloids (–)-talatisamine, (–)-liljestrandisine, and (–)-liljestrandinine have been prepared in 31, 30, and 33 steps, respectively, from phenol. The synthetic approach features a 1,2-addition/semi-pinacol rearrangement as the key fragment coupling tactic. These efforts have also resulted in a correction to the original structure assignment of (–)-liljestrandisine.</p>

scholarly journals Total Syntheses of the C19 Diterpenoid Alkaloids (−)-Talatisamine, (−)-Liljestrandisine, and (−)-Liljestrandinine by a Fragment Coupling Approach

2021 ◽  
Author(s):  
Alice R. Wong ◽  
Nicholas J. Fastuca ◽  
Victor W. Mak ◽  
Jeffrey K. Kerkovius ◽  
Susan M. Stevenson ◽  
...  
Keyword(s):  
Diterpenoid Alkaloids ◽  
Total Syntheses ◽  
Coupling Approach

scholarly journals Bioinspired Oxidative Cyclization of the Geissoschizine Skeleton for the Enantioselective Total Synthesis of Mavacuran Alkaloids

2019 ◽  
Author(s):  
Maxime Jarret ◽  
Victor Turpin ◽  
Aurélien Tap ◽  
Jean-Francois Gallard ◽  
Cyrille Kouklovsky ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Oxidative Coupling ◽  
Indole Alkaloids ◽  
Oxidative Cyclization ◽  
Total Syntheses ◽  
Enantioselective Total Synthesis ◽  
Biosynthetic Precursor ◽  
Monoterpene Indole Alkaloids ◽  
Coupling Approach

We report the enantioselective total syntheses of mavacurans alkaloids, (+)-taberdivarine H, (+)-16-hydoxymethyl-pleiocarpamine, (+)-16-epi-pleiocarpamine, and their postulated biosynthetic precursor 16-formyl-pleiocarpamine. This family of monoterpene indole alkaloids is a target of choice since some of its members are subunits of intricate bisindole alkaloids such as bipleiophylline. Inspired by the biosynthetic hypothesis, we explored an oxidative coupling approach from the geissoschizine framework to form the N1-C16 bond. Quaternization of the aliphatic nitrogen was key to achieve the oxidative coupling induced by KHMDS/I<sub>2 </sub>since<sub> </sub>it hides the nucleophilicity of the aliphatic nitrogen and locks the required cis conformation.

scholarly journals Total Syntheses of Pladienolide-Derived Spliceosome Modulators

Molecules ◽  
2021 ◽  
Vol 26 (19) ◽  
pp. 5938
Author(s):  
Jaehoon Sim ◽  
Eunbin Jang ◽  
Hyun Jin Kim ◽  
Hongjun Jeon
Keyword(s):  
Total Synthesis ◽  
Natural Product ◽  
Structural Features ◽  
Synthetic Approach ◽  
Synthetic Analog ◽  
Phase I Clinical Trials ◽  
Total Syntheses ◽  
Naturally Occurring ◽  
Anti Cancer ◽  
Synthetic Approaches

Pladienolides, an emerging class of naturally occurring spliceosome modulators, exhibit interesting structural features, such as highly substituted 12-membered macrocycles and epoxide-containing diene side chains. The potential of pladienolides as anti-cancer agents is confirmed by H3B-8800, a synthetic analog of this natural product class, which is currently under Phase I clinical trials. Since its isolation in 2004 and the first total synthesis in 2007, a dozen total syntheses and synthetic approaches toward the pladienolide class have been reported to date. This review focuses on the eight completed total syntheses of naturally occurring pladienolides or their synthetic analogs, in addition to a synthetic approach to the main framework of the natural product.

Total Syntheses of Hopeanol and Hopeahainol A Empowered by a Chiral Brønsted Acid Induced Pinacol Rearrangement

2012 ◽  
Vol 124 (17) ◽  
pp. 4156-4160 ◽  
Author(s):  
Scott A. Snyder ◽  
Stephen B. Thomas ◽  
Agathe C. Mayer ◽  
Steven P. Breazzano
Keyword(s):  
Bronsted Acid ◽  
Brønsted Acid ◽  
Total Syntheses ◽  
Pinacol Rearrangement ◽  
Brönsted Acid ◽  
Chiral Bronsted Acid

scholarly journals Total Syntheses of Hopeanol and Hopeahainol A Empowered by a Chiral Brønsted Acid Induced Pinacol Rearrangement

2012 ◽  
Vol 51 (17) ◽  
pp. 4080-4084 ◽  
Author(s):  
Scott A. Snyder ◽  
Stephen B. Thomas ◽  
Agathe C. Mayer ◽  
Steven P. Breazzano
Keyword(s):  
Bronsted Acid ◽  
Brønsted Acid ◽  
Total Syntheses ◽  
Pinacol Rearrangement ◽  
Brönsted Acid ◽  
Chiral Bronsted Acid

Cofactor-Independent Pinacolase Directs Non-Diels-Alderase Biogenesis of the Brevianamides

2019 ◽  
Author(s):  
Ying Ye ◽  
Lei Du ◽  
Xingwang Zhang ◽  
Sean A. Newmister ◽  
Wei Zhang ◽  
...  
Keyword(s):  
Biochemical Analysis ◽  
Mutational Analysis ◽  
Biological Activities ◽  
Wide Spectrum ◽  
Biosynthetic Gene Cluster ◽  
Diels Alder ◽  
Total Syntheses ◽  
Targeted Gene Disruption ◽  
Pinacol Rearrangement

<p>Fungal bicyclo[2.2.2]diazaoctane indole alkaloids demonstrate intriguing structures and a wide spectrum of biological activities. Although biomimetic total syntheses have been completed for representative compounds of this structural family, the details of their biogenesis have remained largely uncharacterized. Among them, Brevianamide A represents the most basic form within this class bearing a dioxopiperazine core structure and a rare 3-<i>spiro</i>-<i>psi</i>-indoxyl skeleton. Here, we identified the Brevianamide A biosynthetic gene cluster from <i>Penicillium brevicompacticum</i> NRRL 864 and fully elucidated the metabolic pathway by targeted gene disruption, heterologous expression, precursor incorporation studies, and <i>in vitro</i> biochemical analysis. In particular, we determined that BvnE is a cofactor-independent isomerase that is essential for selective production of Brevianamide A. Based on a high resolution crystal structure of BvnE, molecular modeling, mutational analysis, and computational studies provided new mechanistic insights into the diastereoselective formation of the 3-<i>spiro</i>-<i>psi</i>-indoxyl moiety in Brevianamide A. This occurs through a biocatalyst controlled semi-Pinacol rearrangement and a subsequent spontaneous intramolecular [4+2] <i>hetero</i>-Diels-Alder cycloaddition.</p>

Rapid Formation of Advanced Scaffolds from Phenols and Anilines

Synlett ◽  
2018 ◽  
Vol 30 (06) ◽  
pp. 647-664
Author(s):  
Sylvain Canesi
Keyword(s):  
Total Synthesis ◽  
Cross Coupling ◽  
Protecting Groups ◽  
Complex Structures ◽  
Protecting Group ◽  
Total Syntheses ◽  
Aniline Derivatives ◽  
Pinacol Rearrangement ◽  
Rapid Formation ◽  
Aromatic Systems

This article is an account of our efforts over the last decade to functionalize phenols and anilines at any position and to use these compounds to generate substituted aromatic systems and advanced unsaturated cyclohexanone moieties, enabling the rapid formation of complex structures. Total syntheses of numerous natural products involving such intermediates were achieved.1 Introduction2 ortho-Functionalization of Phenols and Aniline Derivatives Mediated by Iodanes (III) and Synthesis of Panacene2.1 Cross-Coupling with Aniline Derivatives2.2 Dearomative Cycloaddition of Arenes and Heteroarenes2.3 Total Synthesis of Panacene3 meta-Functionalization of Aniline Derivatives and Synthesis of Erysotramidine3.1 meta-Functionalization of Aniline Derivatives3.2 Total Synthesis of Erysotramidine4 para-Functionalization of Phenols and Applications in Total Synthesis4.1 Bimolecular Approach Mediated by Protecting Groups4.2 ipso-Rearrangement4.3 Oxidative Alkyl Shift4.4 Oxidative Prins-Pinacol Rearrangement4.5 Oxidative Prins-Type Reaction4.6 Total Synthesis of (–)-Fortucine4.7 Total Synthesis of Isostrychnine4.8 Total Synthesis of (–)-Strychnopivotine5 Development of a Functional Protecting Group

Cofactor-Independent Pinacolase Directs Non-Diels-Alderase Biogenesis of the Brevianamides

2019 ◽  
Author(s):  
Ying Ye ◽  
Lei Du ◽  
Xingwang Zhang ◽  
Sean A. Newmister ◽  
Wei Zhang ◽  
...  
Keyword(s):  
Biochemical Analysis ◽  
Mutational Analysis ◽  
Biological Activities ◽  
Wide Spectrum ◽  
Biosynthetic Gene Cluster ◽  
Diels Alder ◽  
Total Syntheses ◽  
Targeted Gene Disruption ◽  
Pinacol Rearrangement

<p>Fungal bicyclo[2.2.2]diazaoctane indole alkaloids demonstrate intriguing structures and a wide spectrum of biological activities. Although biomimetic total syntheses have been completed for representative compounds of this structural family, the details of their biogenesis have remained largely uncharacterized. Among them, Brevianamide A represents the most basic form within this class bearing a dioxopiperazine core structure and a rare 3-<i>spiro</i>-<i>psi</i>-indoxyl skeleton. Here, we identified the Brevianamide A biosynthetic gene cluster from <i>Penicillium brevicompacticum</i> NRRL 864 and fully elucidated the metabolic pathway by targeted gene disruption, heterologous expression, precursor incorporation studies, and <i>in vitro</i> biochemical analysis. In particular, we determined that BvnE is a cofactor-independent isomerase that is essential for selective production of Brevianamide A. Based on a high resolution crystal structure of BvnE, molecular modeling, mutational analysis, and computational studies provided new mechanistic insights into the diastereoselective formation of the 3-<i>spiro</i>-<i>psi</i>-indoxyl moiety in Brevianamide A. This occurs through a biocatalyst controlled semi-Pinacol rearrangement and a subsequent spontaneous intramolecular [4+2] <i>hetero</i>-Diels-Alder cycloaddition.</p>

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