A Short Synthesis of (+)-Brefeldin C via Enantioselective Radical Hydroalkynylation

2019 ◽  
Author(s):  
Lars Gnägi ◽  
Severin Vital Martz ◽  
Daniel Meyer ◽  
Robin Marc Schärer ◽  
Philippe Renaud
Keyword(s):  
Total Synthesis ◽  
Natural Product ◽  
Oxidation State ◽  
Single Step ◽  
Radical Process ◽  
Target Molecule ◽  
Short Synthesis ◽  
The One

<div><div><div><div><p>A very concise total synthesis of (+)-brefeldin C starting from 2-furanylcyclopentene is described. This approach is based on an unprecedented enantioselective radical hydroalkynylation process to introduce the two cyclopentane stereocenters in a single step. The use of a furan substituent allows to achieve a high trans diastereoselectivity during the radical process and it contains the four carbon atoms C1–C4 of the natural product in an oxidation state closely related to the one of the target molecule. The eight-step synthesis require six product purifications and it provides (+)-brefeldin C in 18% overall yield.</p></div></div></div></div>

A Short Synthesis of (+)-Brefeldin C via Enantioselective Radical Hydroalkynylation

2019 ◽  
Author(s):  
Lars Gnägi ◽  
Severin Vital Martz ◽  
Daniel Meyer ◽  
Robin Marc Schärer ◽  
Philippe Renaud
Keyword(s):  
Total Synthesis ◽  
Natural Product ◽  
Oxidation State ◽  
Single Step ◽  
Radical Process ◽  
Target Molecule ◽  
Short Synthesis ◽  
The One

<div><div><div><div><p>A very concise total synthesis of (+)-brefeldin C starting from 2-furanylcyclopentene is described. This approach is based on an unprecedented enantioselective radical hydroalkynylation process to introduce the two cyclopentane stereocenters in a single step. The use of a furan substituent allows to achieve a high trans diastereoselectivity during the radical process and it contains the four carbon atoms C1–C4 of the natural product in an oxidation state closely related to the one of the target molecule. The eight-step synthesis require six product purifications and it provides (+)-brefeldin C in 18% overall yield.</p></div></div></div></div>

scholarly journals Total Synthesis of Nine Longiborneol Sesquiterpenoids Using a Functionalized Camphor Strategy

2021 ◽  
Author(s):  
Robert F. Lusi ◽  
Goh Sennari ◽  
Richmond Sarpong
Keyword(s):  
Chemical Synthesis ◽  
Total Synthesis ◽  
Natural Product ◽  
Late Stage ◽  
Strategy Development ◽  
Topological Complexity ◽  
Efficient Synthesis ◽  
Short Synthesis ◽  
Synthesis Routes ◽  
The 1960S

<p>Natural product total synthesis inspires strategy development in chemical synthesis. In the 1960s, Corey and coworkers demonstrated a visionary preparation of the terpenoid longifolene, using “strategic bond analysis” to craft a synthesis route. This approach proposes that efficient synthesis routes to bridged, polycyclic, structures should be formulated to introduce the bulk of the target’s topological complexity at a late stage. In subsequent decades, similar strategies have proved general for the syntheses of a wide variety of bridged, polycyclic molecules. Here, we demonstrate that an orthogonal strategy, which utilizes a topologically complex bicyclo[2.2.1] starting material accessed through a scaffold rearrangement of (<i>S</i>)-carvone, leads to a remarkably short synthesis of the longifolene-related terpenoid longiborneol. We also employ a variety of late-stage C–H functionalization tactics in divergent syntheses of many longiborneol congeners. Our strategy should prove effective for the preparation of other topologically complex natural products that contain the bicyclo[2.2.1] framework.</p>

scholarly journals A Concise Total Synthesis of the Fungal Isoquinoline Alkaloid TMC-120B

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 521
Author(s):  
Ahmad K. Haidar ◽  
Niels D. Kjeldsen ◽  
Nikolaj S. Troelsen ◽  
Viola Previtali ◽  
Kasper P. Lundquist ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Natural Product ◽  
Isoquinoline Alkaloid ◽  
Total Syntheses ◽  
Antiepileptic Activity ◽  
Short Synthesis

Recent reports of antiepileptic activity of the fungal alkaloid TMC-120B have renewed the interest in this natural product. Previous total syntheses of TMC-120B comprise many steps and have low overall yields (11–17 steps, 1.5–2.9% yield). Thus, to access this compound more efficiently, we herein present a concise and significantly improved total synthesis of the natural product. Our short synthesis relies on two key cyclization steps to assemble the central scaffold: isoquinoline formation via an ethynyl-imino cyclization and an intramolecular Friedel-Crafts reaction to form the furanone.

Total Synthesis of Enisorine D and its Analogues

Synthesis ◽  
2019 ◽  
Vol 51 (24) ◽  
pp. 4601-4610
Author(s):  
Shashi Shashi ◽  
Mulla Althafh Hussain ◽  
Faiz Ahmed Khan
Keyword(s):  
Total Synthesis ◽  
Natural Product ◽  
Carboxylic Acids ◽  
Marine Sponge ◽  
Picolinic Acid ◽  
Cinnamic Acids ◽  
Target Molecule ◽  
Amine Coupling

The first total synthesis of enisorine D, a natural product isolated from the marine sponge Iotrochota cf. iota, is described in 64% overall yield. The target molecule, which is an inhibitor of T3SS-dependent Yope secretion of Y. pseudotuberculosis, is achieved in seven linear steps from tyramine via simple and effective transformations that include bromination, acylation, alkylation, azidation, reduction and routine acid–amine coupling. A total of sixteen analogues are prepared by coupling with eight different cinnamic acids, two bromopyrrole carboxylic acids, five phenyl carboxylic acids and picolinic acid.

scholarly journals From Target-Oriented to Motif-Oriented: A Case Study on Nannocystin Total Synthesis

Molecules ◽  
2020 ◽  
Vol 25 (22) ◽  
pp. 5327
Author(s):  
Weicheng Zhang
Keyword(s):  
Drug Discovery ◽  
Total Synthesis ◽  
Natural Product ◽  
Chemical Space ◽  
Organic Transformations ◽  
Total Syntheses ◽  
Target Molecule ◽  
Structure Activity ◽  
Structural Diversification

Natural product total synthesis is in essence target-oriented in that a set of organic transformations are orchestrated into a workable process, leading ultimately to the target molecule with a predefined architecture. For a bioactive lead, proof of synthetic viability is merely the beginning. Ensuing effort repurposes the initial synthesis for structural diversification in order to probe structure-activity relationship (SAR). Yet accessibility is not equal to flexibility; moving from convergency to divergency, it is not always feasible to explore the chemical space around a particular substructure of interest simply by tweaking an established route. In this situation, the motif-oriented strategy becomes a superior choice, which gives priority to synthetic flexibility at the concerned site such that a route is adopted only if it is capable of implementing diversification therein. This strategy was recently devised by Fürstner et al., enabling them to achieve total synthesis of both natural and non-natural nannocystins varied at an otherwise challenging position. The present review examines seven distinctive nannocystin total syntheses reported thus far and showcases the merits of conventional (target-oriented) as well as motif-oriented strategies, concluding that these two approaches complement each other and are both indispensable for natural product based drug discovery.

Enabling strategies for step efficient syntheses

2018 ◽  
Vol 47 (21) ◽  
pp. 7985-7995 ◽  
Author(s):  
Johannes Schwan ◽  
Mathias Christmann
Keyword(s):  
Natural Products ◽  
Total Synthesis ◽  
Natural Product ◽  
Target Molecule ◽  
Different Types ◽  
Flow Charts ◽  
Synthetic Efficiency

The field of natural product total synthesis has reached the point where synthetic efficiency has become more important than merely defining a viable (yet less ideal) route to the target molecule. Several synthesis of different types of natural products are compared using color-coded flow charts.

scholarly journals Total Synthesis of Nine Longiborneol Sesquiterpenoids Using a Functionalized Camphor Strategy

2021 ◽  
Author(s):  
Robert F. Lusi ◽  
Goh Sennari ◽  
Richmond Sarpong
Keyword(s):  
Chemical Synthesis ◽  
Total Synthesis ◽  
Natural Product ◽  
Late Stage ◽  
Strategy Development ◽  
Topological Complexity ◽  
Efficient Synthesis ◽  
Short Synthesis ◽  
Synthesis Routes ◽  
The 1960S

<p>Natural product total synthesis inspires strategy development in chemical synthesis. In the 1960s, Corey and coworkers demonstrated a visionary preparation of the terpenoid longifolene, using “strategic bond analysis” to craft a synthesis route. This approach proposes that efficient synthesis routes to bridged, polycyclic, structures should be formulated to introduce the bulk of the target’s topological complexity at a late stage. In subsequent decades, similar strategies have proved general for the syntheses of a wide variety of bridged, polycyclic molecules. Here, we demonstrate that an orthogonal strategy, which utilizes a topologically complex bicyclo[2.2.1] starting material accessed through a scaffold rearrangement of (<i>S</i>)-carvone, leads to a remarkably short synthesis of the longifolene-related terpenoid longiborneol. We also employ a variety of late-stage C–H functionalization tactics in divergent syntheses of many longiborneol congeners. Our strategy should prove effective for the preparation of other topologically complex natural products that contain the bicyclo[2.2.1] framework.</p>

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

Total Synthesis of the Antitumor Depsipeptide FE399 and its S-Benzyl Derivative: A Macrolactamization Approach

2020 ◽  
Author(s):  
Takayuki Tonoi ◽  
Miyuki Ikeda ◽  
Teruyuki Sato ◽  
Ryo Kawahara ◽  
Takatsugu Murata ◽  
...  
Keyword(s):  
Molecular Structure ◽  
Total Synthesis ◽  
Natural Product ◽  
Condensation Reaction ◽  
Practical Method ◽  
Equilibrium Mixture ◽  
Conformational Isomers ◽  
Single Isomer

<div>An efficient and practical method for the synthesis of (9R,14R,17R)-FE399, a novel antitumor bicyclic depsipeptide, was developed. A 2-methyl-6-nitrobenzoic anhydride (MNBA)-mediated dehydration condensation reaction was effectively employed for the formation of the 16-membered macrocyclic depsipeptide moiety of FE399. FE399 was found to exist as an inseparable equilibrium mixture of conformational isomers; the mixture was quantitatively transformed into the corresponding S-benzyl product and isolated as a single isomer. Thus, we could confirm that the molecular structure of FE399 obtained by this method is identical to that of the natural product.</div>

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