scholarly journals Unified Total Synthesis of the Brevianamide Alkaloids Enabled by Chemical Investigations into their Biosynthesis.

2021 ◽  
Author(s):  
Robert C. Godfrey ◽  
Helen E. Jones ◽  
Nicholas J. Green ◽  
Andrew L. Lawrence
Keyword(s):  
Natural Products ◽  
Chemical Synthesis ◽  
Total Synthesis ◽  
Scientific Community ◽  
Biological Activities ◽  
Focus Of Attention ◽  
Complex Structures ◽  
Biosynthetic Pathways ◽  
Synthetic Strategy ◽  
Synthetic Studies

The bicyclo[2.2.2]diazaoctane alkaloids are a vast group of natural products which have been the focus of attention from the scientific community for several decades. This interest stems from their broad range of biological activities, their diverse biosynthetic origins, and their topologically complex structures, which combined make them enticing targets for chemical synthesis. In this article, full details of our synthetic studies into the chemical feasibility of a proposed network of biosynthetic pathways towards the brevianamide family of bicyclo[2.2.2]diazaoctane alkaloids are disclosed. Insights into issues of reactivity and selectivity in the biosynthesis of these structures have aided the development of a unified biomimetic synthetic strategy, which has resulted in the total synthesis of all known bicyclo[2.2.2]diazaoctane brevianamides and the anticipation of an as-yet-undiscovered congener.

scholarly journals Chemical Synthesis of (+)-Brevianamide a Supports a Diels–Alderase-Free Biosynthesis

2019 ◽  
Author(s):  
Robert Godfrey ◽  
Nicholas Green ◽  
Gary Nichol ◽  
Andrew Lawrence
Keyword(s):  
Natural Products ◽  
Chemical Synthesis ◽  
Scientific Community ◽  
Biological Activities ◽  
Alder Reaction ◽  
Diels Alder ◽  
Compelling Evidence ◽  
Diels Alder Reaction ◽  
Significant Interest

<div> <div> <div> <p>The fungal-derived bicyclo[2.2.2]diazaoctane alkaloids are of significant interest to the scientific community for their potent and varied biological activities. Within this large and diverse family of natural products the insecticidal metabolite (+)-brevianamide A is particularly noteworthy for its synthetic intractability and inexplicable biogenesis. Despite five decades of research, this alkaloid has never succumbed to chemical synthesis. It has been suggested that a proposed Diels–Alder reaction in the biosynthesis of (+)-brevianamide A requires a Diels–Alderase enzyme. We herein report the first chemical synthesis of (+)-brevianamide A (7 steps, 8.0% overall yield, 750 mg scale), which provides compelling evidence in support of a Diels–Alderase-free biosynthesis; a significant departure from the established biosynthesis of related alkaloids. </p> </div> </div> </div>

Chemical Synthesis of (+)-Brevianamide a Supports a Diels–Alderase-Free Biosynthesis

2019 ◽  
Author(s):  
Robert Godfrey ◽  
Nicholas Green ◽  
Gary Nichol ◽  
Andrew Lawrence
Keyword(s):  
Natural Products ◽  
Chemical Synthesis ◽  
Scientific Community ◽  
Biological Activities ◽  
Alder Reaction ◽  
Diels Alder ◽  
Compelling Evidence ◽  
Diels Alder Reaction ◽  
Significant Interest

<div> <div> <div> <p>The fungal-derived bicyclo[2.2.2]diazaoctane alkaloids are of significant interest to the scientific community for their potent and varied biological activities. Within this large and diverse family of natural products the insecticidal metabolite (+)-brevianamide A is particularly noteworthy for its synthetic intractability and inexplicable biogenesis. Despite five decades of research, this alkaloid has never succumbed to chemical synthesis. It has been suggested that a proposed Diels–Alder reaction in the biosynthesis of (+)-brevianamide A requires a Diels–Alderase enzyme. We herein report the first chemical synthesis of (+)-brevianamide A (7 steps, 8.0% overall yield, 750 mg scale), which provides compelling evidence in support of a Diels–Alderase-free biosynthesis; a significant departure from the established biosynthesis of related alkaloids. </p> </div> </div> </div>

scholarly journals Unified Total Synthesis of the Brevianamide Alkaloids Enabled by Chemical Investigations into their Biosynthesis

2022 ◽  
Author(s):  
Robert C Godfrey ◽  
Helen E Jones ◽  
Nicholas J Green ◽  
Andrew L Lawrence
Keyword(s):  
Natural Products ◽  
Total Synthesis ◽  
Scientific Community ◽  
Focus Of Attention

The bicyclo[2.2.2]diazaoctane alkaloids are a vast group of natural products which have been the focus of attention from the scientific community for several decades. This interest stems from their broad...

Computationally Augmented Retrosynthesis: Total Synthesis of Paspaline A and Emindole PB

2018 ◽  
Author(s):  
Timothy Newhouse ◽  
Daria E. Kim ◽  
Joshua E. Zweig
Keyword(s):  
Chemical Synthesis ◽  
Total Synthesis ◽  
Small Molecules ◽  
First Principles ◽  
Quantum Chemical ◽  
Computational Analysis ◽  
Empirical Evaluation ◽  
Synthetic Strategy ◽  
Catalyzed Reactions ◽  
Enzyme Catalyzed Reactions

The diverse molecular architectures of terpene natural products are assembled by exquisite enzyme-catalyzed reactions. Successful recapitulation of these transformations using chemical synthesis is hard to predict from first principles and therefore challenging to execute. A means of evaluating the feasibility of such chemical reactions would greatly enable the development of concise syntheses of complex small molecules. Herein, we report the computational analysis of the energetic favorability of a key bio-inspired transformation, which we use to inform our synthetic strategy. This approach was applied to synthesize two constituents of the historically challenging indole diterpenoid class, resulting in a concise route to (–)-paspaline A in 9 steps from commercially available materials and the first pathway to and structural confirmation of emindole PB in 13 steps. This work highlights how traditional retrosynthetic design can be augmented with quantum chemical calculations to reveal energetically feasible synthetic disconnections, minimizing time-consuming and expensive empirical evaluation.

Transition-Metal-Catalyzed Reactions Involving Arynes

Synthesis ◽  
2017 ◽  
Vol 50 (01) ◽  
pp. 1-16 ◽  
Author(s):  
Santosh Mhaske ◽  
Ranjeet Dhokale
Keyword(s):  
Natural Products ◽  
Transition Metal ◽  
Total Synthesis ◽  
Scientific Community ◽  
Multicomponent Reactions ◽  
Polycyclic Aromatic Compounds ◽  
Polycyclic Aromatic ◽  
Transition Metal Catalyzed ◽  
Catalyzed Reactions ◽  
Metal Catalyzed

The plethora of transformations attainable by the transition-metal-catalyzed reactions of arynes has found immense contemporary interest in the scientific community. This review highlights the scope and importance of transition-metal-catalyzed aryne reactions in the field of synthetic organic chemistry reported to date. It covers transformations achieved by the combination of arynes and various transition metals, which provide a facile access to a biaryl motif, fused polycyclic aromatic compounds, different novel carbocycles, various heterocycles, and complex natural products.1 Introduction2 Insertion of Arynes3 Annulation of Arynes4 Cycloaddition of Arynes5 Multicomponent Reactions of Arynes6 Miscellaneous Reactions of Arynes7 Total Synthesis of Natural Products Using Arynes8 Conclusion

scholarly journals Development of a Divergent Route to Erythrina Alkaloids

Synlett ◽  
2020 ◽  
Vol 31 (04) ◽  
pp. 327-333 ◽  
Author(s):  
Jesper L. Kristensen ◽  
Sebastian Clementson ◽  
Mikkel Jessing ◽  
Paulo J. Vital
Keyword(s):  
Natural Products ◽  
Total Synthesis ◽  
19Th Century ◽  
First Generation ◽  
Second Generation ◽  
Enantioselective Synthesis ◽  
Third Generation ◽  
Synthetic Strategy ◽  
Erythrina Alkaloids ◽  
The 19Th Century

Erythrina alkaloids were identified at the end of the 19th century and today, more than 100 members of the erythrinane family have been isolated. They are characterized by a unique tetracyclic, α-tertiary spiroamine scaffold. Herein we detail our efforts towards the development of a divergent enantioselective synthesis of (+)-dihydro-β-erythroidine (DHβE) – one of the most prominent members of this intriguing family of natural products.1 Introduction2 Synthetic Strategy2.1 First Generation2.2 Second Generation2.3 Third Generation2.3.1 Radical Endgame2.3.2 Completion of the Total Synthesis3 Conclusion

scholarly journals Synthetic Approaches to Tetracyclic Pyrrole Imidazole Marine Alkaloids

2013 ◽  
Vol 8 (7) ◽  
pp. 1934578X1300800 ◽  
Author(s):  
Takuya Imaoka ◽  
Makoto Iwata ◽  
Takafumi Akimoto ◽  
Kazuo Nagasawa
Keyword(s):  
Natural Products ◽  
Total Synthesis ◽  
Anticancer Activity ◽  
Biological Activities ◽  
Structural Complexity ◽  
Marine Alkaloids ◽  
Ring Systems ◽  
Agonistic Activity ◽  
Synthetic Approaches

Oroidin derived pyrrole imidazole marine alkaloids (PIAs) are attractive targets for synthetic organic chemists because of their structural complexity and diversity as well as their interesting biological activities. A number of efforts have been carried out to develop strategies for the synthesis of these natural products. Members of PIAs ( eg., 2-7) which contain tetracyclic ring systems possessing characteristic cyclic guanidine or urea moieties show significant biological activities including anticancer activity and agonistic activity against the adrenoceptor. In this review investigations of the total synthesis of the representative tetracyclic PIAs dibromophakellin (2) and dibromophakellstatin (3) are described.

scholarly journals Concise and Gram-Scale Total Synthesis of Lansiumamides A and B and Alatamide

Molecules ◽  
2019 ◽  
Vol 24 (20) ◽  
pp. 3764
Author(s):  
Ran Lin ◽  
Xi Lin ◽  
Qian Su ◽  
Binbin Guo ◽  
Yanqin Huang ◽  
...  
Keyword(s):  
Natural Products ◽  
Total Synthesis ◽  
Synthetic Strategy

The total synthesis of potent anti-obesity lansiumamide B was accomplished in four steps using commercially available materials. The synthetic strategy, featured with copper-catalyzed Buchwald coupling, is concise, convergent, practical and can be carried out on a one-gram scale. This approach could give either Z- or E-configured enamide moiety in natural products with absolute stereocontrol and was applied in the total synthesis of natural products.

scholarly journals Linear Triquinane Sesquiterpenoids: Their Isolation, Structures, Biological Activities, and Chemical Synthesis

Molecules ◽  
2018 ◽  
Vol 23 (9) ◽  
pp. 2095 ◽  
Author(s):  
Yi Qiu ◽  
Wen-Jian Lan ◽  
Hou-Jin Li ◽  
Liu-Ping Chen
Keyword(s):  
Chemical Synthesis ◽  
Total Synthesis ◽  
Chemical Structure ◽  
Biological Activities ◽  
Structural Diversity ◽  
Structure Identification ◽  
Important Class ◽  
Soft Corals ◽  
Wide Range ◽  
New Challenges

Linear triquinane sesquiterpenoids represent an important class of natural products. Most of these compounds were isolated from fungi, sponges, and soft corals, and many of them displayed a wide range of biological activities. On account of their structural diversity and complexity, linear triquinane sesquiterpenoids present new challenges for chemical structure identification and total synthesis. 118 linear triquinane sesquiterpenoids were classified into 8 types, named types I–VIII, based on the carbon skeleton and the position of carbon substituents. Their isolation, structure elucidations, biological activities, and chemical synthesis were reviewed. This paper cited 102 articles from 1947 to 2018.

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