Synthetic Strategy for Construction of Highly Congested Tetracyclic Core (6–5–7–4) of Harziane Diterpenoids

2021 ◽  
Author(s):  
Qian Tu ◽  
Zheyuan Wang ◽  
Zhongchao Zhang ◽  
Jun Huang ◽  
Zhen Yang
2019 ◽  
Author(s):  
Florian Bartels ◽  
Manuela Weber ◽  
Mathias Christmann

<div>An efficient strategy for the synthesis of the potent phospholipase A2 inhibitors spongidine A and D is presented. The tetracyclic core of the natural products was assembled via an intramolecular hydrogen atom transfer‐initiated Minisci reaction. A divergent late‐stage functionalization of the tetracyclic ring system was also used to achieve a concise synthesis of petrosaspongiolide L methyl ester.</div>


2018 ◽  
Author(s):  
Erin Stache ◽  
Alyssa B. Ertel ◽  
Tomislav Rovis ◽  
Abigail G. Doyle

Alcohols and carboxylic acids are ubiquitous functional groups found in organic molecules that could serve as radical precursors, but C–O bonds remain difficult to activate. We report a synthetic strategy for direct access to both alkyl and acyl radicals from these ubiquitous functional groups via photoredox catalysis. This method exploits the unique reactivity of phosphoranyl radicals, generated from a polar/SET crossover between a phosphine radical cation and an oxygen centered nucleophile. We first show the desired reactivity in the reduction of benzylic alcohols to the corresponding benzyl radicals with terminal H-atom trapping to afford the deoxygenated product. Using the same method, we demonstrate access to synthetically versatile acyl radicals which enables the reduction of aromatic and aliphatic carboxylic acids to the corresponding aldehydes with exceptional chemoselectivity. This protocol also transforms carboxylic acids to heterocycles and cyclic ketones via intramolecular acyl radical cyclizations to forge new C–O, C–N and C–C bonds in a single step.


2019 ◽  
Author(s):  
Idriss Curbet ◽  
Sophie Colombel-Rouen ◽  
Romane Manguin ◽  
Anthony Clermont ◽  
Alexandre Quelhas ◽  
...  

<div> <div> <div> <div> <p>The synthesis of conjugated triynes by molybdenum-catalyzed alkyne metathesis is reported. Strategic to the success of this approach is the utilization of sterically-hindered diynes that allowed for the site- selective alkyne metathesis to produce the desired con- jugated triyne products. The steric hindrance of alkyne moiety was found to be crucial in preventing the for- mation of diyne byproducts. This novel synthetic strategy was amenable to self- and cross-metathesis providing straightforward access to the corresponding symmetrical and dissymmetrical triynes with high selectivity. </p> </div> </div> </div> </div>


2018 ◽  
Author(s):  
Timothy Newhouse ◽  
Daria E. Kim ◽  
Joshua E. Zweig

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.


2019 ◽  
Author(s):  
Michael Oschmann ◽  
Linus Johansson Holm ◽  
Oscar Verho

Benzofurans are everywhere in nature and they have been extensively studied by medicinal chemists over the years because of their chemotherapeutic and physiological properties. Herein, we describe a strategy that can be used to access elaborate benzo-2-carboxamide derivatives, which involves a synthetic sequence of 8-aminoquinoline directed C–H arylations followed by transamidations. For the directed C–H arylations, Pd catalysis was used to install a wide range of aryl and heteroaryl substituents at the C3 position of the benzofuran scaffold in high efficiency. Directing group cleavage and further diversification of the C3-arylated benzofuran products were then achieved in a single synthetic operation through the utilization of a two-step transamidation protocol. By bocylating the 8-aminoquinoline amide moiety of these products, it proved possible to activate them towards aminolysis with different amine nucleophiles. Interestingly, this aminolysis reaction was found to proceed efficiently without the need of any additional catalyst or additive. Given the high efficiency and modularity of this synthetic strategy, it constitute a very attractive approach for generating structurally-diverse collections of benzofuran derivatives for small molecule screening.


2018 ◽  
Vol 15 (2) ◽  
pp. 230-236 ◽  
Author(s):  
Joana Ferreira da Costa ◽  
Xerardo Garcia-Mera ◽  
David Silva Poceiro ◽  
Olga Caamano

Backiground: Alzheimer's disease is a fatal, complex, neurodegenerative disease over 46 million people live with dementia in the world characterized by the presence of plaques containing β-amyloid and neuronal loss. The GPE acts as a survival factor against β-amyloid insult in brain and suggests a possible new therapeutic strategy for the treatment of Central Nervous System injuries and neurodegenerative disorders. The structural simplicity of GPE makes it a suitable lead molecule for the development of new drugs that to cross the blood-brain barrier. Objective: With these aims in mind, we embarked on a synthetic program focused on the modification of the Lproline residue of GPE in order to investigate its importance on the neuroprotective activities. Method: The general synthetic strategy involved the preparation of several modified proline residues, which were subsequently coupled to N-Boc-glycine-OH and glutamic dimethyl ester hydrochloride. Results: the mixture of compounds 11 was obtained in good yields (72%) under these conditions, and this was readily separated by column chromatography and the components were identified by 1H and 13C NMR spectral, as well as by its EI HRMS. Conclusion: Compound (±)-8 was coupled with L-glutamic dimethyl ester hydrochloride gave a mixture of dipeptides 9a and 9b in a satisfactory yield. The use of T3P as coupling agent of the mixture 10a and 10b with Boc-glycine provided a new analogue of GPE, tripeptide 11, obtained with an overall yield of 65% from (±)-1.


2020 ◽  
Vol 09 ◽  
Author(s):  
Minita Ojha ◽  
R. K. Bansal

Background: During the last two decades, horizon of research in the field of Nitrogen Heterocyclic Carbenes (NHC) has widened remarkably. NHCs have emerged as ubiquitous species having applications in a broad range of fields, including organocatalysis and organometallic chemistry. The NHC-induced non-asymmetric catalysis has turned out to be a really fruitful area of research in recent years. Methods: By manipulating structural features and selecting appropriate substituent groups, it has been possible to control the kinetic and thermodynamic stability of a wide range of NHCs, which can be tolerant to a variety of functional groups and can be used under mild conditions. NHCs are produced by different methods, such as deprotonation of Nalkylhetrocyclic salt, transmetallation, decarboxylation and electrochemical reduction. Results: The NHCs have been used successfully as catalysts for a wide range of reactions making a large number of building blocks and other useful compounds accessible. Some of these reactions are: benzoin condensation, Stetter reaction, Michael reaction, esterification, activation of esters, activation of isocyanides, polymerization, different cycloaddition reactions, isomerization, etc. The present review includes all these examples published during the last 10 years, i.e. from 2010 till date. Conclusion: The NHCs have emerged as versatile and powerful organocatalysts in synthetic organic chemistry. They provide the synthetic strategy which does not burden the environment with metal pollutants and thus fit in the Green Chemistry.


2021 ◽  
Vol 8 (1) ◽  
pp. 18-24
Author(s):  
Xu-Heng Yang ◽  
Jian Huang ◽  
Fang Wang ◽  
Zhuoliang Liu ◽  
Yujiao Li ◽  
...  

A synthetic strategy based on sequential application of aza-Claisen rearrangement, C–H functionalization, C–N coupling and cyclization as key steps has been developed for the synthesis of 6-, 7-, 8-, and 9-membered rings N-heterocycles.


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