scholarly journals The Synthesis of Aigialomycin D Analogues

2021 ◽  
Author(s):  
◽  
Samuel Z.Y. Ting
Keyword(s):  
Total Synthesis ◽  
Functional Group ◽  
Biological Activities ◽  
Biological Testing ◽  
Hsp90 Inhibition ◽  
Vast Array ◽  
Synthetic Strategy ◽  
Structure Activity ◽  
Expansive Group ◽  
Resorcylic Acid Lactones

<p>Aigialomycin D is a fungal natural product possessing kinase inhibition properties. It is a member of a class of compounds known as the resorcylic acid lactones, a expansive group containing compounds exhibiting a vast array of biological activities. These include kinase and Hsp90 inhibition, highly desirable properties in the drug development field. This research project sought to capitalise on previous work involving the successful total synthesis of aigialomycin D. By developing the synthetic methodology, analogues of aigialomycin D could be prepared for biological testing to obtain valuable structure-activity relationship information. The focus of this thesis involves the successful synthesis of aigialomycin D diastereomer, 5',6'-epi,epi-aigialomycin D and the attempted synthesis of 100-epi-aigialomycin D, via the synthetic strategy developed previously in combination with enantiomeric starting material fragments ... The synthesis of functional group analogues, 6'-oxo-aigialomycin D, 7',8'-cyclopropyl aigialomycin D and 5-chloro-agialomycin D were also attempted via derivatisation of late-stage intermediates in the aigialomycin D synthesis. The thesis herein recounts the successes and failures in the synthesis of various aigialomycin D analogues ...</p>

scholarly journals The Synthesis of Aigialomycin D Analogues

2021 ◽  
Author(s):  
◽  
Samuel Z.Y. Ting
Keyword(s):  
Total Synthesis ◽  
Functional Group ◽  
Biological Activities ◽  
Biological Testing ◽  
Hsp90 Inhibition ◽  
Vast Array ◽  
Synthetic Strategy ◽  
Structure Activity ◽  
Expansive Group ◽  
Resorcylic Acid Lactones

<p>Aigialomycin D is a fungal natural product possessing kinase inhibition properties. It is a member of a class of compounds known as the resorcylic acid lactones, a expansive group containing compounds exhibiting a vast array of biological activities. These include kinase and Hsp90 inhibition, highly desirable properties in the drug development field. This research project sought to capitalise on previous work involving the successful total synthesis of aigialomycin D. By developing the synthetic methodology, analogues of aigialomycin D could be prepared for biological testing to obtain valuable structure-activity relationship information. The focus of this thesis involves the successful synthesis of aigialomycin D diastereomer, 5',6'-epi,epi-aigialomycin D and the attempted synthesis of 100-epi-aigialomycin D, via the synthetic strategy developed previously in combination with enantiomeric starting material fragments ... The synthesis of functional group analogues, 6'-oxo-aigialomycin D, 7',8'-cyclopropyl aigialomycin D and 5-chloro-agialomycin D were also attempted via derivatisation of late-stage intermediates in the aigialomycin D synthesis. The thesis herein recounts the successes and failures in the synthesis of various aigialomycin D analogues ...</p>

Synthesis and biological activities of chaetocin and its derivatives

2012 ◽  
Vol 84 (6) ◽  
pp. 1369-1378 ◽  
Author(s):  
Mikiko Sodeoka ◽  
Kosuke Dodo ◽  
Yuou Teng ◽  
Katsuya Iuchi ◽  
Yoshitaka Hamashima ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Caspase 3 ◽  
Biological Activities ◽  
Caspase 8 ◽  
Human Leukemia ◽  
Mechanistic Studies ◽  
Anticancer Activities ◽  
Histone Methyltransferases ◽  
Structure Activity ◽  
Apoptosis Inducer

Chaetocin, a natural product isolated from fungi of Chaetomium species, is a member of the epipolythiodiketopiperazines (ETPs), which have various biological activities, including cytostatic and anticancer activities. Recently, the inhibitory activity toward histone methyltransferases (HMTs) was discovered for chaetocin. We previously reported the first total synthesis of chaetocin and various derivatives. During studies on the structure–activity relationship for HMT inhibition, we found that the enantiomer of chaetocin (ent-chaetocin) is a more potent apoptosis inducer than natural chaetocin in human leukemia HL-60 cells. Mechanistic studies showed that ent-chaetocin induces apoptosis through the caspase-8/caspase-3 pathway.

Total synthesis and biological evaluation of oscillatoxin D, E, and F

2021 ◽  
Author(s):  
Yusuke Araki ◽  
Yusuke Hanaki ◽  
Masaki Kita ◽  
Koutaro Hayakawa ◽  
Kazuhiro Irie ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Cell Line ◽  
Biological Activities ◽  
Biological Evaluation ◽  
Marine Cyanobacteria ◽  
Methyl Group ◽  
Synthetic Strategy ◽  
Target Molecules ◽  
Synthesis And Biological Evaluation

Abstract Oscillatoxins (OTXs) and aplysiatoxins (ATXs) are biosynthetically related polyketides produced by marine cyanobacteria. We previously developed a synthetic route to phenolic O-methyl analogs of OTX-D and 30-methyl-OTX-D during collective synthesis of these natural products. According to our synthetic strategy, we achieved total synthesis of OTX-D, 30-methyl-OTX-D, OTX-E, and OTX-F by deprotecting the O-methyl group in an earlier intermediate, and determined their biological activities. Although OTX-D and 30-methyl-OTX-D have been reported to show anti-leukemic activity against L1210 cell line, we found that their cytotoxicity in vitro against this cell line is relatively weak (IC50: 29–52 μM). In contrast, OTX-F demonstrated cell line-selective anti-proliferative activity against DMS-114 lung cancer cells, which implies that OTXs target as yet unknown target molecules as part of this unique activity.

scholarly journals Total Synthesis of the Natural Chalcone Lophirone E, Synthetic Studies toward Benzofuran and Indole-Based Analogues, and Investigation of Anti-Leishmanial Activity

Molecules ◽  
2022 ◽  
Vol 27 (2) ◽  
pp. 463
Author(s):  
Luca Pozzetti ◽  
Roberta Ibba ◽  
Sara Rossi ◽  
Orazio Taglialatela-Scafati ◽  
Donatella Taramelli ◽  
...  
Keyword(s):  
Natural Products ◽  
Total Synthesis ◽  
Leishmania Infantum ◽  
Anticancer Properties ◽  
Synthetic Strategy ◽  
Pathological Conditions ◽  
Structure Activity ◽  
Small Set ◽  
Synthetic Approaches ◽  
Therapeutic Leads

The potential of natural and synthetic chalcones as therapeutic leads against different pathological conditions has been investigated for several years, and this class of compounds emerged as a privileged chemotype due to its interesting anti-inflammatory, antimicrobial, antiviral, and anticancer properties. The objective of our study was to contribute to the investigation of this class of natural products as anti-leishmanial agents. We aimed at investigating the structure–activity relationships of the natural chalcone lophirone E, characterized by the presence of benzofuran B-ring, and analogues on anti-leishmania activity. Here we describe an effective synthetic strategy for the preparation of the natural chalcone lophirone E and its application to the synthesis of a small set of chalcones bearing different substitution patterns at both the A and heterocyclic B rings. The resulting compounds were investigated for their activity against Leishmania infantum promastigotes disclosing derivatives 1 and 28a,b as those endowed with the most interesting activities (IC50 = 15.3, 27.2, 15.9 μM, respectively). The synthetic approaches here described and the early SAR investigations highlighted the potential of this class of compounds as antiparasitic hits, making this study worthy of further investigation.

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.

A common mechanism links activities of butyrate in the colon

2017 ◽  
Author(s):  
Mohit S. Verma ◽  
Michael J. Fink ◽  
Gabriel L Salmon ◽  
Nadine Fornelos ◽  
Takahiro E. Ohara ◽  
...  
Keyword(s):  
Stem Cells ◽  
Histone Deacetylases ◽  
Biological Activities ◽  
Short Chain Fatty Acids ◽  
Common Mechanism ◽  
Epithelial Stem Cells ◽  
Degree Of Unsaturation ◽  
Structure Activity ◽  
Starting Point ◽  
New Compounds

Two biological activities of butyrate in the colon (suppression of proliferation of colonic epithelial stem cells and inflammation) correlate with inhibition of histone deacetylases. Cellular and biochemical studies of molecules similar in structure to butyrate, but different in molecular details (functional groups, chain-length, deuteration, oxidation level, fluorination, or degree of unsaturation) demonstrated that these activities were sensitive to molecular structure, and were compatible with the hypothesis that butyrate acts by binding to the Zn<sup>2+</sup> in the catalytic site of histone deacetylases. Structure-activity relationships drawn from a set of 36 compounds offer a starting point for the design of new compounds targeting the inhibition of histone deacetylases. The observation that butyrate was more potent than other short-chain fatty acids is compatible with the hypothesis that crypts evolved (at least in part), to separate stem cells at the base of crypts from butyrate produced by commensal bacteria.

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.

Isothiocyanate Synthetic Analogs: Biological Activities, Structure-Activity Relationships and Synthetic Strategies

2014 ◽  
Vol 14 (12) ◽  
pp. 963-977 ◽  
Author(s):  
Andrea Milelli ◽  
Carmela Fimognari ◽  
Nicole Ticchi ◽  
Paolo Neviani ◽  
Anna Minarini ◽  
...  
Keyword(s):  
Biological Activities ◽  
Synthetic Analogs ◽  
Structure Activity Relationships ◽  
Structure Activity

Single Heterocyclic Compounds as Monoamine Oxidase Inhibitors: From Past to Present

2020 ◽  
Vol 20 (10) ◽  
pp. 908-920 ◽  
Author(s):  
Su-Min Wu ◽  
Xiao-Yang Qiu ◽  
Shu-Juan Liu ◽  
Juan Sun
Keyword(s):  
Monoamine Oxidase ◽  
Heterocyclic Compounds ◽  
Biological Activities ◽  
The Past ◽  
Structure Activity ◽  
Receptor Interactions ◽  
Heterocyclic Derivatives ◽  
Inhibitory Activities ◽  
Leading Compounds ◽  
Heterocyclic Moiety

Inhibitors of monoamine oxidase (MAO) have shown therapeutic values in a variety of neurodegenerative diseases such as depression, Parkinson’s disease and Alzheimer’s disease. Heterocyclic compounds exhibit a broad spectrum of biological activities and vital leading compounds for the development of chemical drugs. Herein, we focus on the synthesis and screening of novel single heterocyclic derivatives with MAO inhibitory activities during the past decade. This review covers recent pharmacological advancements of single heterocyclic moiety along with structure- activity relationship to provide better correlation among different structures and their receptor interactions.

scholarly journals Xylochemical Synthesis and Biological Evaluation of Shancigusin C and Bletistrin G

Molecules ◽  
2021 ◽  
Vol 26 (11) ◽  
pp. 3224
Author(s):  
Leander Geske ◽  
Ulrich Kauhl ◽  
Mohamed E. M. Saeed ◽  
Anja Schüffler ◽  
Eckhard Thines ◽  
...  
Keyword(s):  
Total Synthesis ◽  
Biological Activities ◽  
Biological Evaluation ◽  
Aromatic Substitution ◽  
Substitution Reactions ◽  
Total Syntheses ◽  
Wittig Olefination ◽  
Starting Point ◽  
Perkin Reaction ◽  
Synthesis And Biological Evaluation

The biological activities of shancigusin C (1) and bletistrin G (2), natural products isolated from orchids, are reported along with their first total syntheses. The total synthesis of shancigusin C (1) was conducted by employing the Perkin reaction to forge the central stilbene core, whereas the synthesis of bletistrin G (2) was achieved by the Wittig olefination followed by several regioselective aromatic substitution reactions. Both syntheses were completed by applying only renewable starting materials according to the principles of xylochemistry. The cytotoxic properties of shancigusin C (1) and bletistrin G (2) against tumor cells suggest suitability as a starting point for further structural variation.

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