scholarly journals The biology and total syntheses of bisbenzylisoquinoline alkaloids

2021 ◽  
Author(s):  
Viviene K. Nguyen ◽  
Kevin. G. M. Kou
Keyword(s):  
Natural Products ◽  
Biosynthetic Pathway ◽  
Total Syntheses ◽  
Concise Overview ◽  
Bisbenzylisoquinoline Alkaloids ◽  
Bisbenzylisoquinoline Alkaloid

This mini-review provides a concise overview of the biosynthetic pathway and pharmacology of bisbenzylisoquinoline alkaloid (bisBIA) natural products.

Molecular Docking Approaches to Suggest the Anti-Mycobacterial Targets of Natural Products

2020 ◽  
Author(s):  
Rafael Baptista ◽  
Sumana Bhowmick ◽  
Shen Jianying ◽  
Luis Mur
Keyword(s):  
Natural Products ◽  
Molecular Docking ◽  
Free Energies ◽  
Antibiotic Resistant ◽  
Drug Lead ◽  
Bisbenzylisoquinoline Alkaloids ◽  
Docking Approach ◽  
Global Threat ◽  
Physicochemical And Structural Properties

Tuberculosis (TB) is a major global threat mostly due to the development of antibiotic resistant forms of Mycobacterium tuberculosis, the causal agent of the disease. Driven by the pressing need for new anti-mycobacterial agents, several natural products (NPs) have been shown to have in vitro activities against M. tuberculosis. The utility of any NP as a drug lead is augmented when the anti-mycobacterial target(s) is unknown. To suggest these, we used a molecular docking approach to predict the interactions of 53 selected anti-mycobacterial NPs against known ‘druggable’ mycobacterial targets ClpP1P2, DprE1, InhA, KasA, PanK, PknB and Pks13. The docking scores / binding free energies were predicted and calculated using AutoDock Vina along with physicochemical and structural properties of the NPs, using PaDEL descriptors. These were compared to the established inhibitor (control) drugs for each mycobacterial target. The specific interactions of the bisbenzylisoquinoline alkaloids 2-nortiliacorinine, tiliacorine and 13’-bromotiliacorinine against the targets PknB and DprE1 (-11.4, -10.9 and -9.8 kcal.mol-1 ; -12.7, -10.9 and -10.3 kcal.mol-1 , respectively) and the lignan αcubebin and Pks13 (-11.0 kcal.mol-1 ) had significantly superior docking scores compared to controls. Our approach can be used to suggest predicted targets for the NP to be validated experimentally but these in silico steps are likely to facilitate drug optimisation.

Formal Total Syntheses of Crocacin A-D

2005 ◽  
Vol 70 (10) ◽  
pp. 1696-1708 ◽  
Author(s):  
Magnus Besev ◽  
Christof Brehm ◽  
Alois Fürstner
Keyword(s):  
Natural Products ◽  
Aldol Reaction ◽  
Cross Coupling ◽  
Coupling Reactions ◽  
Total Syntheses ◽  
Cross Coupling Reactions ◽  
Palladium Catalyzed ◽  
The Common ◽  
Selective Addition

A concise route to the common polyketide fragment5of crocacin A-D (1-4) is presented which has previously been converted into all members of this fungicidal and cytotoxic family of dipeptidic natural products by various means. Our synthesis features asyn-selective titanium aldol reaction controlled by a valinol-derived auxiliary, a zinc-mediated, palladium-catalyzedanti-selective addition of propargyl mesylate10to the chiral aldehyde9, as well as a comparison of palladium-catalyzed Stille and Suzuki cross-coupling reactions for the formation of the diene moiety of the target.

Enzymatic dimerization in the biosynthetic pathway of microbial natural products

2021 ◽  
Author(s):  
Jiawang Liu ◽  
Anan Liu ◽  
Youcai Hu
Keyword(s):  
Natural Products ◽  
Biosynthetic Pathway ◽  
Structural Diversity ◽  
Cytochrome P450s ◽  
Microbial Natural Products

Cytochrome P450s, laccases, and intermolecular [4 + 2] cyclases, along with other enzymes were utilized to catalyze varied dimerization of matured natural products so as to create the structural diversity and complexity in microorganisms.

scholarly journals Biosynthetic pathways and enzymes involved in the production of phosphonic acid natural products

2021 ◽  
Vol 85 (1) ◽  
pp. 42-52
Author(s):  
Taro Shiraishi ◽  
Tomohisa Kuzuyama
Keyword(s):  
Natural Products ◽  
Biosynthetic Pathway ◽  
Organophosphorus Compounds ◽  
Genome Mining ◽  
Biological Molecules ◽  
Antibacterial Drug ◽  
Gene Encoding ◽  
Quarter Century ◽  
Lead Compounds ◽  
Biosynthetic Machinery

Abstract Phosphonates are organophosphorus compounds possessing a characteristic C−P bond in which phosphorus is directly bonded to carbon. As phosphonates mimic the phosphates and carboxylates of biological molecules to potentially inhibit metabolic enzymes, they could be lead compounds for the development of a variety of drugs. Fosfomycin (FM) is a representative phosphonate natural product that is widely used as an antibacterial drug. Here, we review the biosynthesis of FM, which includes a recent breakthrough to find a missing link in the biosynthetic pathway that had been a mystery for a quarter-century. In addition, we describe the genome mining of phosphonate natural products using the biosynthetic gene encoding an enzyme that catalyzes C–P bond formation. We also introduce the chemoenzymatic synthesis of phosphonate derivatives. These studies expand the repertoires of phosphonates and the related biosynthetic machinery. This review mainly covers the years 2012-2020.

Balancing skeleton and functional groups in total syntheses of complex natural products: a case study of tigliane, daphnane and ingenane diterpenoids

2021 ◽  
Author(s):  
Zhi Liu ◽  
Zhengwei Ding† ◽  
Kai Chen ◽  
Ming Xu ◽  
Tao Yu ◽  
...  
Keyword(s):  
Natural Products ◽  
Functional Groups ◽  
Synthetic Chemistry ◽  
Total Syntheses ◽  
Strategic Balance

The fruitful advancement in synthetic chemistry of the title families of complex diterpenes has stimulated and enjoyed strategic balance between building the skeletons and installing the functional groups.

Pentafulvene for the Synthesis of Complex Natural Products: Total Syntheses of (±)-Pallambins A and B

2015 ◽  
Vol 127 (38) ◽  
pp. 11379-11382 ◽  
Author(s):  
Christian Ebner ◽  
Erick M. Carreira
Keyword(s):  
Natural Products ◽  
Total Syntheses

scholarly journals The Tripod for Bacterial Natural Product Discovery: Genome Mining, Silent Pathway Induction, and Mass Spectrometry-Based Molecular Networking

mSystems ◽  
2018 ◽  
Vol 3 (2) ◽  
Author(s):  
Daniela B. B. Trivella ◽  
Rafael de Felicio
Keyword(s):  
Mass Spectrometry ◽  
Natural Products ◽  
Natural Product ◽  
Biosynthetic Pathway ◽  
Genome Mining ◽  
Chemical Compounds ◽  
Gene Clusters ◽  
Tandem Mass ◽  
Molecular Networking ◽  
Natural Product Discovery

ABSTRACT Natural products are the richest source of chemical compounds for drug discovery. Particularly, bacterial secondary metabolites are in the spotlight due to advances in genome sequencing and mining, as well as for the potential of biosynthetic pathway manipulation to awake silent (cryptic) gene clusters under laboratory cultivation. Further progress in compound detection, such as the development of the tandem mass spectrometry (MS/MS) molecular networking approach, has contributed to the discovery of novel bacterial natural products. The latter can be applied directly to bacterial crude extracts for identifying and dereplicating known compounds, therefore assisting the prioritization of extracts containing novel natural products, for example. In our opinion, these three approaches—genome mining, silent pathway induction, and MS-based molecular networking—compose the tripod for modern bacterial natural product discovery and will be discussed in this perspective.

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