Secondary metabolites from marine sponges of the genus Agelas: a comprehensive update insight on structural diversity and bioactivity

As one of the most common marine sponges in tropical and subtropical oceans, the sponges of the genus Agelas, have emerged as unique and yet under-investigated pools for discovery of natural products with fabulous molecular diversity and myriad interesting biological activities. The present review highlights the chemical structure and biological activity of 355 compounds that have been isolated and characterized from the members of Agelas sponges, over the period of about five decades (from 1971 to November 2021). For a better understanding, these numerous compounds are firstly classified and presented according to their carbon skeleton as well as their biosynthetic origins. Relevant summaries focusing on the source organism and the associated bioactivity of these compounds belonging to different chemical classes are also provided. This review highlights sponges of the genus Agelas as exciting source for discovery of intriguing natural compounds.

The marine sponges of the genus Agelas, are unique and yet under-investigated pools for discovery of natural products with fabulous molecular diversity and myriad interesting biological activities.     

Bioactive natural products from marine sponges belonging to family Hymedesmiidae

Natural products of marine origin exhibit extensive biological activities, and display a vital role in the exploration of new compounds for drug development. Marine sponges have been reported at the top with respect to the discovery of biologically active metabolites that have potential pharmaceutical applications. The family Hymedesmiidae belonging to the Demospongiae class includes ten accepted genera, of which four genera were explored for their bioactive metabolites, namely Phorbas, Hamigera, Hemimycale, and Kirkpatrickia. Genus Phorbas has received more attention due to the isolation of various classes of compounds with unique structures mainly diterpenes, alkaloids, sesterterpenes, and steroids that exhibited diverse biological activities including: antiviral, antimicrobial, and anti-inflammatory, whereas anticancer compounds predominated. This review focuses on the isolated secondary metabolites from family Hymedesmiidae with their biological potential and covers the literature from 1989 to 2020.

Natural products of marine origin exhibit extensive biological activities, and display a vital role in the exploration of new compounds for drug development.     

Arylnaphthalene lactone analogues: synthesis and development as excellent biological candidates for future drug discovery

Arylnaphthalene lactones are natural products extracted from a wide range of different parts of plants. The progressing interest in the synthesis of these compounds is due to their significant biological activities, which have made them potential candidates in drug discovery and development. This review mainly covers recent developments in the synthesis and biological applications of arylnaphthalene lactone analogs.

A review of recent developments in the synthesis and biological applications of arylnaphthalene lactones analogs.     

The genus Micromonospora as a model microorganism for bioactive natural product discovery

This review covers the development of the genus Micromonospora as a model for natural product research and the timeline of discovery progress from the classical bioassay-guided approaches through the application of genome mining and genetic engineering techniques that target specific products. It focuses on the reported chemical structures along with their biological activities and the synthetic and biosynthetic studies they have inspired. This survey summarizes the extraordinary biosynthetic diversity that can emerge from a widely distributed actinomycete genus and supports future efforts to explore under-explored species in the search for novel natural products.

We explore the genus Micromonospora as a model for natural product research and the discovery progress from the classical bioassay-guided approaches through to the application of genome mining and genetic engineering techniques that target specific products.     

Bromo-lactamization of isoxazole via neighboring group participation: toward spiro-isoxazoline γ- and δ-lactams

Spiro-heterocycles containing natural products and synthetic analogues have a broader biomedicinal application due to their rigid 3D conformation and structural implications. In this context, constructing spiro-isoxazoline systems have continued our interest in natural products and synthetic units to investigate their novel biological activities. Herein, a bromo-lactamization mediated neighboring group participation approach has been utilized on various isoxazole-amides to construct an array of spiro-isoxazoline-lactams. The easy synthesis with diverse functionalization in the periphery of a novel 3D framework could be interesting for biomedical investigation.

An efficient bromo-lactamization mediated neighboring group participation approach for synthesizing a novel 3D framework, spiro-isoxazoline-lactam, was developed.     

Mannich bases derived from lawsone and their metal complexes: synthetic strategies and biological properties

Lawsone (2-hydroxynaphthalene-1,4-dione) is a natural product which shows significant biological activity. Aminomethylnaphthoquinone Mannich bases derived from lawsone constitute an interesting class of naphthoquinones and/or their metal complexes have demonstrated a series of important biological properties. So, this review aimed to document the publications concerning the synthesis of aminomethylnaphthoquinone Mannich bases from lowsone, aldehydes and amines and their metal complexes using different conditions, and investigation of their applications.

Lawsone (2-hydroxynaphthalene-1,4-dione) is a natural product which shows significant biological activity.     

Target identification of anticancer natural products using a chemical proteomics approach

In recent years, there has been a strong demand worldwide for the identification and development of potential anticancer drugs based on natural products. Natural products have been explored for their diverse biological and therapeutic applications from ancient time. In order to enhance the efficacy and selectivity and to minimize the undesired side effects of anti cancer natural products (ANPs), it is essential to understand their target proteins and their mechanistic pathway. Chemical proteomics is one of the most powerful tools to connect ANP target identification and quantification where labeling and non-labeling based approaches have been used. Herein, we have discussed the various strategies to systemically develop selective ANP based chemical probes to characterise their specific and non-specific target proteins using a chemical proteomic approach in various cancer cell lysates.

Natural products are one of the most effective therapeutic candidates in cancer treatment. In this review, we briefly discuss the target identification of anticancer natural products in different cancer cell lines through a chemical proteomics approach.     

Applications of Friedel–Crafts reactions in total synthesis of natural products

Over the years, Friedel–Crafts (FC) reactions have been acknowledged as the most useful and powerful synthetic tools for the construction of a special kind of carbon–carbon bond involving an aromatic moiety. Its stoichiometric and, more recently, its catalytic procedures have extensively been studied. This reaction in recent years has frequently been used as a key step (steps) in the total synthesis of natural products and targeted complex bioactive molecules. In this review, we try to underscore the applications of intermolecular and intramolecular FC reactions in the total syntheses of natural products and complex molecules, exhibiting diverse biological properties.

In this review, we try to underscore the applications of intermolecular and intramolecular FC reactions in the total syntheses of natural products and complex molecules, exhibiting diverse biological properties.     

Recent metal-catalysed approaches for the synthesis of cyclopenta[b]indoles

The cyclopenta[b]indole scaffold is ubiquitously present in several bioactive natural products and pharmaceutically interesting compounds. Of the numerous methods known for the synthesis of cyclopenta-fused indoles, this review highlights only the metal-catalysed approaches reported from the year 2015 onwards. This review encompasses our own efforts leading to the synthesis of cyclopentannulated indoles, in addition to the seminal contributions of several other researchers.

This review provides a summary of recent metal-catalysed approaches for the synthesis of cyclopenta[b]indoles.     

Marine unsaturated fatty acids: structures,bioactivities, biosynthesis and benefits

Unsaturated fatty acids (UFAs) are an important category of monounsaturated and polyunsaturated fatty acids with nutritional properties. These secondary metabolites have been obtained from multitudinous natural resources, including marine organisms. Because of the increasing numerous biological importance of these marine derived molecules, this review covers 147 marine originated UFAs reported from 1978 to 2018. The review will focus on the structural characterizations, biological properties, proposed biosynthetic processes, and healthy benefits mediated by gut microbiota of these marine naturally originated UFAs.

Unsaturated fatty acids (UFAs) are an important category of monounsaturated and polyunsaturated fatty acids with nutritional properties.     

The role of biocatalysis in the asymmetric synthesis of alkaloids – an update

Alkaloids are a group of natural products with interesting pharmacological properties and a long history of medicinal application. Their complex molecular structures have fascinated chemists for decades, and their total synthesis still poses a considerable challenge. In a previous review, we have illustrated how biocatalysis can make valuable contributions to the asymmetric synthesis of alkaloids. The chemo-enzymatic strategies discussed therein have been further explored and improved in recent years, and advances in amine biocatalysis have vastly expanded the opportunities for incorporating enzymes into synthetic routes towards these important natural products. The present review summarises modern developments in chemo-enzymatic alkaloid synthesis since 2013, in which the biocatalytic transformations continue to take an increasingly ‘central’ role.

This review article discusses developments in the chemo-enzymatic synthesis of alkaloids since 2013, showcasing how modern methods of organic synthesis and biocatalysis are combined to establish novel routes towards these important natural products.     

Advancements in the synthesis of fused tetracyclic quinoline derivatives

Fused tetracyclic systems containing a quinoline nucleus represent an important class of heterocyclic bioactive natural products and pharmaceuticals because of their significant and wide-spectrum biological properties. Several of these compounds have been obtained with diverse pharmacological and biological activities, such as antiplasmodial, antifungal, antibacterial, potent antiparasitic, antiproliferative, anti-tumor and anti-inflammatory activities. This information will be beneficial for medicinal chemists in the field of drug discovery to design and synthesize new fused tetracyclic quinolines as potent therapeutical agents. This review article provides a comprehensive report regarding the methods developed for the synthesis of fused tetracyclic quinolines reported so far (till October 2019). The article includes synthesis by one-pot domino reaction, microwave synthesis using a catalyst, using ionic liquids, photocatalytic synthesis (UV radiation), Pfitzinger reaction, I₂-catalyzed cyclization reaction, Wittig reaction, cascade reaction, imino Diels–Alder reaction, Friedel–Crafts reaction, CDC reaction, solvent-free reactions and using small chiral organic molecules as catalysts. To the best of our knowledge, this is the first review focused on the synthesis of fused tetracyclic quinolines along with mechanistic aspects.

Fused tetracyclic systems containing a quinoline nucleus represent an important class of heterocyclic bioactive natural products and pharmaceuticals because of their significant and wide-spectrum biological properties.     

Peptidoglycan pathways: there are still more!

The discovery of 3^rd and 4^th generations of currently existing classes of antibiotics has not hindered bacterial resistance, which is escalating at an alarming global level. This review follows WHO recommendations through implementing new criteria for newly discovered antibiotics. These recommendations focus on abandoning old scaffolds and hitting new targets. In light of these recommendations, this review discusses seven bacterial proteins that no commercial antibiotics have targeted yet, alongside their reported chemical scaffolds.

The discovery of 3^rd and 4^th generations of currently existing classes of antibiotics has not hindered bacterial resistance, which is escalating at an alarming global level.     

Application of asymmetric Sharpless aminohydroxylation in total synthesis of natural products and some synthetic complex bio-active molecules

This report illustrates the applications of Asymmetric Sharpless Aminohydroxylation (ASAH) in the stereoselective synthesis of vicinal amino alcohols as important intermediates in the total synthesis of complex molecules and natural products with significant biological activities. The ASHA allows the regio- syn-selective synthesis of 1,2-amino alcohols via reaction of alkenes with salts of N-halosulfonamides, -amides and -carbamates employing osmium tetroxide (OsO₄) as an efficient catalyst. In this reaction, chirality is induced via the addition of dihydroquinine- and dihydroquinidine as derived chiral ligands.

This work shows applications of Asymmetric Sharpless Aminohydroxylation (ASAH) in the stereoselective synthesis of vicinal amino alcohols as important intermediates in the total synthesis of complex molecules and natural products with significant biological activities.     

DiaNat-DB: a molecular database of antidiabetic compounds from medicinal plants

Natural products are an invaluable source of molecules with a large variety of biological activities. Interest in natural products in drug discovery is documented in an increasing number of publications of bioactive secondary metabolites. Among those, medicinal plants are one of the most studied for this endeavor. An ever thriving area of opportunity within the field concerns the discovery of antidiabetic natural products. As a result, a vast amount of secondary metabolites are isolated from medicinal plants used against diabetes mellitus but whose information has not been organized systematically yet. Several research articles enumerate antidiabetic compounds, but the lack of a chemical database for antidiabetic metabolites limits their application in drug development. In this work, we present DiaNat-DB, a comprehensive collection of 336 molecules from medicinal plants reported to have in vitro or in vivo antidiabetic activity. We also discuss a chemoinformatic analysis of DiaNat-DB to compare antidiabetic drugs and natural product databases. To further explore the antidiabetic chemical space based on DiaNat compounds, we searched for analogs in ZINC15, an extensive database listing commercially available compounds. This work will help future analyses, design, and development of new antidiabetic drugs. DiaNat-DB and its ZINC15 analogs are freely available at http://rdu.iquimica.unam.mx/handle/20.500.12214/1186.

Medicinal plants are widely used against diabetes mellitus. Here, we provide DiaNat-DB, the first publicly available database of secondary metabolites from medicinal plants, chemically characterized, and integrated with antidiabetic activity.     

Advances in targeting and heterologous expression of genes involved in the synthesis of fungal secondary metabolites

The revolutionary discovery of penicillin only marks the start of our exploration for valuable fungal natural products. Advanced genome sequencing technologies have translated the fungal genome into a huge reservoir of “recipes” – biosynthetic gene clusters (BGCs) – for biosynthesis. Studying complex fungal genetics demands specific gene manipulation strategies. This review summarizes the current progress in efficient gene targeting in fungal cells and heterologous expression systems for expressing fungal BGCs of fungal secondary metabolites.

Gene targeting involves integration of foreign DNA into the fungal genome by several strategies including Agrobacterium tumefaciens-mediated transformation (ATMT).     

Isolation and synthesis of cryptosanguinolentine (isocryptolepine), a naturally-occurring bioactive indoloquinoline alkaloid

Cryptosanguinolentine (isocryptolepine) is one of the minor naturally-occurring monomeric indoloquinoline alkaloids, isolated from the West African climbing shrub Cryptolepis sanguinolenta. The natural product displays such a simple and unique skeleton, which chemists became interested in well before it was found in Nature. Because of its structure and biological activity, the natural product has been targeted for synthesis on numerous occasions, employing a wide range of different strategies. Hence, discussed here are aspects related to the isolation of isocryptolepine, as well as the various approaches toward its total synthesis.

The isolation and properties of the heterocycle are detailed and the diversity of chemical approaches toward the natural product are systematically ordered and reviewed.     

First total synthesis of versicotide A,B and C

The syntheses of versicotides A–C, natural products containing anthranilic acid and NMe-Ala, were achieved by solid phase peptide synthesis on 2-chlorotrityl resin followed by solution phase macrocyclization. Using an oxyma additive, the difficult coupling reactions to the deactivated aromatic amine of o-aminobenzoic acid, were performed in high yield, avoiding anthranilic rearrangements or side reactions.

Versicotides A–C, natural products containig anthranilic acid and NMe-Ala, were prepared by Fmoc/SPPS and solution phase macrocyclization.     

Decarboxylative cross-coupling reactions for P(O)–C bond formation

Phosphorus-containing compounds are one of the most important classes of organic compounds, which have wide applications in organic chemistry, medicinal chemistry, agricultural chemistry, and materials chemistry. In particular, organophosphorus compounds bearing a P(O)–C bond have attracted significant attention in recent decades due to their widespread biological and pharmacological activities. In this review, we will highlight the most important developments in the construction of P(O)–C bonds through decarboxylative C–P cross-coupling reactions. The literature has been surveyed from 2011 to May 2018.

Phosphorus-containing compounds are one of the most important classes of organic compounds, which have wide applications in organic chemistry, medicinal chemistry, agricultural chemistry, and materials chemistry.     

Rhodium(iii) catalyzed olefination and deuteration of tetrahydrocarbazole

The rhodium-catalyzed olefination and deuteration of tetrahydrocarbazoles in water with the aid of an N,N-dimethylcarbamoyl-protected group is presented. This olefination method features a broad substrate scope, good functional-group tolerance, and high efficiency in water. Practical applications of the protocol are illustrated by the synthesis of various evodiamine derivatives. As such, this environmentally friendly approach to directly modify natural products will attract much attention in academic and industrial research.

The rhodium-catalyzed olefination and deuteration of tetrahydrocarbazoles in water with the aid of an N,N-dimethylcarbamoyl-protected group is presented.