Complex molecular architectures containing cyclopropanes present significant challenges for any synthetic chemist. This review aims to highlight the strategic considerations for introduction of the cyclopropane motif in a collection of recent total syntheses. At first, an overview of the most important and widely used cyclopropanation techniques is presented, followed by a discussion of elegant approaches and clever solutions that have been developed to enable the synthesis of various unique cyclopropane natural products or use of cyclopropanes as versatile strategic intermediates.

Cyclopropanation Strategies in Recent Total Syntheses

Endophytes are abundant in plants and studies are continuously emanating on their ability to protect plants from pathogens that cause diseases especially in the field of agriculture. The advantage that endophytes have over other biocontrol agents is the ability to colonize plant’s internal tissues. Despite this attributes, a deep understanding of the mechanism employed by endophytes in protecting the plant from diseases is still required for both effectiveness and commercialization. Also, there are increasing cases of antibiotics resistance among most causative agents of diseases in human beings, which calls for an alternative drug discovery using natural sources. Endophytes present themselves as a storehouse of many bioactive metabolites such as phenolic acids, alkaloids, quinones, steroids, saponins, tannins, and terpenoids which makes them a promising candidate for anticancer, antimalarial, antituberculosis, antiviral, antidiabetic, anti-inflammatory, antiarthritis, and immunosuppressive properties among many others, even though the primary function of bioactive compounds from endophytes is to make the host plants resistant to both abiotic and biotic stresses. Endophytes still present themselves as a peculiar source of possible drugs. This study elucidates the mechanisms employed by endophytes in protecting the plant from diseases and different bioactivities of importance to humans with a focus on endophytic bacteria and fungi.

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Elucidating Mechanisms of Endophytes Used in Plant Protection and Other Bioactivities With Multifunctional Prospects.

This review presents an update on the current knowledge of the secondary metabolite potential of the major fungal species used in industrial biotechnology, i.e., Aspergillus niger, Aspergillus oryzae, and Trichoderma reesei. These species have a long history of safe use for enzyme production. Like most microorganisms that exist in a challenging environment in nature, these fungi can produce a large variety and number of secondary metabolites. Many of these compounds present several properties that make them attractive for different industrial and medical applications. A description of all known secondary metabolites produced by these species is presented here. Mycotoxins are a very limited group of secondary metabolites that can be produced by fungi and that pose health hazards in humans and other vertebrates when ingested in small amounts. Some mycotoxins are species-specific. Here, we present scientific basis for (1) the definition of mycotoxins including an update on their toxicity and (2) the clarity on misclassification of species and their mycotoxin potential reported in literature, e.g., A. oryzae has been wrongly reported as an aflatoxin producer, due to misclassification of Aspergillus flavus strains. It is therefore of paramount importance to accurately describe the mycotoxins that can potentially be produced by a fungal species that is to be used as a production organism and to ensure that production strains are not capable of producing mycotoxins during enzyme production. This review is intended as a reference paper for authorities, companies, and researchers dealing with secondary metabolite assessment, risk evaluation for food or feed enzyme production, or considerations on the use of these species as production hosts.

/pdf/safety-of-the-fungal-workhorses-of-industrial-biotechnology-3kg2uk9zl3.pdf

Safety of the fungal workhorses of industrial biotechnology: update on the mycotoxin and secondary metabolite potential of Aspergillus niger , Aspergillus oryzae , and Trichoderma reesei

Natural product libraries contain specialized metabolites derived from plants, animals, and microorganisms that play a pivotal role in drug discovery due to their immense structural diversity and wide variety of biological activities. The strategies to greatly extend natural product scaffolds through available biological and chemical approaches offer unique opportunities to access a new series of natural product analogues, enabling the construction of diverse natural product-like libraries. The affordability of these structurally diverse molecules has been a crucial step in accelerating drug discovery. This review provides an overview of various approaches to exploit the diversity of compounds for natural product-based drug development, drawing upon a series of examples to illustrate each strategy.

Strategies to diversify natural products for drug discovery.

A critical review on exploiting the pharmaceutical potential of plant endophytic fungi.

Xanthone derivatives from Aspergillus sydowii, an endophytic fungus from the liverwort Scapania ciliata S. Lac and their immunosuppressive activities

Pallambins A and B, Unprecedented Hexacyclic 19-nor-Secolabdane Diterpenoids from the Chinese Liverwort Pallavicinia ambigua

Bioactivity-guided fractionation of the cytotoxic extract of Aspergillus niger, an endophytic fungus from the Chinese liverwort Heteroscyphus tener (Steph.) Schiffn., afforded five new naphtho-γ-pyrones, rubrofusarin-6-O-α-D-ribofuranoside (1), (R)-10-(3-succinimidyl)-TMC-256A1 (2), asperpyrone E (3), isoaurasperone A (4), and isoaurasperone F (5), as well as four known ones, dianhydroaurasperone C (6), aurasperone D (7), asperpyrone D (8), and asperpyrone A (9), together with a cytotoxic cyclic pentapeptide, malformin A1 (10). Their structures were determined by extensive spectroscopic analysis. The absolute configurations of dimeric naphtho-γ-pyrones 3-9 were also determined by analysis of their respective CD spectra.

Naphtho‐γ‐pyrones from Endophyte Aspergillus niger Occurring in the Liverwort Heteroscyphus tener (Steph.) Schiffn.

Three new metabolites, asperfumigatin (1), isochaetominine (10), and 8'-O-methylasterric acid (21), together with nineteen known compounds, were obtained from the culture of Aspergillus fumigatus, an endophytic fungus from the Chinese liverwort Heteroscyphus tener (Steph.) Schiffn. Their structures were established by extensive analysis of the spectroscopic data. The absolute configurations of 1 and 10 were determined by analysis of their respective CD spectra. Cytotoxicity of these isolates against four human cancer cell lines was also determined.

Secondary Metabolites from Aspergillus fumigatus, an Endophytic Fungus from the Liverwort Heteroscyphus tener (Steph.) Schiffn.

Six new pairs of bibenzyl-based meroterpenoid enantiomers, (±)-rasumatranin A-D (1-4) and (±)-radulanin M and N (5 and 6), and six known compounds were isolated from the adnascent Chinese liverwort, Radula sumatrana. Their structures were elucidated based on spectroscopic data and chiral phase HPLC-ECD analyses. The structures of 1 and 7 were also confirmed by single-crystal X-ray diffraction analysis. Cytotoxicity tests of the isolated compounds showed that 6-hydroxy-3-methyl-8-phenylethylbenzo[b]oxepin-5-one (8) showed activity against the human cancer cell lines MCF-7, PC-3, and SMMC-7721, with IC50 values of 3.86, 6.60, and 3.58 μM, respectively, and induced MCF-7 cell death through a mitochondria-mediated apoptosis pathway.

Jin-Chuan Zhou

Papers

Xanthone derivatives from Aspergillus sydowii, an endophytic fungus from the liverwort Scapania ciliata S. Lac and their immunosuppressive activities

Pallambins A and B, Unprecedented Hexacyclic 19-nor-Secolabdane Diterpenoids from the Chinese Liverwort Pallavicinia ambigua

Naphtho‐γ‐pyrones from Endophyte Aspergillus niger Occurring in the Liverwort Heteroscyphus tener (Steph.) Schiffn.

Secondary Metabolites from Aspergillus fumigatus, an Endophytic Fungus from the Liverwort Heteroscyphus tener (Steph.) Schiffn.

Bibenzyl-Based Meroterpenoid Enantiomers from the Chinese Liverwort Radula sumatrana.