Cytolytic proteins and peptide toxins are classical virulence factors of several bacterial pathogens which disrupt epithelial barrier function, damage cells and activate or modulate host immune responses. Such toxins have not been identified previously in human pathogenic fungi. Here we identify the first, to our knowledge, fungal cytolytic peptide toxin in the opportunistic pathogen Candida albicans. This secreted toxin directly damages epithelial membranes, triggers a danger response signalling pathway and activates epithelial immunity. Membrane permeabilization is enhanced by a positive charge at the carboxy terminus of the peptide, which triggers an inward current concomitant with calcium influx. C. albicans strains lacking this toxin do not activate or damage epithelial cells and are avirulent in animal models of mucosal infection. We propose the name ‘Candidalysin’ for this cytolytic peptide toxin; a newly identified, critical molecular determinant of epithelial damage and host recognition of the clinically important fungus, C. albicans.

Candidalysin is a Fungal Peptide Toxin Critical for Mucosal Infection and Immune Activation

Communications to the Editor.

‘‘The family which had the highest number of species was Lejeuneaceae.’’] Adie, P. A., S. T. Torsabo, U. A. Uno & J. Ajegi. 2014. Funaria hygrometrica moss as bioindicator of atmospheric pollution of heavy metals in Makurdi and environs, north central Nigeria. Research Journal of Chemical Sciences [Nigeria] 4(10): 10–17. Adinugroho, W. C., I N. N. Suryadiputra, B. H. Saharjo & L. Siboro. 2005. Manual for the Control of Fire in Peatlands and Peatland Forest. xxþ 162 pp. Wetlands International, Indonesia Programme, Bogor, Indonesia. [ISBN: 979-99373-7-X.] Afonina, O. M. 2019. Contributions to the moss flora of Altacheisky Sanctuary (Republic of Buryatia). Botanicheskii Zhurnal (Moscow & Leningrad) 104(11–12): 1681–1697. [In Russian with English abstract.] Afonina, O. M., O. V. Lavrinenko & I. A. Lavrinenko. 2019. Mosses in plant communities in northwest of the Bolzhezemelskaya tundra (Nenets Autonomous District). Botanicheskii Zhurnal (Moscow & Leningrad) 104(9): 1333–1354. [In Russian with

https://bioone.org/journals/the-bryologist/volume-123/issue-4/0007-2745-123.4.674/Recent-literature-on-bryophytes--1234/10.1639/0007-2745-123.4.674.pdf

Recent literature on bryophytes — 123(4)

The Birch reduction dearomatizes arenes into 1,4-cyclohexadienes. Despite substantial efforts devoted to avoiding ammonia and cryogenic conditions, the traditional, cumbersome, and dangerous proced...

Scalable Birch reduction with lithium and ethylenediamine in tetrahydrofuran.

Polycyclic natural products are an inexhaustible source of medicinal agents, and their complex molecular architecture renders challenging synthetic targets where innovative and effective approaches for their rapid construction are urgently required. The total synthesis of polycyclic natural products has witnessed exponential progression along with the emergence of new synthetic strategies and concepts, such as sequential C-H functionalizations, radical-based transformations, and functional group pairing strategies. Our group exerts continued interest in the construction of bioactive and structurally complex natural products as well as evaluation of the mode of action of these molecules. In this Account, we will showcase how these new synthetic strategies are employed and guide our total synthesis endeavors.During the last two decades, a series of remarkable advances in C-H functionalization have led to the emergence of many new approaches to directly functionalize C-H bonds into useful functional groups. These selective transformations have provided a great opportunity for the step- and atom-economical construction of key fragments in complex molecule synthesis. We recently furnished the total syntheses for polycyclic natural products: incarviatone A, chrysomycin A, polycarcin V, and gilvocarcin V by employing a multiple C-H bond functionalization strategy. The polysubstituted benzene or naphthalene skeleton was constructed through sequential and site-selective C-H functionalizations from readily available simple starting materials, which reduced the number of steps and streamlined synthesis.Recently, we have also completed the total syntheses for a number of skeletally diverse tetracyclic Isodon diterpenoids inspired by their biogenesis and radical-based retrosynthetic disconnections. Radical transformations are strategically and tactically utilized in our syntheses, and radical-based reactions, including organo-SOMO catalysis, Birch reduction, regioselective 1,6-dienyne reductive cyclization, visible-light-mediated Schenck ene reaction, and photoradical-mediated late-stage skeletal rearrangement, play significant roles in our synthetic endeavors. Protecting-group-free and scalable syntheses are also built into our work to achieve the "ideal" synthesis. Furthermore, our synthetic work reveals that late-stage skeletal rearrangement through a photo radical process is possible in a biological setting in complement with nature's carbocation chemistry in complex natural product biosynthesis.Lycopodium alkaloids are a large family of structurally unique polycyclic natural products with impressive biological activities. Owing to their fascinating polycyclic architectures and diverse biological activities, these alkaloids have continued to serve as targets as well as inspirations for the synthetic community for decades. To access these bioactive natural products or natural product-like molecules for biological exploration and drug discovery, we applied a novel functional group pairing strategy to furnish the total syntheses for several Lycopodium alkaloids and obtained numerous skeletally diverse compounds with structural complexity comparable to natural products.

New Strategies in the Efficient Total Syntheses of Polycyclic Natural Products.

A divergent synthetic approach to biogenetically related diterpenoids such as ent-kauranes, ent-trachylobanes, ent-beyerane, and ent-atisane has been developed. The unified synthetic route involves the De Mayo reaction to rapidly generate the bicyclo[3.2.1]-octane moiety of ent-kaurane. The key reactions also include bioinspired nucleophilic cyclopropanation generating the [3.2.1.02,7 ]-tricyclic core of ent-trachylobane and regioselective cyclopropane fragmentation furnishing ent-beyerane and ent-atisane through the nucleophilic attack and protonation of the cyclopropane ring. This strategy enables the asymmetric total syntheses of six diterpenoids from the commercially available geraniol.

Divergent Total Synthesis of Euphoranginol C, Euphoranginone D, ent‐Trachyloban‐3β‐ol, ent‐Trachyloban‐3‐one, Excoecarin E, and ent‐16α‐Hydroxy‐atisane‐3‐one

Probing the Interconversion of Labdane Lactones from the Chinese Liverwort Pallavicinia ambigua.

An enantioselective synthetic approach for preparing manginoids and guignardones, two types of biogenetically related meroterpenoids, is reported. This bioinspired and divergent synthesis employs an oxidative 1,3-dicarbonyl radical-initiated cyclization and cyclodehydration of the common precursor to forge the central ring of the manginoids and guignardones, respectively, at a late stage. Key synthetic steps include silica-gel-promoted semipinacol rearrangement to form the 6-oxabicyclo[3.2.1]octane skeleton and the Suzuki-Miyaura reaction of vinyl bromide to achieve fragment coupling. This synthesis protocol enables the asymmetric syntheses of four fungal meroterpenoids from commercially available materials.

Yan Zong

Papers

Divergent Total Synthesis of Euphoranginol C, Euphoranginone D, ent‐Trachyloban‐3β‐ol, ent‐Trachyloban‐3‐one, Excoecarin E, and ent‐16α‐Hydroxy‐atisane‐3‐one

Probing the Interconversion of Labdane Lactones from the Chinese Liverwort Pallavicinia ambigua.

Enantioselective Total Syntheses of Manginoids A and C and Guignardones A and C

Terpenoids from the Chinese liverwort Odontoschisma grosseverrucosum and their antifungal virulence activity.