Steroids, Tri- and Meroterpenoids with a Quinone Structure—A Review

Terpenoids with quinoid structures are found as natural products. This includes steroidal quinones, quinones with a secosteroid structure and meroterpenoid quinones. Importantly, catechol estrogens as endogenous metabolites of estradiol and estrone are precursors of reactive quinones and semiquinones, which are thought to contribute to estrogen-induced carcinogenesis. On the other hand, a number of quinones that include substituted naphthoquinones and anthraquinones are highly cytotoxic and have been used in cancer treatment. This makes the structures interesting synthetic targets. The following is a review of important natural and synthetic terpenoid and steroid quinone hybrids.

Meroterpenoids from Ganoderma Species:A Review of Last Five Years

Meroterpenoids are hybrid natural products that partially originate from the terpenoid pathway.Ganoderma meroterpenoids(GMs)are a type of meroterpenoids containing a 1,2,4-trisubstituted phenyl and a polyunsaturated terpenoid part.Over last 5 years,great efforts have been made to conduct phytochemistry research on the genus Ganoderma,which have led to the isolation and identification of a number of GMs.These newly reported GMs showed diverse structures and a wide range of biological activities.This review gives an overview of new GMs from genus Ganoderma and their biological activities and biosynthetic pathway,focusing on the period from 2013 until 2018.

Guajadials C-F, four unusual meroterpenoids from Psidium guajava

Guajadials C-F(1-4),four sesquiterpenoid-based meroterpenoids with unprecedented skeletons were isolated from the leaves of Psidium guajava.Their structures and relative configurations were established by extensive spectroscopic analysis.A possible biosynthetic pathway for 1-4 was also proposed.

Structurally Diverse Polymethylated Phloroglucinol Meroterpenoids from Baeckea frutescens

Phytochemical investigation of the MeOH extract of twigs and leaves of Baeckea frutescens led to the isolation of seven new polymethylated phloroglucinol meroterpenoids(PPMs),named baeckfrutones M-S(1-7).Their structures and absolute configurations were determined by spectroscopic analyses,chiral-phase HPLC analysis,and electronic circular dichroism(ECD)calculations.PPM 1 is a novel meroterpenoid possessing a 6/6/5/3 tetracyclic skeleton in PPMs,whereas 3 and 4 are the first hydroxytasmanone type phloroglucinol-monoterpene hybrids.(+)-2 and 7 displayed potent antiinflammatory activity with IC50 values of 20.86±0.60 and 36.21±1.18 lL,respectively.

Divergent total synthesis of marine meroterpenoids(+)-dysidavarones A–C

Here,we report a concise and divergent enantioselective total synthesis of marine sesquiterpene quinone meroterpenoids(+)-dysidavarones A–C(1–3)using predysidavarone 6 as a key common intermediate.The highly strained and bridged eight-membered carbocycle of predysidavarone 6 was constructed by a one-pot intermolecular alkylation and intramolecular arylation of Wieland–Miescher ketone derivative 11 and benzyl bromide 12.The total synthesis of(+)-dysidavarones A–C(1–3)was achieved from predysidavarone 6 in a divergent manner by a late-stage introduction of the ethoxy group,which reveals the possible source of the ethoxy group within(+)-dysidavarones A–C(1–3)and provides a late-stage modifiable route for the synthesis of dysidavarone analogs for further anti-cancer activity evaluation.

A review of meroterpenoids and of their bioactivity from guava(Psidium guajava L.)

Psidium guajava Linn.(family Myrtaceae),is commonly known as guava.Guava is consumed in large quantities throughout the world due to its ease of cultivation and high nutritional value.As an important perennial fruit tree distributed around the world,guava has been widely used to manage various diseases in traditional medicine.Guava has been shown significant bioactivity such as antioxidant,anti-inflammatory,immunomodulatory,antimicrobial,antidiabetic,and anticancer properties.A large number of studies indicated that guava contains various type of phytochemicals including monoterpenes,sesquiterpenes,triterpenes,phenolics,and meroterpenoids.Among them,meroterpenoids are characteristic components of guava,which are hybrid of acylphloroglucinol with terpenoids(monoterpenes,sesquiterpenes).Modern pharmacological investigations showed intricate Psidium meroterpenoids possess a wide range of bioactivities.Although a large and growing body of literatures have investigated the Psidium meroterpenoids isolated from guava,a comprehensive review of Psidium meroterpenoids and their bioactivities has not been conducted.Therefore,this review provides a comprehensive compile of 75 meroterpenoids isolated from guava and their bioactivities between 2007 and May 2022.Furthermore,the possible biosynthesis way and future directions of Psidium meroterpenoids have also been discussed.

Dimericbiscognienynes B and C: New diisoprenyl-cyclohexene-type meroterpenoid dimers from Biscogniauxia sp.

Dimericbiscognienynes B and C(1 and 2), two new diisoprenyl-cyclohexene-type meroterpenoid dimers,were isolated from Biscogniauxia sp. 71-10-1-1. Their structures, including the absolute configurations,were determined by spectroscopic analyses and ECD experiments. Meroterpenoids are special natural products that originate from mixed terpenoid-nonterpenoid pathway. As a member of meroterpenoid family, diisoprenyl-cyclohexene/ane-type meroterpenoids composed of two isoprenyl chains(C5 unit)and a cyclohexene/ane moiety(C6 unit), featuring diverse skeleton structures with wide range of bioactivities. In these reported diisoprenyl-cyclohexene/ane-type meroterpenoids, only three dimers were identified. The discovery of the two new dimers added members of this rare class of meroterpenoids.

Euphoractone,a cytotoxic meroterpenoid with an unusual entabietane-phloroglucinol skeleton,from Euphorbia fischeriana Steud.

A novel meroterpenoid,euphoractone(1),was isolated from the extracts of the roots of Euphorbia fischeriana Steud.Its structure was determined by spectroscopic methods and X-ray crystallography.1 possesses an unusual ent-abietane-phloroglucinol skeleton.The plausible biosynthetic pathway for 1 was proposed.1 showed inhibitory activities against human lung cancer H23 and H460 cells with the IC_(50)values of 21.07±3.54 and 20.91±4.07 μmol/L.

Guajamers A-I, Rearranged Polycyclic Phloroglucinol Meroterpenoids from Psidium guajava Leaves and Their Antibacterial Activity

Eight new polycyclic phloroglucinol meroterpenoids guajamers A-H(1-8),a methylated benzoylphloroglucinol meroterpenoid guajamer I(9)representing a new skeleton,and two known analogues(10 and 11)were isolated from the leaves of Psidium guajava.The structures of new molecules were elucidated by detailed analysis of spectroscopic data,and those of 1,2,8,and 9 were unambiguously confirmed by single-crystal X-ray diffraction study.Structurally,compounds 1-8 were sesquiterpene and monoterpene-based meroterpenoids with rearranged skeletons,while compound 9 was the first case of 3-alkyl-5-formyl-benzoylphloroglucinol-coupled sesquiterpene containing an unusual C-l-spiro-fused 6/6/9/4 polycyclic skeleton.In addition,all the isolated compounds were evaluated for their antibacterial activity against three bacterial strains,and most of them(compounds 2-7,10,and 11)showed antibacterial activity against Staphylococcus aureus and Staphylococcus epidermidis with MIC values of 8-32 μmol/L.These findings suggested that meroterpenoids isolated from Psidium guajava can be considered as potential antibacterial leading compounds for pharmaceutical industry.

Hyperterpenoids A and B:Two pairs of unprecedented 6/6/4/6/6 polycyclic cyclobutane meroterpenoids with potent neuroprotective and anti-inflammatory activities from Hypericum beanii

Hyperterpenoid A(1)and B(2),two pairs of enantiomers,with an unprecedented 6/6/4/6/6 polycyclic skeleton,along with one known compoud hypermonone A(3)were isolated from Hypericum beanii.The racemate(±)-1 and(±)-2 were successfully separated into the two optically pure enantiomers(ee>99%)using a preparative HPLC system.Their absolute configurations were elucidated by extensive spectroscopic analyses and single-crystal X-ray diffraction method.The related plausible biogenetic pathways were pre sented.Compound 1-3 showed significant neuroprotective activity and potential antiinflammatory activity.The result that(+)-2 and(-)-2 presented different anti-inflammatory properties,may lead us to new discovery of structure activity relationship between racemates,enantiomers,and diastereomers,as well as further research regarding the binding of drugs to target proteins.

Meroterpenthiazole A, a unique meroterpenoid from the deep-sea-derived Penicillium allii-sativi, significantly inhibited retinoid X receptor (RXR)-α transcriptional effect

A novel meroterpenoid,named meroterpenthiazole A(1),was isolated from the deep-sea-derived Penicillium allii-sativi.Its structure was established by extensive spectroscopic and computational methods.Meroterpenthiazole A bears a rare benzothiazole moiety in nature.Compound 1 significantly inhibited retinoid X receptor(RXR)-α transcriptional effect(K_(D)=12.3 μmol/L) through a novel binding mechanism.

New meroterpenoid compounds from the culture of mushroom Panus lecomtei

Two new meroterpenoid compounds(1 and 2) together with five known meroterpenoid derivatives(3–7) were isolated from solid culture of mushroom Panus lecomtei. The structures of new compounds were confirmed by the analysis of NMR and HRESI-MS spectroscopic data. The biosynthetic pathway of 1–7 was postulated. All isolated compounds were evaluated for antibacterial activities against Staphylococcus aureus, Escherichia coli, Bacillus subtilis, Pseudomonas aeruginosa and Bacillus Calmette–Guérin.Compound 3 exhibited weak antibacterial activity against Bacillus Calmette–Guérin with the inhibition rate of 83.6% at 100 μmol·L-1.Other compounds showed no antibacterial activities against all tested pathogens at 100 μmol·L-1.

Activation of an unconventional meroterpenoid gene cluster in Neosartorya glabra leads to the production of new berkeleyacetals

Fungal genomes carry many gene clusters seemingly capable of natural products biosynthesis,yet most clusters remain cryptic or down-regulated. Genome mining revealed an unconventional paraherquonin-like meroterpenoid biosynthetic gene cluster in the chromosome of Neosartorya glabra.The cryptic or down-regulated pathway was activated by constitutive expression of pathway-specific regulator gene ber A encoded within ber biosynthetic gene cluster. Chemical analysis of mutant Ng-OE:ber A extracts enabled the isolation of four berkeleyacetal congeners, in which two of them are new. On the basis of careful bioinformatic analysis of the coding enzymes in the ber gene cluster, the biosynthetic pathway of berkeleyacetals was proposed. These results indicate that this approach would be valuable for discovery of novel natural products and will accelerate the exploitation of prodigious natural products in filamentous fungi.

Psiguamers A-C, three cytotoxic meroterpenoids bearing a methylated benzoylphloroglucinol framework from Psidium guajava and total synthesis of 1 and 2

Three sesquiterpene-based meroterpenoids psiguamers A-C(1-3)with new skeletons were isolated from Psidium guajava leaves.Compounds(±)-1 and(±)-2 were two pairs of humulene-de「ived meroterpenoids bearing a rare methylated benzoylphloroglucinol unit,while 3 was an unprecedented adduct of bicyclogermacrene and methylated benzoylphloroglucinol.Their structures were determined based on comprehensive analyses of spectroscopic data,calculated electronic circular dichroism(ECD)spectra,total synthesis,and X-ray crystallographic data.The biomimetic synthesis of(±)-1 and(±)-2 was achieved.Compound(+)-1 exhibited cytotoxic activities against five human tumor cell lines(HCT-116,HepG2,BGC-823,A549,and U251),with IC_(50) values of 2.94,9.01,6.45,5.42,and 5.33 μmol/L,respectively.

Arnequinol A and arnequinone A, two unique meroterpenoids from Arnebia euchroma

Arnequinol A(1),featuring an unprecedented 6/6/3 tricyclic carbon skeleton fused with a heptatomic oxo-bridge,together with arnequinone A(2)bearing a highly conjugated methyl-shifting benzogeijerene skeleton,were isolated from Arnebia euchroma.Their structures were elucidated by extensive spectro-scopic methods and quantum chemical calculations of the 13 C nuclear magnetic resonance(NMR)data and electronic circular dichroism(ECD)spectra.The plausible biosynthetic pathways for 1 and 2 were presented.In in vitro test,compound 2 showed potent neuroprotective activity against serum-deprivation induced PC12 cell damage at a concentration of 10μmol/L.

Periconones B-E,new meroterpenoids from endophytic fungus Periconia sp.

Periconones B-E（1-4）,four new polyketide-terpenoid hybrid molecules were isolated from the endophytic fungus Periconia sp.F-31.Their structures and absolute configurations were established by extensive spectroscopic data analysis and electronic circular dichroism（ECD）.Compound 4 exhibited in vitro cytotoxic activity against the human MCF-7 tumor cell line with an IC_（50） value of 4.2 μmol/L,and compound 1 displayed anti-HIV activity with an IC_（50） value of 18.0 μmol/L.

Amphichoterpenoids A-C,unprecedented picoline-derived meroterpenoids from the ascidian-derived fungus Amphichorda felina SYSU-MS7908

Amphichoterpenoids A-C(1-3),unprecedented picoline-derived meroterpenoids possessing a pyrano[3,2-c]pyridinyl-g-pyranone scaffold,were characterized from the ascidian-derived fungus Amphichorda felina SYSU-MS7908.Their structures were elucidated by spectroscopic methods,X-ray diffraction and electronic circular dichroism(ECD)calculations.A plausible biosynthetic pathway was proposed.The isolated compounds displayed moderate inhibitory activity against acetylcholinesterase with 50%inhibiting concentration(IC_(50))values of 18.8-53.2 mmol/L.

海洋真菌来源杂萜类化合物的研究进展

海洋真菌生活在高盐、高压、低温、弱光的独特海洋环境中,具有结构独特、代谢多样、活性显著等特点,并产生了一系列功能多样、结构新颖的次级代谢产物,是杂萜类化合物的重要来源。海洋真菌体内复杂的次生代谢途径使获得的杂萜类化合物骨架结构多样,具有抗菌、抗肿瘤、酶活性抑制等丰富的生物活性。介绍了海洋真菌来源杂萜类化合物的研究现状,并对其生物合成途径、发酵与分离方法、生物活性等进行了综述,为海洋真菌来源杂萜类化合物的后续研究提供了一定参考。

Enantiomeric pairs of meroterpenoids from Rhododendron fastigiatum

Five pairs of optically pure meroterpenoid enantiomers(1 a/1 b-5 a/5 b)and two known compounds(6 and 7)were isolated from Rhododendron fastigiatum.Compounds 1 a/1 b-5 a/5 b were resolved from naturally scalemic mixtures by chiral HPLC.Their structures were elucidated by spectroscopic methods,X-ray crystallographic experiments,and ECD analyses.Compounds 1 a/1 b,2 a/2 b,3 b,4 a/4 b,and 5 a/5 b were new meroterpenoids with different polycyclic systems.Two enantiomeric pairs(2 a/2 b and 3 a/3 b),6,and 7 exhibited inhibitory effects on protein tyrosine phosphatase 1 B(PTP1 B)in vitro.

Hyperinoids A and B,two polycyclic meroterpenoids from Hypericum patulum

Hyperinoids A(1)and B(2),two prenylated acylphloroglucinol related meroterpenoids,were isolated from Hypericum patulum.Compound 1 incorporates an unprecedented 11,12-dioxatetracyclo[5.4.3.01,7.04,14]tetradecane system,while 2 possesses a unique 10,11-dioxatetracyclo[5.3.3.01,7.04,13]tridecane syste m.Their structures were established by spectro scopic analysis and X-ray crystallographic data.Compounds 1 and 2 were identified as potent NF-κB inhibitors and suppressed the LPS-induced inflammatory responses in RAW 246.7 macrophages and primary mouse BMDM cells.