Recent developments in the engineered biosynthesis of fungal meroterpenoids

• Zhiyang Quan and
• Takayoshi Awakawa

Beilstein J. Org. Chem. 2024, 20, 578–588, doi:10.3762/bjoc.20.50

• , the combinatorial biosynthesis of diterpene pyrones, derived from a pyrone skeleton and a C20 terpenoid skeleton, has been achieved by combining multiple biosynthetic pathways in a fungal heterologous expression host [16]. First, subA (PKS), subC (PT), subD (GGPP synthase), subE (FMO), and subB (CYC

• combinatorial biosynthesis of diterpene pyrone meroterpenoids. The production of subglutinol A by SubABCDE + DpasF (A), the production of novel diterpene pyrones by SubABCDE + various tailoring enzymes (B), and the production of schearone A by SubACD + EsdpE + EsdpB (C). The biosynthetic reaction from the

Anion–π catalysis on carbon allotropes

• M. Ángeles Gutiérrez López,
• Mei-Ling Tan,
• Giacomo Renno,
• Augustina Jozeliūnaitė,
• J. Jonathan Nué-Martinez,
• Javier Lopez-Andarias,
• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2023, 19, 1881–1894, doi:10.3762/bjoc.19.140

• preferred to maximize orbital overlap (Figure 4) [63]. For π-acidic surfaces, the exo transition state VII is more completely accessible (Figure 4). The 3-hydroxy-2-pyrone (24) was selected as representative diene for the anionic [4 + 2] cycloaddition with maleimide 25 as standard dienophile to afford endo

Secondary metabolites of Diaporthe cameroonensis, isolated from the Cameroonian medicinal plant Trema guineensis

• Bel Youssouf G. Mountessou,
• Élodie Gisèle M. Anoumedem,
• Blondelle M. Kemkuignou,
• Yasmina Marin-Felix,
• Frank Surup,
• Marc Stadler and
• Simeon F. Kouam

Beilstein J. Org. Chem. 2023, 19, 1555–1561, doi:10.3762/bjoc.19.112

• derivative of alternariol, a heptaketide coumarin derivative with a fused tricyclic ring called dibenzo-α-pyrone [31][32]. Alternariol is one of the toxic metabolites isolated from Alternaria strains, that grow on various natural resources such as corn, rice, fruits, vegetables, oilseeds, juices, wins, and

Combining the best of both worlds: radical-based divergent total synthesis

• Kyriaki Gennaiou,
• Antonios Kelesidis,
• Maria Kourgiantaki and
• Alexandros L. Zografos

Beilstein J. Org. Chem. 2023, 19, 1–26, doi:10.3762/bjoc.19.1

• ], and electrochemistry [22] all refuelled the field, allowing for more practical radical disconnections for total synthesis. Divergent synthesis of pyrone diterpenes (Baran 2018) [23]: The modestly sized family of pyrone diterpenes exhibits a wide range of bioactivities, ranging from immunosuppressive

• to hypertensive properties [24][25][26] depending on the subtle substituents in the periphery of a decalin core (Scheme 2). In 2018, the Baran group reported the divergent total synthesis of several pyrone diterpene natural products, relying solely on one-electron-based retrosynthesis. The group

• coupling to 13, 20, 25, and 28, few steps away from the total syntheses of sesquicillin A (18), subglutinols A and B (19 and 24) and higginsianin A (23, Scheme 2). Merged chemoenzymatic and radical synthesis of oxidized pyrone meroterpenoids (Renata 2020) [29]: In 2020, a different approach was

Synthetic study toward tridachiapyrone B

• Morgan Cormier,
• Florian Hernvann and
• Michaël De Paolis

Beilstein J. Org. Chem. 2022, 18, 1741–1748, doi:10.3762/bjoc.18.183

• Morgan Cormier Florian Hernvann Michael De Paolis COBRA, Normandie University, 76000 Rouen, France 10.3762/bjoc.18.183 Abstract A convergent approach to the skeleton of tridachiapyrone B is described taking advantage of the desymmetrization of α,α’-dimethoxy-γ-pyrone leading to α-crotyl-α

• ’-methoxy-γ-pyrone in one step. To construct the quaternary carbon of the 2,5-cyclohexadienone of the target, a strategy based on the Robinson-type annulation of an aldehyde derived from α-crotyl-α’-methoxy-γ-pyrone was applied. The grafting of the simplified target’s side chain was demonstrated through an

• oxidative anionic oxy-Cope rearrangement of the tertiary alcohol arising from the 1,2-addition of a 1,3-dimethylallyl reagent to 2,5-cyclohexadienone connected to the α’-methoxy-γ-pyrone motif. Keywords: α’-methoxy-γ-pyrone; 2,5-cyclohexadienone; oxy-Cope; quaternary carbon; Robinson-type annulation

Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• -dihydro-α-pyrone derivatives, bearing either a distinctive cyclopropane or furan ring and named brevipolides A–O (1–15), have been isolated from the invasive plant Hyptis brevipes Poit. Their fascinating structural features, and the potent biological activities, including cytotoxicity against an array of

• human cancer cell lines and inhibition of the chemokine receptor CCR5, make them attractive synthetic targets. This review article highlights the recent synthetic methodologies and briefly summarizes their biological activities. Keywords: brevipolides; 5,6-dihydro-α-pyrone; Furukawa-modified Simmons

• to determine bioactive chemicals in Hyptis brevipes Poit. and isolated six new 5,6-dihydro-α-pyrone derivatives 1–6 along with other known compounds, including a 5,6-dihydro-α-pyrone derivative 7 [11], from the whole plant collected in Tawangmangu village, Indonesia (Figure 1) [4]. These six new

Natural products in the predatory defence of the filamentous fungal pathogen Aspergillus fumigatus

• Jana M. Boysen,
• Nauman Saeed and
• Falk Hillmann

Beilstein J. Org. Chem. 2021, 17, 1814–1827, doi:10.3762/bjoc.17.124

• region on chromosome 6 [172]. Chemically, pyripyropene (PP) analogs are meroterpenoids containing a fused pyridyl α-pyrone moiety and eight contiguous stereocenters [170]. Metabolically, PPPA non-covalently binds within the fifth transmembrane domain of acyl-coenzyme A (CoA):cholesterol acyltransferase

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• synthesis of the dihydro-3-pyrone 58. Kitahara’s 1st-generation synthesis of the C-1–C-6 fragment of FR901464 (1). Kitahara 1st-generation synthesis of the C-1–C-6 fragment of FR901464 (1). Nimura/Arisawa synthesis of the C-1-phenyl segment. Ghosh synthesis of the C-1–C-6 fragment of FR901464 (1) from (R

Activated carbon as catalyst support: precursors, preparation, modification and characterization

• Melanie Iwanow,
• Tobias Gärtner,
• Volker Sieber and
• Burkhard König

Beilstein J. Org. Chem. 2020, 16, 1188–1202, doi:10.3762/bjoc.16.104

• pyrone or chromene-like structures and aromatic π electrons [108][124][125]. Nowicki et al. showed different acidic and basic conditions on the surface of the activated carbon materials resulting from different activation methods of cherry stones-based carbons. Activation by carbon dioxide led to basic

Pigmentosins from Gibellula sp. as antibiofilm agents and a new glycosylated asperfuran from Cordyceps javanica

• Soleiman E. Helaly,
• Wilawan Kuephadungphan,
• Patima Phainuphong,
• Mahmoud A. A. Ibrahim,
• Kanoksri Tasanathai,
• Suchada Mongkolsamrit,
• Janet Jennifer Luangsa-ard,
• Souwalak Phongpaichit,
• Vatcharin Rukachaisirikul and
• Marc Stadler

Beilstein J. Org. Chem. 2019, 15, 2968–2981, doi:10.3762/bjoc.15.293

• , Thailand Department of Chemistry, Faculty of Science, Prince of Songkla University, Songkhla 90112, Thailand 10.3762/bjoc.15.293 Abstract In the course of our exploration of the Thai invertebrate-pathogenic fungi for biologically active metabolites, pigmentosin A (1) and a new bis(naphtho-α-pyrone

• was determined by HMBC correlations from the methoxy functions to C-7/C-7′. Nevertheless, the NMR data revealed differences in the signals of the α-pyrone moieties, suggesting the presence of two asymmetrical dihydro-α-naphthopyrone motifs in 2. C-3 showed resonances at δC 79.2 and δH 4.86, C-3′ at δC

• /1.97 (C-11′) were observed. Finally, a series of COSY correlations between H-3′, H-11′, H-12′, and H-13′, together with HMBC correlations from H-13′ to C-11′/C-12′ and from H-11′ to C-3′/C-4′/C-12′/C-13′, allowed the assumption that a propan-2-ol moiety was present at C-3′ of the α-pyrone ring on one

Chemical synthesis of tripeptide thioesters for the biotechnological incorporation into the myxobacterial secondary metabolite argyrin via mutasynthesis

• David C. B. Siebert,
• Roman Sommer,
• Domen Pogorevc,
• Michael Hoffmann,
• Silke C. Wenzel,
• Rolf Müller and
• Alexander Titz

Beilstein J. Org. Chem. 2019, 15, 2922–2929, doi:10.3762/bjoc.15.286

• are quite challenging, e.g., as shown in previous studies on polyketide chain engineering in α-pyrone antibiotic biosynthesis [23]. We assumed that the insufficient/missing processing of the SNAc precursors by the NRPS subunit Arg3 is the main culprit for unsuccessful restoration of the argyrin

Emission solvatochromic, solid-state and aggregation-induced emissive α-pyrones and emission-tuneable 1H-pyridines by Michael addition–cyclocondensation sequences

• Natascha Breuer,
• Irina Gruber,
• Christoph Janiak and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2019, 15, 2684–2703, doi:10.3762/bjoc.15.262

• emission solvatochromism. Also a donor-substituted α-pyrone shows pronounced aggregation-induced emission enhancement. Keywords: cyclocondensation; DFT calculations; fluorescence; heterocycles; 1H-pyridines; α-pyrones; Introduction A high sensitivity and precise tuneability of fluorescence colors are

• synthesized a series of α-pyrone derivatives with emission maxima between 400 and 675 nm in the solid state and between 486 and 542 nm in chloroform [16][24][25][26], including fluorescence quantum yields as high as 95% in solution and 58% in the solid state [16][24]. While these fluorophores were synthesized

• ), phenylacetylene (2a), and ethyl cyanoacetate (4) within the AMAC sequence (Scheme 2). Surprisingly, the desired α-pyrone was not isolated, but two other compounds were detected. On the one hand a 1H-pyridine derivative 5a (2% yield) and on the other hand an aniline derivative with two ester groups (4% yield

An anomalous addition of chlorosulfonyl isocyanate to a carbonyl group: the synthesis of ((3aS,7aR,E)-2-ethyl-3-oxo-2,3,3a,4,7,7a-hexahydro-1H-isoindol-1-ylidene)sulfamoyl chloride

• Aytekin Köse,
• Aslı Ünal,
• Ertan Şahin,
• Uğur Bozkaya and
• Yunus Kara

Beilstein J. Org. Chem. 2019, 15, 931–936, doi:10.3762/bjoc.15.89

• , examples for the reaction of carbonyl group containing compounds with CSI are limited in the literature. In particular, compounds containing an amide or pyrone skeletal structure were used in these studies. These reactions were reported by the research groups of Reynolds [12], Sattur [13], Jiménez [14] and

Ring-closing-metathesis-based synthesis of annellated coumarins from 8-allylcoumarins

• Christiane Schultze and
• Bernd Schmidt

Beilstein J. Org. Chem. 2018, 14, 2991–2998, doi:10.3762/bjoc.14.278

• distinguishes between simple coumarins with substituents only at the benzene part (e.g., osthole, a natural product with Ca2+-channel antagonist activity) [9], coumarins with substituents at the pyrone part (e.g., warfarin, a synthetic clinically used anticoagulant) [10], and heteroannellated coumarins, in

Cobalt- and rhodium-catalyzed carboxylation using carbon dioxide as the C1 source

• Tetsuaki Fujihara and
• Yasushi Tsuji

Beilstein J. Org. Chem. 2018, 14, 2435–2460, doi:10.3762/bjoc.14.221

• corresponding pyrone and the Rh(I) species A (step c). Alternatively, the oxidative cyclization of A proceeds as one of the C–C triple bonds of the diyne and CO2 react regioselectively, and rhodacycle D is subsequently formed (step d). Then, the insertion of the alkyne into the Rh–C bond occurs to give

Electrochemical Corey–Winter reaction. Reduction of thiocarbonates in aqueous methanol media and application to the synthesis of a naturally occurring α-pyrone

• Ernesto Emmanuel López-López,
• José Alvano Pérez-Bautista,
• Fernando Sartillo-Piscil and
• Bernardo A. Frontana-Uribe

Beilstein J. Org. Chem. 2018, 14, 547–552, doi:10.3762/bjoc.14.41

• -(pent-1-enyl)-α-pyrone and trans-6-(pent-1,4-dienyl)-α-pyrone, which are naturally occurring metabolites isolated from Trichoderma viride and Penicillium, in high chemical yield and with excellent stereo selectivity. Keywords: Corey–Winter reaction; electrosynthesis; 6-pentyl-2H-pyran-2-ones; reduction

• 1–3 was reported by our research group [7]. These molecules proved to be enantiomers of metabolites isolated from Trichoderma spp and Penicillium isolates. Unfortunately, our efforts for obtaining the natural metabolite trans-6-(pent-1-enyl)-α-pyrone (5) (isolable from Trichoderma viride [8]) via a

• 6 was prepared in two steps from pyrone dioxolane 7 [7]. Acid hydrolysis of 7 to 1,2-diol 8 followed by the reaction with 1,1’-thiocarbonyldiimidazole afforded thiocarbonate precursor 6 in high overall yield (Scheme 3). Compounds 6 and 8 were prepared in a similar manner as described in reference [7

One-pot preparation of 4-aryl-3-bromocoumarins from 4-aryl-2-propynoic acids with diaryliodonium salts, TBAB, and Na₂S₂O₈

• Teppei Sasaki,
• Katsuhiko Moriyama and
• Hideo Togo

Beilstein J. Org. Chem. 2018, 14, 345–353, doi:10.3762/bjoc.14.22

• transformed into 4-phenylcoumarin derivatives bearing C–H, C–S, C–N, and C–C bonds at 3-position. Keywords: 3-aryl-2-propynoic acid; bromo-cyclization; coumarin; diaryliodonium triflate; O-phenylation; Introduction Coumarin is a benzo-α-pyrone and one of the typical heterocyclic compounds. The importance of

Volatiles from the tropical ascomycete Daldinia clavata (Hypoxylaceae, Xylariales)

• Tao Wang,
• Kathrin I. Mohr,
• Marc Stadler and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2018, 14, 135–147, doi:10.3762/bjoc.14.9

• -pyrone 17 exhibited a moderate antifungal and weak antibacterial effect, while the lactone 9 was moderately cytotoxic, but devoid of significant antimicrobial activity. The chlorinated aromatic compound 14 only weakly inhibited the sensitive test organisms Chromobacterium violaceum and Mucor hiemalis

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• one epoxide hydrolase in the biosynthesis of the fungal polyketide aurovertin B (118) is sufficient to form this complex structural motif starting from a polyene-α-pyrone precursor (Scheme 18) [116]. The diene between C3 and C6 in 113 is first expoxidised by the FMO AurC. The epoxide hydrolase AurD

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• phosphonates via ring opening through an intramolecular nucleophilic attack at the 2-position of the pyrone. Thus, the three-component reaction of 75 with hydrazine derivatives 76 or hydroxylamine 79 in the presence of diethyl phosphonate led to pyrazolylphosphonate 78 and oxazolylphosphonate 81, respectively

Marine-derived myxobacteria of the suborder Nannocystineae: An underexplored source of structurally intriguing and biologically active metabolites

• Antonio Dávila-Céspedes,
• Peter Hufendiek,
• Max Crüsemann,
• Till F. Schäberle and
• Gabriele M. König

Beilstein J. Org. Chem. 2016, 12, 969–984, doi:10.3762/bjoc.12.96

• Na a174 yielded a new class of halogenated pyrrole–oxazole compounds 14–18 (Figure 8). Pyrronazols A (14), A2 (15) and B (16), synthesized by Ari7, additionally include an α-pyrone moiety [48]. This is worth noting, since the non-cyclic alkyl moiety in the pyrronazols C1 (17) and C2 (18), found in

Indenopyrans – synthesis and photoluminescence properties

• Andreea Petronela Diac,
• Ana-Maria Ţepeş,
• Albert Soran,
• Ion Grosu,
• Anamaria Terec,
• Jean Roncali and
• Elena Bogdan

Beilstein J. Org. Chem. 2016, 12, 825–834, doi:10.3762/bjoc.12.81

• -benzoquinone (DDQ), led to indeno-α-pyrones 4–6 (Scheme 2), in not very satisfying yields. Investigations carried out for the dehydrogenation reaction of the isomeric mixture 2'a/3''a (Scheme 2) revealed the formation of the α-pyrone 6a (15% yield), which was the oxidation product of isomer 3''a. In the same

• calculated quantum yields relative to 9,10-diphenylanthracene were quite low (<1%). In the crystals of α-pyrone 6a, the asymmetric unit consists of a single molecule. The two phenyl rings attached to the pyran-3-one moiety are disposed in a staggered conformation. The angle between the planes defined by the

Antibiotics from predatory bacteria

• Juliane Korp,
• María S. Vela Gurovic and
• Markus Nett

Beilstein J. Org. Chem. 2016, 12, 594–607, doi:10.3762/bjoc.12.58

• Mxf50 [95][96]. Later, the structurally related corallopyronins were found in different strains of Corallococcus coralloides [97][98][99]. Myxopyronins and corallopyronins share a common scaffold composed of a central pyrone ring carrying two flexible side chains (Figure 3). Structural variability

Biosynthesis of α-pyrones

• Till F. Schäberle

Beilstein J. Org. Chem. 2016, 12, 571–588, doi:10.3762/bjoc.12.56

• Till F. Schaberle Institute for Pharmaceutical Biology, University of Bonn, Nußallee 6, 53115 Bonn, Germany 10.3762/bjoc.12.56 Abstract The α-pyrone moiety is a structural feature found in a huge variety of biologically active metabolites. In recent times new insights into additional biosynthetic

• (Figure 1) [7]. α-Pyrones have also been shown to be HIV protease [8][9][10] and selective COX-2 inhibitors [11][12], and further, signaling functions were attributed to them. Already in the 1990s an unusual dialkyl-substituted α-pyrone (supellapyrone, 7) was detected to be the cockroach sex pheromone [13

• formation yielding in the α-pyrone moiety can be accomplished in different ways. The different biosynthetic routes towards an α-pyrone ring will be presented. The biosynthetic mechanisms to yield saturated lactones, like the statin drug lovastatin, which is in application for lowering cholesterol, will not

A novel and widespread class of ketosynthase is responsible for the head-to-head condensation of two acyl moieties in bacterial pyrone biosynthesis

• Darko Kresovic,
• Florence Schempp,
• Zakaria Cheikh-Ali and
• Helge B. Bode

Beilstein J. Org. Chem. 2015, 11, 1412–1417, doi:10.3762/bjoc.11.152

• mechanism of pyrone formation has been investigated by amino acid exchange and bioinformatic analysis. Additionally, the evolutionary origin of PpyS has been studied by phylogenetic analyses also revealing homologous enzymes in Pseudomonas sp. GM30 responsible for the biosynthesis of pseudopyronines

• including a novel derivative. Moreover this novel class of ketosynthases is only distantly related to other pyrone-forming enzymes identified in the biosynthesis of the potent antibiotics myxopyronin and corallopyronin. Keywords: cell–cell communication; ketosynthase; photopyrones; pseudopyronines; quorum

• sensing; Introduction Chemical compounds containing an α-pyrone moiety are widespread in nature [1][2] and show a high diversity in their biological activity. Members of this class of compounds have been identified with antimicrobial, cytotoxic [3] and antitumor activities [4], as HIV protease inhibitors