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

• ]: Reticuline-type alkaloid oxidative coupling is a well-established biosynthetic pathway that produces important pharmaceutical structures [93], such as (+)-corytuberine, (−)-codeine, (−)-morphine, (+)-sebiferine (181), etc., depending on the regioselectivity of the coupling (Scheme 15) [94]. During this

Synthesis of (−)-halichonic acid and (−)-halichonic acid B

• Keith P. Reber and
• Emma L. Niner

Beilstein J. Org. Chem. 2022, 18, 1629–1635, doi:10.3762/bjoc.18.174

• derived from a common biosynthetic pathway starting from farnesyl pyrophosphate and glycine [5]. This prompted us to investigate a biomimetic synthesis in which the halichonic acids could be prepared from a common imine intermediate via divergent intramolecular aza-Prins cyclizations [8]. Herein, we

• , antifungal, and antimicrobial properties [10][19][20][21][22]. Notably, (+)-4 was also co-isolated with compounds (+)-1 and (+)-2 in sponge extracts, suggesting that these compounds may share a common biosynthetic pathway [4][5]. Both enantiomers of 4 have been previously synthesized [9][23][24], and this

Characterization of a new fusicoccane-type diterpene synthase and an associated P450 enzyme

• Jia-Hua Huang,
• Jian-Ming Lv,
• Liang-Yan Xiao,
• Qian Xu,
• Fu-Long Lin,
• Gao-Qian Wang,
• Guo-Dong Chen,
• Sheng-Ying Qin,
• Dan Hu and
• Hao Gao

Beilstein J. Org. Chem. 2022, 18, 1396–1402, doi:10.3762/bjoc.18.144

• cytotoxic FC-type diterpenoid isolated from T. purpurogenus PP-414 [7]. It will be important to elucidate the biosynthetic pathway of roussoellol C, providing enzymatic tools for expanding the chemical diversity of talaro-7,13-diene related FC-type diterpenoids via combinational biosynthesis [14

• monitored at 254 nm. Biosynthesis of FC-type diterpenoids. A) The biosynthetic pathway of 1, 2 and 4. B) Cyclization mechanisms of 1 and reported FC-type diterpenes. Supporting Information Supporting Information File 328: Experimental methods, nucleotide sequence, tables, and figures. Acknowledgements We

Cytochrome P450 monooxygenase-mediated tailoring of triterpenoids and steroids in plants

• Karan Malhotra and
• Jakob Franke

Beilstein J. Org. Chem. 2022, 18, 1289–1310, doi:10.3762/bjoc.18.135

• scaffold in plants from the Cucurbitaceae family (Figure 3B). CYP87D18 (CYP85 clan) was identified as a multifunctional C11 oxidase involved in the biosynthetic pathway of mogrosides. Mogrosides, isolated from ripe fruits of Siraitia grosvenorii (Cucurbitaceae) are glycosylated triterpenoid saponins with

• protopanaxatriol [76][103]. CYP716A113v1 from Aquilegia coerulea hydroxylates cycloartenol with unknown regiospecificity when expressed in a yeast strain harbouring a tomato cycloartenol synthase gene [79]. CYP712 family members (clan 71) were first identified in the biosynthetic pathway of nor-triterpenoid

A Streptomyces P450 enzyme dimerizes isoflavones from plants

• Run-Zhou Liu,
• Shanchong Chen and
• Lihan Zhang

Beilstein J. Org. Chem. 2022, 18, 1107–1115, doi:10.3762/bjoc.18.113

• clustered into the CYP158 clade that reportedly catalyzes dimerization of type III polyketide synthase (T3PKS) products, such as naphthols. Considering the similar biosynthetic pathway of isoflavones shared, this enzyme was expressed in E. coli and purified for in vitro biochemical assay together with four

New azodyrecins identified by a genome mining-directed reactivity-based screening

• Atina Rizkiya Choirunnisa,
• Kuga Arima,
• Yo Abe,
• Noritaka Kagaya,
• Kei Kudo,
• Hikaru Suenaga,
• Junko Hashimoto,
• Manabu Fujie,
• Noriyuki Satoh,
• Kazuo Shin-ya,
• Kenichi Matsuda and
• Toshiyuki Wakimoto

Beilstein J. Org. Chem. 2022, 18, 1017–1025, doi:10.3762/bjoc.18.102

• was incubated with recombinant Ady1 in the presence of SAM, it was converted to 8, showing that Ady1 can install the methyl ester of azodyrecins (Figure 4). The in vitro characterization of Ady1 and the functional annotation of ady clusters allowed the prediction of the entire biosynthetic pathway of

• biosynthetic gene clusters of valanimycin and KA57-A, respectively. The in vitro characterization of Ady1 suggested the late-stage biosynthetic pathway of azodyrecin: the azoxy bond formation is followed by the Ady1-mediated methyl esterification to form saturated azodyrecins, and then the subsequent

• in the Refseq database. Nodes are colored according to the host organism’s order. Enzymes with known biosynthetic products are colored red. N2H4-detecting colorimetric assay. Proposed biosynthetic pathway of azodyrecin. 1H (500 MHz) and 13C (125 MHz) NMR data for azodyrecin D (7), azodyrecin E (8

Isolation and biosynthesis of daturamycins from Streptomyces sp. KIB-H1544

• Yin Chen,
• Jinqiu Ren,
• Ruimin Yang,
• Jie Li,
• Sheng-Xiong Huang and
• Yijun Yan

Beilstein J. Org. Chem. 2022, 18, 1009–1016, doi:10.3762/bjoc.18.101

• daturamycins was identified through gene knockout and biochemical characterization experiments and the biosynthetic pathway of daturamycins was proposed. Keywords: biosynthesis; diarylcyclopentenone; polyporic acid synthetase; p-terphenyl; Streptomyces; Introduction Natural products containing a terphenyl

• DatA, which catalyzes the Claisen–Dieckmann condensation of phenylpyruvic acid (7) to generate the key intermediate polyporic acid (8). Finally, we proposed a biosynthetic pathway for daturamycins. Results and Discussion Daturamycin A (1), a yellow powder, possessed a molecular formula of C19H16O5 with

• . Diarylcyclopentenones, characteristic constituents of mushrooms [23], were rarely discovered in Streptomyces species. These components exhibit redox activity and are involved in reducing ferric (Fe3+) in the Fenton-based biological decomposition of lignocellulose [24][25]. The biosynthetic pathway of p-terphenyl was

Anti-inflammatory aromadendrane- and cadinane-type sesquiterpenoids from the South China Sea sponge Acanthella cavernosa

• Shou-Mao Shen,
• Qing Yang,
• Yi Zang,
• Jia Li,
• Xueting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 916–925, doi:10.3762/bjoc.18.91

• -dependent density functional theory/electronic circular dichroism (TDDFT-ECD) calculations or X-ray diffraction analysis. A plausible biosynthetic pathway of these sesquiterpenoids and their internal correlation were proposed and discussed. In an in vitro bioassay, (+)-aristolone (3) exhibited promising

• anti-inflammatory activity by the inhibition of LPS-induced TNF-α and CCL2 release in RAW 264.7 macrophages. Keywords: Acanthella cavernosa; anti-inflammatory; biosynthetic pathway; chiral separation; marine sponge; sesquiterpenoid; Introduction Marine sponges of the genus Acanthella (class

• with five related known ones [2, 3, (−)-4, 6, and 7] (Figure 1), were obtained. Herein, we report the isolation, chiral separation of racemic mixtures of 4 and 5, structural elucidation, plausible biosynthetic pathway, and biological evaluation of these isolated compounds. Results and Discussion By the

Efficient production of clerodane and ent-kaurane diterpenes through truncated artificial pathways in Escherichia coli

• Fang-Ru Li,
• Xiaoxu Lin,
• Qian Yang,
• Ning-Hua Tan and
• Liao-Bin Dong

Beilstein J. Org. Chem. 2022, 18, 881–888, doi:10.3762/bjoc.18.89

• production of terpentetriene. The medium screening for terpentetriene production as well as the elucidation of terpentetriene biosynthetic pathway in K. griseola DSM 43859 are underway in our lab. Thus, all essential genes (phoN, ipk, idi, ggdps, tdps, and ttes) for a truncated artificial pathway to produce

• the clerodane diterpene, terpentetriene, were fully collected. The biosynthetic pathway towards ent-kaurene resembles that of terpentetriene. First, a class II DTS catalyzes the cyclization of GGDP into a diphosphate intermediate, ent-copalyl diphosphate (ent-CPP). Next, a class I DTS further cyclizes

The stereochemical course of 2-methylisoborneol biosynthesis

• Binbin Gu,
• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 818–824, doi:10.3762/bjoc.18.82

• processing through (R)-2-Me-LPP [23]. The GPP methyltransferase (GPPMT) and the 2-methylisoborneol synthase (2MIBS) and their coding genes were discovered and functionally characterized, giving further evidence for the biosynthetic pathway to compound 1 [23][24][25]. As we have recently demonstrated, the

Sesquiterpenes from the soil-derived fungus Trichoderma citrinoviride PSU-SPSF346

• Wiriya Yaosanit,
• Vatcharin Rukachaisirikul,
• Souwalak Phongpaichit,
• Sita Preedanon and
• Jariya Sakayaroj

Beilstein J. Org. Chem. 2022, 18, 479–485, doi:10.3762/bjoc.18.50

• . Structures of compounds 1–7 isolated from Trichoderma citrinoviride PSU-SPSF346. 1H-1H COSY, key HMBC, and NOEDIFF data of compounds 1 and 2. ECD spectra of compounds 1 and 3 in MeOH. Proposed biosynthetic pathway for compound 2. The NMR data of compounds 1 and 2 in CD3OD. Supporting Information Supporting

Amamistatins isolated from Nocardia altamirensis

• Till Steinmetz,
• Wolf Hiller and
• Markus Nett

Beilstein J. Org. Chem. 2022, 18, 360–367, doi:10.3762/bjoc.18.40

• reductive degradation of amamistatin-type siderophores. Compound 6 represents a possible shunt product of amamistatin biosynthesis. A similar molecule and its putative biosynthetic pathway were recently described by Jaspars et al. [12]. In accordance with this proposal, salicylic acid and ʟ-threonine would

α-Ketol and α-iminol rearrangements in synthetic organic and biosynthetic reactions

• Scott Benz and
• Andrew S. Murkin

Beilstein J. Org. Chem. 2021, 17, 2570–2584, doi:10.3762/bjoc.17.172

• a biosynthetic pathway for the novel steroid asperflotone (72), it was suggested that its source was asperfloroid (73), a similar steroid isolated from the same source fungus, Aspergillus flocculosus [23]. First, reduction of the C8–C9 double bond and oxidation at C15 would provide α-ketol 74

• of proposed intermediate 78, occurs with base (M = K or Cs), but dehydration to 81 occurs with acid. c) Substrate scope of similar Cs2CO3-catalyzed α-ketol rearrangements. Proposed biosynthetic pathway converting acylphloroglucinol (87) to isolated elodeoidins A–H 92–96. Oxidation at C3 followed by α

Synthesis of O⁶-alkylated preQ₁ derivatives

• Laurin Flemmich,
• Sarah Moreno and
• Ronald Micura

Beilstein J. Org. Chem. 2021, 17, 2295–2301, doi:10.3762/bjoc.17.147

• in the biosynthetic pathway of the hypermodified tRNA nucleoside queuosine (Q) (Scheme 1) [5]. The core structure of the nucleobase is 7-aminomethyl-7-deazaguanine, a pyrrolo[2,3-d]pyrimidine also termed prequeuosine base (preQ1) [6][7]. In many bacteria, preQ1 binds to specific mRNA domains and

• residue in huimycin and to a 2-[4'-(4''-O-methyl-ß-ᴅ-glucopyranosyl)-6'-deoxy-α-ᴅ-glucopyranosyl] moiety in dapiramicin A [19][20]. In the biosynthetic pathway, the conversion of preQ0 into huimycin requires methylation of preQ0 and attachment of the N-acetylglucosamine moiety as final steps [18]. The

Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

• Christopher Liczner,
• Kieran Duke,
• Gabrielle Juneau,
• Martin Egli and
• Christopher J. Wilds

Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76

• Damha [208]. Zhou reasoned that because 3'-O-β-glucosylated nucleocidin, an intermediate in the biosynthetic pathway of nucleocidin, was stable, they may be able to successfully achieve the synthesis of the 4'-F-rU phosphoramidite through a selective protection of the hydroxy groups in stages [211

Synthesis of legonmycins A and B, C(7a)-hydroxylated bacterial pyrrolizidines

• Wilfred J. M. Lewis,
• David M. Shaw and
• Jeremy Robertson

Beilstein J. Org. Chem. 2021, 17, 334–342, doi:10.3762/bjoc.17.31

• pxaAB gene cluster in E. coli, and analysis of the metabolites by differential 2D NMR spectroscopy, led to the isolation and characterization of pyrrolizixenamide A (9) and, subsequently, pyrrolizixenamides B–D (10–12). Ultimately, an analogous biosynthetic pathway to that proposed for the legonmycins

3-Acetoxy-fatty acid isoprenyl esters from androconia of the ithomiine butterfly Ithomia salapia

• Florian Mann,
• Daiane Szczerbowski,
• Lisa de Silva,
• Melanie McClure,
• Marianne Elias and
• Stefan Schulz

Beilstein J. Org. Chem. 2020, 16, 2776–2787, doi:10.3762/bjoc.16.228

• . The position of the double bonds in the acyl chain of the esters can be explained by a biosynthetic pathway described in detail in Scheme 5. The double bond distribution is consistent with both desaturases acting on palmitic acid, leading to the respective hexadecenoic acids. These acids are the

• % HBraq, toluene, 24 h, 110 °C, 79%; b) IBX, EtOAc, 60 °C, 3.15 h, 90%; c) C5H11PPh3Br, LDA, THF, −78 °C, 12 h, 84%; d) i) Mg, 21, THF, ii) (S)-22, Cu(I)I, THF, –30 °C, 12 h, 79%; e) SnOBu2, 140°C, 36 h, 65%; f) Ac2O, pyridine, DMAP, CH2Cl2, 12 h rt, 74%. Proposed biosynthetic pathway of fatty acids

Synthesis of C-glycosyl phosphonate derivatives of 4-amino-4-deoxy-α-ʟ-arabinose

• Lukáš Kerner and
• Paul Kosma

Beilstein J. Org. Chem. 2020, 16, 9–14, doi:10.3762/bjoc.16.2

• were inactive towards enzyme upstream of the biosynthetic pathway to undecaprenyl Ara4N, the peracetylated 4-azido derivative showed modest reduction of Ara4N incorporation into the lipid A part of Salmonella typhimurium [8]. We have recently set out to study the substrate specificity of ArnT enzymes

Terpenes

• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 2966–2967, doi:10.3762/bjoc.15.292

• products. Their remarkable structural complexity and diversity is a result of a unique biosynthetic pathway invented by nature that starts with the formation of only a few acyclic precursors termed oligoprenyl diphosphates. These precursors containing multiple olefinic double bonds can be ionised to

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

• antipseudomonal activity. The biosynthetic pathway for argyrin production in Cystobacter sp. SBCb004 (Arg1, radical SAM-dependent methyltransferase; Arg2/Arg3, nonribosomal peptide synthetases; Arg4, O‑methyltransferase; Arg5, tryptophan 2,3-dioxygenase). The initial tripeptide of the biosynthesis of the argyrins

Bacterial terpene biosynthesis: challenges and opportunities for pathway engineering

• Eric J. N. Helfrich,
• Geng-Min Lin,
• Christopher A. Voigt and
• Jon Clardy

Beilstein J. Org. Chem. 2019, 15, 2889–2906, doi:10.3762/bjoc.15.283

• potential with molecular structure is severely restricted. The canonical terpene biosynthetic pathway uses a single enzyme to form a cyclized hydrocarbon backbone followed by modifications with a suite of tailoring enzymes that can generate dozens of different products from a single backbone. This

Nanangenines: drimane sesquiterpenoids as the dominant metabolite cohort of a novel Australian fungus, Aspergillus nanangensis

• Heather J. Lacey,
• Cameron L. M. Gilchrist,
• Andrew Crombie,
• John A. Kalaitzis,
• Daniel Vuong,
• Peter J. Rutledge,
• Peter Turner,
• John I. Pitt,
• Ernest Lacey,
• Yit-Heng Chooi and
• Andrew M. Piggott

Beilstein J. Org. Chem. 2019, 15, 2631–2643, doi:10.3762/bjoc.15.256

• bacteria, fungi, mammalian cells and plants. Bioinformatics analysis, including comparative analysis with other acyl drimenol-producing Aspergilli, led to the identification of a putative nanangenine biosynthetic gene cluster that corresponds to the proposed biosynthetic pathway for nanangenines. Keywords

• analyses above, a biosynthetic pathway to the nanangenines was proposed (Figure 3). Unlike the ast cluster, where there are multiple HAD-like enzymes encoded (one terpene synthase and two phosphatases), the putative nanangenine cluster only encodes one such enzyme, FE257_006542. However, given that

• biosynthetic gene cluster in A. nanangensis MST-FP2251 and homologs identified in other drimane sesquiterpenoid-producing species of Aspergillus section Usti. Gene models are drawn to scale; shaded boxes that link gene models represent amino acid identity (0% transparent; 100% black). Putative biosynthetic

Analysis of sesquiterpene hydrocarbons in grape berry exocarp (Vitis vinifera L.) using in vivo-labeling and comprehensive two-dimensional gas chromatography–mass spectrometry (GC×GC–MS)

• Philipp P. Könen and
• Matthias Wüst

Beilstein J. Org. Chem. 2019, 15, 1945–1961, doi:10.3762/bjoc.15.190

• (+)-valencene from germacrene A [11]. This biosynthetic pathway could also be confirmed by feeding experiments. The formation of the three aforementioned sesquiterpene hydrocarbons takes place without deuterium loss, so that with the use of d3-MVL as precursor (Scheme 5) nine deuterium atoms and with the use of

• described by Steele et al. for the formation of guaia-6,9-diene and δ-selinene via germacrene C could also be confirmed by feeding experiments (Scheme 7) [9]. Biosynthesis of (E)-β-caryophyllene and α-humulene The biosynthetic pathway postulated by Boland and Garms for the formation of (E)-β-caryophyllene

• from farnesyl pyrophosphate (FPP) is consistent with our feeding experiments (Scheme 8) [29]. The incorporation of deuterium atoms into (E)-β-caryophyllene during biosynthesis is shown by the following mass spectra (Figure 11). The assumed biosynthetic pathway for the formation of (E)-β-caryophyllene

Targeting the Pseudomonas quinolone signal quorum sensing system for the discovery of novel anti-infective pathoblockers

• Christian Schütz and
• Martin Empting

Beilstein J. Org. Chem. 2018, 14, 2627–2645, doi:10.3762/bjoc.14.241

• [38]. HQNO acts through inhibition of complex III in the respiratory chain of bacteria and mitochondria of eukaryotes and, hence, it can be considered a general cytotoxic agent. DHQ, a shunt product of the PQS biosynthetic pathway, is important for P. aeruginosa virulence in a Caenorhabditis elegans

Volatiles from three genome sequenced fungi from the genus Aspergillus

• Jeroen S. Dickschat,
• Ersin Celik and
• Nelson L. Brock

Beilstein J. Org. Chem. 2018, 14, 900–910, doi:10.3762/bjoc.14.77

• biosynthetic pathway from linoleic acid via its hydroperoxide has been suggested [24][25][26], and if the same biosynthetic steps would proceed from linolenic acid, this would result in the assigned structure of 2 (Scheme 1B). The other compounds identified in the headspace extracts of A. fischeri were all