Unraveling the role of prenyl side-chain interactions in stabilizing the secondary carbocation in the biosynthesis of variexenol B

• Moe Nakano,
• Rintaro Gemma and
• Hajime Sato

Beilstein J. Org. Chem. 2023, 19, 1503–1510, doi:10.3762/bjoc.19.107

• biosynthesis of trichobrasilenol [22], by combined methods of computational and experimental chemistry. Recently, Dickschat et al. reported the synthesis of a novel diterpene compound, variexenol B, using a substrate analogue called iso-GGPP (Scheme 1) [23]. This biosynthetic pathway has two interesting

• hyperconjugation determines whether the reaction proceeds in a stepwise or concerted manner. The second interesting aspect of the biosynthesis of variexenol B is that the biosynthetic pathway involves an intermediate with an exomethylene group. A terpene with an exomethylene group as a starting material is rare

• carbocation and the prenyl side chain. Figure 1 shows the computed biosynthetic pathway and energy diagram without cation–π interaction, while Figure 2 shows the computed biosynthetic pathway including cation–π interaction from the prenyl side chain. Our research started with the application of DFT

Functions of enzyme domains in 2-methylisoborneol biosynthesis and enzymatic synthesis of non-natural analogs

• Binbin Gu,
• Lin-Fu Liang and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 1452–1459, doi:10.3762/bjoc.19.104

• for sodorifen [38] – potentially allow for an evolution towards a natural biosynthetic pathway for C12 monoterpenoids. Experimental General synthetic methods Chemicals were purchased from Sigma-Aldrich Chemie GmbH (Steinheim, Germany), Carbolution Chemicals GmbH (St. Ingbert, Germany), or Carl Roth

Cassane diterpenoids with α-glucosidase inhibitory activity from the fruits of Pterolobium macropterum

• Sarot Cheenpracha,
• Ratchanaporn Chokchaisiri,
• Lucksagoon Ganranoo,
• Sareeya Bureekaew,
• Thunwadee Limtharakul and
• Surat Laphookhieo

Beilstein J. Org. Chem. 2023, 19, 658–665, doi:10.3762/bjoc.19.47

• , MeOH); lit. −44 (c 0.05, MeOH)) [18], confirming the same absolute configuration these compounds should be derived from the same biosynthetic pathway. In addition, the ECD spectra of (5S,8R,9S,10R,14S)-1 and its enantiomer were calculated at the B3LYP functional using a TD–DFT method [19]. As

• = 2.7 Hz) and H-6′ (J = 2.7 Hz). The syn orientations of H-15, H-15′, H-16′ and H3-17′ were established from the NOESY correlations of H-15′ to H3-17′, H-16′ and of H-15 to H-16′. From above information, the relative configuration of C-12′ was assigned and supported by the biosynthetic pathway based on

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• compounds available in the literature, there is none which focuses only on combretastatins D and their isomers. Therefore, this review is divided into three main parts: the first comprises the isolation of these compounds from natural sources. In the following part, the biosynthetic pathway and the total

• elucidate the chemical structures of the isolated compounds [19]. 2 Synthesis 2.1 Biosynthetic pathway In the literature, there are two possible biosynthetic pathways for the formation of these compounds. The first one was proposed by Pettit and co-workers [16][17] based on tyrosine as the starting material

• ]. IC50 of compounds against α-glucosidase [19]. Biosynthetic pathway proposed by Pettit and co-workers. Biosynthetic pathway towards corniculatolides or isocorniculatolides proposed by Ponnapalli and co-workers. Retrosynthetic approaches. Attempt of total synthesis of 2 by Boger and co-workers employing

Strategies to access the [5-8] bicyclic core encountered in the sesquiterpene, diterpene and sesterterpene series

• Cécile Alleman,
• Charlène Gadais,
• Laurent Legentil and
• François-Hugues Porée

Beilstein J. Org. Chem. 2023, 19, 245–281, doi:10.3762/bjoc.19.23

Identification and determination of the absolute configuration of amorph-4-en-10β-ol, a cadinol-type sesquiterpene from the scent glands of the African reed frog Hyperolius cinnamomeoventris

• Angelique Ladwig,
• Markus Kroll and
• Stefan Schulz

Beilstein J. Org. Chem. 2023, 19, 167–175, doi:10.3762/bjoc.19.16

• scent gland macrolides can be biosynthesized by the frogs [7], although the macrolides are produced from the fatty acid biosynthetic pathway. The gas chromatographic separation obtained with the chiral phase also allowed the determination of the identity of the minor diastereomers formed during the

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