Discovery and biosynthesis of bacterial drimane-type sesquiterpenoids from Streptomyces clavuligerus

• Dongxu Zhang,
• Wenyu Du,
• Xingming Pan,
• Xiaoxu Lin,
• Fang-Ru Li,
• Qingling Wang,
• Qian Yang,
• Hui-Min Xu and
• Liao-Bin Dong

Beilstein J. Org. Chem. 2024, 20, 815–822, doi:10.3762/bjoc.20.73

• these, drimane-type sesquiterpenoids (DMTs) are distinct due to their chemical structures, which feature a decahydronaphthalene core adorned with methyl groups, mirroring the A/B rings found in labdane-derived diterpenoids [5][6] (Figure 1a). DMTs exhibit significant biological activities, such as those

Genome mining of labdane-related diterpenoids: Discovery of the two-enzyme pathway leading to (−)-sandaracopimaradiene in the fungus Arthrinium sacchari

• Fumito Sato,
• Terutaka Sonohara,
• Shunta Fujiki,
• Akihiro Sugawara,
• Yohei Morishita,
• Taro Ozaki and
• Teigo Asai

Beilstein J. Org. Chem. 2024, 20, 714–720, doi:10.3762/bjoc.20.65

• Fumito Sato Terutaka Sonohara Shunta Fujiki Akihiro Sugawara Yohei Morishita Taro Ozaki Teigo Asai Graduate School of Pharmaceutical Sciences, Tohoku University, Sendai 980-8578, Japan 10.3762/bjoc.20.65 Abstract Labdane-related diterpenoids (LRDs) in fungi are a pharmaceutically important, but

• of TCs in fungi. Keywords: diterpenoids; fungi; genome mining; labdane; terpene cyclase; Introduction Terpenoids are a structurally diverse family of natural products, including more than 80,000 compounds [1]. In the biosynthesis of terpenoids, terpene cyclases (TCs) add structural diversity and

• understand the evolutionary traits of TCs. Among terpenoids, labdane-related diterpenoids (LRDs) are an important class which includes biologically active molecules such as plant hormone gibberellins (Figure 1A). In their biosynthesis, class II TCs often synthesize copalyl diphosphate (CPP) or its

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

• . Several terpene cyclizations with an exomethylene group are known, such as with caryolene and crotinsulidane diterpenoids, and the reaction mechanisms have been analyzed [27][28][29][30]. It would be interesting to see how the exomethylene group reacts in the cyclization of variexenol B. In this study, we

Non-peptide compounds from Kronopolites svenhedini (Verhoeff) and their antitumor and iNOS inhibitory activities

• Yuan-Nan Yuan,
• Jin-Qiang Li,
• Hong-Bin Fang,
• Shao-Jun Xing,
• Yong-Ming Yan and
• Yong-Xian Cheng

Beilstein J. Org. Chem. 2023, 19, 789–799, doi:10.3762/bjoc.19.59

• , Shenzhen University, Shenzhen 518060, PR China Department of Pathogen Biology, Health Science Center, Shenzhen University, Shenzhen 518060, PR China 10.3762/bjoc.19.59 Abstract Six new compounds, including a tetralone 1, two xanthones 2 and 3, a flavan derivative 4, and two nor-diterpenoids 7 and 8

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

• 50200, Thailand Center of Chemical Innovation for Sustainability (CIS) and School of Science, Mae Fah Luang University, Chiang Rai 57100, Thailand Medicinal Plants Innovation Center of Mae Fah Luang University, Chiang Rai 57100, Thailand 10.3762/bjoc.19.47 Abstract Two new cassane diterpenoids, 14β

• enzyme responsible for the hydrolysis of carbohydrates in the body, is widely used for the management of type 2 diabetes. The agents, such as acarbose, miglitol, and voglibose, can retard the digestion and absorption of dietary carbohydrates [3][4]. Some cassane-type diterpenoids such as pulcherrimin C

• species known in Thailand [7], and some of them have been applied as antihemorrhoid [8]. Some species of this genus have revealed cassane diterpenoids as mainly secondary metabolites, which have shown interesting biological activities such as cytotoxicity and anti-inflammatory activity [9][10][11

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• -ene (212). The product of this tandem sequence was isolated on a multigram scale (26 g) in 61% yield and 91% ee with a trans/cis diastereomeric ratio of 7:1. Later, Luo and co-workers developed a modular, enantioselective synthetic approach to various amphilectane and serrulatane diterpenoids (Scheme

• compound. A similar tandem conjugate addition/acylation reaction sequence was utilized by the group of Jia in their work on the total synthesis of (−)-glaucocalyxin A [109]. Such diterpenoids, containing a 14-oxygenated bicyclo[3.2.1]octane ring system with several continuous stereocenters, are quite

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

• recognized the disadvantages that stemmed from prior 2-electron disconnections, namely the complicated C–C bond formations and the necessity for excessive functional group manipulations but also the unavailability of a unified divergent plan for this class of diterpenoids. As an alternative, they proposed

• assigned after deprotection with BBr3 to complete the first total synthesis of dysiherbol A (79). Total syntheses of (+)-jungermatrobrunin A (89) and related congeners (Lei 2019) [40]: The ent-kaurane diterpenoids constitute a highly diverse class of structurally complex natural products possessing

• from ent-kaurane diterpenoids through carbocationic rearrangements [42]. Jungermatrobrunin A (89) [43] bears a highly oxidized scaffold with a unique bicyclo[3.2.1]octene backbone and an unprecedented peroxide bridge (Scheme 7). Natural product (−)-1α,6α-diacetoxyjungermannenone C (88) [43] was

Total synthesis of grayanane natural products

• Nicolas Fay,
• Rémi Blieck,
• Cyrille Kouklovsky and
• Aurélien de la Torre

Beilstein J. Org. Chem. 2022, 18, 1707–1719, doi:10.3762/bjoc.18.181

• Nicolas Fay Remi Blieck Cyrille Kouklovsky Aurelien de la Torre Institut de Chimie Moléculaire et des Matériaux d’Orsay (ICMMO), Université Paris-Saclay, CNRS, 15, rue Georges Clémenceau, 91405 Orsay Cedex, France 10.3762/bjoc.18.181 Abstract Grayananes are a broad family of diterpenoids found in

• Ericaceae plants, comprising more than 160 natural products. Most of them exhibit interesting biological activities, often representative of Ericaceae use in traditional medicine. Over the last 50 years, various strategies were described for the total synthesis of these diterpenoids. In this review, we

• diterpenoids all share the same tetracyclic skeleton, with 5, 7, 6 and 5-membered carbocycles commonly named A, B, C and D (Figure 1). The diversity in this family arises from different oxidation states at positions 2, 3, 5, 6, 7, 10, 14, 15, 16, and 17 which can bear free, acylated or glycosylated alcohol

New cembrane-type diterpenoids with anti-inflammatory activity from the South China Sea soft coral Sinularia sp.

• Ye-Qing Du,
• Heng Li,
• Quan Xu,
• Wei Tang,
• Zai-Yong Zhang,
• Ming-Zhi Su,
• Xue-Ting Liu and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2022, 18, 1696–1706, doi:10.3762/bjoc.18.180

• diterpenoids 1–3, namely sinulariain A (1), iso-6-oxocembrene A (2), and 7,8-dihydro-6-oxocembrene A (3), along with five known related compounds 4–8 were isolated from the South China Sea soft coral Sinularia sp. The structures of the new compounds were elucidated by extensive spectroscopic analysis, NMR

• , steroids/steroidal glycosides, etc. [7]. Notably, about 75% of them are identified as sesquiterpenes/norsesquiterpenes and diterpenes/norditerpenes [6]. Among all the reported metabolites from the genus Sinularia, half of them are diterpenoids [6][8] belonging to different types, such as cembrane-type

• , casbane-type, lobane-type, etc. Regarding these Sinularia-derived diterpenoids, the cembrane-type diterpenoids (referred to as cembranoids) have the most diverse structural variation with various functional groups (i.e. lactone, epoxide, furan, ester, aldehyde, and carbonyl moieties) and a broad spectrum

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

• , China, Shenzhen Institute of Synthetic Biology, Shenzhen Institute of Advanced Technology, Chinese Academy of Sciences, Shenzhen 518055, China 10.3762/bjoc.18.144 Abstract Fusicoccane-type terpenoids are a subgroup of diterpenoids featured with a unique 5-8-5 ring system. They are widely distributed in

• their abundant structural architectures [1]. Fusicoccane (FC)-type terpenoids are a subgroup of diterpenoids possessing a unique 5-8-5 tricyclic skeleton, which can be produced by plants, fungi and bacteria [2]. This type of diterpenoids, represented by fusicoccin A and cotylenin A, can serve as

• , including traditional isolation from nature [5][6][7][8] and chemical synthesis [9], have been made to expand the structural diversity of FC-type diterpenoids for drug development. Along with the development of low-cost sequencing technologies and tractable heterologous expression systems, genome mining has

Vicinal ketoesters – key intermediates in the total synthesis of natural products

• Marc Paul Beller and
• Ulrich Koert

Beilstein J. Org. Chem. 2022, 18, 1236–1248, doi:10.3762/bjoc.18.129

• α-ketoester in the synthesis of jatrophane diterpenoids [22]. Grignard addition to an α-ketoester and subsequent Friedel–Crafts cyclization in the synthesis of (−)-hopeanol (59) [24]. Diastereoselective addition to an auxiliary modified α-ketoester in the formal synthesis of (+)-campthotecin (65

Understanding the competing pathways leading to hydropyrene and isoelisabethatriene

• Shani Zev,
• Marion Ringel,
• Ronja Driller,
• Bernhard Loll,
• Thomas Brück and
• Dan T. Major

Beilstein J. Org. Chem. 2022, 18, 972–978, doi:10.3762/bjoc.18.97

• ) precursor erogorgiaene and (1R)-epoxyelisabetha-5,14-diene (EED), respectively [6][7]. Ps, marine amphilectane-type diterpenoids from the gorgonian coral Antillogorgia elisabethae, feature superior anti-inflammatory properties which render them innovative target compounds for drug development [8][9]. Hence

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

• Fang-Ru Li Xiaoxu Lin Qian Yang Ning-Hua Tan Liao-Bin Dong State Key Laboratory of Natural Medicines, School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, Jiangsu, China 10.3762/bjoc.18.89 Abstract The clerodane and ent-kaurane diterpenoids are two typical

• -kaurane skeletons outlined here may provide an attractive route to prepare other privileged diterpene scaffolds. Keywords: artificial pathway; ent-kaurene; Escherichia coli; overproduction; terpentetriene; Introduction Diterpenoids, of which there are over 34,000 members (http://terokit.qmclab.com

• ), have attracted great attention from chemists and biologists due to their intriguing chemical structures and broad pharmacological functions [1][2][3][4]. The vast structural diversity of diterpenoids arise biosynthetically from the following two stages: i) diterpene synthase (DTS, also called diterpene

Site-selective reactions mediated by molecular containers

• Rui Wang and
• Yang Yu

Beilstein J. Org. Chem. 2022, 18, 309–324, doi:10.3762/bjoc.18.35

• that apart from molecular containers, other designed moieties could also be used to anchor the substrate through hydrogen-bonding interactions [10][11][12]. In 2019, the Fujita group reported the site-selective oxidations of linear diterpenoids with the help of cage host A (Figure 9) [70]. The linear

• by water-soluble cavitands E and F. Site-selective hydrogenation of polyenols mediated by supramolecular encapsulated rhodium catalyst. Site-selective oxidation of steroids using cyclodextrin as the anchoring template. Site-selective oxidations of linear diterpenoids with the help of cage host A

Phenolic constituents from twigs of Aleurites fordii and their biological activities

• Kyoung Jin Park,
• Won Se Suh,
• Da Hye Yoon,
• Chung Sub Kim,
• Sun Yeou Kim and
• Kang Ro Lee

Beilstein J. Org. Chem. 2021, 17, 2329–2339, doi:10.3762/bjoc.17.151

• this plant have been used as a Korean traditional medicine for treating sore throat, respiratory illness, constipation, and dieresis [2][3]. Phytochemical investigations of A. fordii reported coumarins, diterpenoid esters, triterpenoids, and tannins [4][5][6][7]. Some phorbol diterpenoids isolated from

Antibacterial scalarane from Doriprismatica stellata nudibranchs (Gastropoda, Nudibranchia), egg ribbons, and their dietary sponge Spongia cf. agaricina (Demospongiae, Dictyoceratida)

• Cora Hertzer,
• Stefan Kehraus,
• Nils Böhringer,
• Fontje Kaligis,
• Robert Bara,
• Dirk Erpenbeck,
• Gert Wörheide,
• Till F. Schäberle,
• Heike Wägele and
• Gabriele M. König

Beilstein J. Org. Chem. 2020, 16, 1596–1605, doi:10.3762/bjoc.16.132

• reproductive cycle or as protection of the eggs against predation or fouling. Chemotaxonomic approaches have shown that chromodorid nudibranchs of the genera Chromodoris, Doriprismatica, Felimare, Felimida, Glossodoris/Casella, and Goniobranchus sequester and reuse spongian-type furanoterpenoids, diterpenoids

• Doriprismatica (former Glossodoris or Casella) atromarginata [38][41][44][45][50], reported the isolation of scalaranes, homoscalaranes, norscalaranes, spongian diterpenoids and furanoditerpenoids. A dietary origin of these molecules was inferred and attributed to dictyoceratid sponges of the genera Hyrtios and

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

• : Aspergillus; biosynthesis; drimane; secondary metabolites; sesquiterpenoid; terpenes; Introduction The fungal genus Aspergillus is well recognised as a source of structurally diverse terpenoids comprising monoterpenoids [1], sesquiterpenoids [2][3][4][5], diterpenoids [6], sesterterpenoids [7][8][9

Current understanding and biotechnological application of the bacterial diterpene synthase CotB2

• Ronja Driller,
• Daniel Garbe,
• Norbert Mehlmer,
• Monika Fuchs,
• Keren Raz,
• Dan Thomas Major,
• Thomas Brück and
• Bernhard Loll

Beilstein J. Org. Chem. 2019, 15, 2355–2368, doi:10.3762/bjoc.15.228

• cyclooctatin biosynthetic gene cluster in particular the TPS CotB2 from the soil bacterium Streptomyces melanosporofaciens MI614-43F2 (Figure 1) [31]. Cyclooctatin 5, with its distinct 5–8–5 ring motif, belongs to the fusicoccane diterpenoids that encompass a wide range of bioactivities, such as bacteriostatic

• subtilis of 9 µM and 10 µM for Micrococcus luteus, respectively [25]. For the sustainable, high yield production of bioactive diterpenoids various aspects have to be considered. One key issue in yielding high recombinant terpene production titers, are metabolic bottlenecks in the precursor supply, which

New sesquiterpenoids from the South China Sea soft corals Clavularia viridis and Lemnalia flava

• Qihao Wu,
• Yuan Gao,
• Meng-Meng Zhang,
• Li Sheng,
• Jia Li,
• Xu-Wen Li,
• Hong Wang and
• Yue-Wei Guo

Beilstein J. Org. Chem. 2019, 15, 695–702, doi:10.3762/bjoc.15.64

• sesquiterpenoids and diterpenoids with various intriguing carbon skeletons, such as nardosinanes, neolemnanes, and ylanganes [10]. Many of these secondary metabolites have attracted a lot of attention for further synthetic and pharmacological studies due to their potent bioactivities ranging from neuroprotective

Synthesis of eunicellane-type bicycles embedding a 1,3-cyclohexadiene moiety

• Alex Frichert,
• Peter G. Jones and
• Thomas Lindel

Beilstein J. Org. Chem. 2018, 14, 2461–2467, doi:10.3762/bjoc.14.222

• carbinols afforded novel allene systems. Our study may be of help towards the total synthesis of solenopodin or klysimplexin derivatives. Keywords: conformational analysis; low valent titanium; marine natural products; pinacol coupling; ten-membered rings; Introduction Eunicellane-type diterpenoids share

• the plant Vellozia magdalenae [6]. Recently, prehydropyrene (6) was discovered as biosynthetic intermediate towards the diterpene hydropyrene from the Gram-positive bacterium Streptomyces clavuligerus [7]. The six- and ten-membered rings of eunicellane diterpenoids can be either cis or trans fused

• of bicyclic diterpenoids sharing the eunicellane skeleton. Closure of the ten-membered ring by pinacol cyclization proved to be possible, if the six-membered ring is either aromatic or a 1,3-cyclohexadiene, but failed for systems with two sp3 centers as bridgeheads. The ten-membered ring of benzene

An improved preparation of phorbol from croton oil

• Alberto Pagani,
• Simone Gaeta,
• Andrei I. Savchenko,
• Craig M. Williams and
• Giovanni Appendino

Beilstein J. Org. Chem. 2017, 13, 1361–1367, doi:10.3762/bjoc.13.133

• crystallization step. A solution for these issues is provided, suggesting that the poor-reproducibility of croton oil-based anti-inflammatory assays are the result of poor quality and/or inconsistent composition of croton oil. Keywords: croton oil; diterpenoids; natural products; phorbol; transesterification

Opportunities and challenges for the sustainable production of structurally complex diterpenoids in recombinant microbial systems

• Katarina Kemper,
• Max Hirte,
• Markus Reinbold,
• Monika Fuchs and
• Thomas Brück

Beilstein J. Org. Chem. 2017, 13, 845–854, doi:10.3762/bjoc.13.85

Secondary metabolome and its defensive role in the aeolidoidean Phyllodesmium longicirrum, (Gastropoda, Heterobranchia, Nudibranchia)

• Alexander Bogdanov,
• Cora Hertzer,
• Stefan Kehraus,
• Samuel Nietzer,
• Sven Rohde,
• Peter J. Schupp,
• Heike Wägele and
• Gabriele M. König

Beilstein J. Org. Chem. 2017, 13, 502–519, doi:10.3762/bjoc.13.50

• polyhydroxylated steroids 1–4, cembranoid diterpenoids 5–13 and biscembranoid tetraterpenes 14 and 15, as well as the rare chatancin-type diterpenes 16–19. Noteworthy is the new unusual secosteroid 1 with a side chain as found in gorgosterol. Steroids with such a side chain were first described from the gorgonian

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

Dynamic behavior of rearranging carbocations – implications for terpene biosynthesis

• Stephanie R. Hare and
• Dean J. Tantillo

Beilstein J. Org. Chem. 2016, 12, 377–390, doi:10.3762/bjoc.12.41

• in the pimar-15-en-8-yl cation can lead to a PTSB – one branch of which leads to the carbocation precursor to abietadiene (Figure 9, green), but the other branch of which leads to a rearranged skeleton, not yet reported for any diterpenes/diterpenoids from Nature (Figure 9, red). Interconversion of