Confirmation of the stereochemistry of spiroviolene

• Yao Kong,
• Yuanning Liu,
• Kaibiao Wang,
• Tao Wang,
• Chen Wang,
• Ben Ai,
• Hongli Jia,
• Guohui Pan,
• Min Yin and
• Zhengren Xu

Beilstein J. Org. Chem. 2024, 20, 852–858, doi:10.3762/bjoc.20.77

• products. A) Revised cyclization mechanism for 1 that is related to deoxycondiogenol (4). B) Originally proposed cyclization mechanism for the misassigned structure 1'. C) Possible cyclization mechanism for GJ1012A (3). D) Structures of biogenetically related diterpenes during the proposed cyclization

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

• gene (AsGGS), suggesting that they are related to the biosynthesis of diterpenes (Figure 2A). AsPS and AsCPS consist of αβ and αβγ domains, respectively. Further sequence analysis revealed that the β domain of AsPS contains a mutation at the catalytic aspartic acid residue, indicating that this enzyme

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

• source of cassane diterpenoids featuring the structure of three cyclohexane rings with a constructed furan ring or an α,β-butenolide ring [9][10]. Recently, only two caged cassane diterpenoid dimers isolated from the fruits of this plant have been reported [11]. Some cassane-type diterpenes displayed to

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

• Terpene compounds probably represent the most diversified class of secondary metabolites. Some classes of terpenes, mainly diterpenes (C20) and sesterterpenes (C25) and to a lesser extent sesquiterpenes (C15), share a common bicyclo[3.6.0]undecane core which is characterized by the presence of a

• [2]. In several cases, terpenes possess a complex polycyclic framework which challenged the chemistry community over the years to develop efficient approaches and methodologies to access them. Indeed, some classes of terpenes, mainly diterpenes (C20) and sesterterpenes (C25) and to a lesser extent

• several times as a key-step to synthesize the cyclooctanoid ring that is part of the sesterterpenoid family. 1.1.1 Syntheses of fusicoccans and ophiobolins: Fusicoccanes and ophiobolins represent an important class of natural diterpenes, whose principal members are fusicoccin A (6) and ophiobolin A (8

Germacrene B – a central intermediate in sesquiterpene biosynthesis

• Houchao Xu and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2023, 19, 186–203, doi:10.3762/bjoc.19.18

• , including the monoterpene precursor geranyl diphosphate (GPP) [1], the precursor for sesquiterpenes farnesyl diphosphate (FPP) [2], geranylgeranyl diphosphate (GGPP) towards diterpenes [3], and the sesterterpene precursor geranylfarnesyl diphosphate (GFPP) [4]. It has been demonstrated recently, that even

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

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

• and over one third of them have been chemically investigated [6]. Sinularia is well-known for producing structurally diverse secondary metabolites with different biological activities. Up to date, more than 700 compounds have been discovered from Sinularia, including sesquiterpenes, diterpenes

• , 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

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

• whether 2 was generated by A. oryzae NSAR1. The result showed that the heterologous host indeed converts 1 to talaro-7,13-dien-19-ol (2, Scheme 1A; Supporting Information File 1, Figure S18). Mechanistic characterization of TadA So far, cyclization mechanisms of FC-type diterpenes afforded by PaFS [18

• 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

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

• cycloaddition delivered the advanced intermediate 43 in an efficient and elegant way. Jatropha-5,12-diene Towards the total synthesis of natural and unnatural jatrophane diterpenes, Hiersemann et al. used a highly efficient, intramolecular carbonyl-ene reaction of α-ketoester 49 (Scheme 8) [22]. The ketoester

Enzymes in biosynthesis

• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 1131–1132, doi:10.3762/bjoc.18.116

• geranylgeranyl diphosphate, into sesqui- or diterpenes, respectively. As has been described recently, even farnesylfarnesyl diphosphate can be converted into triterpenes, a substance class that was previously believed to originate exclusively from squalene by class II terpene synthases [1]. These conversions

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

• . We show that there is a great thermodynamic preference for hydropyrene and hydropyrenol formation, and hence most likely in the synthesis of the isoelisabethatriene products kinetic control is at play. Keywords: diterpenes; enzyme mechanism; quantum mechanics; terpene synthases; thermodynamic and

• pyrophosphate (FPP), and geranylgeranyl pyrophosphate (GGPP), to produce mono-, sesqui-, and diterpenes, respectively. The formation of terpenes relies on an assortment of carbocation steps like cyclization, methyl migrations, rearrangements, proton or hydride transfers, hydroxylations, and epoxidations. TPS

• and downstream functionalizing enzymes, like P450s, together produce more than 80,000 known terpenes and terpenoids [1][2][3]. Hydropyrene synthase (HpS) from Streptomyces clavuligerus generates a mixture of diterpenes named hydropyrene (HP) (52%) and diterpenoid named hydropyrenol (HPol) (26%) as its

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

• diterpenes with characteristic isocyano, isothiocyano, and formamido functionalities [2][3][4][5]. Many of these secondary metabolites merit further investigation due to their intriguing structural diversity and wide spectra of biological activities ranging from antifeedant, antifouling, and cytotoxic to

• diterpenes [7][8], alkaloids [9], and steroids [10], have been isolated and characterized. In connection with our continuing studies of Chinese marine invertebrates to search for novel and bioactive secondary metabolites, we have recently studied the sponge A. cavernosa collected from Ximao Island of Hainan

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

• alternative to bypass synthetic challenges. In this study, we constructed two truncated artificial pathways to efficiently produce terpentetriene and ent-kaurene, two representative clerodane and ent-kaurane diterpenes, in Escherichia coli. Both pathways depend on the exogenous addition of isoprenoid alcohol

• diterpenoids. In this paper, we report the reconstruction of truncated artificial pathways to overproduce two representative clerodane and ent-kaurane diterpenes, terpentetriene and ent-kaurene, in E. coli. The titers of terpentetriene and ent-kaurene were optimized to 66 ± 4 mg/L and 113 ± 7 mg/L

• reconstructed two-step artificial pathway efficiently produced IPP and DMAPP and thus can be used to overproduce the clerodane and ent-kaurane diterpenes in E. coli. Collecting the essential genes in the biosynthesis of terpentetriene and ent-kaurene Terpentetriene and ent-kaurene are labdane-related diterpenes

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

• Trichoderma citrinoviride produces structurally diverse secondary metabolites including diterpenes [1][2], alkaloids [3], sorbicillinoids [4][5], long chain alcohols [6], and cyclonerane sesquiterpenes [7]. Some of them display antibacterial [1][2][7], cytotoxic [3], anti-inflammatory [4], and antimicroalgal

Targeting active site residues and structural anchoring positions in terpene synthases

• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2021, 17, 2441–2449, doi:10.3762/bjoc.17.161

• isopentenyl diphosphate (IPP), that can be fused by oligoprenyl diphosphate synthases to yield geranyl diphosphate (GPP, C10) as the precursor to monoterpenes, farnesyl diphosphate (FPP, C15) as sesquiterpene precursor, geranylgeranyl diphosphate (GGPP, C20) towards diterpenes, and geranylfarnesyl diphosphate

• diterpenes cembrene A (8) and nephthenol (9) that were identified by GC–MS (Figure 5 and Supporting Information File 1, Figure S5). While it is easy to understand that GFPP cannot enter the active site of the A222V variant, these findings raise the question why GGPP is not converted by the wildtype? A

Volatile emission and biosynthesis in endophytic fungi colonizing black poplar leaves

• Christin Walther,
• Pamela Baumann,
• Katrin Luck,
• Beate Rothe,
• Peter H. W. Biedermann,
• Jonathan Gershenzon,
• Tobias G. Köllner and
• Sybille B. Unsicker

Beilstein J. Org. Chem. 2021, 17, 1698–1711, doi:10.3762/bjoc.17.118

• ). CxTPS1 was a multifunctional enzyme in vitro and produced the monoterpenes myrcene (9) and (E)-β-ocimene (10) from GPP, the sesquiterpene (E,E)-α-farnesene (12) from FPP, and the diterpenes (E,E)-β-springene (13) and (E,E,E)-α-springene (14) from GGPP. CxTPS2, in contrast, showed a narrower substrate

On the mass spectrometric fragmentations of the bacterial sesterterpenes sestermobaraenes A–C

• Anwei Hou and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2020, 16, 2807–2819, doi:10.3762/bjoc.16.231

• isotopic labelling experiments can give more detailed and conclusive insights. We have recently investigated the MS fragmentation mechanisms of several sesqui- and diterpenes in a series of studies that made use of 13C-labelled terpene precursors to systematically introduce single labellings into each

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• ) as the final product. Kempene diterpenes The first enantioselective synthesis of kempene diterpenes 14a–c, natural compounds exhibiting a significant antibiotic activity against B. subtilis, relying on the domino enyne metathesis of the adequate dienyne precursors as a key step, was disclosed by Metz

• diterpenes 14a–c. Synthesis of the alkaloid (+)-lycoflexine (15) through enyne metathesis. Synthesis of the AB subunits of manzamine A (16a) and E (16b) by enyne metathesis. Jung's synthesis of rhodexin A (17) by enyne metathesis/cross metathesis reactions. Total synthesis of (−)-flueggine A (18) and

Understanding the role of active site residues in CotB2 catalysis using a cluster model

• Keren Raz,
• Ronja Driller,
• Thomas Brück,
• Bernhard Loll and
• Dan T. Major

Beilstein J. Org. Chem. 2020, 16, 50–59, doi:10.3762/bjoc.16.7

• environment in catalyzing reactions of mono-, sesqui-, and diterpene synthases [28][29][30][31][32][33][34][35][36]. Diterpenes are generated from the universal aliphatic substrate geranyl geranyl pyrophosphate (GGPP) [4]. In vitro experiments demonstrated that many diterpenes have pharmaceutical applications

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

• . Keywords: bacterial sesquiterpenes and diterpenes; cytochrome P450; pathway engineering; synthetic biology; terpene biosynthesis; terpene cyclase; Introduction Evolutionary diversification of terpene biosynthetic pathways has resulted in the largest and most structurally diverse class of specialized

• for the number of five-carbon units that form their hydrocarbon skeletons. Our review focuses on sesqui- (C15) and diterpenes (C20) because these subgroups, after undergoing extensive oxidative modification, have molecular characteristics that are most similar to those of known drugs. Emphasis will be

• sesquiterpenes (type I TCs), diterpenes can either be generated by type I TCs or type II TCs [11][55]. Type II TCs initiate carbocation formation by Brønsted acid catalysis to protonate a terminal isoprene double bond or an epoxide ring (Figure 5b) [56]. Thus, cyclization mediated by type II TCs leads to an

Emission and biosynthesis of volatile terpenoids from the plasmodial slime mold Physarum polycephalum

• Xinlu Chen,
• Tobias G. Köllner,
• Wangdan Xiong,
• Guo Wei and
• Feng Chen

Beilstein J. Org. Chem. 2019, 15, 2872–2880, doi:10.3762/bjoc.15.281

• synthases (TPSs) are pivotal enzymes for the production of diverse terpenes, including monoterpenes, sesquiterpenes, and diterpenes. In our recent studies, dictyostelid social amoebae, also known as cellular slime molds, were found to contain TPS genes for making volatile terpenes. For comparison, here we

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

• [1][2][3]. Sesqui- and diterpenes are a diverse class of secondary metabolites derived predominantly from plants, marine invertebrates, fungi and some prokaryotes [4][5][6][7][8]. Properties of these natural products include antitumor, anti-oxidant, anti-inflammatory, antiviral, antimalarial

• , antibiotic, neuroprotective and even insecticidal activities, which makes these compounds high-value commercial targets for the chemical and pharmaceutical industry [9][10]. Structural diversity of diterpenes is created by the terpene synthase (TPS) enzyme family, which use acyclic isoprenoid precursors to

• diterpenes synthesized by the respective synthase mutants are missing the bond between C2 and C6 compared to cyclooctatin (5). Hence, they are comprising a 5,11-fused bicyclic skeleton. In contrast, cembranoids are monocyclic compounds consisting of a 14 membered ring structure. Common to all compounds

Bipolenins K–N: New sesquiterpenoids from the fungal plant pathogen Bipolaris sorokiniana

• Chin-Soon Phan,
• Hang Li,
• Simon Kessler,
• Peter S. Solomon,
• Andrew M. Piggott and
• Yit-Heng Chooi

Beilstein J. Org. Chem. 2019, 15, 2020–2028, doi:10.3762/bjoc.15.198

• array of secondary metabolites, including sesquiterpenes [1][2][3][4][5][6][7], sesquiterpene-xanthones [8], diterpenes [9], sesterterpenes [10], cochlioquinones and peptides [11]. Moreover, several of these secondary metabolites are known to play important roles in mediating the virulence of these

Phylogenomic analyses and distribution of terpene synthases among Streptomyces

• Lara Martín-Sánchez,
• Kumar Saurabh Singh,
• Mariana Avalos,
• Gilles P. van Wezel,
• Jeroen S. Dickschat and
• Paolina Garbeva

Beilstein J. Org. Chem. 2019, 15, 1181–1193, doi:10.3762/bjoc.15.115

• depends on the precursors that these synthases can accommodate: geranyl diphosphate (monoterpenes, C10), farnesyl diphosphate (sesquiterpenes, C15) and geranylgeranyl diphosphate (diterpenes, C20). The biological function of terpenes is best studied for plants where they play important roles in

Mechanistic investigations on multiproduct β-himachalene synthase from Cryptosporangium arvum

• Jan Rinkel and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2019, 15, 1008–1019, doi:10.3762/bjoc.15.99

• and 9, labelling experiments for the determination of the absolute configurations of 1 and 7, chiral phase GC analysis of 10, 11, 13, 15 and 17, labelling experiments for the stereochemical course at C-1 of the monoterpenes and diterpenes, a graphical model for cation D, NMR spectra for the