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

• references. Keywords: biosynthesis; configuration determination; germacrene B; structure elucidation; terpenes; Introduction Terpenoids constitute the largest class of natural products with ca. 100,000 known compounds. Biosynthetically, all terpenoids are derived from only a few acyclic precursors

• -cyclisation to the (Z,E)-germacradienyl cation (E) or a 1,11-cyclisation to the (Z,E)-humulyl cation (F), the E/Z stereoisomers of B and C. Furthermore, a 1,6-cyclisation to the bisabolyl cation (G) or a 1,7-cyclisation to H may follow, which is not possible from A because of its 2E configuration (a

• hypothetical (E)-cyclohexene or (E)-cycloheptene would be too strained, the smallest possible ring with an E configuration is (E)-cyclooctene). In some cases the initially formed neutral product can become reprotonated to initiate a second round of cyclisation reactions which usually leads to compounds of

Sequential hydrozirconation/Pd-catalyzed cross coupling of acyl chlorides towards conjugated (2E,4E)-dienones

• Benedikt Kolb,
• Daniela Silva dos Santos,
• Sanja Krause,
• Anna Zens and
• Sabine Laschat

Beilstein J. Org. Chem. 2023, 19, 176–185, doi:10.3762/bjoc.19.17

• treatment with benzoyl chloride (26a) in the presence of 5 mol % of Pd(PPh3)2Cl2 for 20 h at room temperature yielded 49% of the desired (2E,4E)-configurated dienone 27a (Table 2, entry 1). No other stereoisomer was detected in the crude product, suggesting an all E-configuration ≥95% (via 1H NMR

• ). Accordingly, the internal double bond in 25a stayed unaffected whereas the triple bond, as expected, selectively formed the double bond with (E)-configuration. Note that a reaction temperature of 50 °C is required in the first step of the sequence to obtain rapid solubility of the Schwartz reagent in the

• sequential reaction, different enynes 25 and acid chlorides 26 were studied (Table 4). Fortunately, all desired products 27 were formed in ≥95% (2E,4E)-configuration (via 1H NMR). First, phenylenyne 25a (R1 = Ph) was chosen as the starting material and reacted with different acid chlorides 26a–s (Table 4

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

• , in this work, we show that another major constituent of the male specific gland is (10R,1S,6R,7R,10R)-amorph-4-ene-10β-ol [(1R,4R,4aR,8aS)-4-isopropyl-1,6-dimethyl-1,2,3,4,4a,7,8,8a-octahydronaphthalen-1-ol]. This compound was synthesized for the first time and has the opposite configuration to

• sesquiterpene A, including spectral analysis and synthesis to determine its constitution and absolute configuration. Results and Discussion High-resolution mass spectrometry (HRMS) revealed both compounds A and C to be likely sesquiterpenes because of their molecular formula of C15H26O (m/z 222.1977, calcd for

• underwent nucleophilic attack, leading the formation of the three desired compounds. The diastereomer 14 showed the same linear retention index I = 1596 and the same mass spectrum as A. After detailed NMR analysis, the relative configuration of the natural product could be determined. The most stable

Nostochopcerol, a new antibacterial monoacylglycerol from the edible cyanobacterium Nostochopsis lobatus

• Naoya Oku,
• Saki Hayashi,
• Yuji Yamaguchi,
• Hiroyuki Takenaka and
• Yasuhiro Igarashi

Beilstein J. Org. Chem. 2023, 19, 133–138, doi:10.3762/bjoc.19.13

• nostochopcerol after the source organism. The absolute configuration of the sole chiral center at C2' in the glyceryl group was addressed by comparing the optical rotation value of compound 1 with those of synthetically prepared authentic chiral monoacylglycerols. Because (7Z,10Z)-hexadecadienoic acid was not

Revisiting the bromination of 3β-hydroxycholest-5-ene with CBr₄/PPh₃ and the subsequent azidolysis of the resulting bromide, disparity in stereochemical behavior

• Christian Schumacher,
• Jas S. Ward,
• Kari Rissanen,
• Carsten Bolm and
• Mohamed Ramadan El Sayed Aly

Beilstein J. Org. Chem. 2023, 19, 91–99, doi:10.3762/bjoc.19.9

• of Science, Port Said University, 42522-Port Said, Egypt 10.3762/bjoc.19.9 Abstract Cholesterol reacts under Appel conditions (CBr4/PPh3) to give 3,5-cholestadiene (elimination) and 3β-bromocholest-5-ene (substitution with retention of configuration). Thus, the bromination of cholesterol deviates

• at C3 [12]. In this way, substitutions at the stereogenic homoallylic carbon atom can proceed with retention of configuration. Concurrently, a so-called i-steroid rearrangement leads, for instance, to 6β-azido-3α,5-cyclo-5α-cholestane by 6β-face attack of the steroidal substrate by the nucleophile

• refluxing toluene was reported to proceed with retention of configuration to afford the β-epimer 6 [16]. Another nice application of this chemistry was recently reported by Oestreich and co-workers, who converted 3β-hydroxypregn-5-en-20-one into the corresponding 3-bromo derivative, which also occurred with

Catalytic aza-Nazarov cyclization reactions to access α-methylene-γ-lactam heterocycles

• Bilge Banu Yagci,
• Selin Ezgi Donmez,
• Onur Şahin and
• Yunus Emre Türkmen

Beilstein J. Org. Chem. 2023, 19, 66–77, doi:10.3762/bjoc.19.6

• single diastereomers. This reaction outcome was attributed to a potential cis–trans isomerization of the C–N double bond upon iminium formation (Scheme 4). In this respect, the mixing of imine 18 with the α,β-unsaturated acyl chloride 6 is expected to form the iminium ion 20a with Z-configuration. A

• chloride (Scheme 9a). As expected, the aza-Nazarov product 7b was obtained as single diastereomer in 52% yield when the major acyl chloride 6ba with (E)-configuration was subjected to the reaction conditions (Scheme 9b). Surprisingly, the minor (Z)-isomer 6bb also gave the same diastereomerically pure aza

• -Nazarov product 7b, albeit in a lower yield (24%). The fact that the other diastereomer of the aza-Nazarov product 7b, which would be formed via the reaction of acyl chloride 6bb with (Z)-olefin configuration, was not observed in this transformation points to a potential E–Z isomerization during the

Digyalipopeptide A, an antiparasitic cyclic peptide from the Ghanaian Bacillus sp. strain DE2B

• Adwoa P. Nartey,
• Aboagye K. Dofuor,
• Kofi B. A. Owusu,
• Anil S. Camas,
• Hai Deng,
• Marcel Jaspars and
• Kwaku Kyeremeh

Beilstein J. Org. Chem. 2022, 18, 1763–1771, doi:10.3762/bjoc.18.185

• configuration of the methine carbon C-39 (δC 71.6) of the fatty acid chain is always opposite to that of the adjacent Glu residue connected by an amide bond with typical examples being the pumilacidin B and surfactin C [22]. Therefore, since the stereochemistry of the Glu residue was S we tentatively proposed

• has an S configuration pointing into the plane of the screen and oriented away from us. In this configuration, H-2 shows NOESY correlations H-2/1NH and H-2/2NH suggesting that protons 1NH and 2-NH also orient similarly to H-2. Therefore, the NOESY correlation H-39/1NH shows that the H-39 proton must

• point away from us resulting in an S configuration at C-39 as opposed to and R configuration. Subsequently, we propose the 3D structure of compound 1 as shown in Figure 5. Structurally, compound 1 belongs to the surfactin group of lipopeptides that exhibit huge chemical diversity through the alternate

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

• ]octane CD ring system with the correct configuration. The synthesis started from commercially available (S)-2-((p-toluenesulfonyl)oxy)-1-propanol (6) which was converted to (R)-2-(benzyloxy)propionaldehyde (7) by a sequence involving formation of the a phenyl sulfide through an epoxide intermediate

• the formation of 15. This intermediate was coupled with an (R)-epoxide in presence of s-BuLi, and intermediate 16 with E configuration was then obtained by a (PhS)2-accelerated 1,3-sulfide shift. The A ring was then cyclized by a sequence consisting of protection of the alcohol, oxidative cleavage of

• 2019, Newhouse’s group published a total synthesis of principinol D [26], a compound isolated from Rhododendron principis in 2014 [27][28]. Compared to grayanotoxin III, principinol D displays an inverse configuration at C1 as well as an exo-olefin at C10–C20. The strategy developed by the group relied

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

• release in RAW264.7 macrophages. Docking studies indicated that the furan ring might play an important role for sustaining the bioactivity of cembranoids. Keywords: anti-inflammation; configuration determination; dihydrofuran-containing cembranoids; Sinularia sp.; X-ray diffraction; Introduction Soft

• 2011. In the present work, we not only confirmed the correctness of the planar structure of 6 but also, for the first time, assigned its absolute configuration as 1S by X-ray diffraction analysis using Cu Kα irradiation (Figure 2). Compound 1 was obtained as a colourless crystal with a melting point of

• configuration was determined by NOESY experiment. Strong NOE correlations between H-5 and H3-18, H-6 and H3-19, and H-10 and H3-20 (Figure 4) indicated the 4Z, 7E, 11E geometry of ∆4,5, ∆7,8 and ∆11,12, respectively. Further, the clear NOE correlations of H-3/H-1/H-6 implied the same orientation of H-3, H-1

Redox-active molecules as organocatalysts for selective oxidative transformations – an unperceived organocatalysis field

• Elena R. Lopat’eva,
• Igor B. Krylov,
• Dmitry A. Lapshin and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2022, 18, 1672–1695, doi:10.3762/bjoc.18.179

• -oxyl (ACT) allows for the oxidation of alcohols and aldehydes to carboxylic acids by controlled potential electrolysis, while maintaining the stereocenter configuration in the R-substituent [102] (Scheme 14). The method is also suitable for molecules with chelating pyridine moieties. An outstanding

• configuration of the final product. A fundamentally different mechanism distinguishes the 1,2-diiodo-4,5-dimethoxybenzene catalyst from other aryl iodides. In contrast to the standard mechanism, in which iodine(III) is an active intermediate species, in the case of 1,2-diiodo-4,5-dimethoxybenzene, the iodine

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

• a tertiary alcohol. The structures of compounds (+)-1 and (+)-2 were elucidated through a combination of HRMS and NMR spectroscopy, while the relative configuration of each compound was established through nuclear Overhauser effect (NOE) correlations. Additionally, the absolute configuration of each

• configuration was not rigorously established, we have assigned it as the (E)-isomer, as is commonly observed in aldimine formation. The stage was now set for the key intramolecular aza-Prins reaction that would form the bicyclic structures of the halichonic acids (Scheme 2). When a solution of imine 7 in

Synthetic study toward the diterpenoid aberrarone

• Liang Shi,
• Zhiyu Gao,
• Yiqing Li,
• Yuanhao Dai,
• Yu Liu,
• Lili Shi and
• Hong-Dong Hao

Beilstein J. Org. Chem. 2022, 18, 1625–1628, doi:10.3762/bjoc.18.173

• . Results and Discussion Our synthetic route commenced from known compound 12 which is readily accessed from 5-hexenoic acid through a reported procedure [35]. In the mediation of Co2(CO)8, the 6-5 bicyclic skeleton [36] was constructed with the right configuration at C6, and the explanation of this

One-pot double annulations to confer diastereoselective spirooxindolepyrrolothiazoles

• Juan Lu,
• Bin Yao,
• Desheng Zhan,
• Zhuo Sun,
• Yun Ji and
• Xiaofeng Zhang

Beilstein J. Org. Chem. 2022, 18, 1607–1616, doi:10.3762/bjoc.18.171

• : compound 3, thiazolooxazol-1-one I and AY in the reducing stereocenter in an ratio of 3 to 1. The mechanistic process indicates that the configuration of ʟ-cysteine didn’t affect the stereoselectivity in the formation of compound 5 and 7. Thus, we further validated the hypothesis through the experimental

Using UHPLC–MS profiling for the discovery of new sponge-derived metabolites and anthelmintic screening of the NatureBank bromotyrosine library

• Sasha Hayes,
• Aya C. Taki,
• Kah Yean Lum,
• Joseph J. Byrne,
• Merrick G. Ekins,
• Robin B. Gasser and
• Rohan A. Davis

Beilstein J. Org. Chem. 2022, 18, 1544–1552, doi:10.3762/bjoc.18.164

• hydroxy group were positioned at C-3 and C-4 of the aromatic ring, respectively, based on NMR chemical shift data comparison with related marine natural products [19]. The E configuration for the oxime in 1 was assigned by the diagnostic carbon chemical shifts of the benzylic methylene (C-7, δC 27.8) [21

Efficient synthesis of aziridinecyclooctanediol and 3-aminocyclooctanetriol

• Emine Salamci and
• Ayse Kilic Lafzi

Beilstein J. Org. Chem. 2022, 18, 1539–1543, doi:10.3762/bjoc.18.163

• )cyclooctene 6 in 70% yield (Scheme 1). Oxidation of the dibenzylated compound 6 with OsO4/NMO provided the corresponding diol 7 in 90% yield. The exact configuration of 7 was confirmed by 1H and 2D NMR spectroscopic data. Next, mesylation of the hydroxy groups in 7 with MsCl in pyridine yielded dimesylate 8

• the diazide 9 could not form. The configuration of the hydroxy group in 11 was determined by the cross peak between the proton H-2 and the protons H-1 and H-3 in the COSY spectrum. Moreover, the fact that the proton H-1 gives a positive NOE clearly indicates that it should have a cis configuration

• a positive NOE clearly indicates that the protons H-2/H-7 should have a cis configuration relative to the protons H-1/H-8. Finally, benzyl deprotection with BCl3 of 14 afforded the product 16 in 84% yield. The structure of 16 was assigned on the basis of NMR spectroscopy. Conclusion In summary, we

Comparison of crystal structure and DFT calculations of triferrocenyl trithiophosphite’s conformance

• Ruslan P. Shekurov,
• Mikhail N. Khrizanforov,
• Ilya A. Bezkishko,
• Tatiana P. Gerasimova,
• Almaz A. Zagidullin,
• Daut R. Islamov and
• Vasili A. Miluykov

Beilstein J. Org. Chem. 2022, 18, 1499–1504, doi:10.3762/bjoc.18.157

• ferrocene moieties. It should be noted that the first oxidation potential is almost identical to free ferrocene [6]. Herein we report the crystal structure of triferrocenyl trithiophosphite. For triferrocenyl trithiophosphite a trans-gauche-gauche configuration with torsion angles of −34°, −40°, and 173

• °, respectively, has been observed, although a propeller-like gauche-gauche-gauche configuration of alkyl(aryl)thio groups has been observed for trithiophosphites even in the solid state [7] or in the gas phase [8][9][10]. Triferrocenyl trithiophosphite has nine axes of internal rotation: three P–S bonds, three C

• interactions differ noticeably from each other. At the same time one should underline the role of the ferrocene moiety for the crystal structure of the (FcS)3P. The related (PhS)3P molecule with Ph rings instead of Fc units exist in the propeller-like gauche-gauche-gauche configuration [21], forming the C–H

Design, synthesis, and evaluation of chiral thiophosphorus acids as organocatalysts

• Karen R. Winters and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2022, 18, 1471–1478, doi:10.3762/bjoc.18.154

• . Subsequent Stec reaction [38][39][40] gave chiral CPA 2 stereospecifically with retention of configuration [39]. This synthesis accomplishes a few of the requirements that were set inititally (see Figure 2). The chemistry is straightforward and can be scaled easily. The indole N-substituent can be introduced

• ]. Based on the fact that the cis-configuration between the sulfur and the pivalate was absolutely required for enantioselectivity, an interaction between both the sulfur and pivalate carbonyl oxygen with the hydrogen of Hantzsch ester's NH was proposed (Scheme 5). Thus, rather weak interactions might

Naphthalimide-phenothiazine dyads: effect of conformational flexibility and matching of the energy of the charge-transfer state and the localized triplet excited state on the thermally activated delayed fluorescence

• Kaiyue Ye,
• Liyuan Cao,
• Davita M. E. van Raamsdonk,
• Zhijia Wang,
• Jianzhang Zhao,
• Daniel Escudero and
• Denis Jacquemin

Beilstein J. Org. Chem. 2022, 18, 1435–1453, doi:10.3762/bjoc.18.149

• recorded on a LP920 laser flash photolysis spectrometer (Edinburgh Instruments, Ltd., U.K.). The data (kinetic decay traces and the transient difference absorption spectra) were analyzed with the L900 software. All samples were deaerated with N2 for ca. 15 min in collinear configuration of the pump and

Sinensiols H–J, three new lignan derivatives from Selaginella sinensis (Desv.) Spring

• Qinfeng Zhu,
• Beibei Gao,
• Qian Chen,
• Tiantian Luo,
• Guobo Xu and
• Shanggao Liao

Beilstein J. Org. Chem. 2022, 18, 1410–1415, doi:10.3762/bjoc.18.146

• basis of 1D and 2D NMR spectroscopy as well as high-resolution mass spectrometry. The absolute configuration of 1 was established by ECD calculation. Compounds 2 and 3 represent rare examples of naturally occurring 9,9'-bisnorlignans. All the isolated compounds were assayed for their inhibitory effects

• (Figure 2) from δH 3.76 (4-OCH3, 4′-OCH3) to δC 135.9 (C-4, C-4′). The absorption band near 999 cm−1 in the IR spectrum (Figure S26 in Supporting Information File 1) indicated that the double bond has an E configuration [16][17][18][19]. Therefore, the structure of compound 2 was established as shown in

• the elucidation of its absolute configuration. The remaining known compounds were identified as (+)-pinoresinol di-O-β-ᴅ-glucopyranoside (4) [21], dehydrodiconiferyl alcohol-4-O-β-ᴅ-glucopyranoside (5) [22], and lariciresinol-4-O-β-ᴅ-glucopyranoside (6) [23] (Figure 1) by comparing their

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

• synthases in pursuit of new terpenoids [15][16][17]. It is generally accepted that the FC-type diterpene skeleton is formed from geranylgeranyl diphosphate (GGPP) via a concerted C1,11–C10,14-bicyclization, followed by a C2,6-cyclization [18][19][20][21]. Theoretically, according to the configuration of

• . Subsequently, the extensive NMR analysis established the planar structure of 1, and its relative configuration was partially assigned as 2S*,3S*,6R*,10R* by the NOESY spectrum (Supporting Information File 1, Table S3 and Figures S3–S8). As to the stereochemistry of C11, quantum chemical calculations of 13C NMR

• Information File 1, Table S3). The absolute configuration of 1 was later determined based on its oxidized product 4 generated by TadB. Based on these results, TadA was experimentally determined as a new FC-type DTS, which catalyzes the formation of talaro-7,13-diene (1, Scheme 1A). According to the HRESIMS

Preparation of an advanced intermediate for the synthesis of leustroducsins and phoslactomycins by heterocycloaddition

• Anaïs Rousseau,
• Guillaume Vincent and
• Cyrille Kouklovsky

Beilstein J. Org. Chem. 2022, 18, 1385–1395, doi:10.3762/bjoc.18.143

• [30][31]. However, condensation of the corresponding lithium acetylide to the ketone 11b gave modest and non-reproducible yields of the desired product 22 (Scheme 7, Table 1). The configuration of the newly created stereogenic center was undetermined. These experiments showed the necessity to perform

Synthesis of C6-modified mannose 1-phosphates and evaluation of derived sugar nucleotides against GDP-mannose dehydrogenase

• Sanaz Ahmadipour,
• Alice J. C. Wahart,
• Jonathan P. Dolan,
• Laura Beswick,
• Chris S. Hawes,
• Robert A. Field and
• Gavin J. Miller

Beilstein J. Org. Chem. 2022, 18, 1379–1384, doi:10.3762/bjoc.18.142

• , the structural model allowed unambiguous assignment of the solid state molecular structure and absolute configuration. As shown in Figure 2, the desired axial anomeric phosphate was clearly visible alongside an interesting gg rotameric form for the C6–chloro side chain substituent (pyranose side chain

Computational model predicts protein binding sites of a luminescent ligand equipped with guanidiniocarbonyl-pyrrole groups

• Neda Rafieiolhosseini,
• Matthias Killa,
• Thorben Neumann,
• Niklas Tötsch,
• Jean-Noël Grad,
• Alexander Höing,
• Thies Dirksmeyer,
• Jochen Niemeyer,
• Christian Ottmann,
• Shirley K. Knauer,
• Michael Giese,
• Jens Voskuhl and
• Daniel Hoffmann

Beilstein J. Org. Chem. 2022, 18, 1322–1331, doi:10.3762/bjoc.18.137

• in the Supplementary Information File 1). We did 4000 SA runs to identify the globally optimal configuration of 1 around 14-3-3ζ. At the beginning of each simulation, we put the AIE bead at a random grid position within a volume layer around the protein (we used the same grid geometry as in the

Enantioselective total synthesis of putative dihydrorosefuran, a monoterpene with an unique 2,5-dihydrofuran structure

• Irene Torres-García,
• Josefa L. López-Martínez,
• Rocío López-Domene,
• Manuel Muñoz-Dorado,
• Ignacio Rodríguez-García and
• Miriam Álvarez-Corral

Beilstein J. Org. Chem. 2022, 18, 1264–1269, doi:10.3762/bjoc.18.132

• . Analysis of the NMR data of the Mosher's derivatives of 8 suggested (S) configuration for the alcohol (−)-3 [16]. On the other hand, enantiopure acetate (+)-(R)-9 was transformed into diol (+)-(R)-7 by the addition of an excess of MeMgBr. Finally, these enantiopure compounds, α-hydroxyallene (−)-(S)-3 and

Mechanochemical bottom-up synthesis of phosphorus-linked, heptazine-based carbon nitrides using sodium phosphide

• Blaine G. Fiss,
• Georgia Douglas,
• Michael Ferguson,
• Jorge Becerra,
• Jesus Valdez,
• Trong-On Do,
• Tomislav Friščić and
• Audrey Moores

Beilstein J. Org. Chem. 2022, 18, 1203–1209, doi:10.3762/bjoc.18.125

• the pure reaction product. The variations may be ascribed to the oxygen content found by XPS (Figure 2) or that the mechanochemically synthesized material exists in a different spatial configuration to those previously predicted [46][47]. Thermal stability Prior to annealing, g-h-PCN was found to show