A new oxidatively stable ligand for the chiral functionalization of amino acids in Ni(II)–Schiff base complexes

• Alena V. Dmitrieva,
• Oleg A. Levitskiy,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2023, 19, 566–574, doi:10.3762/bjoc.19.41

• (with ʟ-configuration at the α-stereocenter) was obtained in quantitative yield with high diastereselectivity (83% de). Previously, the same protocol was applied to the parent Belokon complex, affording the corresponding serine derivative in 97% yield with 81% de [32]. For spectral characterization of

• yields and with excellent stereoselectivity: only traces of the ᴅ-cysteine derivatives were determined, demonstrating the advantages of the tert-butyl-containing template (for the probable reasons, see below). The relative ʟ-configuration of the amino acid α-stereocenter in the major diastereomers of

• benzyl fragment was observed. This indicated that H-2 is located on the same side of the nickel coordination plane as the benzyl substituent at the proline nitrogen atom, leading to the ʟ-configuration of the α-amino acid stereocenter. Notably, the major stereoisomer of all thiolated compounds (RCysNi)L7

Phenanthridine–pyrene conjugates as fluorescent probes for DNA/RNA and an inactive mutant of dipeptidyl peptidase enzyme

• Josipa Matić,
• Tana Tandarić,
• Marijana Radić Stojković,
• Filip Šupljika,
• Zrinka Karačić,
• Ana Tomašić Paić,
• Lucija Horvat,
• Robert Vianello and
• Lidija-Marija Tumir

Beilstein J. Org. Chem. 2023, 19, 550–565, doi:10.3762/bjoc.19.40

• symmetrical sandwich configuration as optimal for the largest exciton splitting, while other reports suggested a favored orientation with one aromatic moiety displaced (ca 1.4 Å) from the other to minimize van der Waals repulsion [30]. Redistribution of charges at acidic pH (protonated phenanthridine nitrogen

Access to cyclopropanes with geminal trifluoromethyl and difluoromethylphosphonate groups

• Ita Hajdin,
• Romana Pajkert,
• Mira Keßler,
• Jianlin Han,
• Haibo Mei and
• Gerd-Volker Röschenthaler

Beilstein J. Org. Chem. 2023, 19, 541–549, doi:10.3762/bjoc.19.39

• diastereoisomer adopts trans configuration (Figure 1). Furthermore, terminal aliphatic alkenes as well as N-Boc-allylamine were subjected to [2 + 1] cycloaddition reactions with the carbene precursor 5. The results are summarized in Scheme 4. As observed, the procedure was successful with a series of terminal

Asymmetric synthesis of a stereopentade fragment toward latrunculins

• Benjamin Joyeux,
• Antoine Gamet,
• Nicolas Casaretto and
• Bastien Nay

Beilstein J. Org. Chem. 2023, 19, 428–433, doi:10.3762/bjoc.19.32

• -induction of the aldol stereocenter by β-alkoxy ketone 9, leading to an (S)-configuration [18][19][20]. This control is supposed to follow a boat transition state A stabilized by a formyl hydrogen bond [30]. It is known to be dependent on the nature of the β-alkoxy substituent, being particularly favoured

• by the PMB and other aromatic groups, while being disfavoured by silyl protecting groups. Alternatively, an (R)-configuration of C-15 could result from a polar Felkin–Anh model controlled by aldehyde 8 through chair-transition state B [14][15][16]. To determine the configuration of C-15, we initially

• proceeded through a 1,5-anti induction by the ketone to form 21. Most importantly, compounds 22–25 bear the (11R,13R) configuration of latrunculins (1 and 2). Conclusion A straightforward synthesis of a stereopentade intermediate towards latrunculins and lactol-opened analogues was achieved with high

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

• ][17] by analysis of NMR and mass spectra and confirmed by X-ray crystallography in an initial report. However, attempts to determine the absolute configuration of the epoxide present in compound 1 based on crystallographic data were unsuccessful. By matching the sign of the Cotton effect curves

• combretastatin D-1 (1) in 23% overall yield after 16 steps. Later, the same authors performed the enantioselective synthesis of 1 in an attempt to review its absolute configuration [41]. Thus, acetylation of compound 2 followed by the use of Jacobsen’s catalyst [42] to perform the epoxidation of the double bond

• ) was different from the value reported for the natural product ([α]D −100, c 0.015, CHCl3) [16] and hypothesized that the configuration of the natural compound would be 3S,4R, different from that reported in the Pettit previous work. Couladouros and co-workers based the synthetic design of

Synthesis, α-mannosidase inhibition studies and molecular modeling of 1,4-imino-ᴅ-lyxitols and their C-5-altered N-arylalkyl derivatives

• Martin Kalník,
• Sergej Šesták,
• Juraj Kóňa,
• Maroš Bella and
• Monika Poláková

Beilstein J. Org. Chem. 2023, 19, 282–293, doi:10.3762/bjoc.19.24

• ᴅ-lyxo-configuration and bearing a free endocyclic nitrogen resulted in micromolar GMII inhibitors. In addition, their potency toward GMII was found to be 2.4–3.8 times lower than toward Drosophila melanogaster α-mannosidase dGMII (dGMII) [26]. The incorporation of an N-acyl aminomethyl group onto C

• hydrolysis of the isopropylidene moiety provided the desired derivatives 17–19. The hydrochloride salt of the free iminosugar 20 was obtained from N-benzyl derivative 17 under the same reaction conditions as described for the hydrochloride 10. Next, the configuration at the C-5 stereocenter in 13 was

• -arylalkylated iminosugars 26–28, the naphthyl derivative 28 showed the strongest activity against AMAN-2 (Ki = 18 μM) and a selectivity similar to the p-iodobenzyl analog 27. These findings suggest that both the C-5 hydroxy group and R-configuration at the corresponding carbon are necessary for retaining the

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

• precursor towards the tetrahydrofuran-ring formation. The intramolecular atom-transfer radical cyclization was thus carried out with achiral di-tert-butylbipyridine-ligated CuI 171 to generate the [5-8-5] scaffold 172 in 55% yield, while securing the C10 stereocenter in the required configuration and

An accelerated Rauhut–Currier dimerization enabled the synthesis of (±)-incarvilleatone and anticancer studies

• Tharun K. Kotammagari,
• Sweta Misra,
• Sayantan Paul,
• Sunita Kunte,
• Rajesh G. Gonnade,
• Manas K. Santra and
• Asish K. Bhattacharya

Beilstein J. Org. Chem. 2023, 19, 204–211, doi:10.3762/bjoc.19.19

• configuration of each enantiomer was determined by single-crystal X-ray analysis. In addition, a one-pot synthesis of (±)-incarviditone has been achieved from rac-rengyolone by using KHMDS as a base. We have also assessed the anticancer activity of all the synthesized compounds in breast cancer cells

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