Enhancing structural diversity of terpenoids by multisubstrate terpene synthases

• Min Li and
• Hui Tao

Beilstein J. Org. Chem. 2024, 20, 959–972, doi:10.3762/bjoc.20.86

• . Classically, these prenyl analogs have been used as co-crystallization ligands [38], inhibitors of specific TSs [39], and tools to study the reaction mechanisms of cyclization cascades [40][41] which have been comprehensively addressed in important previous reviews [8][13]. Currently, noncanonical prenyl

Activity assays of NnlA homologs suggest the natural product N-nitroglycine is degraded by diverse bacteria

• Kara A. Strickland,
• Brenda Martinez Rodriguez,
• Ashley A. Holland,
• Shelby Wagner,
• Michelle Luna-Alva,
• David E. Graham and
• Jonathan D. Caranto

Beilstein J. Org. Chem. 2024, 20, 830–840, doi:10.3762/bjoc.20.75

• and kinetic experiments or crystallization of the active homodimer will be required to resolve the catalytic mechanism. If NnlA is specific for NNG as suggested by these results, it is worth speculating about potential functions of NNG and other nitramine natural products. Bacterial natural products

Synthesis and biological profile of 2,3-dihydro[1,3]thiazolo[4,5-b]pyridines, a novel class of acyl-ACP thioesterase inhibitors

• Jens Frackenpohl,
• David M. Barber,
• Guido Bojack,
• Birgit Bollenbach-Wahl,
• Ralf Braun,
• Rahel Getachew,
• Sabine Hohmann,
• Kwang-Yoon Ko,
• Karoline Kurowski,
• Bernd Laber,
• Rebecca L. Mattison,
• Thomas Müller,
• Anna M. Reingruber,
• Dirk Schmutzler and
• Andrea Svejda

Beilstein J. Org. Chem. 2024, 20, 540–551, doi:10.3762/bjoc.20.46

• binding affinity to enzyme targets, e.g., acyl-ACP thioesterases, belonging to the protein family of FATs, was demonstrated by using co-crystallization, fluorescence-based thermal shift assays, and chemoproteomics techniques [3]. Likewise, methiozolin (2) is a recently assigned FAT inhibitor that has

Spatial arrangements of cyclodextrin host–guest complexes in solution studied by ¹³C NMR and molecular modelling

• Konstantin Lebedinskiy,
• Ivan Barvík,
• Zdeněk Tošner,
• Ivana Císařová,
• Jindřich Jindřich and
• Radim Hrdina

Beilstein J. Org. Chem. 2024, 20, 331–335, doi:10.3762/bjoc.20.33

• crystallization of host–guest complexes and their crystallographic analysis. Keywords: anisotropy; 13C NMR; cyclodextrin; host–guest complexes; Introduction Complexation of organic and inorganic compounds with α-, β-, or γ-cyclodextrins and their derivatives [1] is an established tool used in medicine for drug

Elucidating the glycan-binding specificity and structure of Cucumis melo agglutinin, a new R-type lectin

• Jon Lundstrøm,
• Emilie Gillon,
• Valérie Chazalet,
• Nicole Kerekes,
• Antonio Di Maio,
• Ten Feizi,
• Yan Liu,
• Annabelle Varrot and
• Daniel Bojar

Beilstein J. Org. Chem. 2024, 20, 306–320, doi:10.3762/bjoc.20.31

• crystallography. We obtained several hits for the full-length protein after sparse screening using a crystallization robot at the HTX platform, EMBL, Grenoble. Pill-shaped crystals obtained under conditions of a high salt concentration, in particular ammonium sulfate (Figure S3, Supporting Information File 2

• using the free software “data entry”. The IC50 was calculated using https://www.aatbio.com/tools/ic50-calculator. X-ray crystallography All consumables for crystallization and crystal handling were purchased at Molecular Dimensions, Calibre Scientific, Rotherham, UK, unless stated otherwise. CMA1

• concentrated at 5.7 or 3.5 mg/mL in 20 mM HEPES pH 8, 100 mM NaCl, and 14 mM GalNAc was subjected to crystallization screening using the robotized HTXlab platform (EMBL, Grenoble, France) with 200 nL sitting drops at 20 °C using a 1:1 ratio. Wizard I and II screen (Rigaku) and SaltRX (Hampton Research) screens

Substitution reactions in the acenaphthene analog of quino[7,8-h]quinoline and an unusual synthesis of the corresponding acenaphthylenes by tele-elimination

• Ekaterina V. Kolupaeva,
• Narek A. Dzhangiryan,
• Alexander F. Pozharskii,
• Oleg P. Demidov and
• Valery A. Ozeryanskii

Beilstein J. Org. Chem. 2024, 20, 243–253, doi:10.3762/bjoc.20.24

• this case, hydrolytic degradation of chloranil also occurred during crystallization (base 5 could act as a catalyst for such degradation), because of which yellowish needles were obtained (neither 5 nor chloranil crystallize in this form), which turned out to be the hydrochloride dihydrate of compound

• antiparallel orientation of the closely spaced cationic fragments of base 5 can be reversed to the opposite. This can be achieved with 4,6-dichlororesorcinol, a well-known molecular organizer and coordinating agent [20][21]. Thus, the joint crystallization of dipyridoacenaphthene 5 and 4,6-dichlororesorcinol

• of quinoquinolines, their planar structure, and very easy coordination to acidic and electrophilic sites (including water [15][22] or the C–H bond of chloroform [11]) almost always lead to co-crystallization. For example, there is no such crystallographic information for quinoquinoline 3 itself. In

Comparison of glycosyl donors: a supramer approach

• Anna V. Orlova,
• Nelly N. Malysheva,
• Maria V. Panova,
• Nikita M. Podvalnyy,
• Michael G. Medvedev and
• Leonid O. Kononov

Beilstein J. Org. Chem. 2024, 20, 181–192, doi:10.3762/bjoc.20.18

• . The residue was purified by silica gel column chromatography (column volume 140 mL, elution with gradient CH2Cl2 → acetone/CH2Cl2 20:80). The crude product was dissolved in acetone (3 mL) and t-BuOMe (3 mL), then petroleum ether was slowly added until crystallization commenced. The precipitate formed

Aromatic systems with two and three pyridine-2,6-dicarbazolyl-3,5-dicarbonitrile fragments as electron-transporting organic semiconductors exhibiting long-lived emissions

• Karolis Leitonas,
• Brigita Vigante,
• Dmytro Volyniuk,
• Audrius Bucinskas,
• Pavels Dimitrijevs,
• Sindija Lapcinska,
• Pavel Arsenyan and
• Juozas Vidas Grazulevicius

Beilstein J. Org. Chem. 2023, 19, 1867–1880, doi:10.3762/bjoc.19.139

• analysis (TGA) and differential scanning calorimetry (DSC), respectively. The experimental data are shown in Figure 5 and the characteristics are collected in Table 1. An amorphous character of the derivatives was identified. No endothermic (melting) or exothermic (crystallization) transitions were

• nitrogen environment. DSC allows us to investigate the enthalpy changes associated with phase transitions, crystallization, and other thermal events occurring in the samples. The choice of a nitrogen atmosphere in both TGA and DSC experiments is significant as it helps to prevent undesired reactions with

Selectivity control towards CO versus H₂ for photo-driven CO₂ reduction with a novel Co(II) catalyst

• Lisa-Lou Gracia,
• Philip Henkel,
• Olaf Fuhr and
• Claudia Bizzarri

Beilstein J. Org. Chem. 2023, 19, 1766–1775, doi:10.3762/bjoc.19.129

• ). Efforts to selectively achieve one polymorph, through differentiated crystallization processes, were unsuccessful. When analyzing the molecular structure in both crystals, the cobalt core is hexacoordinated, as expected. The two isothiocyanate ions are oriented cis to each other and trans to the

Charge carrier transport in perylene-based and pyrene-based columnar liquid crystals

• Alessandro L. Alves,
• Simone V. Bernardino,
• Carlos H. Stadtlober,
• Edivandro Girotto,
• Giliandro Farias,
• Rodney M. do Nascimento,
• Sergio F. Curcio,
• Thiago Cazati,
• Marta E. R. Dotto,
• Juliana Eccher,
• Leonardo N. Furini,
• Hugo Gallardo,
• Harald Bock and
• Ivan H. Bechtold

Beilstein J. Org. Chem. 2023, 19, 1755–1765, doi:10.3762/bjoc.19.128

• 1758 cm−1 (C=O). X-ray diffraction (XRD) measurements of 1 and 2 are shown in Figure 2. The Miller indices indicate the Colhex and Colrect character of the mesophases [31]. Despite crystallization of 2, the Colrect order is partially preserved at room temperature. The Colhex lattice parameter (a

Unprecedented synthesis of a 14-membered hexaazamacrocycle

• Anastasia A. Fesenko and
• Anatoly D. Shutalev

Beilstein J. Org. Chem. 2023, 19, 1728–1740, doi:10.3762/bjoc.19.126

• with a noticeable increase in the macrocycle yield up to 41% (Table 1, entries 20 and 21). The extremely poor solubility of product 5 in most organic solvents allowed to purify it from all admixtures, including byproduct 6, by a single crystallization from boiling DMF. Thus, pure product 5 was prepared

• noteworthy that triazole 10 was the major product in dioxane (10/5/6 = 86.5:13:0.5, Table 1, entry 23). Again, macrocycle 5 was separated from this mixture by crystallization from DMF, and pyrazolyl-1,2,4-triazole 10 was isolated from the mother liquor. The structure of compound 10 was established based on

• , 3 h) followed by crystallization of the crude product from DMF. The use of compound 8 as a starting material affords the target product 5 with higher purity and yield compared with the use of imidate 4. Moreover, pyrazolopyrimidine 8 itself is much more stable than imidate 4, and its intermediate

Effects of the aldehyde-derived ring substituent on the properties of two new bioinspired trimethoxybenzoylhydrazones: methyl vs nitro groups

• Dayanne Martins,
• Roberta Lamosa,
• Talis Uelisson da Silva,
• Carolina B. P. Ligiero,
• Sérgio de Paula Machado,
• Daphne S. Cukierman and
• Nicolás A. Rey

Beilstein J. Org. Chem. 2023, 19, 1713–1727, doi:10.3762/bjoc.19.125

• beige and light-yellow solids with 78% and 44% yield, respectively. Thermal analyses between 25 and 350 °C were performed in order to verify the hydration status of the bulk. Regarding hdz-CH3, a weight loss of 9.78% from around 80 to 190 °C was observed, suggesting the presence of two crystallization

• the structures (Figure 2A) shows that spatial arrangements are nearly the same and even the crystallization water molecules were allocated in nearby sites, interacting as H-acceptors in a hydrogen bond with the respective N2H groups. In spite of these similarities, the compounds were indexed in

CO₂ complexation with cyclodextrins

• Cecilie Høgfeldt Jessen,
• Jesper Bendix,
• Theis Brock Nannestad,
• Heloisa Bordallo,
• Martin Jæger Pedersen,
• Christian Marcus Pedersen and
• Mikael Bols

Beilstein J. Org. Chem. 2023, 19, 1021–1027, doi:10.3762/bjoc.19.78

• yields was sufficient time for the crystallization, while the pressure was found less important. From the binding constant measured below and the 1:1 stoichiometry (Kg = 0.18 bar−1, Table 2) we know that 1/2 to 3/4 of the cyclodextrin is filled with CO2 at the pressures used as shown in the 5th column of

• Table 1. As CO2 is in large excess high crystal yields can be obtained even though the CD cavity is only partially filled, because more CO2 is bound in solution as crystallization proceeds. When equilibrium is reached as in entries 1–3 (Table 1) the concentration of 1·CO2 is 0.04 M which must be the

• lipophilic cyclodextrin derivative. It suggests that stronger CO2 binders can be found by improving on these two traits. Experimental Crystallization experiments. A cyclodextrin solution was prepared by dissolving 1 in Milli-Q water to the indicated concentration (Table 1) . The solution was then filtered

First synthesis of acylated nitrocyclopropanes

• Kento Iwai,
• Rikiya Kamidate,
• Khimiya Wada,
• Haruyasu Asahara and
• Nagatoshi Nishiwaki

Beilstein J. Org. Chem. 2023, 19, 892–900, doi:10.3762/bjoc.19.67

• the same way, and the obtained product 9 was converted to the 2,4-dinitrophenylhydrazone 10 to facilitate the crystallization for X-ray crystallography, which showed that a 2,3-dihydrofuran framework had formed (Scheme 4, bottom). Hence, we clarified that product 8b was not the desired cyclopropane

Light-responsive rotaxane-based materials: inducing motion in the solid state

• Adrian Saura-Sanmartin

Beilstein J. Org. Chem. 2023, 19, 873–880, doi:10.3762/bjoc.19.64

• Photoresponsive rotaxane discrete crystals A complete understanding of the crystallization mechanisms accompanied by a rational design can lead to the obtention of crystalline molecular materials which allow the dynamics of the counterparts to take place [35][36][37]. Indeed, the motion of the cyclic counterparts

Nucleophile-induced ring contraction in pyrrolo[2,1-c][1,4]benzothiazines: access to pyrrolo[2,1-b][1,3]benzothiazoles

• Ekaterina A. Lystsova,
• Maksim V. Dmitriev,
• Andrey N. Maslivets and
• Ekaterina E. Khramtsova

Beilstein J. Org. Chem. 2023, 19, 646–657, doi:10.3762/bjoc.19.46

• reaction of APBTT 1a with benzylamine (Scheme 11). As we expected, this reaction proceeded similarly to the reaction of APBTTs 1 with alcohols 2, and we obtained the desired PBTA 7a in a good isolated yield (44%). The product 7a was isolated by simple crystallization from the reaction mixture. Next, the

• (11a, Scheme 16). This reaction proceeded similarly to reactions of APBTTs 1 with alcohols 2 and benzylamine, and we obtained the desired PBTA 12aa in a moderate isolated yield (40%). The product 12aa was isolated by simple crystallization from the reaction mixture. Next, the conditions (Table 3) of

• isolated by a simple crystallization from the reaction mixture. Moreover, we observed the formation of compounds 17 during acylation of enamines 15 with oxalyl chloride to prepare the starting APBTTs 1 (Scheme 21). We noticed that in this case, compounds 17 were formed when HCl was not effectively removed

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

• -methylcorniculatolide A (5, 10 mg), 12-hydroxy-11-O-methylcorniculatolide A (6, 1 mg) and 11-O-methylisocorniculatolide A (8, 2 mg). The authors had some difficulties to isolate isocorniculatolide A (5) using chromatography, however, it was obtained by crystallization from hexane and acetone (4 mg). The same strategy

Discrimination of β-cyclodextrin/hazelnut (Corylus avellana L.) oil/flavonoid glycoside and flavonolignan ternary complexes by Fourier-transform infrared spectroscopy coupled with principal component analysis

• Nicoleta G. Hădărugă,
• Gabriela Popescu,
• Dina Gligor (Pane),
• Cristina L. Mitroi,
• Sorin M. Stanciu and
• Daniel Ioan Hădărugă

Beilstein J. Org. Chem. 2023, 19, 380–398, doi:10.3762/bjoc.19.30

• -crystallization [10]. Omega-3 FA glycerides such as eicosapentaenoic and docosahexaenoic acid glycerides (EPA and DHA glycerides) from fish oil are less stable against oxidation. Their thermal and oxidative stabilities were significantly increased by CD nanoencapsulation as was shown for fish oil from common

• kneading method as the most appropriate one for obtaining β-CD/hazelnut (Corylus avellana L.) oil/flavonoid glycoside or flavonolignan ternary complexes. Kneading allows for higher recovery yields of complexes in comparison with the co-crystallization method because only small amounts of solvent are needed

• (common barbel, Pontic shad, European wels catfish, common bleak) by CDs [11][17]. Moreover, this TG behavior does not depend on the method of synthesis (kneading or co-crystallization) or the method of water determination (TG as mass loss or Karl Fischer water titration, KFT) [6][68]. It was observed

Continuous flow synthesis of 6-monoamino-6-monodeoxy-β-cyclodextrin

• János Máté Orosz,
• Dóra Ujj,
• Petr Kasal,
• Gábor Benkovics and
• Erika Bálint

Beilstein J. Org. Chem. 2023, 19, 294–302, doi:10.3762/bjoc.19.25

• most cases, the preparation of these compounds is based on the use of a limited amount of the reagent. However, due to the very similar reactivity of hydroxy groups, oversubstitution cannot be avoided during the reaction, thus chromatography or crystallization steps are essential for the preparation of

• -CD (2), overreacted byproducts, and starting β-CD (1). However, in previous studies this has been reported as a clean product with a yield of almost 50% [31][33]. Recrystallization is mandatory to obtain pure Ts-β-CD (2) [38][39]. The best results are obtained by crystallization of the crude product

• monosubsituted compound was performed after this last modification. After precipitation, an apparent yield of more than 90% was noted; however, this value did not take into account native β-CD (1) as byproduct. On the other hand, if purification by column chromatography or crystallization is also used, yields of

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

• flash chromatography (petroleum ether) to afford compound 5 (2.47 g, 63%) as faint creamy sticks upon crystallization from Et2O. Rf = 0.26 (petroleum ether); mp: 98 °C [10] (reported mp: 114−115 °C [18]; IR: ν 2081 (N3 str) cm−1; 1H NMR (600 MHz, CDCl3) δ 5.39 (t, J = 2.3, 4.8 Hz, 1H, H-6), 3.87 (t, J

Inclusion complexes of the steroid hormones 17β-estradiol and progesterone with β- and γ-cyclodextrin hosts: syntheses, X-ray structures, thermal analyses and API solubility enhancements

• Alexios I. Vicatos,
• Zakiena Hoossen and
• Mino R. Caira

Beilstein J. Org. Chem. 2022, 18, 1749–1762, doi:10.3762/bjoc.18.184

• to prepare complexes by spray-drying, freeze-drying, co-grinding, kneading and solution-based crystallization; however, this modest type of ‘fingerprinting’ has not generally been pursued further to deduce important features of CD complexes such as the crystal packing of the CD host molecules

Inline purification in continuous flow synthesis – opportunities and challenges

• Jorge García-Lacuna and
• Marcus Baumann

Beilstein J. Org. Chem. 2022, 18, 1720–1740, doi:10.3762/bjoc.18.182

• exploited to achieve effective and reliable flow processes. This perspective article summarizes recent applications of different inline purification techniques such as chromatography, extractions, and crystallization from academic and industrial laboratories. A discussion of the advantages and drawbacks of

• stationary phases is simulated by periodically shifting the two inlet and outlet ports in the direction of the mobile phase flow after a certain time. This technique was also applied to isolate artemisinin from a continuously produced reaction mixture. However, an offline crystallization had to be added to

• , this strategy is attractive for rapid small-scale syntheses of such scaffolds and the optimization of the used solvents can broaden the uptake of this strategy. Inline precipitation and crystallization One of the most widely acknowledged challenges within the field of flow chemistry is the necessity to

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

• intermediates 13a and 13b, respectively. Next, conversion of ethyl phosphinate 13 into phosphinamide 14 was accomplished uneventfully [38] with inexpensive (S)-1-phenylethylamine (15 $/mol) as the chiral element. A single diastereoisomer of phosphinamide 14b was easily obtained by crystallization in 20% yield

• obtained in moderate yield. Crystallization gave a single diastereoisomer in 20% yield. Stec reaction [38][39][40] finally gave the desired CPA 4. Although the entire sequence proceeded in only 6% overall yield, it was conducted on a multigram-scale so that more than 0.4 g of 4 was obtained. Evaluation of

• accomplished easily, either by chromatography over silica gel or crystallization. Subsequent Stec reaction proved to be a reliable method to convert the resolved amide into the chiral thiophosphorus acids. The CPAs synthesized clearly failed to induce any significant asymmetry. It is interesting to note

Derivatives of benzo-1,4-thiazine-3-carboxylic acid and the corresponding amino acid conjugates

• Péter Kisszékelyi,
• Tibor Peňaška,
• Klára Stankovianska,
• Mária Mečiarová and
• Radovan Šebesta

Beilstein J. Org. Chem. 2022, 18, 1195–1202, doi:10.3762/bjoc.18.124

• decomposed in solution. During the preparation of 10ac, dimers 11a and 11b were also detected in most experiments (TLC analysis), and they could be isolated by crystallization from MeOH or hexane. Performing the reaction in the dark with freshly degassed ethanol at lower temperature did bring about somewhat

Facile and diastereoselective arylation of the privileged 1,4-dihydroisoquinolin-3(2H)-one scaffold

• Dmitry Dar’in,
• Grigory Kantin,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1070–1078, doi:10.3762/bjoc.18.109

• anticancer cytotoxic agents. Diverse bioactive compounds based on the privileged 1,4-DHIQ scaffold. Strategy investigated in this work. Preparation of 3(2H)-isoquinolones 11. aObtained as a 10:1 mixture of regioisomers; purified by crystallization. bEmployed in the next step without purification (not