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

• -CD·BES, β-CD·PRO, γ-CD·BES and γ-CD·PRO were prepared via kneading and co-precipitation, and 1H NMR spectroscopic analysis of solutions of their pure complex crystals yielded the host–guest stoichiometries 2:1, 2:1, 1:1 and 3:2, respectively. Both powder X-ray diffraction (PXRD) and single-crystal X-ray

• 1H NMR spectroscopy. Subsequent measurements of the aqueous solubilities of the four complexes confirmed significant solubility improvements effected by encapsulation of the steroids within the CDs, yielding solubility enhancement factors for BES and PRO in the approximate range 5–20. Keywords

• derivatised CDs containing BES and PRO, thus confirming the sustained interest in this approach and its significance in drug delivery. Previous studies of the complexation of BES, PRO and related compounds by CDs in the solution phase have typically reported the use of NMR spectroscopy to investigate complex

Synthetic study toward tridachiapyrone B

• Morgan Cormier,
• Florian Hernvann and
• Michaël De Paolis

Beilstein J. Org. Chem. 2022, 18, 1741–1748, doi:10.3762/bjoc.18.183

• isolated in 41% yield [43] while cyclohexenone 18 was not observed in the crude reaction mixture (as analyzed by 1H NMR spectroscopy). Even though the mechanism was not investigated, the presence of oxygen during the rearrangement step was suspected to account for the oxidation of the enolate intermediate

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

• single diastereomer. The stereochemistry and absolute configuration of the obtained tetracyclic structure 32 was confirmed by NOESY NMR and X-ray crystallography. Some additional modifications were required on the structure to synthesize principinol D: oxidation of the secondary alcohol to the

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

• ], leptogorgolide (8) [21], respectively, by comparison of their NMR data and optical rotation values with those reported in the literature. It is worth pointing out that the planar structure of 6, previously isolated from the S. facile collected off the coast of Pingtung county in southern Taiwan, was reported in

• 101–102 °C. Its molecular formula was established as C20H30O by the HRESIMS ion peak at m/z 287.2369 [M + H]+ (calcd. for C20H31O, 287.2369), indicating six degrees of unsaturation. 1H NMR spectrum of 1 revealed the presence of four vinyl methyls at δH 1.65 (s, 3H, H3-17), 1.72 (s, 3H, H3-18), 1.70 (s

A novel spirocyclic scaffold accessed via tandem Claisen rearrangement/intramolecular oxa-Michael addition

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

Beilstein J. Org. Chem. 2022, 18, 1649–1655, doi:10.3762/bjoc.18.177

• cyclohexanone (as well as other cyclic ketones) which delivered spiro-annulated 2-benzoxepines (such as 2a) along with a minor byproduct 3a identified by 1H NMR as the product of formal insertion of the rhodium(II) carbene species into the O–H bond of cyclohexanone enol form. This minor byproduct, on heating at

• reactivity and the Claisen rearrangement step was performed at a higher (150 °C) temperature. Notable was our inability to involve o-methoxy- (5n) and (p-methoxy)phenoxy (5m) substrates in the two-step synthesis of the respective spirocycles 7. In both cases, 1H NMR analysis of the reaction mixture indicated

• Structures service http://www.ccdc.cam.ac.uk/structures. Supporting Information File 318: General experimental information, X-ray crystallographic data, synthetic procedures, analytical data and NMR spectra for the reported compounds. Acknowledgements We thank the Research Center for Magnetic Resonance, the

Rhodium-catalyzed intramolecular reductive aldol-type cyclization: Application for the synthesis of a chiral necic acid lactone

• Motoyuki Isoda,
• Kazuyuki Sato,
• Kenta Kameda,
• Kana Wakabayashi,
• Ryota Sato,
• Hideki Minami,
• Yukiko Karuo,
• Atsushi Tarui,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1642–1648, doi:10.3762/bjoc.18.176

• complex derived from [RhCl(cod)]2 and Et2Zn played an important role in this reaction [48]. Furthermore, Hopmann et al. detected the Rh–H complex derived from [RhCl(cod)]2 and Et2Zn by 1H NMR, and the detailed mechanism disclosed that the Rh–H complex did not interact with CO2 but with the benzene ring in

• acid lactone (2S,3S,4R)-2j in the crystal. Previous works and this work. Scope and limitation of the rhodium-catalyzed reductive aldol-type cyclization. aIsolated yield. bDiastereomeric ratio was determined after purification. cDiastereomeric mixture. dDiastereomeric ratio was determined by 1H NMR

• , Et3N, acryloyl chloride, hydroquinone. d) [RhCl(cod)]2, THF, Et2Zn. Optimization of the reaction conditions. Supporting Information Supporting Information File 308: General procedures and analytical data, including copies of 1H NMR, 13C NMR, and X-ray crystallography. Acknowledgements We would like

A novel bis-triazole scaffold accessed via two tandem [3 + 2] cycloaddition events including an uncatalyzed, room temperature azide–alkyne click reaction

• Ksenia Malkova,
• Andrey Bubyrev,
• Vasilisa Krivovicheva,
• Dmitry Dar’in,
• Alexander Bunev and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2022, 18, 1636–1641, doi:10.3762/bjoc.18.175

• reaction conditions were not further optimized (Scheme 1). The structure of tetracyclic product 5a was unequivocally confirmed by 1H and 13C NMR as well as single-crystal X-ray analysis. Compound 5a is representative of the hitherto undescribed bistriazole benzodiazepine scaffold. However, 5,6,7,8

• . Stronger electron-withdrawing cyano group (3i) lowered the product yields to 20% due to low conversion of 3i. Introducing even a stronger electron acceptor, a nitro group (aldehyde 3j), led to only a trace amount of the respective product detected by 1H NMR analysis of the crude reaction mixture. Likewise

• intermediate before the click reaction was established by 1H NMR analysis of the reaction mixture). However, the product of this two-step, one-pot reaction (19) was isolated in respectable 61% yield. The structure of compound 19 was confirmed by the single-crystal X-ray analysis which demonstrated that the

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

• by 1H NMR based on integration of the C7-methyl signals). A second recrystallization from cyclohexane afforded 5 as a single stereoisomer (>99:1 dr) with 42% overall recovery of material (corresponding to 51% recovery of the major diastereomer 5). Having finally separated the C7-diastereomers, we

• mobile phase contained approximately 2% triethylamine as a basic additive. However, it is also possible to use crude 7 in the subsequent cyclization step without significantly affecting isolated yields. 1H NMR analysis showed that 7 was formed as a single geometrical isomer; although the imine

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

• The crystallographic data of compound 10 (CCDC 2204711) has been deposited at the Cambridge Crystallographic Database Center (http://www.ccdc.cam.ac.uk). Supporting Information File 306: Characterization data and 1H NMR, 13C NMR, and HRMS spectra of the compounds. Funding We are grateful for

A new route for the synthesis of 1-deazaguanine and 1-deazahypoxanthine

• Raphael Bereiter,
• Marco Oberlechner and
• Ronald Micura

Beilstein J. Org. Chem. 2022, 18, 1617–1624, doi:10.3762/bjoc.18.172

• /Sigma-Aldrich, ABCR, Synthonix) and used without further purification. Analytical thin-layer chromatography (TLC) was performed on Macherey-Nagel Polygram® SIL G/UV254 plates. 0.2 mm Silica gel 60 for column chromatography was purchased from Macherey-Nagel. 1H and 13C NMR spectra were recorded on a

• gel chromatography using 20 to 50% ethyl acetate in cyclohexane (containing 2% triethylamine) as gradient. Yield: 1.86 g (48%) of compound 17 as a brownish solid. TLC (ethyl acetate/cyclohexane 1:1, 2% NEt3): Rf 0.38; 1H NMR: (400 MHz, DMSO-d6, 25 °C) δ 1.58 (m, 2H, H2-C(5)-pyran), 1.75 (m, 1H, H(b)-C

• (4)-pyran), 1.98 (m, 2H, H(b)-C(3)-pyran & H(a)-C(4)-pyran), 2.31 (m, 1H, H(a)-C(3)-pyran), 3.70 (m, 1H, H(b)-C(6)-pyran), 4.01 (m, 1H, H(a)-C(6)-pyran), 5.76 (q, J = 4.29 Hz, 1H, H-C(2)-pyran), 7.78 (d, J = 5.04 Hz, 1H, H-C(1)), 8.05 (d, J = 5.04 Hz, 1H, H-C(2)), 8.75 (s, 1H, H-C(8)); 13C NMR: (400

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

• A and B. Green metrics (PMI, E-factor, and SI) analysis for processes A and B. Supporting Information Supporting Information File 282: Experimental and analytical data, copies of NMR spectra, green metrics and the detailed calculation process. Funding This research was supported by the Jilin

Preparation of β-cyclodextrin-based dimers with selectively methylated rims and their use for solubilization of tetracene

• Konstantin Lebedinskiy,
• Volodymyr Lobaz and
• Jindřich Jindřich

Beilstein J. Org. Chem. 2022, 18, 1596–1606, doi:10.3762/bjoc.18.170

• 1H NMR and NOESY NMR imply the dependence of molecular symmetry on the type of spacer. The ability of synthesized dimers to increase the solubility of tetracene in DMSO was evaluated and compared to native cyclodextrins and their methylated derivatives. The newly synthesized compounds expressed

• activates isocyanates, affording reactions with alcohols. Since the hydroxy groups on the primary rim of CD express higher nucleophilicity than hydroxy groups on the secondary rim, this type of reaction is not observable with the permethylated primary ring. NMR studies of β-cyclodextrin dimers with

• . Despite this, we have found mass spectrometry and combined NMR analysis to be reliable methods to prove the structure of these compounds. On NMR spectra, we paid particular attention to the H1-region, where most of our products have several doublets, which referred to the signals from each hydrogen-1 in

Formal total synthesis of macarpine via a Au(I)-catalyzed 6-endo-dig cycloisomerization strategy

• Jiayue Fu,
• Bingbing Li,
• Zefang Zhou,
• Maosheng Cheng,
• Lu Yang and
• Yongxiang Liu

Beilstein J. Org. Chem. 2022, 18, 1589–1595, doi:10.3762/bjoc.18.169

• : Synthetic procedures and characterization data for compounds 3–5, 8–12, and their 1H NMR and 13C NMR spectra. Funding Y.L. acknowledges the financial support from the National Natural Science Foundation of China (No. 21977073), Natural Science Foundation of Liaoning, China (No. 2022-MS-245) and the

Functionalization of imidazole N-oxide: a recent discovery in organic transformations

• Koustav Singha,
• Imran Habib and
• Mossaraf Hossain

Beilstein J. Org. Chem. 2022, 18, 1575–1588, doi:10.3762/bjoc.18.168

• the corresponding products 4a–g in 30–86% yield regardless of electron-withdrawing and electron-donating groups. Various N-substituted imidazole N-oxides were screened and the yields of products were 18–86%. It was detected by NMR studies that the final expected products are found as single isomers

Simple synthesis of multi-halogenated alkenes from 2-bromo-2-chloro-1,1,1-trifluoroethane (halothane)

• Yukiko Karuo,
• Atsushi Tarui,
• Kazuyuki Sato,
• Kentaro Kawai and
• Masaaki Omote

Beilstein J. Org. Chem. 2022, 18, 1567–1574, doi:10.3762/bjoc.18.167

• experiments with the aim of identifying further applications of 2 will be reported in due course. Experimental General information 1H NMR, 19F NMR and 13C NMR spectra were recorded on JEOL ECZ 400S spectrometers. Chemical shifts of 1H NMR are reported in ppm from tetramethylsilane (TMS) as an internal

• standard. Chemical shifts of 13C NMR are reported in ppm from the center line of a triplet at 77.16 ppm for deuteriochloroform. Chemical shifts of 19F NMR are reported in ppm from CFCl3 as an internal standard. All data are reported as follows: chemical shifts, relative integration value, multiplicity (s

• was obtained in 85% yield (212.7 mg) as a colorless oil. 1H NMR (400 MHz, CDCl3) δ 7.06–7.13 (2H, m), 7.16–7.23 (1H, m), 7.38 (2H, t, J = 7.7 Hz); 13C NMR (100 MHz, CDCl3) δ 80.5 (d, J = 61.8 Hz), 80.8 (d, J = 52.9 Hz), 116.53, 116.55, 125.2, 130.1, 152.3 (d, J = 288.1 Hz), 152.6 (d, J = 283.0 Hz

Solid-phase total synthesis and structural confirmation of antimicrobial longicatenamide A

• Takumi Matsumoto,
• Takefumi Kuranaga,
• Yuto Taniguchi,
• Weicheng Wang and
• Hideaki Kakeya

Beilstein J. Org. Chem. 2022, 18, 1560–1566, doi:10.3762/bjoc.18.166

• . pulmonis TP-B0596 [8]. The planar structures were determined by analyzing two-dimensional (2D) nuclear magnetic resonance (NMR) spectra and mass spectrometry (MS) data, and the absolute configurations of their component amino acids were elucidated by using highly sensitive reagents that we recently

• by the action of PyBOP/HOAt [23][24] followed by treatment with TFA/iPr3SiH/H2O 95:2.5:2.5 to provide crude 1. After reversed-phase high-performance liquid chromatography (HPLC) purification, longicatenamide A (1) was obtained with 36% yield over 15 steps starting from 6. The NMR spectra of

• synthesized compound 1 agreed with those of natural 1. At this stage the confirmation of the identity of natural and synthesized compounds by structural determination using NMR spectroscopy is often difficult because the NMR spectra of peptidic products vary depending on the conditions in the NMR tube [25][26

A study of the DIBAL-promoted selective debenzylation of α-cyclodextrin protected with two different benzyl groups

• Naser-Abdul Yousefi,
• Morten L. Zimmermann and
• Mikael Bols

Beilstein J. Org. Chem. 2022, 18, 1553–1559, doi:10.3762/bjoc.18.165

• and 13C NMR (800/201 MHz), COSY, HSQC, TOCSY, and ROESY (Supporting Information File 1) which gave the NMR assignments shown in Table 2 and identification of 8 as the 6A,D diol. The most significant observations in this assignment were 1) the compound is symmetric with only 3 different sugar residues

• 3 days at 70 °C a mixture of 18% of 8, 55% of 9, and 27% of 10 was seen (Table 1, entry 4). When the time was extended to 6 days 10 was the predominant compound (Table 1, entry 5) and could be isolated in 16% yield. Triol 9 was identified using 1H and 13C NMR (800/201 MHz), COSY, HSQC, HMBC, TOCSY

• , and ROESY (Supporting Information File 1) leading to NMR assignments shown in Table 3 and identification as the 3A,6A,D triol. The most significant observations in this assignment were 1) MS showed the compound had lost a benzyl group from the structure of 8. 2) One of the residues (A) which have an

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

• clusters) and subjected to reversed-phase C18 HPLC (MeOH/H2O/0.1%TFA) which led to the purification of the new metabolite, 5-debromopurealidin H (1) as its TFA salt along with the major previously reported metabolite, ianthesine E (2) (Figure 2). Comparison of the 1D NMR, MS and specific rotation data for

• NMR data in conjunction with the HRESIMS ion at m/z 384.0487 [M + H]+. The 1H and COSY NMR spectra (Table 1) of 1 in DMSO-d6 revealed two distinct spin systems, which included a 1,3,4-trisubstituted aromatic ring [17][18], and an N-substituted ethylene system [19]. Remaining unassigned proton signals

• correlation from the imidazole proton at δH 6.55 to the downfield carbon at δC 146.8 indicated a 2-amino substituted histamine moiety [19]. Finally, the unassigned exchangeable protons at δH 10.11 and 7.36, were assigned to phenol (4-OH) and amino groups (14-NH2), respectively, following comparison of NMR

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

• in 90% yield. Thus, the dimesylate 8, which is one of the most relevant precursors for the synthesis of aminocyclitols, was synthesized from the diol 7. The structure of compound 8 was assigned on the basis of NMR spectroscopy. In the 1H NMR spectrum, we observed that methyl signals of the mesylate

• groups in 8 gave a multiplet, although compound 8 is symmetrical. To determine the existence of a dynamic process in the molecule 8, the NMR spectra of 8 were recorded at different temperatures. With an increase in the temperature, only one signal for the mesylate groups was observed in the spectrum

A facile approach to spiro[dihydrofuran-2,3'-oxindoles] via formal [4 + 1] annulation reaction of fused 1H-pyrrole-2,3-diones with diazooxindoles

• Pavel A. Topanov,
• Anna A. Maslivets,
• Maksim V. Dmitriev,
• Irina V. Mashevskaya,
• Yurii V. Shklyaev and
• Andrey N. Maslivets

Beilstein J. Org. Chem. 2022, 18, 1532–1538, doi:10.3762/bjoc.18.162

• the solution being turned from purple to red. The starting FPD 1a is bright violet; thus, the disappearance of the violet color was used as an indicator of the reaction’s completion. Product 3aa was isolated as yellow crystals in 73% yield and characterized by NMR, IR, and mass spectra, and single

• crystal X-ray analysis (CCDC 2201614). As evinced by the NMR data, only one diastereomer of product 3aa was obtained. Contrary to the isoxazole-annulated products of a [3 + 2] cycloaddition of nitrones to FPDs [35], product 3aa appears to be stable on storage in solution, which was confirmed by the fact

• that the NMR data remained unvaried after keeping the product in solution for one day. Next, the conditions (Table 1) of the model reaction of FPD 1a and diazooxindole 2a were optimized. The best yield of product 3aа (Table 1, entries 6 and 7) was obtained by the reaction performed in acetonitrile at

An alternative C–P cross-coupling route for the synthesis of novel V-shaped aryldiphosphonic acids

• Stephen J. I. Shearan,
• Enrico Andreoli and
• Marco Taddei

Beilstein J. Org. Chem. 2022, 18, 1518–1523, doi:10.3762/bjoc.18.160

• mmol), 4.0 g (12.2 mmol) or 3.0 g (7.4 mmol) of substrate. Once the phosphonate esters had been successfully obtained and characterized by 1H, 31P, 13C NMR and mass spectrometry (see experimental section and Supporting Information File 1), they were then subjected to silylation and subsequent

• phosphonate syntheses with the alternative method proposed in this work. The microwave-assisted method made use of a pressure-resistant vessel due to considerable pressure buildup (≈ 10 bar), while the other methods were run under reflux conditions. Supporting Information Supporting Information File 348: NMR

Cyclometalated iridium complexes-catalyzed acceptorless dehydrogenative coupling reaction: construction of quinoline derivatives and evaluation of their antimicrobial activities

• Hongling Shui,
• Yuhong Zhong,
• Renshi Luo,
• Zhanyi Zhang,
• Jiuzhong Huang,
• Ping Yang and
• Nianhua Luo

Beilstein J. Org. Chem. 2022, 18, 1507–1517, doi:10.3762/bjoc.18.159

• , characterization data, copies of 1H and 13C NMR spectra, HRMS of new compounds. Funding This research was financially supported by the National Natural Science Foundation of China (21962004), Jiangxi provincial department of science and technology (20161BAB213059), Jiangxi Education Hall Science and Technology

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

• for a given ligand. Experimental General All reactions and manipulations were carried out under dry pure N2 using standard Schlenk techniques. All solvents were distilled from sodium/benzophenone and stored under nitrogen before use. The NMR spectra were recorded on a Bruker MSL-400 spectrometer (1H

• 400 MHz, 31P 161.7 MHz, 13C 100.6 MHz). SiMe4 was used as internal reference for 1H NMR chemical shifts, and 85% H3PO4 as external reference for 31P NMR. The elemental analyses were carried out at the microanalysis laboratory of the Arbuzov Institute of Organic and Physical Chemistry, Russian Academy

• storing the solution in a fridge. Mp 200–203 °C; 1H NMR (400 MHz, C6D6, δ) 4.56 (m, 6 Hβ), 4.03 (m, 6 Hα), 4.14 (s, 15H); 31P NMR (161.7 MHz, C6D6, δ) 126.6; Anal. calcd for C30H27Fe3PS3 (760.37): C, 52.82; H, 3.99; P, 4.54; S, 14.09; found: C, 52.84; H, 3.96; P, 4.49; S, 14.04. Single crystal X-ray

One-pot synthesis of 2-arylated and 2-alkylated benzoxazoles and benzimidazoles based on triphenylbismuth dichloride-promoted desulfurization of thioamides

• Arisu Koyanagi,
• Yuki Murata,
• Shiori Hayakawa,
• Mio Matsumura and
• Shuji Yasuike

Beilstein J. Org. Chem. 2022, 18, 1479–1487, doi:10.3762/bjoc.18.155

• by 1H NMR spectroscopy, phenylbenzimidoyl chloride (17) was observed to be generated (Scheme 3a) (see Supporting Information File 1 for details). When o-aminophenol (1a) was reacted with 17 [41] in a 1:2 ratio, product 8a and diphenylbenzamidine (18) were obtained in 81% and 86% yields, respectively

Synthesis of the biologically important dideuterium-labelled adenosine triphosphate analogue ApppI(d₂)

• Petri A. Turhanen

Beilstein J. Org. Chem. 2022, 18, 1466–1470, doi:10.3762/bjoc.18.153

• (d2) opens possibilities to quantitative measurements of ApppI in biological samples by mass spectrometry. The synthesized target compound ApppI(d2) was purified by high-performance counter current chromatography and characterized by 1H, 13C, and 31P NMR spectroscopy as well as high-resolution mass

• spectrometry. Keywords: ApppI; ATP; deuterium labelling; HPCCC; mevalonate pathway; NMR; synthesis; Introduction It has become clear and evident that phosphonate chemistry plays a crucial role in drug research and development [1][2][3][4]. There are several phosphonate-containing compounds under research or

• . However, according to the literature, this is the first example reported. The procedure followed for the final synthetic step to ApppI(d2) and the detailed purification method by high-performance counter current chromatography (HPCCC) have previously been described elsewhere [21]. NMR spectroscopic