Synthesis of 1,4-azaphosphinine nucleosides and evaluation as inhibitors of human cytidine deaminase and APOBEC3A

• Maksim V. Kvach,
• Stefan Harjes,
• Harikrishnan M. Kurup,
• Geoffrey B. Jameson,
• Elena Harjes and
• Vyacheslav V. Filichev

Beilstein J. Org. Chem. 2024, 20, 1088–1098, doi:10.3762/bjoc.20.96

• -neutral phosphinamide and a negatively charged phosphinic acid derivative had excellent stability in water at pH 7.4, but only the charge-neutral compound inhibited human CDA, similar to previously described 2'-deoxyzebularine (Ki = 8.0 ± 1.9 and 10.7 ± 0.5 µM, respectively). However, under basic

• conditions, the charge-neutral phosphinamide was unstable, which prevented the incorporation into DNA using conventional DNA chemistry. In contrast, the negatively charged phosphinic acid derivative was incorporated into DNA instead of the target 2'-deoxycytidine using an automated DNA synthesiser, but no

• phosphinic acid 7 was further protected with benzyl alcohol by a procedure adopted from reference [67] using TBTU and Et3N in refluxing dichloroethane. Compound 8 was obtained in 65% yield after silica gel column chromatography. To synthesise a nucleobase for nucleosides Va and Vb, we first obtained

Synthesis of ether lipids: natural compounds and analogues

• Marco Antônio G. B. Gomes,
• Alicia Bauduin,
• Chloé Le Roux,
• Romain Fouinneteau,
• Wilfried Berthe,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2023, 19, 1299–1369, doi:10.3762/bjoc.19.96

Synthesis of tryptophan-dehydrobutyrine diketopiperazine and biological activity of hangtaimycin and its co-metabolites

• Houchao Xu,
• Anne Wochele,
• Minghe Luo,
• Gregor Schnakenburg,
• Yuhui Sun,
• Heike Brötz-Oesterhelt and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 1159–1165, doi:10.3762/bjoc.18.120

• -butyloxycarbonyl (Boc)-protected threonine using bis(2-oxo-3-oxazolidinyl)phosphinic chloride (BOP-Cl) [14][15] and Hünig’s base to give 9. Cleavage of the Boc group with 5% TFA followed by basic treatment resulted in the cyclisation to the dioxopiperazine 10. Acetylation and subsequent treatment with LiClO4 and

Synthetic strategies for the preparation of γ-phostams: 1,2-azaphospholidine 2-oxides and 1,2-azaphospholine 2-oxides

• Jiaxi Xu

Beilstein J. Org. Chem. 2022, 18, 889–915, doi:10.3762/bjoc.18.90

• -iodotoluene (7) and diethyl methylphosphonite gave ethyl 2-methylphenyl(methyl)phosphinate (8) in an excellent yield under the catalysis of anhydrous NiCl2 (Scheme 3) [23]. Ethyl 2-methylphenyl(methyl)phosphinate (8) was converted into 2-methylphenyl(methyl)phosphinic chloride (9) in 94% yield by treatment

• with excess PCl5. However, the radical chlorination of 2-methylphenyl(methyl)phosphinic chloride (9) gave the desired 2-chloromethylphenyl(methyl)phosphinic chloride (10) in 65% yield with unreacted starting 9 in 25–30%, and the dichlorinated product 11 in 5–10%. The reaction of 2-chloromethylphenyl

• (methyl)phosphinic chloride (10) with amines generated N-aryl-2-chloromethylphenyl(methyl)phosphinamides 12 in 52–99% yields, which were further treated with DBU in refluxing THF, affording 2-aryl-1-methyl-2,3-dihydrobenzo[c][1,2]azaphosphole 1-oxides 13 in 40–100% yield (Scheme 3) [23]. This is a general

Synthesis of (Z)-3-[amino(phenyl)methylidene]-1,3-dihydro-2H-indol-2-ones using an Eschenmoser coupling reaction

• Lukáš Marek,
• Lukáš Kolman,
• Jiří Váňa,
• Jan Svoboda and
• Jiří Hanusek

Beilstein J. Org. Chem. 2021, 17, 527–539, doi:10.3762/bjoc.17.47

• occurs to give 3-methoxy-2-oxoindolin-3-yl acetate. Other reducing agents recommended in the literature for the reduction of unprotected isatin (sodium dithionite, zinc, phosphinic acid, etc.) also failed or caused an acetyl group removal. Therefore, we abandoned this strategy. Configuration of products

Chemical synthesis of tripeptide thioesters for the biotechnological incorporation into the myxobacterial secondary metabolite argyrin via mutasynthesis

• David C. B. Siebert,
• Roman Sommer,
• Domen Pogorevc,
• Michael Hoffmann,
• Silke C. Wenzel,
• Rolf Müller and
• Alexander Titz

Beilstein J. Org. Chem. 2019, 15, 2922–2929, doi:10.3762/bjoc.15.286

• permeability of the mutasynthons. Experimental Protocols and methods can be found in Supporting Information File 1. Abbreviations Boc: tert-Butyloxycarbonyl, BOP-Cl: bis(2-oxo-3-oxazolidinyl)phosphinic chloride, CDI: carbonyldiimidazole, DIPEA: diisopropylethylamine, EDC: N-(3-Dimethylaminopropyl)-N

One-pot syntheses of blue-luminescent 4-aryl-1H-benzo[f]isoindole-1,3(2H)-diones by T3P^® activation of 3-arylpropiolic acids

• Melanie Denißen,
• Alexander Kraus,
• Guido J. Reiss and
• Thomas J. J. Müller

Beilstein J. Org. Chem. 2017, 13, 2340–2351, doi:10.3762/bjoc.13.231

• ]-cycloaddition of phenylpropiolic acid anhydrides. Usually, this synthesis requires harsh reaction conditions starting from phenylpropiolic acids [42][43]. However, employing bis(2-oxooxazolidin-3-yl)phosphinic chloride as an activating agent represents a suitable access [44]. Alternative approaches include the

Phosphonic acid: preparation and applications

• Charlotte M. Sevrain,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2017, 13, 2186–2213, doi:10.3762/bjoc.13.219

• that can be used for the synthesis of phosphonic acids from dialkyl or diaryl phosphonate, from dichlorophosphine or dichlorophosphine oxide, from phosphonodiamide, or by oxidation of phosphinic acid. Direct methods that make use of phosphorous acid (H3PO3) and that produce a phosphonic acid functional

• simultaneously to the formation of phosphonic acid (section 6) or the oxidation of phosphinic acid (section 7). The last section (section 8) includes additional miscellaneous methods to prepare phosphonic acids. Of note, the biosynthesis of phosphonic acid, which is a dynamic field of research aiming to discover

• it was recently reviewed [235]. 7. Preparation of phosphonic acid by oxidation of phosphinic acid Phosphinic acid derivatives (also identified as phosphonous acid) are prepared by reaction of hypophosphorous acid (Figure 35) on alkene or alkyne (hydrophosphonation) [236], by its addition on aldehyde

Aerobic addition of secondary phosphine oxides to vinyl sulfides: a shortcut to 1-hydroxy-2-(organosulfanyl)ethyl(diorganyl)phosphine oxides

• Svetlana F. Malysheva,
• Alexander V. Artem’ev,
• Nina K. Gusarova,
• Nataliya A. Belogorlova,
• Alexander I. Albanov,
• C. W. Liu and
• Boris A. Trofimov

Beilstein J. Org. Chem. 2015, 11, 1985–1990, doi:10.3762/bjoc.11.214

• adducts are not observed in detectable amounts (31P NMR). The main byproducts are phosphinic acids, R2P(O)OH, formed by air oxidation of secondary phosphine oxides 1a–f. As seen from Table 1, the reaction is applicable to both aryl- (1b) and arylalkyl-substituted (1a,c–e) secondary phosphine oxides. The

Synthesis of γ-hydroxypropyl P-chirogenic (±)-phosphorus oxide derivatives by regioselective ring-opening of oxaphospholane 2-oxide precursors

• Iris Binyamin,
• Shoval Meidan-Shani and
• Nissan Ashkenazi

Beilstein J. Org. Chem. 2015, 11, 1332–1339, doi:10.3762/bjoc.11.143

• starting materials, without isolation of intermediate 6 (Scheme 3). This method was found to be superior to two other protocols: reaction of phenyl disulfide with 3-hydroxypropyl(phenyl)phosphine oxide [30] and reaction of allyl alcohol with benzene phosphinic acid monobutyl ester in the presence of di

Synthesis of α-amino amidines through molecular iodine-catalyzed three-component coupling of isocyanides, aldehydes and amines

• Praveen Reddy Adiyala,
• D. Chandrasekhar,
• Jeevak Sopanrao Kapure,
• Chada Narsimha Reddy and
• Ram Awatar Maurya

Beilstein J. Org. Chem. 2014, 10, 2065–2070, doi:10.3762/bjoc.10.214

• -amino amidines can be obtained depending on the nucleophile used. However, the reaction does not lead to acceptable product yields of products without using proper catalysts except when the nucleophile is carboxylate. For instance, among various catalysts screened, only phosphinic acid and boric acid

Synthesis of ethoxy dibenzooxaphosphorin oxides through palladium-catalyzed C(sp²)–H activation/C–O formation

• Seohyun Shin,
• Dongjin Kang,
• Woo Hyung Jeon and
• Phil Ho Lee

Beilstein J. Org. Chem. 2014, 10, 1220–1227, doi:10.3762/bjoc.10.120

• phosphoryl-related directing groups have been reported by our [24][25][26][27][28][29][30][31][32] and other groups [33][34][35][36][37][38][39][40][41]. More recently, we developed a method allowing for synthetic access to benzoxaphosphole 1- and 2-oxides starting from phosphonic and phosphinic acids via Pd

Atherton–Todd reaction: mechanism, scope and applications

• Stéphanie S. Le Corre,
• Mathieu Berchel,
• Hélène Couthon-Gourvès,
• Jean-Pierre Haelters and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2014, 10, 1166–1196, doi:10.3762/bjoc.10.117

• species [67]. Phosphinous acid (R2POH) was less extensively studied as a phosphorus-based substrate in AT reactions. However, one full study was reported by Bondarenko et al. [72]. These authors reported three different methods to produce phosphinic amides by reacting primary or secondary amines with

Group-assisted purification (GAP) chemistry for the synthesis of Velcade via asymmetric borylation of N-phosphinylimines

• Jian-bo Xie,
• Jian Luo,
• Timothy R. Winn,
• David B. Cordes and
• Guigen Li

Beilstein J. Org. Chem. 2014, 10, 746–751, doi:10.3762/bjoc.10.69

• purification without the need for column chromatography; GAP washing can lead to a single isomeric product, which was deprotected with quantitative recovery of the phosphinic acid as shown in Scheme 2. Results and Discussion We started our synthesis with (2S,5S)-1-amino-2,5-diphenylphospholane 1-oxide (1

• consisting of H2O and MeOH (2:1) was examined. It was found that treatment of the aminoboronic ester with 1.5 equiv of HCl for 16 hours resulted in complete deprotection; work-up consisted of extraction with DCM followed by concentration to give product 4 as a white solid in 92% yield. Pure phosphinic acid 5

Phosphinate-containing heterocycles: A mini-review

• Olivier Berger and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2014, 10, 732–740, doi:10.3762/bjoc.10.67

• rare. The growing availability of synthetic methods will undoubtedly change this situation in the near future. Keywords: amino acid; heterocyle; organophosphorus; phosphinic; phosphorus; Introduction The preparation of P-heterocycles has been the subject of many studies over the years, and the field

• organophosphorus compounds: the phosphinates R1R2P(O)(OR) [9]. Because the phosphinic acid moiety P(O)OH can mimic carboxylic acids, its incorporation into heterocycles may offer new opportunities for the discovery of biologically active analogs. However, little or no biological data is available at this time

• phosphinic acid using different alcohols in large excess (Scheme 1) [11][12]. Six phospholes 2a–f were prepared in yields up to 94%. Montchamp and coworkers have synthesized phospholes 4a,b by ring closing metathesis using 2 or 5 mol % of 2nd generation Grubbs’ catalyst (Scheme 2) [13][14]. Two compounds 4a

A novel family of (1-aminoalkyl)(trifluoromethyl)- and -(difluoromethyl)phosphinic acids – analogues of α-amino acids

• Natalia V. Pavlenko,
• Tatiana I. Oos,
• Yurii L. Yagupolskii,
• Igor I. Gerus,
• Uwe Doeller and
• Lothar Willms

Beilstein J. Org. Chem. 2014, 10, 722–731, doi:10.3762/bjoc.10.66

• Ukraine, Murmanskaya str. 1, 02660 Kiev-94, Ukraine Bayer CropScience Aktiengesellschaft BCS AG-R-WC-WCC-C2 Weed Control Chemistry 2, Frankfurt, G836, 101, Germany 10.3762/bjoc.10.66 Abstract A series of novel (1-aminoalkyl)(trifluoromethyl)- and -(difluoromethyl)phosphinic acids – analogues of

• proteinogenic and nonproteinogenic α-amino acids were prepared. The synthetic methodology was based on nucleophilic addition of (trifluoromethyl)phosphinic acid or (difluoromethyl)phosphinic acid or its ethyl ester to substrates with C=N or activated C=C double bonds. Analogues of glycine, phenylglycine

• , alanine, valine, proline, aminomalonic and aspartic acids were thus prepared. Three-component one-pot reactions of (trifluoromethyl)phosphinic acid and dibenzylamine with aldehydes were also tested to prepare the title compounds. Keywords: (1-aminoalkyl)phosphinic acids; ethyl (difluoromethyl)phosphinate

New developments in gold-catalyzed manipulation of inactivated alkenes

• Michel Chiarucci and
• Marco Bandini

Beilstein J. Org. Chem. 2013, 9, 2586–2614, doi:10.3762/bjoc.9.294

• the titled reaction turned out to be the complex 20b bearing an electron-rich phosphinic ligand. When 20b was mixed with AgOTf (1:1 ratio) the intramolecular hydroamination of alkenyl ammonium salts 45/47 took place at 80–100 °C affording pyrrolidines and piperidines 46/48 in moderate to good yields

Screening of ligands for the Ullmann synthesis of electron-rich diaryl ethers

• Nicola Otto and
• Till Opatz

Beilstein J. Org. Chem. 2012, 8, 1105–1111, doi:10.3762/bjoc.8.122

• . This decrease of catalytic activity may be due to oxidation and subsequent hydrolysis of the air- and water-sensitive phosphinites to their corresponding phosphinic acids and 8-hydroxyquinoline (L47), which showed a comparable catalytic activity. It was found that the conversion within a specific time

Multicomponent synthesis of artificial nucleases and their RNase and DNase activity

• Anton V. Gulevich,
• Lyudmila S. Koroleva,
• Olga V. Morozova,
• Valentina N. Bakhvalova,
• Vladimir N. Silnikov and
• Valentine G. Nenajdenko

Beilstein J. Org. Chem. 2011, 7, 1135–1140, doi:10.3762/bjoc.7.131

• ); 13C NMR (100 MHz, CDCl3) δ 155.6 (t, J = 5.9 Hz, NC), 41.1 (t, J = 6.6 Hz, (CH2CH2CH2NC)2), 28.5, 25.2; IR (cm−1) 2150 (NC); Anal. calcd for C8H12N2: C, 70.55; H, 8.88; found: C, 70.34; H, 8.62. General procedure for the synthesis of 4a–g The corresponding isocyanide 3 (3 mmol) and phenyl phosphinic

A practical route to tertiary diarylmethylamides or -carbamates from imines, organozinc reagents and acyl chlorides or chloroformates

• Erwan Le Gall,
• Antoine Pignon and
• Thierry Martens

Beilstein J. Org. Chem. 2011, 7, 997–1002, doi:10.3762/bjoc.7.112

• such as sulfinic or phosphinic chloride derivatives (ClS(O)R and ClP(O)R2), whose N–AG bond might be cleaved easily upon acidic work-up. In addition, chiral versions of such activators would be of further interest for potential asymmetric couplings (at least with benzylzinc reagents), as the