Dipeptide analogues of fluorinated aminophosphonic acid sodium salts as moderate competitive inhibitors of cathepsin C

• Karolina Wątroba,
• Małgorzata Pawełczak and
• Marcin Kaźmierczak

Beilstein J. Org. Chem. 2023, 19, 434–439, doi:10.3762/bjoc.19.33

• the catalytic cysteine Cys234 [10]. Phosphonates, as well as their analogues phosphonic acids, can be modified in a number of ways, one of which is the introduction of a fluorine atom into their molecules by fluorination or alkylfluorination [11][12][13][14]. However, the reaction of β-aminoalcohols

• to the corresponding phosphonic acids or their salts is often a necessary step to measure activity in enzyme inhibition bioassays [16][17][18][19][20][21][22]. Therefore, our goal was to determine the best conditions for carrying out the solvolysis reaction of synthesized dipeptide analogues of

• phosphonic acids 8 and 10 with a 1 M aqueous NaOH solution. Based on the literature data, alternatively to this method [30][31][32], phosphonic acids can be passed through an ion exchange column [33]. The reactions of compounds 8 and 10 with 1 M NaOH were carried out at room temperature (Scheme 2). When a

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

• Abstract The synthesis of phosphonate esters is a topic of interest for various fields, including the preparation of phosphonic acids to be employed as organic linkers for the construction of metal phosphonate materials. We report an alternative method that requires no solvent and involves a different

• three novel aryl diphosphonate esters which were subsequently transformed to phosphonic acids through silylation and hydrolysis. Keywords: arylphosphonic acids; cross-coupling reaction; phosphonate esters; transition-metal catalysis; Introduction Phosphonates and phosphonic acids are a very

• work is the phosphonylation of the commercially available bromo-substituted N-aryl precursors bis(4-bromophenyl)amine (Br2BPA), 3,6-dibromocarbazole (Br2DPC), and 4-bromo-N-(4-bromophenyl)-N-phenylaniline (Br2DPPA) (see Scheme 1). In light of using the resulting phosphonic acids as linkers for the

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

Beilstein J. Org. Chem. 2021, 17, 461–484, doi:10.3762/bjoc.17.41

• -chain phosphonic acids. Review Synthesis of phosphonodepsipeptides via the phosphonylation of hydroxy esters with phosphonochloridates The phosphonylation of hydroxy esters 2 with alkyl N-protected aminoalkylphosphonochloridates 3 is a general and widely applied method for the synthesis of α-, β-, and γ

• -aminoalkylphosphonic acids 32 and 4-nitrobenyl 2-hydroxyalkanoates 33 in the presence of SOCl2 in DMF. This was an efficient coupling reaction for the synthesis of phosphonodepsipeptides from N-protected phosphonic acids and hydroxy esters. The phosphonodepsidipeptide 31 (R1 = R2 = H, Scheme 6) was converted to the

• free phosphonodepsidipeptide 34 in 80% yield and the N-Cbz-phosphonodepsidipeptide 35 in 85% yield, respectively, via hydrogenolysis and basic hydrolysis, respectively (Scheme 6) [23]. The method actually is a convenient and direct method to synthesize phosphonodepsipeptides from N-protected phosphonic

Convenient access to pyrrolidin-3-ylphosphonic acids and tetrahydro-2H-pyran-3-ylphosphonates with multiple contiguous stereocenters from nonracemic adducts of a Ni(II)-catalyzed Michael reaction

• Alexander N. Reznikov,
• Dmitry S. Nikerov,
• Anastasiya E. Sibiryakova,
• Victor B. Rybakov,
• Evgeniy V. Golovin and
• Yuri N. Klimochkin

Beilstein J. Org. Chem. 2020, 16, 2073–2079, doi:10.3762/bjoc.16.174

• ,6R)-13b. Intermolecular N-methylation of reduction product 7. Synthesis of pyrrolidinyl phosphonic acids 11a–d. Synthesis of tetrahydropyranylphosphonates 13a–f via diastereoselective Henry/acetalyzation reaction. Synthesis of (3,4-dihydro-2H-pyran-5-yl)phosphonate 14. Optimization of the conditions

The McKenna reaction – avoiding side reactions in phosphonate deprotection

• Katarzyna Justyna,
• Joanna Małolepsza,
• Damian Kusy,
• Waldemar Maniukiewicz and
• Katarzyna M. Błażewska

Beilstein J. Org. Chem. 2020, 16, 1436–1446, doi:10.3762/bjoc.16.119

• the typical side processes accompanying the McKenna reaction, but also uncovered new ones. Further, we discovered that some commonly recommended precautions did not always circumvent the side reactions. The proposed results and recommendations may facilitate the synthesis of phosphonic acids

• recommended by Björnmalm and Caruso [21] and to report failures, as a tool to facilitate and accelerate new studies requiring the synthesis of phosphonic acids. To the best of our knowledge, this is the first systematic study on side reactions accompanying the McKenna reaction. It is important to distinguish

• esters, without affecting carboxyester groups. However, the formation of phosphonic acids in the solvolysis step of the Mc Kenna reaction could lead to the cleavage of acid-labile groups [52][53]. In order to prevent this reaction, the solvolysis step commonly is performed in buffered solutions [53]. In

Different reactivity of phosphorylallenes under the action of Brønsted or Lewis acids: a crucial role of involvement of the P=O group in intra- or intermolecular interactions at the formation of cationic intermediates

• Stanislav V. Lozovskiy,
• Alexander Yu. Ivanov and
• Aleksander V. Vasilyev

Beilstein J. Org. Chem. 2019, 15, 1491–1504, doi:10.3762/bjoc.15.151

• phosphonic acids and other phosphorus-containing compounds. Contrary to Brønsted acids, 3-methylbuta-1,2-dien-1-ylphosphonic dichloride [Cl2(O=)P–HC=C=CMe2] reacted with the Lewis acid AlCl3 in an intermolecular way forming noncyclic intermediates, which were investigated by NMR spectroscopy and DFT

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

• oxygen atoms (two hydroxy groups and one P=O double bond) and one carbon atom, is employed for many applications due to its structural analogy with the phosphate moiety or to its coordination or supramolecular properties. Phosphonic acids were used for their bioactive properties (drug, pro-drug), for

• synthesis of phosphonic acids a determinant question for numerous research projects. This review gives, first, an overview of the different fields of application of phosphonic acids that are illustrated with studies mainly selected over the last 20 years. Further, this review reports the different methods

• 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

Phenylsilane as an effective desulfinylation reagent

• Wanda H. Midura,
• Aneta Rzewnicka and
• Jerzy A. Krysiak

Beilstein J. Org. Chem. 2017, 13, 1513–1517, doi:10.3762/bjoc.13.150

• sulfoxide substituent. Compounds 2 and 3 were obtained by us earlier [23] in diastereomerically pure form as key intermediates in our approach to constrained phosphonic acids by the reaction of phosphoryl acrylates with (S)-dimethylsulfonium(p-tolylsulfinyl)methylide. The carboxylate moiety was geminal to

Beta-hydroxyphosphonate ribonucleoside analogues derived from 4-substituted-1,2,3-triazoles as IMP/GMP mimics: synthesis and biological evaluation

• Tai Nguyen Van,
• Audrey Hospital,
• Corinne Lionne,
• Lars P. Jordheim,
• Charles Dumontet,
• Christian Périgaud,
• Laurent Chaloin and
• Suzanne Peyrottes

Beilstein J. Org. Chem. 2016, 12, 1476–1486, doi:10.3762/bjoc.12.144

• -protected nucleotides 3a–o (Scheme 2) in moderate to good yields. Removal of the sugar protecting groups (acetyl and benzoyl) in basic conditions resulted in the formation of the nucleotides 4a–q (Scheme 2), which were then treated by trimethylsilyl bromide (TMSBr) to generate the corresponding phosphonic

• acids. Thus, nucleoside phosphonate analogues 1a–q (Scheme 2) were isolated as their sodium salts with yields ranging from 21 to 77% over three steps. Structures of all final compounds were unambiguously confirmed on the basis of NMR (1H, 13C and 31P) and MS (MS and HRMS) data analysis (see Supporting

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• in high yield and excellent enantioselectivity (85–94% yield, 98:2 to 99:1 er). With sterically bulky α-substituents (R = Ph, t-Bu), competitive formation of the achiral internal alkene was preferred. Enantioenriched α-amino phosphonic acids and their derivatives are important motifs that have been

Pyrrolidine nucleotide analogs with a tunable conformation

• Lenka Poštová Slavětínská,
• Dominik Rejman and
• Radek Pohl

Beilstein J. Org. Chem. 2014, 10, 1967–1980, doi:10.3762/bjoc.10.205

• ), exist at a very low pD value (<3) as free phosphonic acids with a deuterated pyrrolidine nitrogen atom (Figure 6). The phosphonic acid moiety goes through a two-stage deuteration/dedeuteration transition at pD ~ 3 and 5 and the pyrrolidine nitrogen atom stays deuterated until pD ~ 9. This suggests that

Application of cyclic phosphonamide reagents in the total synthesis of natural products and biologically active molecules

• Thilo Focken and
• Stephen Hanessian

Beilstein J. Org. Chem. 2014, 10, 1848–1877, doi:10.3762/bjoc.10.195

• diastereoselectivity and further hydrolyzed to the corresponding enantiomerically pure α-substituted phosphonic acids 33 [22][29][30]. Other asymmetric alkylation methodologies using chiral phosphonamides were reported by the groups of Denmark [3][4] and Steglich [7]. Remarkably, the alkylation of α-dithioalkylimino

• to the electrophile compared to the conventionally accepted model [31]. The use of other electrophiles for the stereoselective formation of C–N bonds has also been reported. Thus, α-amino-α-alkyl phosphonic acids [32][33][34] could be obtained through amination and azidation of phosphonamide anions

• dichlorides can be obtained either from chlorination of phosphonic acids [65][66] or from treatment of an allyl chloride such as 61 with phosphorus trichloride followed by hydrolysis to give 62 [15][67]. Reactions of unsymmetrical amines or aminoalcohols such as ephedrine with phosphonic acid dichlorides

Methylidynetrisphosphonates: Promising C₁ building block for the design of phosphate mimetics

• Vadim D. Romanenko and
• Valery P. Kukhar

Beilstein J. Org. Chem. 2013, 9, 991–1001, doi:10.3762/bjoc.9.114

• dephosphonylation than the parent trisphosphonate esters, HC(PO3R2)3, or their α-carbo-substituted derivatives. In particular, in the case of aminotrisphosphonate ester 1a all standard synthetic routes to phosphonic acids (A–C) via acidic hydrolysis of phosphonate esters lead to the elimination of one phosphonyl

Multistep organic synthesis of modular photosystems

• Naomi Sakai and
• Stefan Matile

Beilstein J. Org. Chem. 2012, 8, 897–904, doi:10.3762/bjoc.8.102

• ferricyanide reduction in solution, and by absorption spectroscopy (Scheme 4). The obtained monolayers of 48 were annealed for 1 h in the oven at 120 °C. These conditions are known to improve the covalent bonding between phosphonic acids and the ITO substrate [26]. The disulfide protecting groups on the

Regioselective ester cleavage during the preparation of bisphosphonate methacrylate monomers

• Kamel Chougrani,
• Gilles Niel,
• Bernard Boutevin and
• Ghislain David

Beilstein J. Org. Chem. 2011, 7, 364–368, doi:10.3762/bjoc.7.46

• the phosphonic acids by using first trimethylsilyl bromide followed by a methanolysis step [27]. The first step is known to transform alkyl phosphonates into the corresponding trimethylsilyl phosphonates which are then cleaved to the phosphonic acids under hydrolytic conditions [28]. Phosphonates 1c

• . Concentration of the reaction mixture furnished phosphonic acids 1a–3a and 6a, 7a in good yields (Table 1, entries 1 and 2) while methanolysis of compounds 4b and 5b resulted in a mixture of the desired phosphonic acids 4a and 5a, HEMA (22) and the phosphonic acids 20 and 21, respectively (entries 4 and 5). In

• phosphonates 4b and 5b with methanol in the presence of aqueous ammonia (reaction time 1 h) to obtain the target phosphonic acids 4a and 5a in quantitative yields as their ammonium salts. Conclusion In conclusion we were able to prepare new bifunctional monomers bearing a methacrylate function and a

A novel and efficient method to prepare 2-aryltetrahydrofuran-2-ylphosphonic acids

• Vsevolod V. Komissarov,
• Anatoly M. Kritzyn and
• Jouko J. Vepsäläinen

Beilstein J. Org. Chem. 2010, 6, No. 63, doi:10.3762/bjoc.6.63

• result of anchimeric assistance of the phosphonic acid group. Keywords: 4-chloro-1-aryl-1-butanones; cyclization; furan; heterocycle; phosphonic acids; Introduction Our laboratory has conducted systematic evaluation of polymethylene derivatives of nucleic bases with various terminal functional groups

• in Scheme 1. The yields of the prepared cyclic compounds 2b–e are summarized in Table 1. The synthesized phosphonic acids 2 can be easily converted into diethyl esters 4 by refluxing in triethyl orthoformate in the presence of p-TSA [12]. Previously, these esters 4 were prepared directly from 1a–d by

• refluxing in an excess of P(OEt)3. However, this procedure provides high yields of 2-aryltetrahydrofuran-2-ylphosphonic acid esters 4 only if the starting ketones have electron donating substituents at the para-position of the aromatic ring [13][14]. The structures of phosphonic acids 2 were established

Molecular recognition of organic ammonium ions in solution using synthetic receptors

• Andreas Späth and
• Burkhard König

Beilstein J. Org. Chem. 2010, 6, No. 32, doi:10.3762/bjoc.6.32

N-alkyl-N-(phosphonoethyl) substituted (meth)acrylamides – new adhesive monomers for self-etching self-priming one part dental adhesive

• Joachim E. Klee and
• Uwe Lehmann

Beilstein J. Org. Chem. 2009, 5, No. 72, doi:10.3762/bjoc.5.72

• cleavage. Adhesion of phosphonic acids 3 One of the fundamental assumptions is that the adhesion of self-etching adhesives on enamel mainly depends on the acidity and consequently on the etch pattern that is formed. With the help of REM investigations the etch pattern of Conditioner 36, monomer 3g and

• Clearfil SE Primer are compared in Figure 2a–Figure 2c which illustrates that it seems possible to generate a deeper and more structured etch pattern than the one caused by the Clearfil SE Primer. However, the strong etch pattern of Conditioner 36 is not surpassed. The adhesion of phosphonic acids 3c, 3e

• (Dentsply) mainly consist of phosphoric acid. Clearfil SE (Kuraray) is a water-free two-part self-etching adhesive containing 10-(methacryloyloxy)decyl dihydrogen phosphate. The two (meth)acrylamido phosphonic acids 3a and 3b (Table 1) were synthesized according to the following general procedure. 1. (Meth

Synthesis of phosphonate and phostone analogues of ribose-1-phosphates

• Pitak Nasomjai,
• David O'Hagan and
• Alexandra M. Z. Slawin

Beilstein J. Org. Chem. 2009, 5, No. 37, doi:10.3762/bjoc.5.37

• of 23a and 23b with TMSBr and then TFA yielded the free phosphonic acids which were neutralised with cyclohexylamine [12] to generate the non-hygroscopic salts 8a, b and 9a, b which could be recrystallised from MeOH/acetone. X-Ray structure analysis of a suitable crystal of the fluoromethyl