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

• Poznań, Uniwersytetu Poznańskiego 10, 61-614 Poznań, Poland 10.3762/bjoc.19.33 Abstract In this paper, we present the solvolysis reaction of dipeptide analogues of fluorinated aminophosphonates with simultaneous quantitative deprotection of the amino group. To the best of our knowledge, this work is the

• first reported example of the application of fluorinated aminophosphonates in cathepsin C inhibition studies. The new molecules show moderate inhibition of the cathepsin C enzyme, which opens the door to consider them as potential therapeutic agents. Overall, our findings provide a new avenue for the

• development of fluorinated aminophosphonate-based inhibitors. Keywords: aminophosphonates; cathepsin C; dipeptide; fluorine; solvolysis; Introduction Cathepsin C, also known as dipeptidyl peptidase I (DPPI) belongs to the family of lysosomal cysteine proteases encompassing 11 human enzymes (cathepsins B, C

Advances in mercury(II)-salt-mediated cyclization reactions of unsaturated bonds

• Sumana Mandal,
• Raju D. Chaudhari and
• Goutam Biswas

Beilstein J. Org. Chem. 2021, 17, 2348–2376, doi:10.3762/bjoc.17.153

• diastereomers 30a,b and 32a,b was obtained, respectively. trans-Isomers were formed as major products over cis-isomers (Scheme 12) [52]. Five- and six-membered N-containing heterocyclic phosphonates were synthesized by intramolecular cyclization of alkenyl α-aminophosphonates in a similar way with the treatment

• cyclization of alkenyl α-aminophosphonates. Cyclization of 4-cycloocten-1-ol with Hg(OAc)2 forming fused bicyclic products. trans-Amino alcohol formation through Hg(II)-salt-mediated cyclization. Hg(OAc)2-mediated 2-aza- or 2-oxa-bicyclic ring formations. Hg(II)-salt-induced cyclic peroxide formation. Hg(OAc

Efficient synthesis of dipeptide analogues of α-fluorinated β-aminophosphonates

• Marcin Kaźmierczak and
• Henryk Koroniak

Beilstein J. Org. Chem. 2020, 16, 756–762, doi:10.3762/bjoc.16.69

• Herein, we present an efficient synthesis of dipeptide analogues of α-fluorinated β-aminophosphonates. Each step of the synthesis was optimized to provide excellent yields. Moreover, the absolute configuration of the obtained compounds was determined by X-ray analysis, which proved the stereochemistry

• that was proposed based on NMR studies. Keywords: dipeptide analogues; fluorinated aminophosphonates; fluorine; nucleophilic fluorination; phosphorus; Introduction The chemistry of fluorinated aminophosphonates is constantly being developed, mainly due to their wide spectra of applications. What is

• more, they are valuable targets for biomedical investigations. Due to the strong interest in this type of compounds, several marvelous reviews about the synthesis and application of fluorinated aminophosphonates have been published in recent years [1][2][3]. To the best of our knowledge, among the many

The synthesis of α-aryl-α-aminophosphonates and α-aryl-α-aminophosphine oxides by the microwave-assisted Pudovik reaction

• Erika Bálint,
• Ádám Tajti,
• Anna Ádám,
• István Csontos,
• Konstantin Karaghiosoff,
• Mátyás Czugler,
• Péter Ábrányi-Balogh and
• György Keglevich

Beilstein J. Org. Chem. 2017, 13, 76–86, doi:10.3762/bjoc.13.10

• Economics, 1521 Budapest, Hungary Department Chemie, Ludwig-Maximilians-Universität München, 81377 München, Germany Hungarian Academy of Sciences, Research Centre for Natural Sciences, Institute of Organic Chemistry, 1519 Budapest, Hungary 10.3762/bjoc.13.10 Abstract A family of α-aryl-α-aminophosphonates

• was evaluated by DFT calculations. Two α-aminophosphonates were subjected to an X-ray study revealing a racemic dimer formation made through a N–H···O=P intermolecular hydrogen bridges pair. Keywords: α-aryl-α-aminophosphine oxides; α-aryl-α-aminophosphonates; microwave; Pudovik reaction

• ; Introduction α-Aminophosphonates and related derivatives, considered as the structural analogues of α-amino acids, have significant importance, especially in medicinal [1][2][3] and agricultural chemistry [4][5], due to their potential biological activity. The two major synthetic routes towards α

First DMAP-mediated direct conversion of Morita–Baylis–Hillman alcohols into γ-ketoallylphosphonates: Synthesis of γ-aminoallylphosphonates

• Marwa Ayadi,
• Haitham Elleuch,
• Emmanuel Vrancken and
• Farhat Rezgui

Beilstein J. Org. Chem. 2016, 12, 2906–2915, doi:10.3762/bjoc.12.290

• biological potentials. Aminophosphonates and their derivatives [22][23][24][25][26] are thus recognized as promising compounds and a new class of drugs that are widely used in a variety of commercial applications. Indeed, they are known to influence various biochemical processes in plants, modifying or

• inhibiting them, or to have biological activities as for example antibiotics, antibacterial, anti-cancer or antithrombotic agents [22][23][24][25][26]. In this context, α-aminophosphonates have particularly attracted considerable attention owing to their biological activities [27][28][29][30][31][32][33

• ] since they are considered as important surrogates for α-amino carboxylic acids, peptide mimics as well as versatile intermediates for the design of potential anticancer agents. β-Aminophosphonates present also an important place among the various compounds containing both a P–C bond and an amino group

Enantioselective addition of diphenyl phosphonate to ketimines derived from isatins catalyzed by binaphthyl-modified organocatalysts

• Hee Seung Jang,
• Yubin Kim and
• Dae Young Kim

Beilstein J. Org. Chem. 2016, 12, 1551–1556, doi:10.3762/bjoc.12.149

• isatins has been achieved. This method affords practical and efficient access to chiral 3-amino-3-phosphonyl-substituted oxindole derivatives in high yields with excellent enantioselectivities (up to 99% ee). Keywords: 3-amino-3-phosphonyl-substituted oxindole; α-aminophosphonates; bifunctional

• organocatalyst; ketimines; organocatalysis; squaramide; Introduction α-Aminophosphonate derivatives are important compounds as structural mimics of natural α-amino acids [1][2][3]. Chiral α-aminophosphonates have been shown a wide range of biological activities including antibacterial [4] and anticancer

• properties [5], enzyme inhibition [6], peptide mimetic function [7], and herbicidal properties [8]. Since the biological activity of α-aminophosphonate derivatives is dependent upon the chirality of the α-position to the phosphorus atom, asymmetric synthesis of α-aminophosphonates has received considerable

Multicomponent reactions: A simple and efficient route to heterocyclic phosphonates

• Mohammad Haji

Beilstein J. Org. Chem. 2016, 12, 1269–1301, doi:10.3762/bjoc.12.121

• modifications The one-pot three-component reaction between aldehydes 19 (or ketones), amines 20 and dialkyl phosphonates 21 to afford α-aminophosphonates 22 is traditionally known as the Kabachnik–Fields reaction. This reaction was first reported in 1952 by Kabachnik, Medved and Fields (Scheme 6) [29][30]. Due

• to their wide range of biological activities, α-aminophosphonates have been extensively investigated and several reviews about their syntheses through the Kabachnik–Fields reaction have been reported [31][32][33]. However, an important feature of this reaction is that it provides an efficient route

• -aminophosphonates. Unfortunately there are only a few examples of Kabachnik–Fields reactions of heterocycloalkanones in the literature. The tetra(tert-butyl)phthalocyanine–AlCl complex catalyzed three component reaction of N-Boc-piperidin-4-one (23) with (EtO)2P(O)H (24) and benzylamine (25) afforded the cyclic α

Synthesis, fluorescence properties and the promising cytotoxicity of pyrene–derived aminophosphonates

• Jarosław Lewkowski,
• Maria Rodriguez Moya,
• Anna Wrona-Piotrowicz,
• Janusz Zakrzewski,
• Renata Kontek and
• Gabriela Gajek

Beilstein J. Org. Chem. 2016, 12, 1229–1235, doi:10.3762/bjoc.12.117

• further reaction without purification. Aminophosphonates 3Aa–h, 3Ba–e and 3Ca–d, 3Cg have been synthesized via an aza-Pudovik reaction [22], i.e., the addition of the appropriate phosphite 2A–C to the azomethine bond of the Schiff bases 1a–h. Nevertheless, the important modifications had to be introduced

• solution was to apply phosphites simultaneously as solvents and reactants, which however forced to use them in a high excess. This necessity resulted in troubles with purification, implicating a particular approach to each case. Dimethyl aminophosphonates 3Aa–Ah were purified by washing their

• additionally carried out. The isolation and purification of diethyl aminophosphonates 3Ba–e required a different method. To isolate them, the crude reaction mixtures were dissolved in a minimum amount of diethyl ether and triturated until a yellow precipitate formed. This operation was repeated twice

Friedel–Crafts-type reaction of pyrene with diethyl 1-(isothiocyanato)alkylphosphonates. Efficient synthesis of highly fluorescent diethyl 1-(pyrene-1-carboxamido)alkylphosphonates and 1-(pyrene-1-carboxamido)methylphosphonic acid

• Anna Wrona-Piotrowicz,
• Janusz Zakrzewski,
• Anna Gajda,
• Tadeusz Gajda,
• Anna Makal,
• Arnaud Brosseau and
• Rémi Métivier

Beilstein J. Org. Chem. 2015, 11, 2451–2458, doi:10.3762/bjoc.11.266

• dimers were already observed in the crystals of some aminophosphonates [34]. The dimers form strings along the crystallographic [001] direction, bound by relatively short (H···O distances of less than 2.75 Å) and intermolecular hydrogen C–H···O bonds (Table 4). On the other hand, the pyrenyl moieties

A new method for the synthesis of α-aminoalkylidenebisphosphonates and their asymmetric phosphonyl-phosphinyl and phosphonyl-phosphinoyl analogues

• Anna Kuźnik,
• Roman Mazurkiewicz,
• Mirosława Grymel,
• Katarzyna Zielińska,
• Jakub Adamek,
• Ewa Chmielewska,
• Marta Bochno and
• Sonia Kubica

Beilstein J. Org. Chem. 2015, 11, 1418–1424, doi:10.3762/bjoc.11.153

• Discussion Recently we developed a simple and effective two-step transformation of N-acyl-α-amino acids into their phosphonic analogues that allows for easy access to a variety of structurally diversified N-acyl-α-aminophosphonates 5 (Scheme 1) [36][37]. Despite the electron-withdrawing inductive effect of N

• -acylamino- and dialkoxyphosphonyl groups of 1-aminophosphonates 5, the electrophilicity of these compounds’ α-carbon is displayed only after functionalisation of the α-position with a nucleofuge group, e.g. by α-bromination of 1-aminophosphonates with N-bromosuccinimide [28][38][39][40][41] or by

• alkoxylation or aryloxylation of this position [20][29][30]. As we demonstrated, electrophilic activation of the α-carbon of 1-aminophosphonates can easily be achieved by electrochemical α-methoxylation of these compounds in methanol, mediated with NaCl (Scheme 1, Table 2). α-Methoxylations were carried out in

Synthesis of fluorescent (benzyloxycarbonylamino)(aryl)methylphosphonates

• Michał Górny vel Górniak,
• Anna Czernicka,
• Piotr Młynarz,
• Waldemar Balcerzak and
• Paweł Kafarski

Beilstein J. Org. Chem. 2014, 10, 741–745, doi:10.3762/bjoc.10.68

• (benzyloxycarbonylamino)(aryl)methylphosphonic acids is described by means of the Oleksyszyn reaction. The library was enlarged by the application of a Suzuki–Miayra approach and by preparation of mixed esters. Keywords: aminophosphonates; Oleksyszyn reaction; organophosphorus; Z-aminophosphonate esters; Introduction

• procedure we have synthesized a small library of diaryl esters of aromatic Z-aminophosphonates (Scheme 2). They were obtained in satisfactory yields (55–84%). When using 5-anthracenylaldehyde a complex mixture of products was obtained and the product was isolated by column chromatography in a low yield of 1

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

• of its strong electronegativity. This enables modulation of the lipophilicity profile, of electrostatic interactions with the target structure and inhibition of some metabolic pathways [7][8][9]. Data concerning the biological activity and synthetic approaches toward fluorinated aminophosphonates

Synthesis and quantitative structure–activity relationship study of substituted imidazophosphor ester based tetrazolo[1,5-b]pyridazines as antinociceptive/anti-inflammatory agents

• Wafaa M. Abdou,
• Neven A. Ganoub and
• Eman Sabry

Beilstein J. Org. Chem. 2013, 9, 1730–1736, doi:10.3762/bjoc.9.199

• of our continued interest in the development of convenient synthetic approaches to β-enamino- and α-aminophosphonates with anti-inflammatory properties [13][14][15][16][17][18][19][20], we recently successfully synthesized a series of mono- and bisphosphonate-based tetrazolo[1,5-a]quinolines with

• experiments; the antinociceptive capacity was expressed as the percentage change compared to writhing controls. The results shown in Table 1 indicated that β-enaminobisphosphonate 15 is the most potent antinociceptive structure (86.4%), which was followed by α-aminophosphonates 13 (84%) and 7 (81%). Indeed

α,β-Aziridinylphosphonates by lithium amide-induced phosphonyl migration from nitrogen to carbon in terminal aziridines

• David. M. Hodgson and
• Zhaoqing Xu

Beilstein J. Org. Chem. 2010, 6, 978–983, doi:10.3762/bjoc.6.110

• excellent yield (89%), and without any degradation of enantiopurity (>99% ee, as determined by chiral HPLC analysis of the benzoyl derivative 17). Hydrogenolytic ring-opening of aziridinylphosphonates provides an attractive entry to α- or β-aminophosphonates [6]. α,β-Aziridinylphosphonates bearing a β-aryl

• group undergo cleavage at the formally benzylic C–N bond, leading to α-aminophosphonates. With β-alkyl groups, regioselectivity is influenced by the presence or absence of an N-substituent. N-Ts Cis-β-alkyl-substituted aziridinylphosphonates give β-aminophosphonates [32], whereas both N-Boc cis- and

• trans-β-alkyl-substituted aziridinylphosphonates lead to α-aminophosphonates. For example, hydrogenolysis of N-Boc trans-aziridinylphosphonate 14 (Bn instead of the C4H9 group) using 10% Pd/C (H2 (1 atm), EtOH, 12 h) has been reported to give the corresponding N-Boc α-aminophosphonate (63%) [31]. In the