Synthesis of medium and large phostams, phostones, and phostines

• Jiaxi Xu

Beilstein J. Org. Chem. 2023, 19, 687–699, doi:10.3762/bjoc.19.50

• -azaphosphocin-1(4H)-yl)acetate (4), respectively, in the presence of the Grubbs first generation catalyst via ring closing metathesis. The products 3 and 4 were further transformed to antitumor agents 5, 6, 9 and 10 through aminolysis with O-TMS hydroxylamine or hydrogenolysis followed by aminolysis with O-TMS

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

• of 2-ethoxy-1-methyl-γ-phosphonolactam (6) for potential insecticides. Diethyl 3-bromopropylphosphonate (3) was first monochlorinated with phosphorus pentachloride in carbon tetrachloride followed by aminolysis with methylamine, affording ethyl N-methyl-(3-bromopropyl)phosphonamidate (5). Compound 5

• -phenyl-3-phenylamino-2,3,3a,9a-tetrahydro-4H-1,2-azaphospholo[5,4-b]chromen-4-one (215) in 44% yield through the Michael addition and subsequent intramolecular aminolysis (Scheme 34) [15]. The products are potential anti-inflammatory agents. In 2013, to develop potent anti-inflammatory agents, Abdou and

• intramolecular aminolysis. Under similar conditions, the reaction of 2-imino-2H-chromene-3-carboxamide (228) and tris(2-chloroethyl) phosphite (232) generated 4-amino-1-(2-chloroethoxy)-9b-hydrochromeno[4,3-c][1,2]azaphosphol-3(2H)-one 1-oxide (233) in 30% yield through the Michael addition and subsequent

Synthesis and HDAC inhibitory activity of pyrimidine-based hydroxamic acids

• Virginija Jakubkiene,
• Gabrielius Ernis Valiulis,
• Markus Schweipert,
• Asta Zubriene,
• Daumantas Matulis,
• Franz-Josef Meyer-Almes and
• Sigitas Tumkevicius

Beilstein J. Org. Chem. 2022, 18, 837–844, doi:10.3762/bjoc.18.84

• followed by aminolysis of the obtained esters with hydroxylamine. Oxidation of the 2-methylthio group to the methylsulfonyl group and following treatment with amines resulted in the formation of the corresponding 2-amino-substituted derivatives, the ester group of which reacted with hydroxylamine to give

• both the HDAC4 and HDAC8 isoforms, with an IC50 of 16.6 µM and 1.2 µM, respectively. Keywords: alkylation; aminolysis; HDAC inhibitors; hydroxamic acid; pyrimidine; Introduction Histone deacetylases (HDACs) are a family of intracellular proteins responsible for removing acetyl groups in histones

• ][28][29][30]. In this work, the pyrimidine-based hydroxamic acids were synthesized by aminolysis of the corresponding esters. The required esters 3 and 4 were obtained by alkylation of pyrimidinones 1 and 2 with ethyl 2-bromoethanoate in triethylamine in the presence of tetrabutylammonium bromide at

Recent advances in organocatalytic asymmetric aza-Michael reactions of amines and amides

• Pratibha Sharma,
• Raakhi Gupta and
• Raj K. Bansal

Beilstein J. Org. Chem. 2021, 17, 2585–2610, doi:10.3762/bjoc.17.173

• tertiary amine-thiourea catalyst (cat. 82). This cascade reaction afforded aza-Michael adducts in 77–92% yields with high ee (up to 90%) (Table 19) [55]. Du et al. developed an enantioselective catalytic tandem aminolysis/aza-Michael addition for the asymmetric total synthesis of two natural Apocynaceae

Icilio Guareschi and his amazing “1897 reaction”

• Gian Cesare Tron,
• Alberto Minassi,
• Giovanni Sorba,
• Mara Fausone and
• Giovanni Appendino

Beilstein J. Org. Chem. 2021, 17, 1335–1351, doi:10.3762/bjoc.17.93

• to name type-I Guareschi pyridone synthesis the two-component reaction between a β-aminocarbonyl and a cyanoacetic ester, a reaction first reported in 1893 [34]. It is a classic combination of a Knoevenagel condensation and ester aminolysis typical for many heterocyclic syntheses. The type-II

Beyond ribose and phosphate: Selected nucleic acid modifications for structure–function investigations and therapeutic applications

• Christopher Liczner,
• Kieran Duke,
• Gabrielle Juneau,
• Martin Egli and
• Christopher J. Wilds

Beilstein J. Org. Chem. 2021, 17, 908–931, doi:10.3762/bjoc.17.76

• kinetics and higher solubility in organic solvents, useful for automated synthesis, such as the Beaucage reagent [86]. Conveniently, during deprotection of the support-bound oligonucleotide, aminolysis removes the β-thiobenzoylethyl group from the backbone to generate the free PS2-modified oligonucleotide

Valorisation of plastic waste via metal-catalysed depolymerisation

• Francesca Liguori,
• Carmen Moreno-Marrodán and
• Pierluigi Barbaro

Beilstein J. Org. Chem. 2021, 17, 589–621, doi:10.3762/bjoc.17.53

• (a solvent is the reagent and solvolyses include hydrolysis, glycolysis, alcoholysis and aminolysis) and hydrogenolysis reactions (H2 as reagent). Hydrolysis (sometimes called hydrocracking) is in between thermochemical and chemolytic processing, basically consisting of depolymerisation by the

• (DEG), dipropylene glycol (DPG)) aminolysis (2-aminoethanol, 3-amino-1-propanol, ethylenediamine). Advantages of catalytic processes are obvious and can be witnessed in the hydrolysis and the glycolysis reactions of poly(ethylene terephthalate) (PET) [82][83]. Representative data are reported in

• conditions. For instance, for polyesters, alcoholysis may provide mixed monomers formally derived from transesterification reactions [89][90], while aminolysis provides amides and alcohols [91][92]. In the search of “greener” technologies for plastic recycling, catalytic hydrogenolysis processes have been

Synthetic strategies of phosphonodepsipeptides

• Jiaxi Xu

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

• -protected phosphonodepsitetrapeptides 63 were obtained and further transformed to the N-protected phosphonodepsipeptide ester lithium salts 58 after aminolysis with tertiary butylamine and treatment with Dowex-Li+ (Scheme 10) [26]. Synthesis of β-phosphonodepsipeptides To develop iminocyclitol-based small

• -glutamic acid (80) was first transformed to the corresponding dimethyl phosphonate 81. After aminolysis and chlorination the corresponding phosphonochloridate 83 was obtained. The latter was further reacted with diethyl 2-hydroxyglutarate (84), affording γ-phosphonodepsidipeptide 79 in only 6.7% yield

• reaction of benzyl carbamate, aldehydes, and trialkyl phosphites in acetyl chloride gave rise to N-Cbz-1-aminoalkylphosphonates [40]. When the reactions were conducted in benzene followed by an aminolysis or alcoholysis, phosphonamidates [41], phosphonopeptide [42], and mixed esters [43][44] were obtained

Progress in the total synthesis of inthomycins

• Bidyut Kumar Senapati

Beilstein J. Org. Chem. 2021, 17, 58–82, doi:10.3762/bjoc.17.7

• with HF·pyridine in acetonitrile [22] gave double silyl deprotected triene (+)-132 which was then converted into inthomycin B ((+)-2) via aminolysis of the corresponding pentaflurophenyl ester (+)-133. The synthetic inthomycin B ((+)-2) showed well-matched spectroscopic properties with that of both

Recent synthesis of thietanes

• Jiaxi Xu

Beilstein J. Org. Chem. 2020, 16, 1357–1410, doi:10.3762/bjoc.16.116

• corresponding mesylated thietane-fused nucleosides 128 and 131, which generated the final thietane-fused nucleosides 129 and 132 after the reactions with benzoic acid and CsF and subsequent aminolysis [54] (Scheme 25). The methyl 2,3-anhydro-α- and β-D-ribofuranosides 133 were used as starting materials and

Efficient synthesis of piperazinyl amides of 18β-glycyrrhetinic acid

• Dong Cai,
• ZhiHua Zhang,
• Yufan Meng,
• KaiLi Zhu,
• LiYi Chen,
• ChangXiang Yu,
• ChangWei Yu,
• ZiYi Fu,
• DianShen Yang and
• YiXia Gong

Beilstein J. Org. Chem. 2020, 16, 798–808, doi:10.3762/bjoc.16.73

• ]. The estimated structure was supported by crystal structures of similar structural compounds [23]. Figure 2b suggests that the steric hindrance around the C30 ester group of intermediate 6 has a remarkable influence on the aminolysis reaction. The mechanism of the aminolysis reaction revealed that a

• 48 h. In contrast, 1-Boc-piperazine (2.5 equiv) exhibited high performance, thereby leading to the preparation of compound 8 in 95% yield (Table 2, entry 8), which essentially completed conversion of the intermediate 6 within 10 h. Alternatively, the aminolysis reaction of the isolated intermediate 6

• intermediate 6; b) Possible aminolysis process. Crystal structure of conpound 18. Synthesis of compound 4. Reagents and conditions: (a) Ac2O, NEt3, DMF (cat.), DCM, 25 °C, 1 day; (b) oxalyl chloride, NEt3, DMF (cat.), DCM, 25 °C, 5 h, then piperazine, DCM, NEt3, DMAP, 0/25 °C, 30 min. Synthesis of compound 4

Towards the total synthesis of chondrochloren A: synthesis of the (Z)-enamide fragment

• Jan Geldsetzer and
• Markus Kalesse

Beilstein J. Org. Chem. 2020, 16, 670–673, doi:10.3762/bjoc.16.64

• provided alcohol 11 in an excellent yield which was subjected to aminolysis to provide amide 3 in seven steps and an overall yield of 16% [16][17][18][19][20]. Synthesis of (Z)-bromide 4 For the synthesis of (Z)-bromide 4 we chose a palladium-catalyzed, stereoselective dehalogenation as the key step

Architecture and synthesis of P,N-heterocyclic phosphine ligands

• Wisdom A. Munzeiwa,
• Bernard Omondi and
• Vincent O. Nyamori

Beilstein J. Org. Chem. 2020, 16, 362–383, doi:10.3762/bjoc.16.35

• solvents may substantially influence reaction kinetics and product formation [102]. Biricik et al. [98] reported the preparation of polydentate aminophosphine 111 through a condensation–elimination–aminolysis reaction (Scheme 21). Reactions performed in diethyl ether and toluene resulted in bisphosphine

N-(1-Phenylethyl)aziridine-2-carboxylate esters in the synthesis of biologically relevant compounds

• Iwona E. Głowacka,
• Aleksandra Trocha,
• Andrzej E. Wróblewski and
• Dorota G. Piotrowska

Beilstein J. Org. Chem. 2019, 15, 1722–1757, doi:10.3762/bjoc.15.168

• elaborated although they are more complex [23][24][25]. Enzymatically-catalyzed aminolysis of a mixture of (2R,1'R)-5a and (2S,1'R)-5a provided diastereoisomerically pure (de >99%) methyl ester (2R,1'R)-5a and amide (2S,1'R)-8 (Figure 2). The same selectivity was observed for (2R,1'S)-5a and (2S,1'S)-5a and

Electrophilic oligodeoxynucleotide synthesis using dM-Dmoc for amino protection

• Shahien Shahsavari,
• Dhananjani N. A. M. Eriyagama,
• Bhaskar Halami,
• Vagarshak Begoyan,
• Marina Tanasova,
• Jinsen Chen and
• Shiyue Fang

Beilstein J. Org. Chem. 2019, 15, 1116–1128, doi:10.3762/bjoc.15.108

• . The HPLC profiles of crude and pure 30c are given in Figure 4. Its PAGE and MALDI–TOF MS images are in Figure 5 and Figure 6, respectively. All analytical data for 30d,e are given in Supporting Information File 2. It is noted that aminolysis and hydrolysis of the sensitive groups in the ODNs, which

Catalyst-free synthesis of 4-acyl-NH-1,2,3-triazoles by water-mediated cycloaddition reactions of enaminones and tosyl azide

• Lu Yang,
• Yuwei Wu,
• Yiming Yang,
• Chengping Wen and
• Jie-Ping Wan

Beilstein J. Org. Chem. 2018, 14, 2348–2353, doi:10.3762/bjoc.14.210

• intermediate 5 can undergo aminolysis and/or hydrolysis to provide the target products 3. The participation of water throughout the reaction also explains the high efficiency of the method using water as reaction medium. Conclusion In summary, by means of the cycloaddition reactions between tertiary enaminones

Binding abilities of polyaminocyclodextrins: polarimetric investigations and biological assays

• Marco Russo,
• Daniele La Corte,
• Annalisa Pisciotta,
• Serena Riela,
• Rosa Alduina and
• Paolo Lo Meo

Beilstein J. Org. Chem. 2017, 13, 2751–2763, doi:10.3762/bjoc.13.271

• -free aminolysis at 60 °C for 48 h of the heptakis(6-deoxy-6-iodo)-β-CD with a 140-fold mole-to-mole excess of the proper linear polyamine, i.e., 3-(N,N-dimethylamino)propylamine (A1) for CD1, bis(3-aminopropyl)methylamine (A2) for CD2 and bis-1,2-[(3-aminopropyl)amino]ethane (A3) for CD3. The products

Conjugated nitrosoalkenes as Michael acceptors in carbon–carbon bond forming reactions: a review and perspective

• Yaroslav D. Boyko,
• Valentin S. Dorokhov,
• Alexey Yu. Sukhorukov and
• Sema L. Ioffe

Beilstein J. Org. Chem. 2017, 13, 2214–2234, doi:10.3762/bjoc.13.220

• -hydroxytryptophan derivative 79 using aminolysis and reduction with (CH3)3N·BH3 complex [47][49][69]. Acylation of 79 with pyruvoyl chloride gave amide 80, which was converted into dioxopiperazine 81 upon the action of trifluoroacetic acid. Subsequent water elimination furnished the title neoechinulin B analogue 77

A mechanochemical approach to access the proline–proline diketopiperazine framework

• Nicolas Pétry,
• Hafid Benakki,
• Eric Clot,
• Pascal Retailleau,
• Farhate Guenoun,
• Fatima Asserar,
• Chakib Sekkat,
• Thomas-Xavier Métro,
• Jean Martinez and
• Frédéric Lamaty

Beilstein J. Org. Chem. 2017, 13, 2169–2178, doi:10.3762/bjoc.13.217

• aminolysis. This strategy has been extensively used [1], involving milder conditions and provides access to unsymmetrical dipeptides and DKPs. Furthermore, substituted prolines could be obtained by nucleophilic substitution of benzylamine from dimethyl dibromoadipate, allowing the addition of functional

Block copolymers from ionic liquids for the preparation of thin carbonaceous shells

• Sadaf Hanif,
• Bernd Oschmann,
• Dmitri Spetter,
• Muhammad Nawaz Tahir,
• Wolfgang Tremel and
• Rudolf Zentel

Beilstein J. Org. Chem. 2017, 13, 1693–1701, doi:10.3762/bjoc.13.163

• (see Figure S5, Supporting Information File 1). In the last step the aminolysis of the reactive ester block with dopamine was performed, which leads also to a partial removal of the thioester end group. For this purpose a large excess of dopamine was applied. The 1H NMR spectrum in Figure 3 proves the

A speedy route to sterically encumbered, benzene-fused derivatives of privileged, naturally occurring hexahydropyrrolo[1,2-b]isoquinoline

• Olga Bakulina,
• Alexander Ivanov,
• Vitalii Suslonov,
• Dmitry Dar’in and
• Mikhail Krasavin

Beilstein J. Org. Chem. 2017, 13, 1413–1424, doi:10.3762/bjoc.13.138

• ) N-acylation of the imine component followed by intramolecular Mannich reaction or (b) Mannich-type addition of the HPA enolate to a protonated imine component followed by intramolecular aminolysis of the cyclic anhydride moiety in Mannich adduct 13 (Scheme 3) [1]. Investigation of the CCR leading to

Synthesis of ribavirin 2’-Me-C-nucleoside analogues

• Fanny Cosson,
• Aline Faroux,
• Jean-Pierre Baltaze,
• Jonathan Farjon,
• Régis Guillot,
• Jacques Uziel and
• Nadège Lubin-Germain

Beilstein J. Org. Chem. 2017, 13, 755–761, doi:10.3762/bjoc.13.74

• with tetrabutylammonium fluoride leading to the mixture of diols 17 and 18 in quantitative yield which were easily separated (Scheme 3). Finally, the aminolysis of compound 17 followed by catalytic hydrogenolysis in the presence of palladium chloride led to the desired compound 3 [22] (Scheme 4

New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation

• Pavel Nagorny and
• Zhankui Sun

Beilstein J. Org. Chem. 2016, 12, 2834–2848, doi:10.3762/bjoc.12.283

• activation is accomplished through a C–H hydrogen bond with cyclic ester carbonyls. The following study by the Bibal group described the use of catalysts L11 as hydrogen bond donors for the activation of epoxides toward ring-opening aminolysis with amines (Scheme 6) [54]. Significant rate enhancement was

Potent triazine-based dehydrocondensing reagents substituted by an amido group

• Munetaka Kunishima,
• Daiki Kato,
• Nobu Kimura,
• Masanori Kitamura,
• Kohei Yamada and
• Kazuhito Hioki

Beilstein J. Org. Chem. 2016, 12, 1897–1903, doi:10.3762/bjoc.12.179

• intermediate in Scheme 1b, basically shows the same reactivity for aminolysis and alcoholysis regardless of which tertiary amine 5 was used (Scheme 1b,d). Therefore, it is reasonable to modify the activity of the 1,3,5-triazine ring that is involved in both steps shown in Scheme 1b by introducing another

• spectra of crude mixtures obtained from the reactions using III (THF solvent, Table 1a) or VII (THF solvent, Table 1c) and identified N-acetyl-2-phenylethylamine in 29% and 25% yields, respectively. This byproduct was formed by the aminolysis of the N-methylacetamido group on the triazine ring by 2a. A

• similar phenomenon was observed for IV or VIII in THF. Notably, such a byproduct was not obtained in the case of V, IX, VI, and X. In MeOH, no such byproduct resulting from aminolysis was observed in all the cases. We employed X to further study the synthesis of various amides with a particular focus on

Towards the total synthesis of keramaphidin B

• Pavol Jakubec,
• Alistair J. M. Farley and
• Darren J. Dixon

Beilstein J. Org. Chem. 2016, 12, 1096–1100, doi:10.3762/bjoc.12.104

• turn be synthesised by an aminolysis/oxidation/olefination sequence of the terminal alcohol 6, following traceless nitro group removal. 5-Nitropiperidin-2-one 6 in turn could be accessed by a nitro-Mannich lactamisation cascade reaction between Michael adduct 7, formaldehyde and a suitable primary

• piperidin-2-one 17 in 71% yield. Lactonisation under Lewis acidic conditions afforded spirocyclic malonamate 18 possessing the correct relative stereochemistry for keramaphidin B, in 84% yield. Aminolysis under neat conditions with hex-5-en-1-amine (19) gave the primary alcohol 20 (67% yield), which was

• compromised during a subsequent three-step nitro-Mannich lactamisation cascade, aminolysis and lactonisation sequence. Further manipulation of the pendant functional groups allowed the synthesis of target compound 5 bearing two alkynes and two terminal alkenes for successive RCM reactions to construct the 11