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

Design, synthesis, and evaluation of chiral thiophosphorus acids as organocatalysts

• Karen R. Winters and
• Jean-Luc Montchamp

Beilstein J. Org. Chem. 2022, 18, 1471–1478, doi:10.3762/bjoc.18.154

• cross-coupling [34] in excellent yield. Esterification of 6 with monomethyl H-phosphonate tert-butylamine salt [35] resulted in the mixed H-phosphonate ester 7 in excellent yield. Cyclization using our homolytic aromatic substitution methodology [36] gave P-heterocycle 8 in modest yield. Other methods

Cationic oligonucleotide derivatives and conjugates: A favorable approach for enhanced DNA and RNA targeting oligonucleotides

• Mathias B. Danielsen and
• Jesper Wengel

Beilstein J. Org. Chem. 2021, 17, 1828–1848, doi:10.3762/bjoc.17.125

• (Table 8) [106]. In contrast to the dinucleotide which was synthesized by solution phase chemistry [105], the modified ONs were synthesized on solid-support employing H-phosphonate chemistry, followed by the oxidative coupling with the appropriate diamines to give the desired N-ethyl-2-morpholino

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

• '-aminonucleoside couples to the 5'-H-phosphonate in the presence of a base (Scheme 1) [64]. In comparison with natural phosphodiester oligonucleotides, these modified oligonucleotides display improved nuclease resistance and an enhanced duplex thermal stability of 2.3–2.6 °C per linkage independent of nucleotide

Silver-catalyzed synthesis of β-fluorovinylphosphonates by phosphonofluorination of aromatic alkynes

• Yajing Zhang,
• Qingshan Tian,
• Guozhu Zhang and
• Dayong Zhang

Beilstein J. Org. Chem. 2020, 16, 3086–3092, doi:10.3762/bjoc.16.258

• extremely low yield. Another H-phosphonate, namely dimethyl phosphite, was a suitable substrate for this transformation and provided the products 3 in good yield (Scheme 3). The well-known radical-trapping reagent 2,2,6,6-tetramethylpiperidine-N-oxyl (TEMPO) was used to gain an insight into the reaction

Nonenzymatic synthesis of anomerically pure, mannosyl-based molecular probes for scramblase identification studies

• Giovanni Picca,
• Markus Probst,
• Simon M. Langenegger,
• Oleg Khorev,
• Peter Bütikofer,
• Anant K. Menon and
• Robert Häner

Beilstein J. Org. Chem. 2020, 16, 1732–1739, doi:10.3762/bjoc.16.145

• . Reports of using phosphoramidite chemistry for the preparation of carbohydrates via the anomeric position are relatively rare [18][19][20][21][22][23]. Alternatively, the H-phosphonate approach has been used to convert carbohydrates into phosphate-linked derivatives at the anomeric center [24][25][26][27

Oligonucleotide analogues with cationic backbone linkages

• Melissa Meng and
• Christian Ducho

Beilstein J. Org. Chem. 2018, 14, 1293–1308, doi:10.3762/bjoc.14.111

• oligonucleotide analogues was performed on solid support using H-phosphonate chemistry (Scheme 1). Thus, solid phase-linked thymidine 12 was coupled with 5'-dimethoxytrityl-(DMTr)-protected thymidine 3'-H-phosphonate 13 to give dimeric H-phosphonate 14, which was then acidically DMTr-deprotected to furnish 15

• accessible by means of chemical synthesis, which is either based on the application of H-phosphonate (for i) or phosphoramidite-based (for iv) DNA synthesis, or on a massively modified version of DNA synthesis (for ii and iii), or on solid phase-supported peptide synthesis (for iv). Studies on the properties

Preparation of trinucleotide phosphoramidites as synthons for the synthesis of gene libraries

• Ruth Suchsland,
• Bettina Appel and
• Sabine Müller

Beilstein J. Org. Chem. 2018, 14, 397–406, doi:10.3762/bjoc.14.28

• proceed by either phosphite triester chemistry or phosphotriester chemistry with the latter being the more robust method. Also H-phosphonate chemistry has been used for assembling short oligomers in solution [34], although not with the aim of generating trinucleotide synthons for gene synthesis. 2

• released by a transesterification mechanism [35]. The 3'-start nucleoside is bound to one of the primary hydroxy groups of CPG-linked glycerol via an H-phosphonate linkage (Figure 5B). The removal of the TBDMS group from the remaining primary alcohol of glycerol induces the spontaneous cleavage of the H

• strategy and syntheses will be described elsewhere. 3. Preparation of trinucleotides by inverse solid-phase synthesis Interestingly, also the use of polymer-supported reagents for H-phosphonate or phosphoramidite activation and phosphite oxidation has been described [34][39], thereby combining the

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

Beilstein J. Org. Chem. 2018, 14, 25–53, doi:10.3762/bjoc.14.3

Synthesis of oligonucleotides on a soluble support

• Harri Lönnberg

Beilstein J. Org. Chem. 2017, 13, 1368–1387, doi:10.3762/bjoc.13.134

• byproducts after each coupling, oxidation and deprotection step. The techniques applied so far include precipitation, extraction, chromatography and nanofiltration. As regards coupling, all conventional chemistries, viz. phosphoramidite, H-phosphonate and phosphotriester strategies, have been attempted

• . While P(III)-based phosphoramidite and H-phosphonate chemistries are almost exclusively used on a solid support, the “outdated” P(V)-based phosphotriester chemistry still offers one major advantage for the synthesis on a soluble support; the omission of the oxidation step simplifies the coupling cycle

• protected nucleoside 3´-(2-cyanoethyl-N,N-dialkylphosphoramidite)s (1 in Scheme 1) or 3´-(H-phosphonate)s are usually preferred as building blocks [3] (2 in Scheme 1). The attacking 5´-OH apart, all other nucleophilic functionalities must be kept protected during the coupling. The primary amino groups of

Nucleic acids through condensation of nucleosides and phosphorous acid in the presence of sulfur

• Tuomas Lönnberg

Beilstein J. Org. Chem. 2016, 12, 670–673, doi:10.3762/bjoc.12.67

• elemental sulfur. Desulfurization and subsequent digestion of the products by P1 nuclease revealed that nearly 80% of the internucleosidic linkages thus formed were of the canonical 3´,5´-type. Keywords: H-phosphonate; nucleic acid; polymerization; phosphite; sulfurization; Introduction Arguably the most

• phosphorous acid are hydrolytically stable compounds that are readily formed upon concentration of aqueous solutions of alcohols and phosphite salts [12]. The monoesters may react further to H-phosphonate diesters but this is an equilibrium process that under aqueous conditions favors the starting materials

• [13]. Oxidation of the H-phosphonate diester products, however, converts them to the stable phosphodiester counterparts. It is interesting to note that this reaction is faster for H-phosphonate diesters than for the respective monoesters or phosphorous acid itself [12], providing the driving force for

DNA display of glycoconjugates to emulate oligomeric interactions of glycans

• Alexandre Novoa and
• Nicolas Winssinger

Beilstein J. Org. Chem. 2015, 11, 707–719, doi:10.3762/bjoc.11.81

• cycloaddition (CuAAC) [25][26] has naturally inspired the use of this powerful conjugation method to prepare glycan–DNA conjugates. Chevolot and co-workers used this method to conjugate glycans at the 3’-end of DNA [27]. The DNA synthesis was initiated with H-phosphonate that was converted to a phosphoramidate

Synthesis of dinucleoside acylphosphonites by phosphonodiamidite chemistry and investigation of phosphorus epimerization

• William H. Hersh

Beilstein J. Org. Chem. 2015, 11, 184–191, doi:10.3762/bjoc.11.19

• of the structures was possible via oxidation and conversion to the known diastereomeric phosphorothioates. As shown by Hata et al., acylphosphonate 3b (Scheme 1) was converted to the corresponding phosphorothioate by treatment with a base (to give the H-phosphonate via loss of carboxylate) followed

• by elemental sulfur [43]. As shown in Scheme 3, oxidation of 12 and 13 with anhydrous tert-butyl hydroperoxide gave the acylphosphonates 14 and 15. These products were immediately hydrolyzed by addition of approximately 2 equiv of aqueous triethylammonium bicarbonate (TEAB) to give the H-phosphonate

Synthesis and immunological evaluation of protein conjugates of Neisseria meningitidis X capsular polysaccharide fragments

• Laura Morelli,
• Damiano Cancogni,
• Marta Tontini,
• Alberto Nilo,
• Sara Filippini,
• Paolo Costantino,
• Maria Rosaria Romano,
• Francesco Berti,
• Roberto Adamo and
• Luigi Lay

Beilstein J. Org. Chem. 2014, 10, 2367–2376, doi:10.3762/bjoc.10.247

• by the in vitro bactericidal assay recently developed for the evaluation of MenX CPS conjugates [18]. Results and Discussion Improvements in α-H-phosphonate synthesis Our previous synthesis of oligomers 1–3 featured the use of 2-azido-2-deoxy glucopyranosyl building blocks and their corresponding

• , when the hemiacetal 6 was treated with salicylchlorophosphite in pyridine at room temperature the α-H-phosphonate 7 was obtained as a single anomer in only 2 h in 62% yield. We reasoned that the occurrence of an intramolecular hydrogen bond involving the acetamido group could be the main responsible

• for the high selectivity observed in the formation of compound 6 and, consequently, for the attainment of the pure α-H-phosphonate 7. Indeed, the desilylation of the 2-azido counterpart of intermediate 5 provided a mixture of anomers. On the other hand, the same reaction carried out on a 2-acetamido

Solution phase synthesis of short oligoribonucleotides on a precipitative tetrapodal support

• Alejandro Gimenez Molina,
• Amit M. Jabgunde,
• Pasi Virta and
• Harri Lönnberg

Beilstein J. Org. Chem. 2014, 10, 2279–2285, doi:10.3762/bjoc.10.237

• solution phase approach, allowing assembly of short RNAs in a hundreds of milligrams scale. While several such methods for the synthesis of DNA, based either the phosphoramidite [11][12][13][14][15][16], H-phosphonate [17][18][19] or phosphotriester chemistry [20][21][22], have been introduced, none of

Synthesis of 6-PEtN-α-D-GalpNAc-(1–>6)-β-D-Galp-(1–>4)-β-D-GlcpNAc-(1–>3)-β-D-Galp-(1–>4)-β-D-Glcp, a Haemophilus influenzae lipopolysacharide structure, and biotin and protein conjugates thereof

• Andreas Sundgren,
• Martina Lahmann and
• Stefan Oscarson

Beilstein J. Org. Chem. 2010, 6, 704–708, doi:10.3762/bjoc.6.80

• group from the primary position of the non-reducing end residue produced a free hydroxy group which was phosphorylated using H-phosphonate chemistry to yield the phosphoethanolamine-containing protected pentasaccharide. Partial deprotection afforded the phosphorylated target pentasaccharide with a free

• phosphoethanolamine. Compound 19 was also completely deprotected by sodium methoxide treatment followed by catalytic hydrogenolysis to give the non-phosphorylated target structure 20 (66%, Scheme 4), to be used as a reference in biological experiments. Earlier we used the Cbz-protected ethanolamine H-phosphonate

• monoester as a reagent in the formation of phosphoethanolamines [29]. Since the amino group in the spacer was already Cbz-protected and we wanted to be able to differentiate between the two amino groups during conjugation, a Boc-protected H-phosphonate monoester 21 was synthesised and used in the

Unexpected degradation of the bisphosphonate P-C-P bridge under mild conditions

• Petri A. Turhanen and
• Jouko J. Vepsäläinen

Beilstein J. Org. Chem. 2008, 4, No. 7, doi:10.1186/1860-5397-4-7

• reaction conditions in two of the prepared etidronate derivatives. Earlier, Szymczak et. al. [24] have described the formation of H-phosphonate (also known as phosphite) and phosphate components from a phosphonate-phosphate compound (same kind of structure as 8 in Scheme 1) either in CH3CN/Et3N/H2O (v/v