Synthesis of tetrafluorinated piperidines from nitrones via a visible-light-promoted annelation reaction

• Vyacheslav I. Supranovich,
• Igor A. Dmitriev and
• Alexander D. Dilman

Beilstein J. Org. Chem. 2020, 16, 3104–3108, doi:10.3762/bjoc.16.260

• from nitrones and a fluorinated building block is described. The annelation is based on a sequence of visible-light-promoted redox processes and a substitution reaction, and involves the cleavage of the N–O bond. The construction of tetrafluorinated piperidines from nitrones. The scope of the

UV resonance Raman spectroscopy of the supramolecular ligand guanidiniocarbonyl indole (GCI) with 244 nm laser excitation

• Tim Holtum,
• Vikas Kumar,
• Daniel Sebena,
• Jens Voskuhl and
• Sebastian Schlücker

Beilstein J. Org. Chem. 2020, 16, 2911–2919, doi:10.3762/bjoc.16.240

• wavenumber values were scaled by a factor of 0.964 [26] and 0.960 for B3LYP-D3 and B2PLYP-D3, respectively. A HWHM of 4 cm−1 and a Lorentzian line shape were used for simulating the theoretical spectrum in Figure 5. The GCP building block was synthesized according to a known literature procedure [27

• ], followed by further functionalization with ethylamine at the carboxylic acid in two steps to obtain the GCP ethyl amide, which has been synthesized before, by a different method [9]. The novel building block for GCI was synthesized in a 4-step synthesis adapted from a previous work [28] and then

Changed reactivity of secondary hydroxy groups in C8-modified adenosine – lessons learned from silylation

• Jennifer Frommer and
• Sabine Müller

Beilstein J. Org. Chem. 2020, 16, 2854–2861, doi:10.3762/bjoc.16.234

• being preferentially formed. Optimization of the protection scheme lead to a new and economic route to the desired C8-alkynylated building block and its incorporation in RNA. Keywords: nucleoside chemistry; protecting groups; RNA synthesis; Sonogashira reaction; Introduction Oligoribonucleotides

• nucleic acids via Förster Resonance Energy Transfer (FRET) [20]. More recently, we started an effort to develop an efficient strategy for the preparation of a linker-modified adenosine building block, which in a future project is to be used for post synthetic conjugation of reporters or functional

• synthesis strategy was re-designed, allowing the preparation of building block 9 (Scheme 2) ready for use in solid-phase RNA synthesis with excellent yield. Here, we report on the selectivity problem in 2’-O-silylation of adenosine derivative 7 (Scheme 1) and the optimized synthesis strategy for the

Easy access to a carbohydrate-based template for stimuli-responsive surfactants

• Thomas Holmstrøm,
• Daniel Raydan and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2020, 16, 2788–2794, doi:10.3762/bjoc.16.229

• Caparica, Portugal 10.3762/bjoc.16.229 Abstract In this paper we describe the synthesis of a new carbohydrate-based building block functionalized with azido or amino groups on the 2 and 4 positions. The building block can be synthesized in anomerically pure form in only five scalable steps starting from

• commercially available levoglucosan. It was shown that the building block could undergo alkylations under strongly basic conditions. The building block with azido groups could furthermore take part in CuAAC reactions, generating derivatives with ester or carboxylic acid functionalities. In addition, the

• anomeric mixture of the building block was used for the synthesis of a molecule that could act as an emulsifier only in the presence of Zn2+ ions. Keywords: carbohydrates; emulsifiers; stimuli-responsive; surfactants; synthesis; Introduction Surfactants (surface-active agents) are molecules with both a

3-Acetoxy-fatty acid isoprenyl esters from androconia of the ithomiine butterfly Ithomia salapia

• Florian Mann,
• Daiane Szczerbowski,
• Lisa de Silva,
• Melanie McClure,
• Marianne Elias and
• Stefan Schulz

Beilstein J. Org. Chem. 2020, 16, 2776–2787, doi:10.3762/bjoc.16.228

• originate from the terpene building block 3-methyl-3-butenyl (isoprenyl) pyrophosphate. Because isoprenyl pyrophosphate is partly converted to 3-methyl-2-butenyl (prenyl) pyrophosphate during terpene biosynthesis, the presence of prenyl esters could not be excluded. Nevertheless, the two ester types can be

Synthesis and characterization of S,N-heterotetracenes

• Astrid Vogt,
• Florian Henne,
• Christoph Wetzel,
• Elena Mena-Osteritz and
• Peter Bäuerle

Beilstein J. Org. Chem. 2020, 16, 2636–2644, doi:10.3762/bjoc.16.214

• -heteroacenes, dimeric thieno[3,2-b]pyrrole [8] and trimeric dithieno[3,2-b:2’,3’-d]pyrrole (DTP) [9], are long known but still frequently used as building block for organic electronic materials [10]. By application of Pd-catalyzed Buchwald–Hartwig amination/cyclization reactions of brominated thiophene-based

• fused thiophene unit by a pyrrole ring. For TTA various synthetic methods have been developed and it has been broadly implemented as building block into materials for organic electronic devices [32][33]. We have disclosed the first SN4 derivative with the heteroatom sequence ‘SSNS’ in the context of

Design and synthesis of a bis-macrocyclic host and guests as building blocks for small molecular knots

• Elizabeth A. Margolis,
• Rebecca J. Keyes,
• Stephen D. Lockey IV and
• Edward E. Fenlon

Beilstein J. Org. Chem. 2020, 16, 2314–2321, doi:10.3762/bjoc.16.192

• ]. Herein the synthesis of a unique bis-macrocyclic host 1 is described (Figure 1). Host 1 was designed to be a second-generation building block in the thread–link–cut (TLC) approach to molecular knots [13]. The two 25-atom macrocycles are electron-rich and complementary to the electron-deficient guests bis

Synthetic approaches to bowl-shaped π-conjugated sumanene and its congeners

• Shakeel Alvi and
• Rashid Ali

Beilstein J. Org. Chem. 2020, 16, 2212–2259, doi:10.3762/bjoc.16.186

• sensory material for selective recognition of cesium cations in water. In another event, Hirao’s group has prepared trioxosumanene 40 in the presence of RuCl3 and t-BuO2H which could be used as a key building block to generate diverse significant electroactive materials by virtue of nucleophilic addition

• mono-substituted sumanene derivatives 49b–d in a stereoselective manner as can be inspected from Scheme 10 [41][42]. In another event, Amaya, Ito, Katoh and Hirao reported a vital building block 53 to extend the π-conjugation bidirectionally through regioselective functionalization (Scheme 11) [43]. To

• sumanene building block 204. Furthermore, the precursor 204 was converted to the 1,4,5,8,9,12-hexaiodotriphenylene 208 via ring-opening with KI in the presence of a copper/diamine catalyst (Scheme 50). Gratefully, compound 208 was also used as building block for the construction of heterasumaneness 151

Naphthalene diimide bis-guanidinio-carbonyl-pyrrole as a pH-switchable threading DNA intercalator

• Poulami Jana,
• Filip Šupljika,
• Carsten Schmuck and
• Ivo Piantanida

Beilstein J. Org. Chem. 2020, 16, 2201–2211, doi:10.3762/bjoc.16.185

• spectroscopy methods (FDCD, CPL), the sensitivity of response is approaching the classical fluorimetric probes [14]. Our systematic work on aryl-guanidiniocarbonyl-pyrrole (GCP) derivatives characterised the GCP moiety as very useful building block in the design of new small molecules targeting DNA/RNA. The

Syntheses of spliceostatins and thailanstatins: a review

• William A. Donaldson

Beilstein J. Org. Chem. 2020, 16, 1991–2006, doi:10.3762/bjoc.16.166

• . Review Synthesis of the (2Z,4S)-4-acetoxy- or protected (2Z,4S)-4-hydroxy-2-butenoic acid fragment The (2Z,4S)-4-acetoxy-2-butenoic acid fragment is common to all of the spliceostatins/thailanstatins. The various routes to this building block (Scheme 1) serve as a tutorial on the methodology for the

A complementary approach to conjugated N-acyliminium formation through photoredox-catalyzed intermolecular radical addition to allenamides and allencarbamates

• Olusesan K. Koleoso,
• Matthew Turner,
• Felix Plasser and
• Marc C. Kimber

Beilstein J. Org. Chem. 2020, 16, 1983–1990, doi:10.3762/bjoc.16.165

• innovative transformations, including cycloadditions [5][6][7][8][9], intramolecular cyclizations and intermolecular addition reactions [10][11][12][13][14][15][16][17][18], as well as the use of the allenamide building block in natural product synthesis [1]. Addition reactions of allenamides, which can also

• undergoes an addition reaction with a suitable nucleophile (Scheme 1). Importantly, the electrophilic mediated formation of this key intermediate 2 have been the cornerstone for allenamide chemistry over the past 15 years. Therefore, given the importance of the allenamide building block we sought a new

• synthetic methodology that could generate this conjugated N-acyliminium intermediate 2, that would not be dependent on conventional electrophilic activation modes (Scheme 2). In principle, a new method for its generation could greatly enhance the value of the allenamide building block, as well as

Synthesis of monophosphorylated lipid A precursors using 2-naphthylmethyl ether as a protecting group

• Jundi Xue,
• Ziyi Han,
• Gen Li,
• Khalisha A. Emmanuel,
• Cynthia L. McManus,
• Qiang Sui,
• Dongmian Ge,
• Qi Gao and
• Li Cai

Beilstein J. Org. Chem. 2020, 16, 1955–1962, doi:10.3762/bjoc.16.162

• with LiOH gave (R)-3-(2-naphthylmethoxy)tetradecanoic acid (7) in 78% yield over two steps. The glucosamine building block 14 was synthesized using the procedures described in previous literature [20] (Scheme 2). The protection of the free amine of glucosamine with a 2,2,2-trichloroethoxycarbonyl (Troc

• with (R)-3-(2-naphthylmethoxy)tetradecanoic acid (7) using 1-ethyl-3-(3-dimethylaminopropyl)carbodiimide (EDC) and 4-dimethylaminopyridine (DMAP) as the activation reagents [14] to give the key/common building block 15 in good yield (Scheme 2). Glycosyl acceptor 18 and donor 20 were thus conveniently

• prepared from the common building block 15 through multiple protecting group manipulations (Scheme 2). The N-Troc group in 15 was removed by treatment with zinc in a mixture of acetic acid and CH2Cl2. The resulting amine 16 was protected immediately as fluorenylmethylenoxy (Fmoc) carbamate by reaction with

Synthesis of Streptococcus pneumoniae serotype 9V oligosaccharide antigens

• Sharavathi G. Parameswarappa,
• Claney L. Pereira and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2020, 16, 1693–1699, doi:10.3762/bjoc.16.140

• ] glycosylation. The synthesis of disaccharide donor 29 started with the glycosylation of glucuronic acid building block 8 with galactose acceptor 9 to obtain disaccharide 26 in 92% yield with 3:1 (α:β) selectivity (Scheme 3). To improve the selectivity for the late stage [2 + 3] glycosylation, disaccharide 26

Rearrangement of o-(pivaloylaminomethyl)benzaldehydes: an experimental and computational study

• Csilla Hargitai,
• Györgyi Koványi-Lax,
• Tamás Nagy,
• Péter Ábrányi-Balogh,
• András Dancsó,
• Gábor Tóth,
• Judit Halász,
• Angéla Pandur,
• Gyula Simig and
• Balázs Volk

Beilstein J. Org. Chem. 2020, 16, 1636–1648, doi:10.3762/bjoc.16.136

• isomeric dimers in the crude product mixtures, only the major isomers 3a,b, and 8a,b could be isolated. The main structural difference between the dimer-like products 3a,b and 8a,b concerns the position of the linkage of the ortho-formylated N-pivaloylaminobenzyl moiety to the isoindoline building block

A dynamic combinatorial library for biomimetic recognition of dipeptides in water

• Florian Klepel and
• Bart Jan Ravoo

Beilstein J. Org. Chem. 2020, 16, 1588–1595, doi:10.3762/bjoc.16.131

• CXC peptide building block design (single-letter code) were the terminal amino acids are cysteine (C) and the X can be any amino acid (Scheme 1a). This allows for rapid synthesis of various new building bocks by standard Fmoc based SPPS using Trt protecting groups for cysteine, which are subsequently

Highly selective Diels–Alder and Heck arylation reactions in a divergent synthesis of isoindolo- and pyrrolo-fused polycyclic indoles from 2-formylpyrrole

• Carlos H. Escalante,
• Eder I. Martínez-Mora,
• Carlos Espinoza-Hicks,
• Alejandro A. Camacho-Dávila,
• Fernando R. Ramos-Morales,
• Francisco Delgado and
• Joaquín Tamariz

Beilstein J. Org. Chem. 2020, 16, 1320–1334, doi:10.3762/bjoc.16.113

• activity [15][16] and great diversity as building block [17][18]. Among the tetracyclic scaffolds, isoindolo[2,1-a]indoles have attracted a particular interest from the synthetic point of view, either as the target or the motif for designing novel annulation methodologies [19][20][21]. Indeed, isoindole

Fluorinated phenylalanines: synthesis and pharmaceutical applications

• Laila F. Awad and
• Mohammed Salah Ayoup

Beilstein J. Org. Chem. 2020, 16, 1022–1050, doi:10.3762/bjoc.16.91

• analogue of sitagliptin which was developed for the same application [109][117], but compound 184 appears to have an improved activity [118]. Retagliptin showed efficacy in clinical trials and is now entering phase III studies. (R)-2,4,5-Trifluorophenylalanine 38b is used as a building block in the

• emerged as a promising approach for treatment. (R)-2,5-Difluorophenylalanine is a required building block for the synthesis of LY2497282 [50][124] (Figure 9). 5.2.5. Ulimorelin: Ulimorelin (187) is a small cyclic peptide containing ᴅ-4-FPhe. Ulimorelin acts as a selective agonist of the ghrelin/growth

Combining enyne metathesis with long-established organic transformations: a powerful strategy for the sustainable synthesis of bioactive molecules

• Valerian Dragutan,
• Ileana Dragutan,
• Albert Demonceau and
• Lionel Delaude

Beilstein J. Org. Chem. 2020, 16, 738–755, doi:10.3762/bjoc.16.68

• metathesis between the formed propargylic derivative and an appropriate allylic alcohol promoted by the Grubbs second-generation catalyst, finally produced in high yield (85%) the intermediate diene 6, as an essential building block for the southern fragment (Scheme 9). Several other asymmetric transition

Rhodium-catalyzed reductive carbonylation of aryl iodides to arylaldehydes with syngas

• Zhenghui Liu,
• Peng Wang,
• Zhenzhong Yan,
• Suqing Chen,
• Dongkun Yu,
• Xinhui Zhao and
• Tiancheng Mu

Beilstein J. Org. Chem. 2020, 16, 645–656, doi:10.3762/bjoc.16.61

• reprocessing of readily available industrial raw materials into more functionalized products. These processes generally utilize carbon monoxide (CO), currently the most important C1 building block used in numerous industrial carbonylation processes [6][7][8] and widely applied in industrial productions [9][10

Exploring the scope of DBU-promoted amidations of 7-methoxycarbonylpterin

• Anna R. Bockman and
• Jeffrey M. Pruet

Beilstein J. Org. Chem. 2020, 16, 509–514, doi:10.3762/bjoc.16.46

• molybdopterin [1]. Owing to this biological relevance, pterins are an attractive building block in the development of various pharmaceuticals, with methotrexate being the most well-known [2]. In addition to pteridine derivatives being used as inhibitors of dihydrofolate reductase and dihydropteroate synthase

Synthesis of 4-amino-5-fluoropyrimidines and 5-amino-4-fluoropyrazoles from a β-fluoroenolate salt

• Tobias Lucas,
• Jule-Philipp Dietz and
• Till Opatz

Beilstein J. Org. Chem. 2020, 16, 445–450, doi:10.3762/bjoc.16.41

• fluorinated C3 building block recently described and used by our laboratory for the synthesis of 2 [36]. Herein, we present the synthesis of fluorinated pyrimidines and pyrazoles from the same precursor. Potassium (Z)-2-cyano-2-fluoroethenolate (8) was synthesized in three steps starting from chloroacetamide

• ) of potassium formate, which could not easily be removed without risking the decomposition of the enolate salt (Scheme 1). As the fluorine atom is part of a building block, harsh conditions for a late-stage fluorination can be avoided, and even products with sensitive functionalities are accessible

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

• was very low after trapping 75 with diphenylchlorophosphine [79]. The PTA motif is water soluble, thermally, air and moisture stable. The PTA building block can be synthesized by coupling tris(hydroxymethyl)phosphine (73) with formaldehyde and ammonia in ice water or with hexamethylenetetramine. A

• relatively good yields. Notably, a low isolated yield was reported when starting from 2-(4-chlorobutyl)pyridine (n = 4) and this was attributed to the competing cyclization reaction affording cyclic pyridinium salts. The prominent 2-(diphenylphosphine)pyridine (4) has proved to be an interesting building

• block for the assembly of homo and hetero-organometallic complexes. The 3- and 4-pyridylphosphine derivatives 5 have also been successfully used as templates for assembling supramolecular structures and coordination polymers [54][59]. Halogenated ring-fused pyridine reagents can also be used to generate

Photocontrolled DNA minor groove interactions of imidazole/pyrrole polyamides

• Sabrina Müller,
• Jannik Paulus,
• Jochen Mattay,
• Heiko Ihmels,
• Veronica I. Dodero and
• Norbert Sewald

Beilstein J. Org. Chem. 2020, 16, 60–70, doi:10.3762/bjoc.16.8

• acted as a building block inducing a reverse turn, which favored hydrogen bonds between the pyrrole/imidazole amide and the DNA bases. In contrast, the E-configured polyamides did not induce any ICD characteristic for minor groove binding. The incorporation of the photoswitchable azobenzene unit is a

• -methylimidazole units were introduced by employing diamino derivatives 3 (Scheme 2A) [40]. Moreover, it turned out that coupling the subsequent building block to an N-terminal Im building block was problematic because the amino group of the imidazole derivative 2b is a weak nucleophile, and therefore the Fmoc–Py

• in DMF for the synthesis of P2. However, in the case of P1 and P3, the formation of tetramethylguanidinium side products was detected by MALDI–TOF MS. This irreversible N-guanylation of the polyamide N-terminus resulted from slow carboxy activation of the building block by HBTU and the presence of an

Starazo triple switches – synthesis of unsymmetrical 1,3,5-tris(arylazo)benzenes

• Andreas H. Heindl and
• Hermann A. Wegner

Beilstein J. Org. Chem. 2020, 16, 22–31, doi:10.3762/bjoc.16.4

• . The azobenzene building block 8, with an unsubstituted phenyl ring and two orthogonal nitrogen substituents in the 3- and 5-position (Scheme 3), was prepared. The synthesis commenced with the acetylation of 3,5-dinitroaniline (4) in 95% yield, followed by the selective reduction of one nitro group

• using an aqueous ammonium sulfide solution to furnish aniline 6 in 65% yield [20]. After oxidation of 6 to its nitroso analogue 7 [21], a Baeyer–Mills reaction with aniline yielded the targeted azobenzene building block 8 in 87% yield (i.e., 53% yield over four steps). After the successful synthesis of

• . Synthetic strategy towards 1,3,5-tris(arylazo)benzenes 3 based on consecutive Baeyer–Mills reactions. Preparation of tris(arylazo)benzenes 3 by Pd-catalyzed cross-coupling reactions of N-Boc-arylhydrazides and bromo-substituted ABs, followed by oxidation. Synthesis of azobenzene building block 8. Synthesis

SnCl₄-catalyzed solvent-free acetolysis of 2,7-anhydrosialic acid derivatives

• Kesatebrhan Haile Asressu and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2019, 15, 2990–2999, doi:10.3762/bjoc.15.295

• , De Meo and co-workers have reported the significant effect of O-substituents on atom C-7 on the reactivity of thiosialoside donors and on the anomeric stereoselectivity of chemical sialylations [21]. Thus, 2,7-anhydro-Neu5Ac can serve as a promising building block for the chemical synthesis of