Strategies for the synthesis of brevipolides

• Yudhi D. Kurniawan and
• A'liyatur Rosyidah

Beilstein J. Org. Chem. 2021, 17, 2399–2416, doi:10.3762/bjoc.17.157

• ester group was reduced to the primary alcohol 67 (95%). After protection as tert-butyldiphenylsilyl (TBDPS) ether 68 (98%), a Simmons–Smith cyclopropanation was attempted yet no desired product was obtained. Hence, the PMB-protecting group was first removed and the cyclopropyl product 69 was

• derivative in 80% yield. The TBS protecting group was removed under acidic conditions to give secondary alcohol 93 (85%). Afterwards, the 5,6-dihydro-α-pyrone functionality was constructed by applying a cross-metathesis protocol and the stereochemistry at C6’ was inverted with (E)-p-methoxycinnamic acid (17

Recent advances in the syntheses of anthracene derivatives

• Giovanni S. Baviera and
• Paulo M. Donate

Beilstein J. Org. Chem. 2021, 17, 2028–2050, doi:10.3762/bjoc.17.131

• -dibromo-2,5-dimethylbenzene (101), with subsequent Suzuki cross-coupling of compound 102 with potassium vinyltrifluoroborate, removal of the N-Boc protecting group of 103 with trifluoroacetic acid, and borylative cyclization of precursor aminostyrene 104 [58]. Sparr’s research group developed the 1,5

Sustainable manganese catalysis for late-stage C–H functionalization of bioactive structural motifs

• Jongwoo Son

Beilstein J. Org. Chem. 2021, 17, 1733–1751, doi:10.3762/bjoc.17.122

• future, such as protecting-group-free methodologies, peptide biosensors, and facile functionalizations within unexplored realms of complex peptides. Proposed reaction mechanism of C–H fluorination by a manganese porphyrin catalyst. Proposed mechanism of C–H radiofluorination. Proposed reaction mechanism

Chemical synthesis of C6-tetrazole ᴅ-mannose building blocks and access to a bioisostere of mannuronic acid 1-phosphate

• Eleni Dimitriou and
• Gavin J. Miller

Beilstein J. Org. Chem. 2021, 17, 1527–1532, doi:10.3762/bjoc.17.110

•  2). This second route commenced with a three-step protecting group manipulation of primary alcohol 6, delivering 7 in 63% yield over three steps (Scheme 2). Alcohol 7 was then subjected to Parikh–Doering oxidation to deliver a crude aldehyde in 98% yield, from which oxime 8 was subsequently formed

• try and improve the N1-PMB/N2-PMB ratio, converting 5 to a triethylammonium salt form in 94% yield was adopted [18]. Subsequent reaction with PMBCl gave 11 and 12, but in a largely unchanged ratio (N1-PMB/N2-PMB = 1:1.1). A comparative attempt to install a benzyl protecting group using this method

• oligosaccharide synthesis strategy. With such capability effectively demonstrated, we next explored the provision of ᴅ-manno C6-tetrazoles without an orthogonal C4-protecting group. Accordingly, a synthesis initiating from alcohol 15 [19] enabled access to C6-nitrile 16 in three steps (Scheme 4) and an improved

Total synthesis of ent-pavettamine

• Memory Zimuwandeyi,
• Manuel A. Fernandes,
• Amanda L. Rousseau and
• Moira L. Bode

Beilstein J. Org. Chem. 2021, 17, 1440–1446, doi:10.3762/bjoc.17.99

• -pavettamine rather than pavettamine. Chain extension and stereoselective ketone reduction were achieved using the (R)-methyl p-tolyl sulfoxide chiral auxiliary to give the desired 1,3-syn-diol C5 unit. A protecting-group strategy was also developed for the orthogonal protection of the alcohol and amine

• retaining the stereogenic center. Divergence from the original route to pavettamine occurred after recovery of diol 5; and a different protecting group strategy was applied to arrive at synthon 4. The primary alcohol of the diol 5 was regioselectively protected using the trityl group under basic conditions

• yielding 6 in quantitative yield. Our choice of the trityl protecting group was based on the fact that it could be selectively added in the presence of the secondary alcohol and selectively removed at a later stage in the presence of an orthogonally-protected secondary alcohol [16]. At this stage, the

Double-headed nucleosides: Synthesis and applications

• Vineet Verma,
• Jyotirmoy Maity,
• Vipin K. Maikhuri,
• Ritika Sharma,
• Himal K. Ganguly and
• Ashok K. Prasad

Beilstein J. Org. Chem. 2021, 17, 1392–1439, doi:10.3762/bjoc.17.98

• -headed nucleoside 6. The removal of the silyl protecting group with NEt3·3HF in THF yielded 2′-(N-benzoylcytosin-1-yl)methyl-arabinofuranosyl-N-benzoylcytosine (7, Scheme 2) [42]. The double-headed nucleoside 7 was dimethoxytritylated and phosphitylated following the standard procedure and incorporated

• hydroxy group was protected by reaction with pixyl chloride to afford the nucleoside 99. The removal of the tert-butyldimethylsilyl protecting group under standard conditions afforded the double-headed nucleoside 100 (Scheme 22) [14]. Opening of the epoxide ring in nucleoside 97 with sodium azide in DMF

• nucleoside 102 with phenylacetylene in the presence of sodium ascorbate and copper sulfate in a solvent mixture of t-BuOH, water and pyridine, followed by the removal of the tert-butyldimethylsilyl protecting group gave nucleoside 103 (Scheme 22) [14]. Under similar reaction conditions, the treatment of

A comprehensive review of flow chemistry techniques tailored to the flavours and fragrances industries

• Guido Gambacorta,
• James S. Sharley and
• Ian R. Baxendale

Beilstein J. Org. Chem. 2021, 17, 1181–1312, doi:10.3762/bjoc.17.90

N-tert-Butanesulfinyl imines in the asymmetric synthesis of nitrogen-containing heterocycles

• Joseane A. Mendes,
• Paulo R. R. Costa,
• Miguel Yus,
• Francisco Foubelo and
• Camilla D. Buarque

Beilstein J. Org. Chem. 2021, 17, 1096–1140, doi:10.3762/bjoc.17.86

• the stereoselective synthesis of spiro β-lactam 57 from chiral (RS)-N-tert-butanesulfinyl isatin ketimine 53 (R1 = H), with a bulky trityl protecting group bonded to the nitrogen indolic atom (Tr = triphenylmethyl), and ethyl bromoacetate. The Zn/Cu-mediated Reformatsky-type reaction furnished

Synthesis of multiply fluorinated N-acetyl-D-glucosamine and D-galactosamine analogs via the corresponding deoxyfluorinated glucosazide and galactosazide phenyl thioglycosides

• Vojtěch Hamala,
• Lucie Červenková Šťastná,
• Martin Kurfiřt,
• Petra Cuřínová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2021, 17, 1086–1095, doi:10.3762/bjoc.17.85

• . Deoxyfluorination at C6 should then afford intermediates 6. Protecting-group manipulation of intermediates 4 and 6 should deliver the required fluoro analogs. The initially contemplated conversion of intermediates 3 into acetates 5 [26], followed by base-catalyzed O-deacetylation, led to substantial decomposition

• a robust protecting group and to conduct final deprotection under neutral conditions. After initial experimentation with benzyl glycosides (Scheme 1, PG = OBn), phenyl thioglycosides (Scheme 1, PG = SPh), readily available from 1,6-anhydropyranoses [39] as we described earlier [40] were found to

Recent advances in palladium-catalysed asymmetric 1,4–additions of arylboronic acids to conjugated enones and chromones

• Jan Bartáček,
• Jan Svoboda,
• Martin Kocúrik,
• Jaroslav Pochobradský,
• Alexander Čegan,
• Miloš Sedlák and
• Jiří Váňa

Beilstein J. Org. Chem. 2021, 17, 1048–1085, doi:10.3762/bjoc.17.84

• -protecting group (Table 21) [49]. In other experiments, Stoltz and co-workers showed the ineffectiveness of the L9/Pd(TFA)2 catalytic system for the addition of phenylboronic acid to nonsubstituted 2-cyclohexenone, yielding the product with very low enantioselectivity (18%; entry 1, Table 22). Furthermore

• intermediate, the protecting group was removed and the product was obtained in 88% yield and 80% ee. The enantiomeric excess of the obtained (S)-3-(hydroxymethyl)-3-phenyl-2-cyclopentanone could be increased by double recrystallization to up to 97% ee (Scheme 15) [4]. The catalytic system L9/Pd(TFA)2 was

Metal-free glycosylation with glycosyl fluorides in liquid SO₂

• Krista Gulbe,
• Jevgeņija Lugiņina,
• Edijs Jansons,
• Artis Kinens and
• Māris Turks

Beilstein J. Org. Chem. 2021, 17, 964–976, doi:10.3762/bjoc.17.78

• [27]) and coupling partners [28], great attention has been paid to a stereoselective glycosylation by sterically fixed glycosyl fluorides as glycosyl donors [29][30][31]. The enhanced stability of glycosyl fluorides has also allowed to develop a straightforward protecting-group-free strategy towards

• through the neighboring ester type protecting group assistance. At lower temperatures the glycosylation yield was lower, although full conversion of glucosyl fluoride β-9 was still observed. Compared to the analogue mannose derivative α-1a, glucose β-9 turned out to be less stable and more prone to

• various side-reactions. A series of side-products formed by hydrolysis and protecting group migrations were detected and their structures are proposed (see Supporting Information File 1). Next, glycosyl fluorides α-11 and α-12 containing more acid-sensitive acetyl protecting groups were applied for the

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

• of NaHMDS in order to selectively alkylate the 2'-OH, followed by TBAF treatment to remove the MDPS protecting group. The 2'-O-MOE soon became the gold standard alkyl modification, owing to its improvement in therapeutically relevant properties. Compared to 2'-OMe RNA, the 2'-O-MOE RNA analogue has

Total synthesis of pyrrolo[2,3-c]quinoline alkaloid: trigonoine B

• Takashi Nishiyama,
• Erina Hamada,
• Daishi Ishii,
• Yuuto Kihara,
• Nanase Choshi,
• Natsumi Nakanishi,
• Mari Murakami,
• Kimiko Taninaka,
• Noriyuki Hatae and
• Tominari Choshi

Beilstein J. Org. Chem. 2021, 17, 730–736, doi:10.3762/bjoc.17.62

• -iodoaniline (12) and 3-(4,4,5,5-tetramethyl-1,3,2-dioxaborolan-2-yl)-1-[tris(1-methylethyl)silyl]-1H-pyrrole (13) according to Pratt’s conditions (Scheme 3) [29]. Subsequently, to remove the triisopropylsilyl (TIPS) protecting group, compound 14 was treated with tetra-n-butylammonium fluoride (TBAF) in THF

• prepared from an appropriate carboxylic acid through a Curtius rearrangement reaction (50–98% yield). Treatment of urea derivatives 19a–d with CBr4, PPh3, and Et3N afforded carbodiimides 20a–d in 64–75% yield. Compounds 21a–d were obtained in situ following the removal of the TIPS protecting group in 20a–d

Synthesis and properties of oligonucleotides modified with an N-methylguanidine-bridged nucleic acid (GuNA[Me]) bearing adenine, guanine, or 5-methylcytosine nucleobases

• Naohiro Horie,
• Takao Yamaguchi,
• Shinji Kumagai and
• Satoshi Obika

Beilstein J. Org. Chem. 2021, 17, 622–629, doi:10.3762/bjoc.17.54

• Discussion Synthesis of the GuNA[Me] phosphoramidites bearing either an A, G, or mC nucleobase The preparation of the GuNA[Me]-A, -G, and -mC phosphoramidites 3a–c needed for the synthesis of the GuNA[Me]-modified oligonucleotides is detailed in Scheme 1. The acetyl group was selected as a protecting group

Menthyl esterification allows chiral resolution for the synthesis of artificial glutamate analogs

• Kenji Morokuma,
• Shuntaro Tsukamoto,
• Kyosuke Mori,
• Kei Miyako,
• Ryuichi Sakai,
• Raku Irie and
• Masato Oikawa

Beilstein J. Org. Chem. 2021, 17, 540–550, doi:10.3762/bjoc.17.48

• ). Enantiospecific synthesis of TKM-38 For the enantiospecific synthesis of TKM-38, which uniquely bears an eight-membered azacycle as the ring C, we explored 1) the amino-protecting group and 2) the conditions for the cyclization of the medium-sized ring by ring-closing metathesis (RCM). Finally, the established

Synthesis and physicochemical evaluation of fluorinated lipopeptide precursors of ligands for microbubble targeting

• Masayori Hagimori,
• Estefanía E. Mendoza-Ortega and
• Marie Pierre Krafft

Beilstein J. Org. Chem. 2021, 17, 511–518, doi:10.3762/bjoc.17.45

• structure [30]. These lipopeptides have a discrete molecular weight and are produced by Fmoc (fluorenylmethoxycarbonyl protecting group) SPPS, a procedure in which the peptide chain is assembled stepwise while attached to an insoluble resin support, which allows the easy removal of the byproducts at each

Synthesis of legonmycins A and B, C(7a)-hydroxylated bacterial pyrrolizidines

• Wilfred J. M. Lewis,
• David M. Shaw and
• Jeremy Robertson

Beilstein J. Org. Chem. 2021, 17, 334–342, doi:10.3762/bjoc.17.31

• protecting group under acidic conditions was accompanied by cyclization in situ [14][15][34][35] and pyrrolizinone derivative 17 was obtained efficiently on a multigram scale over two steps. Originally, it was expected that adapting the conditions (NaH, RCOCl, THF) used for the acylation step in the

Recent progress in the synthesis of homotropane alkaloids adaline, euphococcinine and N-methyleuphococcinine

• Dimas J. P. Lima,
• Antonio E. G. Santana,
• Michael A. Birkett and
• Ricardo S. Porto

Beilstein J. Org. Chem. 2021, 17, 28–41, doi:10.3762/bjoc.17.4

• subjected to simultaneous catalytic hydrogenation and hydrogenolysis of the protecting group Cbz to give (−)-adaline (1) in 90% yield. The asymmetric synthesis achieved by Liebeskind et al. presented a high enantiomeric excess and good yields. Also, the proposed route differed from the previously mentioned

Pentannulation of N-heterocycles by a tandem gold-catalyzed [3,3]-rearrangement/Nazarov reaction of propargyl ester derivatives: a computational study on the crucial role of the nitrogen atom

• Giovanna Zanella,
• Martina Petrović,
• Dina Scarpi,
• Ernesto G. Occhiato and
• Enrique Gómez-Bengoa

Beilstein J. Org. Chem. 2020, 16, 3059–3068, doi:10.3762/bjoc.16.255

• studied computationally (Figure 2). To this end, a model substrate bearing p-toluensulfonyl as the protecting group on the nitrogen atom was chosen owing to the compatibility with such a process [16]. The structures were located using the B3LYP density functional theory method as implemented in the

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

• adenosine [33][34]. The 3′,5′-O-di-tert-butylsilyl protecting group, in contrast to the Markiewicz group (1,1,3,3-tetraisopropyldisiloxane) can be selectively removed with HF-pyridine [35][36]. It was used for the iodination of cytosine residues previously [37], but to the best of our knowledge never for

• the iodination of a purine nucleobase, which is achieved under harsher conditions. Thus, the 3′,5′-O-di-tert-butylsilyl protecting group was introduced, followed by reaction of the 2’-OH group with TBDMS chloride to generate intermediate 10 (Scheme 2). Subsequently, the iodination was carried out

• migration of the TBDMS protecting group and consequently formation of the 3’-O-TBDMS isomer under Sonogashira conditions, which accounts for the reduced yield. This certainly can be counteracted by further reducing the reaction temperature of the Sonogashira coupling. Under the conditions applied here

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

• . Cyclization to form the second pyrrole ring was achieved by selective Buchwald–Hartwig amination of dibromide 31 with n-propylamine to give TIPS-protected SN4'' 32 in 61% yield. Final removal of the TIPS-protecting group by TBAF gave the novel SN4''-system 33 in 98% yield (Scheme 6). All prepared S,N

Photosensitized direct C–H fluorination and trifluoromethylation in organic synthesis

• Shahboz Yakubov and
• Joshua P. Barham

Beilstein J. Org. Chem. 2020, 16, 2151–2192, doi:10.3762/bjoc.16.183

• was achieved with exclusive regioselectivity in peptides, with modest to moderate diastereomeric ratios of the fluorinated products (Scheme 29). With the optimum PSCat in hand, it was necessary to find a protecting group (PG) for the amine that would not undergo fluorination or oxidation when treated

Naphthalene diimide–amino acid conjugates as novel fluorimetric and CD probes for differentiation between ds-DNA and ds-RNA

• Annike Weißenstein,
• Myroslav O. Vysotsky,
• Ivo Piantanida and
• Frank Würthner

Beilstein J. Org. Chem. 2020, 16, 2032–2045, doi:10.3762/bjoc.16.170

• treatment with 1 M HCl solution the Boc protecting group was split off (third step), and the desired NDI derivatives 3a and 3b were obtained in a yield of 39% and 44%, respectively. For the preparation of NDI 5, compound 1 was first monofunctionalized at the core with 2-dimethylaminoethylamine in a

pH- and concentration-dependent supramolecular self-assembly of a naturally occurring octapeptide

• Goutam Ghosh and
• Gustavo Fernández

Beilstein J. Org. Chem. 2020, 16, 2017–2025, doi:10.3762/bjoc.16.168

• nanostructures as well as the secondary structures. Results and Discussion Solid-phase peptide synthesis and purification The target octapeptide was synthesized in the solid phase following four steps, including: i) deprotection of the Fmoc protecting group, ii) coupling of an amino acid, iii) cleavage of 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

• removal of the silyl protecting group, followed by a carboxylation and acylation gave 13. Koide’s group [13] reported a second-generation route to 13, which utilized the Corey–Bakshi–Shibata chiral oxazaborolidine catalyst 21 [20] for the asymmetric reduction of the THP-protected 5-hydroxy-3-pentyn-2-one

• Kitahara’s synthesis [8][9], the Wittig olefination of 24, followed by a catalytic hydrogenation, removal of the dimethylaminal protecting group, and lactonization gave 25 as a mixture of diastereomers (Scheme 2). The further transformation of 25 afforded the dihydropyran 26, which upon catalytic

• metathesis using Grubbs’ 2nd generation catalyst (G-II, Scheme 3) [13]. Replacing the N-Boc protecting group with an N-tosyl group and allylic oxidation gave 30. The introduction of the allyl group at C-11 made use of the Kishi protocol [22] of the allyl-Grignard addition, followed by an ionic reduction. The