Direct synthesis of acyl fluorides from carboxylic acids using benzothiazolium reagents

• Lilian M. Maas,
• Alex Haswell,
• Rory Hughes and
• Matthew N. Hopkinson

Beilstein J. Org. Chem. 2024, 20, 921–930, doi:10.3762/bjoc.20.82

• benzothiazolimine species 6 which results from Boc-deprotection and subsequent condensation of the amide product onto the benzothiazolium core. Although the other identified by-product, thiourea 7, is not derived from the limiting carboxylic acid substrate, it was found to coelute with the amide product

• , complicating isolation (Scheme 3a). As Boc-deprotection is seemingly feasible under the reaction conditions, to avoid formation of by-product 6, the process was tested using the N-Cbz-valine (1s). Moreover, the BT-SCF3 reagent was substituted for the longer chain BT-reagent BT-SC5F11. The use of this

(Bio)isosteres of ortho- and meta-substituted benzenes

• H. Erik Diepers and
• Johannes C. L. Walker

Beilstein J. Org. Chem. 2024, 20, 859–890, doi:10.3762/bjoc.20.78

• , deiodination at the bridgehead position, and nucleophilic substitution at the alkyl chloride. From 1,2-BCP (±)-4, a variety of 1,2-BCPs were prepared through basic chemical transformations (Scheme 1B) [26]. Selective deprotection gave access to free alcohol-containing 1,2-BCPs (±)-5 and (±)-8. Oxidation and

• reduction. Deprotection of the alcohol followed by two-step oxidation to the carboxylic acid yielded the non-natural β-amino acid (±)-50, which could then be transformed into diamine (±)-51 by Curtius rearrangement. Recently, Mykhailiuk and co-workers also reported the synthesis of 1,2-BCHs using an

• -cubanes (Scheme 9B) [51]. Partial deprotection of diester 88 led to acid 89 as a key intermediate and in situ activation of the acid as the hypervalent iodine complex enabled a photoredox decarboxylative amination to 1,2-cubane 90. Alternatively, conversion of the acid moiety of 89 to redox active esters

Synthesis and characterization of water-soluble C₆₀–peptide conjugates

• Yue Ma,
• Lorenzo Persi and
• Yoko Yamakoshi

Beilstein J. Org. Chem. 2024, 20, 777–786, doi:10.3762/bjoc.20.71

• and subsequent deprotection of the t-Bu group under acidic conditions, without affecting the C60 cage (Figure 1b). Challenges in this step included finding suitable conditions to conjugate one C60 moiety and two peptide anchors on the resin. Preliminarily, the reaction conditions were optimized using

• acid-substituted C60 derivative 3 and the peptides on resin 2a–c were performed by SPPS to provide the C60–oligopeptides on resin 4a–c (Figure 1a). Subsequently, the last step of the reaction – the cleavage of the C60–peptide conjugate from the resin and the simultaneous deprotection of the amino acid

• NMM (8 equiv) in DMF. Each Fmoc deprotection step of the peptide N-terminus was conducted by the repeated treatment of the peptide on resin with 20% piperidine in DMF (2 × 10 min). After each coupling reaction, the resin was washed with DMF. Synthesis of C60–peptide conjugates 5a–c The synthetic

Substrate specificity of a ketosynthase domain involved in bacillaene biosynthesis

• Zhiyong Yin and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2024, 20, 734–740, doi:10.3762/bjoc.20.67

• ester 5 was coupled with the carboxylic acid (S)-8, derived from ʟ-leucine ((S)-6) via hydroxyacid (S)-7, to yield the amide (S)-9. Deprotection through catalytic hydrogenation to (S)-10, saponification of the acetate ester and Steglich esterification with N-acetylcysteamine gave access to the desired

Development of a chemical scaffold for inhibiting nonribosomal peptide synthetases in live bacterial cells

• Fumihiro Ishikawa,
• Sho Konno,
• Hideaki Kakeya and
• Genzoh Tanabe

Beilstein J. Org. Chem. 2024, 20, 445–451, doi:10.3762/bjoc.20.39

• deprotection of the 5′-OH group using 25% trifluoroacetic acid in tetrahydrofuran. Subsequently, the 5′-OH group of compounds 12a–e were reacted with sulfamoyl chloride in the presence of NaH. Compounds 13a–e were coupled to pre-activated Boc-ʟ-Phe-OSu in the presence of Cs2CO3. Removal of the Boc and TBS

Synthesis of π-conjugated polycyclic compounds by late-stage extrusion of chalcogen fragments

• Aissam Okba,
• Pablo Simón Marqués,
• Kyohei Matsuo,
• Naoki Aratani,
• Hiroko Yamada,
• Gwénaël Rapenne and
• Claire Kammerer

Beilstein J. Org. Chem. 2024, 20, 287–305, doi:10.3762/bjoc.20.30

• endoperoxide formation. To overcome these issues, the “precursor approach” was developed and relies on the synthesis, purification and characterization of soluble and stable precursors of the target active π-CPCs, followed by their (solution) processing and their final deprotection once assembled in thin-films

• precursors inherently limits the applicability of these reactions to the synthesis of π-CPCs containing linearly-fused benzene rings in their core scaffold (i.e., at least an anthracene pattern), or to the deprotection of peripheral benzene rings. To reach a wider variety of structures, novel synthetic

Optimizations of lipid II synthesis: an essential glycolipid precursor in bacterial cell wall synthesis and a validated antibiotic target

• Milandip Karak,
• Cian R. Cloonan,
• Brad R. Baker,
• Rachel V. K. Cochrane and
• Stephen A. Cochrane

Beilstein J. Org. Chem. 2024, 20, 220–227, doi:10.3762/bjoc.20.22

• Supporting Information File 1 for comprehensive information on the synthesis details of the tetrapeptide). To avoid loss of valuable material through HPLC purification, crude 7 is used directly in the next step, and purification performed after the final prenyl phosphate coupling and global deprotection

• . Finally, the benzyl-protecting groups in compound 7 were cleaved via hydrogenolysis, followed by co-evaporation of the resulting crude product in pyridine. This yielded a monopyridyl salt, setting the stage for the final lipid coupling and deprotection sequence. To establish the vital lipid diphosphate

• mixture underwent a cross-coupling reaction with prenyl monophosphates [46] in DMF/THF over a four-day period, yielding fully protected versions of lipid II and its analogues. Subsequent global deprotection reactions, using aqueous NaOH, led to the formation of lipid II (11), with an overall yield of 16

Correction: Synthesis of highly substituted fluorenones via metal-free TBHP-promoted oxidative cyclization of 2-(aminomethyl)biphenyls. Application to the total synthesis of nobilone

• Ilya A. P. Jourjine,
• Lukas Zeisel,
• Jürgen Krauß and
• Franz Bracher

Beilstein J. Org. Chem. 2024, 20, 170–172, doi:10.3762/bjoc.20.16

• title compound nobilone (1d). Finally, it should be noted that the sesquihydrate of K2CO3 rather than anhydrous K2CO3 was used. In the original publication, we stated that the TBHP-mediated cyclization of compound 23 (929 mg, 1.96 mmol) to give compound 24 and the subsequent deprotection of crude

Long oligodeoxynucleotides: chemical synthesis, isolation via catching-by-polymerization, verification via sequencing, and gene expression demonstration

• Yipeng Yin,
• Reed Arneson,
• Alexander Apostle,
• Adikari M. D. N. Eriyagama,
• Komal Chillar,
• Emma Burke,
• Martina Jahfetson,
• Yinan Yuan and
• Shiyue Fang

Beilstein J. Org. Chem. 2023, 19, 1957–1965, doi:10.3762/bjoc.19.146

• methacrylamide group. Detritylation was not carried out in the last synthetic cycle, which would otherwise remove the polymerizable tag. A portion of the CPG was subsequently subjected to deprotection and cleavage. To prevent the potential Michael addition side reaction of acrylonitrile to nucleobases, the 2

• typical deprotection and cleavage conditions using concentrated ammonium hydroxide at elevated temperature. At this stage, the mixture contained the desired full-length sequence 3 and impurities such as failure sequences 4 and small molecules from ODN deprotection (Scheme 1). It is noted that the full

• the formation of 2,6-diaminopurine from a capping-modified guanine base during ammonium hydroxide ODN deprotection and subsequent reading as dA during PCR [26][27][28]. The dT-to-dC substitution could have been resulted from amination of dT to give 5-methyl-dC, which is recognized as dC in PCR as well

N-Boc-α-diazo glutarimide as efficient reagent for assembling N-heterocycle-glutarimide diads via Rh(II)-catalyzed N–H insertion reaction

• Grigory Kantin,
• Pavel Golubev,
• Alexander Sapegin,
• Alexander Bunev and
• Dmitry Dar’in

Beilstein J. Org. Chem. 2023, 19, 1841–1848, doi:10.3762/bjoc.19.136

• -phenylpyrazolin-3-one, an exceptionally low conversion of the starting heterocycle was observed. In the next step, we have demonstrated the possibility of removing the protective Boc group under mild conditions without acid or base catalysis (Scheme 4). Deprotection occurs in high, near quantitative yields

• %); bNMR yield; cstructure confirmed by single-crystal X-ray data; dcalculated yield based on incomplete conversion of NH-substrate. Examples of N-deprotection of α-modified glutarimides 1. Preparation of NH2-containing derivative 10 via reduction of 6n. Supporting Information Deposition number 2298240

N-Sulfenylsuccinimide/phthalimide: an alternative sulfenylating reagent in organic transformations

• Fatemeh Doraghi,
• Seyedeh Pegah Aledavoud,
• Mehdi Ghanbarlou,
• Bagher Larijani and
• Mohammad Mahdavi

Beilstein J. Org. Chem. 2023, 19, 1471–1502, doi:10.3762/bjoc.19.106

• the presence of N-(2-bromophenylthio)succinimide 1’ and copper catalyst led to intermolecular sulfenoamination of alkenes and subsequent C–N coupling to produce dihydrobenzothiazine structures 27 in a one-pot manner. Furthermore, deprotection of the amine unit by K2CO3 and Na metal was performed in

α-(Aminomethyl)acrylates as acceptors in radical–polar crossover 1,4-additions of dialkylzincs: insights into enolate formation and trapping

• Angel Palillero-Cisneros,
• Paola G. Gordillo-Guerra,
• Fernando García-Alvarez,
• Olivier Jackowski,
• Franck Ferreira,
• Fabrice Chemla,
• Joel L. Terán and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2023, 19, 1443–1451, doi:10.3762/bjoc.19.103

• concomitant deprotection of the nitrogen and the ester groups. The sample was found to have a negative optical rotation, thereby indicating that the major enantiomer present had S configuration [26]. This allowed to establish that the configuration of the major diastereomer present in (RS)-14b was (RS,S), and

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

• alcohol functions of 4.5 were deprotected in acidic media to produce 3-O-octadecyl-sn-glycerol (4.6). The enantiomer of 4.6 was obtained from 4.4 by protecting the primary alcohol with a benzyl group to give 4.7. Then, the deprotection of the two alcohol functions with H2SO4 in water followed by the

• hydrogenolysis to produce 1-O-octadecyl-sn-glycerol (4.10). It must be noted that the authors, after the deprotection of the two alcohol functions of 4.7, attempted the direct alkylation of the primary alcohol with octadecyltosylate. However, a mixture of mono and dialkylation was formed and were separated by

• benzylation produced 4.13. Then, the deprotection of the primary alcohol in acidic conditions allows introducing the phosphocholine polar head group by using POCl3 and the choline tosylate salt as reagents to yield 4.14. Finally, the debenzylation of the secondary alcohol and its acylation produce PAF 4.15. b

CO₂ complexation with cyclodextrins

• Cecilie Høgfeldt Jessen,
• Jesper Bendix,
• Theis Brock Nannestad,
• Heloisa Bordallo,
• Martin Jæger Pedersen,
• Christian Marcus Pedersen and
• Mikael Bols

Beilstein J. Org. Chem. 2023, 19, 1021–1027, doi:10.3762/bjoc.19.78

• , in our hands the direct tosylations were difficult to handle and the protection–deprotection route proved a more reliable route to pure compounds. For 2 and 3 we found no binding which is in line with the absence of gas-crystals from these cyclodextrins. The lack of binding must, in part, be linked

Linker, loading, and reaction scale influence automated glycan assembly

• Marlene C. S. Dal Colle,
• Manuel G. Ricardo,
• Nives Hribernik,
• José Danglad-Flores,
• Peter H. Seeberger and
• Martina Delbianco

Beilstein J. Org. Chem. 2023, 19, 1015–1020, doi:10.3762/bjoc.19.77

• (BBs) [1][2]. Iterative cycles of glycosylation, capping, and selective deprotection afford the support-bound glycan with a programmable sequence (Figure 1A). The protected glycan is then cleaved from the solid support and subjected to post-AGA deprotection steps to reveal the target glycan. AGA is

• , but isolated in relatively low yields. The optimization procedures are focused on glycan elongation (i.e., glycosylation and deprotection steps), whereas less attention is given to variables associated with the solid support [17]. In contrast, substantial knowledge exists on how loading [18], reaction

• that cleavage and/or purification are the major bottlenecks of these syntheses. Higher yields (30–57%) were obtained for compound 6b, isolated after the post-AGA procedure path B (Figure 2D). This is surprising since the path B procedure involved additional deprotection steps. Therefore, we wondered

Clauson–Kaas pyrrole synthesis using diverse catalysts: a transition from conventional to greener approach

• Dileep Kumar Singh and
• Rajesh Kumar

Beilstein J. Org. Chem. 2023, 19, 928–955, doi:10.3762/bjoc.19.71

• compared to other organic solvents. In addition, the use of water as the green solvent for this conversion contributed more to the development of a green reaction. The proposed mechanism is depicted in Scheme 11b, in which the methoxy group of 2,5-DMTHF (2) is opened by the deprotection in acidic medium

• aniline bearing an electron-donating group produced slightly higher yields than aromatic amines with an electron-withdrawing group. The authors also proposed a tentative mechanism for this reaction, in which intermediate A was first formed by deprotection of 2,5-DMTHF (2), and then A reacted with amines

• –98% yields by reacting various amines 60 and 2,5-DMTHF 2 under solvent-free conditions in the presence of 5 mol % molecular iodine as catalyst (Scheme 29a). These synthesized products were tested against various cancer cells in vitro. In the proposed mechanism, deprotection of the methoxy group of

Construction of hexabenzocoronene-based chiral nanographenes

• Ranran Li,
• Di Wang,
• Shengtao Li and
• Peng An

Beilstein J. Org. Chem. 2023, 19, 736–751, doi:10.3762/bjoc.19.54

• dibenzocyclooctyne 8 and tetracyclone 2 in a 91% yield. After a subsequent sequence of deprotection and oxidation, ketone 10 was obtained. Through the oxidative cyclodehydrogenation reaction of 10 in the presence of DDQ and trifluoromethanesulfonic acid (TfOH), a saddle-helix hybrid nanographene 11, bearing an

Strategies in the synthesis of dibenzo[b,f]heteropines

• David I. H. Maier,
• Barend C. B. Bezuidenhoudt and
• Charlene Marais

Beilstein J. Org. Chem. 2023, 19, 700–718, doi:10.3762/bjoc.19.51

• ]oxepine in good yield (65%). Subsequent deprotection of the isopropyloxy group with BCl3 gave 13 in good yield. Bergmann et al. [71] described an early method of synthesising dihydrodibenzo[b,f] oxepine 2b and -azepine 136 via a C–C intramolecular Wurtz reaction of tethered benzyl bromides 134 and 135

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

• refluxing acetonitrile for 6 h. It underwent a radical cyclization in refluxing benzene for 20 h to give rise to a nine-membered phostone thieno[2,3-d]pyrimidine-fused 2-hydroxy-1,2-oxaphosphonane 2-oxide 46 as a potential inhibitor after the deprotection of the benzyl group in the presence of DABCO in

Enolates ambushed – asymmetric tandem conjugate addition and subsequent enolate trapping with conventional and less traditional electrophiles

• Péter Kisszékelyi and
• Radovan Šebesta

Beilstein J. Org. Chem. 2023, 19, 593–634, doi:10.3762/bjoc.19.44

• enantiomeric purity. Further transformations of the products were demonstrated in several examples, including reduction, acidic deprotection and subsequent base-mediated cyclization, or Baeyer–Villiger oxidation. At about the same time, Huang and co-workers have developed similar asymmetric tandem sequences

Access to cyclopropanes with geminal trifluoromethyl and difluoromethylphosphonate groups

• Ita Hajdin,
• Romana Pajkert,
• Mira Keßler,
• Jianlin Han,
• Haibo Mei and
• Gerd-Volker Röschenthaler

Beilstein J. Org. Chem. 2023, 19, 541–549, doi:10.3762/bjoc.19.39

• (5). This compound was synthesized smoothly within three steps in 16.6% overall yield. The synthetic route commenced from the preparation of N-protected amine 3, followed by the deprotection of benzylamine 3 to furnish 4 and ended with the diazotization of 4 using tert-butyl nitrite. As a result, the

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

• fluorinated aminophosphonates [23][24] with the simultaneous deprotection of the amino group. The free amines were subjected to kinetic studies to investigate their interaction with cathepsin C. The required steps should be simple and fast, and the conditions of the reactions should be as mild as possible

• fluorinated aminophosphonates with the simultaneous deprotection of the amino group. The resulting acids were converted into the corresponding salts. All the reactions proceeded quantitatively. Obtained compounds were subjected to kinetic studies against cathepsin C, and the results indicated that they are

Asymmetric synthesis of a stereopentade fragment toward latrunculins

• Benjamin Joyeux,
• Antoine Gamet,
• Nicolas Casaretto and
• Bastien Nay

Beilstein J. Org. Chem. 2023, 19, 428–433, doi:10.3762/bjoc.19.32

• synthesize latrunculin analogues for chemical biology studies. In particular, our initial goal was to protect an inactive lactol-opened form of latrunculins, which could cyclize in vivo upon deprotection under a specific stimulus (light or enzyme, for instance) for biological applications. This challenge

• –Tishchenko method [31][32], in presence of SmI2 and an aldehyde (Scheme 4). para-Nitrobenzaldehyde was used [33] to introduce a labile para-nitrobenzoate on the product, planning an easy deprotection of the alcohol. This would also pave the way to an orthogonal manipulation of protecting groups on the

Combretastatins D series and analogues: from isolation, synthetic challenges and biological activities

• Jorge de Lima Neto and
• Paulo Henrique Menezes

Beilstein J. Org. Chem. 2023, 19, 399–427, doi:10.3762/bjoc.19.31

• gave the corresponding epoxide 51 in low enantioselectivity and only 44% yield. The subsequent deprotection reaction led to compound 1 in 86% yield (Scheme 9). Besides the low enantioselectivity, the authors observed that the optical rotation value of the synthesized compound ([α]D +36.9, c 0.55, CHCl3

• provided the seco-acid 75. Employing the same Mitsunobu conditions previously described [35], the authors were able to obtain the macrolide 76 in 81% yield which was then subjected to deprotection to give compound 77 (Scheme 14). The synthesis of 2 from compound 77 was achieved after hydrogenolysis of the

• hydroxybenzaldehyde 80 into the corresponding acetal followed by Ullmann-type coupling with 52, led to the formation of diaryl ether 83. Subsequent Corey–Fuchs reaction [49] and in situ alkylation led to formation of the propargylic alcohol 85. Deprotection of the aldehyde followed by chain elongation through the

CuAAC-inspired synthesis of 1,2,3-triazole-bridged porphyrin conjugates: an overview

• Dileep Kumar Singh

Beilstein J. Org. Chem. 2023, 19, 349–379, doi:10.3762/bjoc.19.29

• reaction and was subjected to deprotection of the triisopropylsilyl group with tetra-n-butylammonium fluoride (Bu4NF). Similarly triad 121 was prepared by the click reaction between dyads 119 and azido-ferrocene 120 in a 40% overall yield. The photophysical investigation revealed that dyad 119 exhibited

• 124 in the presence of copper bromide and tris((1-benzyl-4-triazolyl)methyl)amine (TBTA) in DMSO/H2O to give a porphyrin-lantern (PL)-DNA sequence in 45% yield after cleavage and deprotection. These PL-DNA sequences were further used to construct strong and fluorescent G-wires that could be useful for