A study of the DIBAL-promoted selective debenzylation of α-cyclodextrin protected with two different benzyl groups

• Naser-Abdul Yousefi,
• Morten L. Zimmermann and
• Mikael Bols

Beilstein J. Org. Chem. 2022, 18, 1553–1559, doi:10.3762/bjoc.18.165

• cleavage [16] or from 1 by selective protection of the primary OH groups with tert-butyldimethylsilyl groups, followed by benzylation and desilylation [17][18]. We used both methods to prepare 6: The acetolysis method is convenient when perbenzyl α-cyclodextrin (2) is at hand but requires very strict

New triazole-substituted triterpene derivatives exhibiting anti-RSV activity: synthesis, biological evaluation, and molecular modeling

• Elenilson F. da Silva,
• Krist Helen Antunes Fernandes,
• Denise Diedrich,
• Jessica Gotardi,
• Marcia Silvana Freire Franco,
• Carlos Henrique Tomich de Paula da Silva,
• Ana Paula Duarte de Souza and
• Simone Cristina Baggio Gnoatto

Beilstein J. Org. Chem. 2022, 18, 1524–1531, doi:10.3762/bjoc.18.161

• . Initially, 1-azido-3-nitrobenzene (c) was obtained from m-nitroaniline (a) (Scheme 1) with excellent yields (98%), as previously described [41]. The protection of the 3β-OH group of the triterpene skeleton was carried out by acetylation using acetic anhydride to prevent cleavage in acidic conditions, which

An alternative C–P cross-coupling route for the synthesis of novel V-shaped aryldiphosphonic acids

• Stephen J. I. Shearan,
• Enrico Andreoli and
• Marco Taddei

Beilstein J. Org. Chem. 2022, 18, 1518–1523, doi:10.3762/bjoc.18.160

• Supporting Information File 1, Scheme S3 [41][42]. Prior to using this method, the standard hydrolysis under prolonged reflux in 6 M HCl was attempted, though these conditions proved too harsh, and often led to cleavage of the C–P bond. Thus, this popular method was abandoned in favor of using the less harsh

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

• based on silver either gave a complex mixture or unreacted starting material. Phosphonate 8 was converted into the corresponding thiophosphonate 9 in moderate yield using Lawesson's reagent. Cleavage of the methyl ester was easily accomplished in quantitative yield, producing racemic tryptophol CPA 1

1,4,6,10-Tetraazaadamantanes (TAADs) with N-amino groups: synthesis and formation of boron chelates and host–guest complexes

• Artem N. Semakin,
• Ivan S. Golovanov,
• Yulia V. Nelyubina and
• Alexey Yu. Sukhorukov

Beilstein J. Org. Chem. 2022, 18, 1424–1434, doi:10.3762/bjoc.18.148

• treatment of secondary amine 11 with ene-nitrosoacetal 12 [36] (Scheme 2b). The synthesis of products 7a,b containing two oxime groups was accomplished via double oximinoalkylation of benzylamine to give dioxime 13 [36], cleavage of the N-benzyl group, and reaction of the secondary amine 14 with α

Preparation of an advanced intermediate for the synthesis of leustroducsins and phoslactomycins by heterocycloaddition

• Anaïs Rousseau,
• Guillaume Vincent and
• Cyrille Kouklovsky

Beilstein J. Org. Chem. 2022, 18, 1385–1395, doi:10.3762/bjoc.18.143

• on the synthesis and the coupling of three main fragments. The central fragment was synthesized via a regio-and stereoselective nitroso Diels–Alder reaction with an enol phosphate, followed by reductive cleavage of the phosphate to the ketone 11b. Coupling studies of this fragment with the lactone

• both fragments for the synthesis of an advanced intermediate. The synthetic strategy for the synthesis of the central fragment takes advantage of the proximity between the terminal amino function and the hydroxy function at C9. It was anticipated that both functions could arise from the cleavage of a N

• conditions. Cleavage of enol phosphate with Red-Al. Synthesis of the protected central fragment 11b. Synthesis and derivatization of the lactone fragment. Coupling reaction between alkyne 19 and ketone 11b. Coupling reaction between vinyl iodide 20 and ketone 11b. Oxidation of the acetal to the lactone

Cyclodextrin-based Schiff base pro-fragrances: Synthesis and release studies

• Attila Palágyi,
• Jindřich Jindřich,
• Juraj Dian and
• Sophie Fourmentin

Beilstein J. Org. Chem. 2022, 18, 1346–1354, doi:10.3762/bjoc.18.140

• present an advantage compared to simple encapsulation and to other substrates as they will not only ensure very low volatility of the obtained pro-fragrance but also be able to encapsulate the guest after the cleavage of the covalent bond, leading to a two-in-one system. Indeed, encapsulation in CDs is

Cytochrome P450 monooxygenase-mediated tailoring of triterpenoids and steroids in plants

• Karan Malhotra and
• Jakob Franke

Beilstein J. Org. Chem. 2022, 18, 1289–1310, doi:10.3762/bjoc.18.135

• (12) scaffold to 7β-hydroxythalianol, while CYP705A5 is a desaturase and introduces a double bond at C15 [41]. The related Arabidopsis CYP705A1 (also from clan 71) accepts a slightly different scaffold, arabidiol (11), triggering cleavage of the side chain at the same C15 instead of dehydrogenation

Modular synthesis of 2-furyl carbinols from 3-benzyldimethylsilylfurfural platforms relying on oxygen-assisted C–Si bond functionalization

• Sebastien Curpanen,
• Per Reichert,
• Gabriele Lupidi,
• Giovanni Poli,
• Julie Oble and
• Alejandro Perez-Luna

Beilstein J. Org. Chem. 2022, 18, 1256–1263, doi:10.3762/bjoc.18.131

• carbanion (by exocyclic cleavage) rather than a 3-furanyl anion (by endocyclic cleavage). As a consequence, the failure to promote C3–Si activation of intermediates E (SiR3 = SiEt3 or SiMe2t-Bu) according to our initially envisaged scenario depicted in Scheme 3, did not seem to be related to the difficulty

• -catalyzed arylation reactions (Scheme 7). Fluoride-promoted arylation reactions of benzyldimethyl(alkenyl)silanes have been reported, and it is established that they proceed through the cleavage of the benzyl moiety from the benzyldimethylsilyl groups, leading to either dimethylsilanols or cyclic siloxanes

Polymer and small molecule mechanochemistry: closer than ever

• José G. Hernández

Beilstein J. Org. Chem. 2022, 18, 1225–1235, doi:10.3762/bjoc.18.128

• to promote the thermodynamically disfavored SN2 cleavage of an individual protein disulfide bond by poorly nucleophilic organic thiols [21]. On the other hand, as for the connection or correlation between polymer and small molecule mechanochemistry, this Perspective article discusses recent studies

• cleavage of the polymer chains [23], a strategy that is still of relevance today [24][25] and also complements the recent application of ball milling for the synthesis of polymers [26]. As an example for the use of ball milling to activate mechanophores incorporated in polymers, Baytekin, Akkaya, and co

• -free ball milling has enabled to surpass the insolubility and recalcitrant reactivity of cellulose [36][37], chitin [38][39], and lignin (Figure 2) [40][41]. In addition to allowing solvent-free reactions, mechanical forces generated inside ball mills can depolymerize biomass through cleavage pathways

Reductive opening of a cyclopropane ring in the Ni(II) coordination environment: a route to functionalized dehydroalanine and cysteine derivatives

• Oleg A. Levitskiy,
• Olga I. Aglamazova,
• Yuri K. Grishin and
• Tatiana V. Magdesieva

Beilstein J. Org. Chem. 2022, 18, 1166–1176, doi:10.3762/bjoc.18.121

• ). Notably, insertion of the second COOR group in the starting cyclopropane complex 4 completely suppresses this reaction channel: intramolecular cyclization of the anions formed in the reductive cleavage of the three-membered ring was not observed. This may be attributed to the decreased nucleophilicity as

Synthesis of tryptophan-dehydrobutyrine diketopiperazine and biological activity of hangtaimycin and its co-metabolites

• Houchao Xu,
• Anne Wochele,
• Minghe Luo,
• Gregor Schnakenburg,
• Yuhui Sun,
• Heike Brötz-Oesterhelt and
• Jeroen S. Dickschat

Beilstein J. Org. Chem. 2022, 18, 1159–1165, doi:10.3762/bjoc.18.120

• -tryptophan (5) that was converted through a standard transformation into the methyl ester 6 and then through sequential reductive aminations with benzaldehyde and paraformaldehyde into 7 (Scheme 2) [13]. Cleavage of the benzyl group by catalytic hydrogenation afforded 8 that was coupled with tert

• -butyloxycarbonyl (Boc)-protected threonine using bis(2-oxo-3-oxazolidinyl)phosphinic chloride (BOP-Cl) [14][15] and Hünig’s base to give 9. Cleavage of the Boc group with 5% TFA followed by basic treatment resulted in the cyclisation to the dioxopiperazine 10. Acetylation and subsequent treatment with LiClO4 and

Electrochemical formal homocoupling of sec-alcohols

• Kosuke Yamamoto,
• Kazuhisa Arita,
• Masashi Shiota,
• Masami Kuriyama and
• Osamu Onomura

Beilstein J. Org. Chem. 2022, 18, 1062–1069, doi:10.3762/bjoc.18.108

• -2a was subjected to the present reaction conditions, oxidative C–C bond cleavage of dl-2a proceeded to give the corresponding ketone 3a (Scheme 5b) [48]. Recovered 2a was found to be a mixture of dl and meso isomers, indicating that homocoupling of in situ-generated ketone 3a occurred under the

First series of N-alkylamino peptoid homooligomers: solution phase synthesis and conformational investigation

• Maxime Pypec,
• Laurent Jouffret,
• Claude Taillefumier and
• Olivier Roy

Beilstein J. Org. Chem. 2022, 18, 845–854, doi:10.3762/bjoc.18.85

• ]. In this seminal publication, hydrazones were utilized as submonomers in the displacement step of resin-bound bromoacetylated peptoids and cleavage from the resin with TFA containing 5% of triethylsilane resulted in a concomitant reduction of the imine functions in N-alkylamino groups. In this work

Structural basis for endoperoxide-forming oxygenases

• Takahiro Mori and
• Ikuro Abe

Beilstein J. Org. Chem. 2022, 18, 707–721, doi:10.3762/bjoc.18.71

• , natural and (semi)synthetic endoperoxides with wide structural diversity show antimalarial activity against Plasmodium falciparum malaria. In this case, the reductive activation of the endoperoxide ring with the homolytic cleavage of the O–O bond leads to the generation of carbon-centered free radicals

• intermediate of fumitremorgin B, and is incorporated without cleavage of the O–O bond in the enzyme reaction catalyzed by FtmOx1. Biochemical and biophysical analyses of FtmOx1 have been reported by many different groups, and the structures of FtmOx1 wild type and variants have been solved in the apo and

Mechanochemical halogenation of unsymmetrically substituted azobenzenes

• Dajana Barišić,
• Mario Pajić,
• Ivan Halasz,
• Darko Babić and
• Manda Ćurić

Beilstein J. Org. Chem. 2022, 18, 680–687, doi:10.3762/bjoc.18.69

• proceeds by electrophilic cleavage with neutral NBS or the hydrogen bond complex NBS∙∙∙TsOH as a bromine source. Here we present the mechanochemical selective halogenation of unsymmetrically substituted azobenzenes by NXS (X = Cl, Br, or I). The liquid-assisted grinding of para-halogenated derivatives of

Direct C–H amination reactions of arenes with N-hydroxyphthalimides catalyzed by cuprous bromide

• Dongming Zhang,
• Bin Lv,
• Pan Gao,
• Xiaodong Jia and
• Yu Yuan

Beilstein J. Org. Chem. 2022, 18, 647–652, doi:10.3762/bjoc.18.65

• -electron transfer (SET) between CuBr and intermediate 5 forms intermediate 6, which initiates the N–O bond homolytic cleavage resulting in forming an N-centred phthalimidyl radical 7 (PhthN•) and anion 8. Meanwhile, Cu(I) is oxidized to Cu(II) in this step. Next, radical 7 attacks the benzene via radical

The asymmetric Henry reaction as synthetic tool for the preparation of the drugs linezolid and rivaroxaban

• Martin Vrbický,
• Karel Macek,
• Jaroslav Pochobradský,
• Jan Svoboda,
• Miloš Sedlák and
• Pavel Drabina

Beilstein J. Org. Chem. 2022, 18, 438–445, doi:10.3762/bjoc.18.46

• intermediate 11 was accompanied with simultaneous cleavage of the Boc group. However, attempts of achieving a selective deacetalation of 11 by the treatment with several reagents (e.g., I2/acetone [15], FeCl3·6H2O/acetaldehyde [16], Ce(OTf)3 [17]) were unsuccessful. Therefore, an alternative synthesis [18] was

Recent developments and trends in the iron- and cobalt-catalyzed Sonogashira reactions

• Surendran Amrutha,
• Sankaran Radhika and
• Gopinathan Anilkumar

Beilstein J. Org. Chem. 2022, 18, 262–285, doi:10.3762/bjoc.18.31

• with an electrophile results in the formation of a cobalt(III) intermediate. Subsequent homolytic cleavage and generation of cobalt(II) complex C and radical D the radical undergoes addition to phenylacetylene to provide cobalt(III) intermediate E. The targeted compound 1-methyl-4-(2-phenylethynyl

Organocatalytic asymmetric nitroso aldol reaction of α-substituted malonamates

• Ekta Gupta,
• Narendra Kumar Vaishanv,
• Sandeep Kumar,
• Raja Krishnan Purshottam,
• Ruchir Kant and
• Kishor Mohanan

Beilstein J. Org. Chem. 2022, 18, 217–224, doi:10.3762/bjoc.18.25

• ). Disappointingly, the reactions carried out by varying the α-substitution did not afford the desired product. In order to demonstrate the synthetic utility of the oxyaminated compounds, the reductive cleavage of the N–O bond was attempted under Zn/AcOH conditions. Pleasingly, the reaction afforded the aniline

Anomeric 1,2,3-triazole-linked sialic acid derivatives show selective inhibition towards a bacterial neuraminidase over a trypanosome trans-sialidase

• Peterson de Andrade,
• Sanaz Ahmadipour and
• Robert A. Field

Beilstein J. Org. Chem. 2022, 18, 208–216, doi:10.3762/bjoc.18.24

• both enzymes (Figure 3A) (and TcTS transferase activity in the presence of an acceptor substrate, such as lactose – Figure 3B) by releasing the fluorophore 4-methylumbelliferone (MU) for detection upon cleavage of the substrate 2'-(4-methylumbelliferyl) α-ᴅ-N-acetylneuraminic acid (MUNANA). Compounds

Synthesis and late stage modifications of Cyl derivatives

• Phil Servatius and
• Uli Kazmaier

Beilstein J. Org. Chem. 2022, 18, 174–181, doi:10.3762/bjoc.18.19

• +. Subsequent attack of water forms a tetrahedral intermediate which results in a cleavage of the acetylated lysine. Most HDAC inhibitors act as substrate mimics and contain a zinc-binding motif. They competitively interact with the HDACs to form stable intermediates and therewith block the active site. Many

Earth-abundant 3d transition metals on the rise in catalysis

• Nikolaos Kaplaneris and
• Lutz Ackermann

Beilstein J. Org. Chem. 2022, 18, 86–88, doi:10.3762/bjoc.18.8

• witnessed major momentum in metal-catalyzed C–H activation [4][5] as a more resource-economical strategy. This approach involves the efficient and selective cleavage of otherwise inert, yet omnipresent C–H bonds. This strategy avoids a variety of steps and reduces the amount of chemical waste. Very recently

Efficient and regioselective synthesis of dihydroxy-substituted 2-aminocyclooctane-1-carboxylic acid and its bicyclic derivatives

• İlknur Polat,
• Selçuk Eşsiz,
• Uğur Bozkaya and
• Emine Salamci

Beilstein J. Org. Chem. 2022, 18, 77–85, doi:10.3762/bjoc.18.7

• . Results and Discussion Initially, we focused on the synthesis of β-lactam 2, which was prepared by the cycloaddition of chlorosulfonyl isocyanate (CSI) to cis,cis-1,3-cyclooctadiene, as described in the literature [26]. β-Lactam 2 was transformed into cis-amino ester 3 by cleavage of the lactam ring with

Peptide stapling by late-stage Suzuki–Miyaura cross-coupling

• Hendrik Gruß,
• Rebecca C. Feiner,
• Ridhiwan Mseya,
• David C. Schröder,
• Michał Jewgiński,
• Kristian M. Müller,
• Rafał Latajka,
• Antoine Marion and
• Norbert Sewald

Beilstein J. Org. Chem. 2022, 18, 1–12, doi:10.3762/bjoc.18.1

• macrocyclisation product, which was confirmed by MALDI-ToF-MS of the crude reaction mixture after test cleavage (see Supporting Information File 1, Figure S1). However, deboronation and dehalogenation were observed as side reactions to some extent as well as oxidation, most likely of methionine (Met) [79]. The

• oxidation could be minimised by improved cleavage conditions under argon. Replacing sSPhos by tri(o-tolyl)phosphine (P(o-Tol)3), that had successfully been applied for peptide cyclisation by on-resin SMC [78][80], led to incomplete conversion. The cyclisation of the same peptide with the regioisomer 6

• stability of both peptides P5 and P6 was tested against proteinase K digestion. Whilst the linear analogue P6 is cleaved within a period of 120 min to give three fragments, the stapled peptide P5 allows access to only one of the three cleavage sites: i.e., proteolysis of the Leu–Asp bond within the