Glycosylation reactions mediated by hypervalent iodine: application to the synthesis of nucleosides and carbohydrates

• Yuichi Yoshimura,
• Hideaki Wakamatsu,
• Yoshihiro Natori,
• Yukako Saito and
• Noriaki Minakawa

Beilstein J. Org. Chem. 2018, 14, 1595–1618, doi:10.3762/bjoc.14.137

• by manipulations of 5. After acetal hydrolysis and the subsequent hydride reduction, 4-thioarabinose derivative 9 was obtained in good yield. Introduction of a TBDPS group at the primary hydroxy group of 9, oxidation and Wittig reaction, followed by deprotection of the benzyl group, gave allyl

A selective removal of the secondary hydroxy group from ortho-dithioacetal-substituted diarylmethanols

• Anna Czarnecka,
• Emilia Kowalska,
• Agnieszka Bodzioch,
• Joanna Skalik,
• Marek Koprowski,
• Krzysztof Owsianik and
• Piotr Bałczewski

Beilstein J. Org. Chem. 2018, 14, 1229–1237, doi:10.3762/bjoc.14.105

• bond and consequently the reduction of the former should a priori occur preferentially [53][54][55]. According to the best of our knowledge, there are no literature reports concerning selective reductions of dibenzylic hydroxy groups in the presence of ortho-acetal or ortho-thioacetal functions. Such

• , only few applications of the ZnI2-Na(CN)BH3 system in DCE have been described for reduction of diarylmethanols that do not contain acid-sensitive, formyl protecting, acetal or thioacetal groups [20][27][57][58][59][60] and for the reduction of aromatic aldehydes and ketones [28]. The bromo function in

One hundred years of benzotropone chemistry

• Arif Dastan,
• Haydar Kilic and
• Nurullah Saracoglu

Beilstein J. Org. Chem. 2018, 14, 1120–1180, doi:10.3762/bjoc.14.98

• ]annulenes as a novel series of potent and specific αv integrin antagonists starting from 4,5-benzotropone (11) (Figure 4 and Scheme 13) [73]. TBS-enol ether intermediate 68 was first formed by the Mukaiyama–Michael reaction of O-silyl ketene acetal to 4,5-benzotropone (11) at low temperature in the presence

• synthesis and cycloaddition of tropone ethylene acetal and benzotropone ethylene acetal 157 (Scheme 27) [133]. The ketal 157 was prepared from the reaction of 4,5-benzotropone (11) with ethylene glycol in the presence of triethyloxonium tetrafluoroborate. The cycloaddition of 157 with 4-phenyl-1,2,4

• to 2-cyclopentenone acetal (228) followed by hydrolysis and subsequent oxidation of the resultant ketone 229 with DDQ. Irradiation (>300 nm) of 230 in EPA (a 5:5:2 mixture of ether, isopentane, and ethanol) at −196 °C led to the formation of 13, which exhibited the development of characteristic UV

Selective carboxylation of reactive benzylic C–H bonds by a hypervalent iodine(III)/inorganic bromide oxidation system

• Toshifumi Dohi,
• Shohei Ueda,
• Kosuke Iwasaki,
• Yusuke Tsunoda,
• Koji Morimoto and
• Yasuyuki Kita

Beilstein J. Org. Chem. 2018, 14, 1087–1094, doi:10.3762/bjoc.14.94

• acetoxylation at the activated benzyl carbon adjacent to an oxygen atom proceeded smoothly as shown by the formation of the pseudo acetal 2g (Table 2, entry 6). Diphenylmethane and its derivatives were very good substrates for our system and were less sensitive to the electronic effects of the aromatic ring

On the design principles of peptide–drug conjugates for targeted drug delivery to the malignant tumor site

• Eirinaios I. Vrettos,
• Gábor Mező and
• Andreas G. Tzakos

Beilstein J. Org. Chem. 2018, 14, 930–954, doi:10.3762/bjoc.14.80

• , there are certain bonds like imine, oxime, hydrazone, orthoester, acetal, vinyl ether and polyketal [103] that are known to undergo hydrolysis at acidic pH, while being extremely stable during blood circulation. Therefore, acid-labile bonds could be hydrolyzed in the slightly acidic microenvironment and

Investigations towards the stereoselective organocatalyzed Michael addition of dimethyl malonate to a racemic nitroalkene: possible route to the 4-methylpregabalin core structure

• Denisa Vargová,
• Rastislav Baran and
• Radovan Šebesta

Beilstein J. Org. Chem. 2018, 14, 553–559, doi:10.3762/bjoc.14.42

• . This transformation is perhaps similar to acetal hydrolysis in neat water under microwave irradiation [41]. Because of this efficient process, compound 11 was isolated in one synthetic operation in 80% yield from amine 9. In the last step, precursor 11 reacted with either amine (R,R)-12 or (S,S)-12, to

Addition of dithi(ol)anylium tetrafluoroborates to α,β-unsaturated ketones

• Yu-Chieh Huang,
• An Nguyen,
• Simone Gräßle,
• Sylvia Vanderheiden,
• Nicole Jung and
• Stefan Bräse

Beilstein J. Org. Chem. 2018, 14, 515–522, doi:10.3762/bjoc.14.37

• former approaches to the synthesis of the target compounds 4 or 5 (see Scheme 1). The systematic analysis of the effect of the acetal ring size and substituents on the electrophilic and the nucleophilic component was used to reveal the influence of steric but also electronic changes on the outcome of the

Latest development in the synthesis of ursodeoxycholic acid (UDCA): a critical review

• Fabio Tonin and
• Isabel W. C. E. Arends

Beilstein J. Org. Chem. 2018, 14, 470–483, doi:10.3762/bjoc.14.33

• mechanism for this step is analogous to the mechanism for ketal or acetal formation except sulphur replaces oxygen as the nucleophile attacking the carbonyl group. In a second step, the dithioketal is reduced to the corresponding methylene compound by hydrogenolysis in presence of Raney Nickel (actually

Stimuli-responsive oligonucleotides in prodrug-based approaches for gene silencing

• Françoise Debart,
• Christelle Dupouy and
• Jean-Jacques Vasseur

Beilstein J. Org. Chem. 2018, 14, 436–469, doi:10.3762/bjoc.14.32

• partially modified 2’-O-PivOM RNAs (Scheme 11) [49]. The strategy involves standard labile acyl groups for nucleobases, cyanoethyl groups for phosphates, a Q-linker to the solid support [50] and two acetal ester groups for 2’-OH, namely, propionyloxymethyl (PrOM) and PivOM exhibiting different stability

• duplex was observed and the A-form duplex was maintained [52]. Moreover, all PivOM-modified siRNAs (1 nM) showed control of gene expression activity after transfection into ECV304 cells expressing the firefly luciferase gene. Nevertheless, the RNAi activity of such 2’-O-acetal ester siRNAs taken up by

• properties can be improved by adding positive charges to ONs to counterbalance the overall negative charge of these compounds. In this context and in extension of the previous work with the 2’-O-acetal ester modifications cited above, new modified ONs were designed with amino or guanidino-containing 2’-O

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

• -carboxyethyl)phosphine (TCEP, Figure 6) leaving all other protecting groups intact. The resulting hemi-(S,O)-acetal at the nucleotiode 3'-terminus is spontaneously degraded into the alcohol and thioformaldehyde, thus delivering the trimer with free 3'-OH group for subsequent phosphitylation. The detailed

One-pot sequential synthesis of tetrasubstituted thiophenes via sulfur ylide-like intermediates

• Jun Ki Kim,
• Hwan Jung Lim,
• Kyung Chae Jeong and
• Seong Jun Park

Beilstein J. Org. Chem. 2018, 14, 243–252, doi:10.3762/bjoc.14.16

• already been achieved by the intramolecular aldol-type condensation of N,S-acetal 7a (Figure 2C). Subsequently, we investigated the scope of the reaction using our optimized conditions (Scheme 1). As shown in Scheme 1, various isothiocyanates containing aryl and alkyl groups were applied, and the desired

• yield (32%). Starting from malonitrile, compound 8an was also prepared in a moderate yield (50%) via a Thorpe–Ziegler-type cyclization of N,S-acetal 7an. In this case, the intramolecular cyclization reaction was carried out at 100 °C for 3 h. With 5,5-dimethylcyclohexane-1,3-dione, thiophene 8ao was

• position (Table 1, entries 1 to 5). Interestingly, the 2-pyridyl moiety provided stable and reactive N,S-acetal 7aa, which could be isolated and afforded the desired thiophene 8aa in an excellent yield (92%, Table 1, entry 1). The substrate containing a 3-pyridyl group only afforded S-alkylated compound 7b

5-Aminopyrazole as precursor in design and synthesis of fused pyrazoloazines

• Ranjana Aggarwal and
• Suresh Kumar

Beilstein J. Org. Chem. 2018, 14, 203–242, doi:10.3762/bjoc.14.15

• CaCO-2. Lin et al. [52] developed the synthesis of pyrazolo[3,4-b]pyridine derivatives 45 via aza-Diels–Alder reaction of pyrazolylimines 43 with maleimides 44 (Scheme 8). Pyrazolylimines 43 were in turn obtained from the reaction of 5-aminopyrazole 16 with diisopropylformamide dimethyl acetal (R

• of 5-amino-4-cyanopyrazole 208 with N,N-dimethylformamide dimethyl acetal (DMFDMA) in acetonitrile at reflux temperature. Amidines 219 were condensed with appropriate 2-amino-5-subsitituted-1,3,4-thiadiazoles 220 under microwave irradiation in acetic acid for the generation of the desired pyrazolo

Nucleophilic fluoroalkylation/cyclization route to fluorinated phthalides

• Masanori Inaba,
• Tatsuya Sakai,
• Shun Shinada,
• Tsuyuka Sugiishi,
• Yuta Nishina,
• Norio Shibata and
• Hideki Amii

Beilstein J. Org. Chem. 2018, 14, 182–186, doi:10.3762/bjoc.14.12

• (Scheme 4) [12]. Only diastereoisomer 6 was detected in the NMR analysis. Acid-promoted deprotection of hemiaminal 6 and subsequent oxidation of acetal 7 gave the enantiopure phthalide 1a in good yield. Although a high control of diastereoselectivity (using stoichiometric auxiliary strategy) was achieved

Gram-scale preparation of negative-type liquid crystals with a CF₂CF₂-carbocycle unit via an improved short-step synthetic protocol

• Tatsuya Kumon,
• Shohei Hashishita,
• Takumi Kida,
• Shigeyuki Yamada,
• Takashi Ishihara and
• Tsutomu Konno

Beilstein J. Org. Chem. 2018, 14, 148–154, doi:10.3762/bjoc.14.10

• leads to the formation of the corresponding magnesium acetal Int-D, (ii) the alkoxide attacks another ester carbonyl moiety in the molecule to form the corresponding 5-membered ring acetal intermediate (Int-E) [15][16][17], after which immediate hydrolysis leads to the exclusive formation of the

Aminomethylation/hydrogenolysis as an alternative to direct methylation of metalated isoquinolines – a novel total synthesis of the alkaloid 7-hydroxy-6-methoxy-1-methylisoquinoline

• Benedikt C. Melzer,
• Jan G. Felber and
• Franz Bracher

Beilstein J. Org. Chem. 2018, 14, 130–134, doi:10.3762/bjoc.14.8

• starting aldehyde 2 was subjected to a reductive amination with aminoacetaldehyde dimethyl acetal and NaBH4, followed by N-tosylation and hydrochloric acid-mediated cyclization under concomitant N-detosylation and aromatization. Direct ring metalation of 3 with TMPMgCl∙LiCl was performed as described by us

Aminosugar-based immunomodulator lipid A: synthetic approaches

• Alla Zamyatina

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

• starting from azide 1 by first protecting the 3-OH group with an allyloxycarbonyl (Alloc) protecting group followed by regioselective reductive opening of the 4,6-O-benzylidene acetal using NaCNBH3 and HCl in diethyl ether, and successive phosphitylation of the liberated 4’-OH functionality with N,N

• reductive opening of benzylidene acetal using the borane−THF complex in the presence of Bu2BOTf. Regioselective TMSOTf-catalysed glycosylation of the diol 4 by the imidate donor 3 resulted in the formation of a single product, the β(1→6)-linked disaccharide 5. After the 2’-N-Fmoc group in 5 was removed with

• the azido function with zinc in acetic acid followed by acylation of the liberated amino group with the long-chain acyloxyacyl fatty acid furnished fully acylated 16. In the next steps, the isopropylidene acetal and anomeric TDS ether were removed by treatment with aqueous TFA and the anomeric

Quinone-catalyzed oxidative deformylation: synthesis of imines from amino alcohols

• Xinyun Liu,
• Johnny H. Phan,
• Benjamin J. Haugeberg,
• Shrikant S. Londhe and
• Michael D. Clift

Beilstein J. Org. Chem. 2017, 13, 2895–2901, doi:10.3762/bjoc.13.282

• this reaction sequence, (thio)silyl ketene acetal 10 was united with 2-phenylglycinol and para-anisidine in a two-step, one-pot process to provide β-amino acid derivative 11 in a 60% yield. The overall reaction sequence provides a unique method for the production of the high-value β-amino acid

The synthesis of the 2,3-difluorobutan-1,4-diol diastereomers

• Robert Szpera,
• Nadia Kovalenko,
• Kalaiselvi Natarajan,
• Nina Paillard and
• Bruno Linclau

Beilstein J. Org. Chem. 2017, 13, 2883–2887, doi:10.3762/bjoc.13.280

• substituents is of interest. Here we describe optimisation efforts in the synthesis of anti-2,3-difluorobutane-1,4-diol, as well as the synthesis of the corresponding syn-diastereomer. Both targets were synthesised using an epoxide opening strategy. Keywords: acetal isomerization; deoxyfluorination; epoxide

• increase). An investigation to use the much smaller acetonide protecting group, which can be used for the cis-1,4-butenediol starting material, was carried out. It was found that the use of Et3N·3HF for the epoxide opening step also lead to acetal rearrangement, leading to a more stable 1,3-dioxolane ring

CF₃SO₂X (X = Na, Cl) as reagents for trifluoromethylation, trifluoromethylsulfenyl-, -sulfinyl- and -sulfonylation. Part 1: Use of CF₃SO₂Na

• Hélène Guyon,
• Hélène Chachignon and
• Dominique Cahard

Beilstein J. Org. Chem. 2017, 13, 2764–2799, doi:10.3762/bjoc.13.272

• allowing access to various β-trifluoromethyl ketones 24 featuring aryl, alkyl, functionalised alkyl, alkenyl, acetal, silylated alcohol, pyran, and piperidine functionalities (R group in 24). Mechanistic studies by 19F NMR allowed to identify CF3 complexes of copper(I) and copper(III) and the predominance

Asymmetric synthesis of propargylamines as amino acid surrogates in peptidomimetics

• Matthias Wünsch,
• David Schröder,
• Tanja Fröhr,
• Lisa Teichmann,
• Sebastian Hedwig,
• Nils Janson,
• Clara Belu,
• Jasmin Simon,
• Shari Heidemeyer,
• Philipp Holtkamp,
• Jens Rudlof,
• Lennard Klemme,
• Alessa Hinzmann,
• Beate Neumann,
• Hans-Georg Stammler and
• Norbert Sewald

Beilstein J. Org. Chem. 2017, 13, 2428–2441, doi:10.3762/bjoc.13.240

• (OiPr)4 and AlMe3 and gave only low yields of the desired N-sulfinyl propargylamine 6k. The reaction of crude 5k in the presence of the Lewis acid Ti(OiPr)4 afforded the N/O-acetal 9k, whereas the attempt of activation with AlMe3 provided the methylated sulfinamide 10k. Both side products were isolated

• as colorless crystalline solids. It is assumed, that the undesired side products 9k and 10k were formed by a ligand transfer from the Lewis acids to imine 5k. Nucleophilic substitution of N/O-acetal 9k with two equivalents of (trimethylsilyl)ethynyllithium, in analogy to the conversions reported by

Phosphonic acid: preparation and applications

• Charlotte M. Sevrain,
• Mathieu Berchel,
• Hélène Couthon and
• Paul-Alain Jaffrès

Beilstein J. Org. Chem. 2017, 13, 2186–2213, doi:10.3762/bjoc.13.219

• is illustrated by the recent works reporting the reaction of bis(diethylamino)chlorophosphine (95) with the acetal 96 in the presence of a Lewis acid to yield the phosphonodiamide 97. Then the nucleophilic addition of adenine and the hydrolysis of the phosphonodiamide function in phosphonic acid

Intramolecular glycosylation

• Xiao G. Jia and
• Alexei V. Demchenko

Beilstein J. Org. Chem. 2017, 13, 2028–2048, doi:10.3762/bjoc.13.201

• by Ito and Ogawa who implemented DDQ-mediated oxidative transformation of the p-methoxybenzyl (PMB) protecting group at the C-2 position of the donor into a tethering mixed acetal with a hydroxy group of the acceptor [94]. The early studies have successfully applied this PMB-based IAD method to the

• stereoselectivity. Thus, mixed acetal 76 can be readily formed in 2 h by the addition of DDQ to a mixture of donor 74 and acceptor 75. Without further purification, the latter mixture can be glycosylated in the presence of MeOTf and DTBMP followed by acetylation to give disaccharide 77 in an excellent yield of 90

Accessing simply-substituted 4-hydroxytetrahydroisoquinolines via Pomeranz–Fritsch–Bobbitt reaction with non-activated and moderately-activated systems

• Marco Mottinelli,
• Mathew P. Leese and
• Barry V. L. Potter

Beilstein J. Org. Chem. 2017, 13, 1871–1878, doi:10.3762/bjoc.13.182

• could be telescoped into a one-pot reaction was investigated. This reaction proceeded to deliver good to excellent yields of the desired aminoacetals 9a–g,i–p accompanied by only a small amount of side products (Table 1). As an exception to the above, the acetal 9h did not form, which could be

• the acetal 9l to give the corresponding aldehyde followed by its rapid conversion into THIQ 10l within the first ten minutes of the reaction. Despite the indication that the reaction proceeded through an initial complete conversion of the acetal to the aldehyde, in certain cases the formation of the

• ethers 15 was identified (Scheme 5). The formation of the two derivatives could be controlled through changes in the reaction concentration (Table 3). When 9f was dissolved in sufficient 6 M HCl necessary to provide a 1 M solution of the acetal, the main product obtained was the 4-hydroxy-THIQ. However

The chemistry and biology of mycolactones

• Matthias Gehringer and
• Karl-Heinz Altmann

Beilstein J. Org. Chem. 2017, 13, 1596–1660, doi:10.3762/bjoc.13.159

• acidic conditions furnished the acetal-protected extended core structure 28. In summary, Kishi’s 1st generation synthesis provided the extended mycolactone core in a longest linear sequence of 17 steps in 1.3% overall yield from known homoallylic silyl ether 20 [133]; the latter had to be prepared in

Synthesis of oligonucleotides on a soluble support

• Harri Lönnberg

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

• commercially available building blocks turned out to be too hydrophobic to allow precipitation of the support-bound oligonucleotides from MeOH. The 1-methoxy-1-methylethyl group could be removed quantitatively as a dimethyl acetal of acetone upon acid-catalyzed transesterification in MeOH. The 3'-terminal