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

Synthesis of alkynyl-substituted camphor derivatives and their use in the preparation of paclitaxel-related compounds

• M. Fernanda N. N. Carvalho,
• Rudolf Herrmann and
• Gabriele Wagner

Beilstein J. Org. Chem. 2017, 13, 1230–1238, doi:10.3762/bjoc.13.122

• the sensitivity of the alkyne to oxidising conditions. Our next strategy was to modify the carbonyl group in the 3-position and introduce the alkyne at the sulfonamide side, as shown in Scheme 5 and Scheme 6. The carbonyl group in 3 can be selectively protected as an acetal by reaction with

• for the synthesis of 12 and 13 introduced the alkyne into the 2-position of the camphor skeleton, to provide the sultams 17. The removal of the acetal-protecting group occurred under comparatively mild conditions by stirring a mixture of 17 with acetone and conc. HCl. Acetone as solvent was best as it

• allows for trans-acetalisation to acetone dimethylacetal and 12 rather than hydrolysis to methanol and 12. Overall, yields are higher throughout when the methyl acetal is used. To obtain the camphor-derived hydroxysultam 18 bearing an alkyne substituent in 2-position rather than in 3-position, 12 was

Sugar-based micro/mesoporous hypercross-linked polymers with in situ embedded silver nanoparticles for catalytic reduction

• Qing Yin,
• Qi Chen,
• Li-Can Lu and
• Bao-Hang Han

Beilstein J. Org. Chem. 2017, 13, 1212–1221, doi:10.3762/bjoc.13.120

• .13.120 Abstract Porous hypercross-linked polymers based on perbenzylated monosugars (SugPOP-1–3) have been synthesized by Friedel–Crafts reaction using formaldehyde dimethyl acetal as an external cross-linker. Three perbenzylated monosugars with similar chemical structure were used as monomers in order

• -linkers [4], and self-polycondensation of small molecular monomers [5]. Since the Tan group proposed the new synthetic strategy that "knits" low functionality rigid aromatic compounds with formaldehyde dimethyl acetal (FDA) as an external cross-linking agent through a Friedel–Crafts reaction to synthesize

• AgNPs/SugPOP-1 composite. Time-dependent UV–vis spectral changes (a) and the kinetic curve (b) for the catalytic reduction of 4-nitrophenol (4-NP) to 4-aminophenol (4-AP) at room temperature. Preparation of polymers SugPOP-1–3 (FDA: formaldehyde dimethyl acetal). The preparation of AgNPs/SugPOP-1

Synthesis of D-manno-heptulose via a cascade aldol/hemiketalization reaction

• Yan Chen,
• Xiaoman Wang,
• Junchang Wang and
• You Yang

Beilstein J. Org. Chem. 2017, 13, 795–799, doi:10.3762/bjoc.13.79

• spectra of 8 (see Supporting Information File 1 for details). Cleavage of the isopropylidene acetal group in 8 under acidic conditions gave diol 9 (50%). However, oxidative cleavage of diol 9 with sodium periodate resulted in the unexpected formation of α,β-unsaturated aldehyde 10 in 71% yield, indicating

• isopropylidene acetal group in 7 was cleaved under acidic conditions to produce triol 11 in 86% yield (Scheme 3). Cleavage of the resulting vicinal diol in 11 with sodium periodate led to the C4 aldehyde 3 in nearly 60–70% yield. In this oxidative cleavage reaction, almost no elimination product was found based

• excellent yield (91%). Saponification of all esters in 16 with potassium carbonate followed by acidic cleavage of the isopropylidene acetal group with aqueous acetic acid furnished D-manno-heptulose (1, 76% over two steps). The structure of 1 was found to be in good agreement with those reported for α-D

Synthesis of ribavirin 2’-Me-C-nucleoside analogues

• Fanny Cosson,
• Aline Faroux,
• Jean-Pierre Baltaze,
• Jonathan Farjon,
• Régis Guillot,
• Jacques Uziel and
• Nadège Lubin-Germain

Beilstein J. Org. Chem. 2017, 13, 755–761, doi:10.3762/bjoc.13.74

• a partially deprotected compound (only acetal deprotected), stemming from 9b, demonstrating the different hydrolysis rate of each regioisomer. An HPLC analysis of the disappearance of 9a and 9b and the formation of 10a and 10b showed a ratio of 2:1 in favor of regioisomer 10a. The hydrolysis was

Fluorescent carbon dots from mono- and polysaccharides: synthesis, properties and applications

• Stephen Hill and
• M. Carmen Galan

Beilstein J. Org. Chem. 2017, 13, 675–693, doi:10.3762/bjoc.13.67

• uniform surface state giving a single quantum dot-like emission profile. This interesting report highlights the fact that a reducing sugar is not essential to produce CDs and that under acidic and forcing conditions this type of starting materials can still undergo acetal hydrolysis, dehydration

Total synthesis of a Streptococcus pneumoniae serotype 12F CPS repeating unit hexasaccharide

• Peter H. Seeberger,
• Claney L. Pereira and
• Subramanian Govindan

Beilstein J. Org. Chem. 2017, 13, 164–173, doi:10.3762/bjoc.13.19

• subsequently converted to the fucosyl trichloroacetimidate building block 8 (Scheme 5). Galactosyl thioglycoside 9 was prepared from D-galactose following published procedures [32]. Reductive opening of the benzylidene acetal of known galactosyl thioglycoside 29 [33] with triethylsilane [34] in TFA/CH2Cl2

Solution-phase automated synthesis of an α-amino aldehyde as a versatile intermediate

• Hisashi Masui,
• Sae Yosugi,
• Shinichiro Fuse and
• Takashi Takahashi

Beilstein J. Org. Chem. 2017, 13, 106–110, doi:10.3762/bjoc.13.13

• -8503, Japan 10.3762/bjoc.13.13 Abstract A solution-phase automated synthesis of the versatile synthetic intermediate, Garner’s aldehyde, was demonstrated. tert-Butoxycarbonyl (Boc) protection, acetal formation, and reduction of the ester to the corresponding aldehyde were performed utilizing our

• originally developed automated synthesizer, ChemKonzert. The developed procedure was also useful for the synthesis of Garner’s aldehyde analogues possessing fluorenylmethyloxycarbonyl (Fmoc) or benzyloxycarbonyl (Cbz) protection. Keywords: acetal formation; amino acid; automated synthesis; Garner’s aldehyde

• manually concentrated in vacuo. The obtained residue was purified manually using silica gel column chromatography. Carbamate 2a was obtained in 82% yield. Acetal formation was also demonstrated using ChemKonzert. A solution of substrate 2a in dichloromethane was stirred at 25 °C in the reaction vessel (RF1

Silyl-protective groups influencing the reactivity and selectivity in glycosylations

• Mikael Bols and
• Christian Marcus Pedersen

Beilstein J. Org. Chem. 2017, 13, 93–105, doi:10.3762/bjoc.13.12

• 3,5-O-(tetraisopropyldisilylene)acetal and also found the arabinofuranolysations to be β-selective, despite the more flexible system [63]. Interestingly it was recently found that exchanging the 3,5-DTBS group with trifluoroacetates retained a high β-selectivity, which suggests that the

New approaches to organocatalysis based on C–H and C–X bonding for electrophilic substrate activation

• Pavel Nagorny and
• Zhankui Sun

Beilstein J. Org. Chem. 2016, 12, 2834–2848, doi:10.3762/bjoc.12.283

• followed by anion exchange. The resultant oxocarbenium/tetraphenylborate ion pair undergoes a nucleophilic attack by silyl ketene acetal, which is followed by scavenging the trimethylsilyl cation with a chloride anion to result in chlorotrimethylsilane and the product. Mechanistic studies were conducted to

O-Alkylated heavy atom carbohydrate probes for protein X-ray crystallography: Studies towards the synthesis of methyl 2-O-methyl-L-selenofucopyranoside

• Roman Sommer,
• Dirk Hauck,
• Annabelle Varrot,
• Anne Imberty,
• Markus Künzler and
• Alexander Titz

Beilstein J. Org. Chem. 2016, 12, 2828–2833, doi:10.3762/bjoc.12.282

• and 4 in selenofucoside 1. The introduction of a 3,4-O-benzylidene protecting group using benzaldehyde dimethyl acetal under standard conditions was ineffective and degradation was observed by TLC. However, the formation of the 3,4-O-benzylidene acetal could be achieved through in situ evaporation of

Facile synthesis of a 3-deazaadenosine phosphoramidite for RNA solid-phase synthesis

• Elisabeth Mairhofer,
• Elisabeth Fuchs and
• Ronald Micura

Beilstein J. Org. Chem. 2016, 12, 2556–2562, doi:10.3762/bjoc.12.250

• . An authentic reference sample that was synthesized according to the previously established 12-step route was used for direct spectroscopic comparison (see Supporting Information File 1) and additionally confirmed its identity. Then, treatment with N,N-dibutylformamide dimethyl acetal [31] resulted in

• amidine protection of the exocyclic C6-NH2 group. At the same time, the applied excess of the reagent allowed to transiently form the corresponding nucleoside 2’,3’-O-acetal [32], leaving the primary 5’-OH group available for selective tritylation with 4,4’-dimethoxytrityl chloride to give compound 6

• -deazaadenosine (6). Compound 5 (199 mg, 747 µmol) was weighed into a 25 mL two-necked flask and dried in high vacuum for 1 hour. Under an argon atmosphere dry pyridine (5 mL) and N,N-dibutylformamide dimethyl acetal (0.40 mL, 1.74 mmol) were added and stirred for 1.5 h at room temperature. Afterwards, all

Combined experimental and theoretical studies of regio- and stereoselectivity in reactions of β-isoxazolyl- and β-imidazolyl enamines with nitrile oxides

• Ilya V. Efimov,
• Marsel Z. Shafikov,
• Nikolai A. Beliaev,
• Natalia N. Volkova,
• Tetyana V. Beryozkina,
• Wim Dehaen,
• Zhijin Fan,
• Viktoria V. Grishko,
• Gert Lubec,
• Pavel A. Slepukhin and
• Vasiliy A. Bakulev

Beilstein J. Org. Chem. 2016, 12, 2390–2401, doi:10.3762/bjoc.12.233

• from the corresponding 5-methylazoles by reaction with dimethylformamide dimethyl acetal (DMF-DMA) adapting synthetic procedures published earlier [26][27][28][29][30]. Their structures can be unambiguously assigned as the trans-isomers by observing the coupling constant (J = 13.0–13.6 Hz) for the

Enduracididine, a rare amino acid component of peptide antibiotics: Natural products and synthesis

• Darcy J. Atkinson,
• Briar J. Naysmith,
• Daniel P. Furkert and
• Margaret A. Brimble

Beilstein J. Org. Chem. 2016, 12, 2325–2342, doi:10.3762/bjoc.12.226

• ], halogenated [36], acetal [37][38][39], benzoxazole [40], thiobenzoxazole [40], ester and carbonate [41] analogues were synthesised and evaluated for antibacterial activity. Only the semisynthetic derivatives possessing hydrophobic groups on the terminal sugar moiety (green) exhibited comparable antibacterial

Experimental and theoretical investigations into the stability of cyclic aminals

• Edgar Sawatzky,
• Antonios Drakopoulos,
• Martin Rölz,
• Christoph Sotriffer,
• Bernd Engels and
• Michael Decker

Beilstein J. Org. Chem. 2016, 12, 2280–2292, doi:10.3762/bjoc.12.221

• ; Introduction The aminal system (N,N-acetal) is the structurally equivalent analogue of the O,O-acetal. In the literature this moiety is found as a core element in various important structures, for example in the naturally occurring alkaloids tetraponerine T1 to T8 from the venom of the New Guinean ant

Hydroxy-functionalized hyper-cross-linked ultra-microporous organic polymers for selective CO₂ capture at room temperature

• Partha Samanta,
• Priyanshu Chandra and
• Sujit K. Ghosh

Beilstein J. Org. Chem. 2016, 12, 1981–1986, doi:10.3762/bjoc.12.185

• dimethyl acetal (FDA) as the cross linker [25][26][27]. Here, aromatic small organic compounds are used to polymerise via C–C cross coupling to produce the targeted porous and physicochemical stable organic hyper-cross-linked polymeric materials. One huge advantage of this material is the low-cost

• synthesis, the cost-effective formaldehyde dimethyl acetal (FDA), FeCl3 and that organic small molecules can produce very low cost materials with high yield [28]. Hyper-cross-linking prevents the close packing of polymeric chains in this type of material to impart the intrinsic porosity. Hyper-cross-linked

TMSBr-mediated solvent- and work-up-free synthesis of α-2-deoxyglycosides from glycals

• Mei-Yuan Hsu,
• Yi-Pei Liu,
• Sarah Lam,
• Su-Ching Lin and
• Cheng-Chung Wang

Beilstein J. Org. Chem. 2016, 12, 1758–1764, doi:10.3762/bjoc.12.164

• dithiol acetal side product 9. Inspired by the results obtained in the synthesis of S-2-deoxyglycosides, we explored the use of numerous alcohols as acceptors in order to directly synthesize O-2-deoxyglycosides from glycals. In Table 2 the reaction of glucal 1 and benzyl alcohol (12) under similar

Rearrangements of organic peroxides and related processes

• Ivan A. Yaremenko,
• Vera A. Vil’,
• Dmitry V. Demchuk and
• Alexander O. Terent’ev

Beilstein J. Org. Chem. 2016, 12, 1647–1748, doi:10.3762/bjoc.12.162

• 105a–g with performic acid generated in situ provides a new route to dicarboxylic acids 106a–g and hydroxycarboxylic acids 107a–g (Table 8) [286]. The proposed mechanism of the oxidation of acetal 105f is shown in Scheme 34. In the first step of the reaction, the elimination of methanol from 105f and

• peroxyacetate 138 (Scheme 41) [295]. Later on, the Criegee rearrangement was extended [296] to peroxides 139, 142, and 145 which made it possible to selectively synthesize both cyclic 140, 141, 144 and acyclic enol esters 146 and acetal 143 (Scheme 42). The Criegee rearrangement of 1-hydroperoxy-2

One-pot synthesis of 4′-alkyl-4-cyanobiaryls on the basis of the terephthalonitrile dianion and neutral aromatic nitrile cross-coupling

• Roman Yu. Peshkov,
• Elena V. Panteleeva,
• Wang Chunyan,
• Evgeny V. Tretyakov and
• Vitalij D. Shteingarts

Beilstein J. Org. Chem. 2016, 12, 1577–1584, doi:10.3762/bjoc.12.153

• yield in the reaction with acetal 6f is probably due to the latter’s lower reactivity compared to other alkylating reagents, what was indicated by increased yield of dicyanobiphenyl 4 (14% vs 5% formed in reactions with 6b–e). To demonstrate the effects of varying the aromatic moiety, a set of aromatic

Biosynthesis of oxygen and nitrogen-containing heterocycles in polyketides

• Franziska Hemmerling and
• Frank Hahn

Beilstein J. Org. Chem. 2016, 12, 1512–1550, doi:10.3762/bjoc.12.148

• ’-oxoaverantin (101) into averufin (102) by intramolecular acetal formation [87]. To date, it is not clear, how exactly the OAVN cyclase participates in this process [88]. Interestingly, the OAVN cyclase operates cofactor-free, although it contains a NAD(P)+-binding Rossman fold. Furthermore, this enzyme is also