Chemical tuning of photoswitchable azobenzenes: a photopharmacological case study using nicotinic transmission

• Lorenzo Sansalone,
• Jun Zhao,
• Matthew T. Richers and
• Graham C. R. Ellis-Davies

Beilstein J. Org. Chem. 2019, 15, 2812–2821, doi:10.3762/bjoc.15.274

• acetylcholine seems impossible to derivatize with a photochemical protecting group, a biologically inert photo-activatable agonist such 2 could be useful for neurophysiological studies. The long-term thermal stability of the 4FAB core allows a "stock" of the biologically inert cis PSS to be made. Since thermal

AgNTf₂-catalyzed formal [3 + 2] cycloaddition of ynamides with unprotected isoxazol-5-amines: efficient access to functionalized 5-amino-1H-pyrrole-3-carboxamide derivatives

• Ziping Cao,
• Jiekun Zhu,
• Li Liu,
• Yuanling Pang,
• Laijin Tian,
• Xuejun Sun and
• Xin Meng

Beilstein J. Org. Chem. 2019, 15, 2623–2630, doi:10.3762/bjoc.15.255

• 10ka–na were obtained in 50–98% yields. In addition, the Ts protecting group could be changed for other sulfonyl groups such as Ms (10na, 98%), o-Ns (10oa, 99%) and p-Ns (10pa, 99%), while the cyclic carbamate-derived ynamides such as 4q are no good substrates, leading to the formation of a complex

Safe and highly efficient adaptation of potentially explosive azide chemistry involved in the synthesis of Tamiflu using continuous-flow technology

• Cloudius R. Sagandira and
• Paul Watts

Beilstein J. Org. Chem. 2019, 15, 2577–2589, doi:10.3762/bjoc.15.251

• loading, no protecting group chemistry and absence of halogenated solvents [1][13]. Generally, this approach is attractive for large scale manufacturing, however, the safety concerns posed by the use of azide chemistry needs to be addressed especially at large scale where the risk is very high. In an

A new approach to silicon rhodamines by Suzuki–Miyaura coupling – scope and limitations

• Thines Kanagasundaram,
• Antje Timmermann,
• Carsten S. Kramer and
• Klaus Kopka

Beilstein J. Org. Chem. 2019, 15, 2569–2576, doi:10.3762/bjoc.15.250

• methodologies need, e.g., an ester, orthoester or oxazoline protecting group for the acid. But also the tert-butyl ester-functionalized boroxine 25 is suitable for the cross coupling. With the current catalytic system, coupling of 2-substituted boroxines (26, 27) remains challenging, but optimizing the

Chemical synthesis of the pentasaccharide repeating unit of the O-specific polysaccharide from Escherichia coli O132 in the form of its 2-aminoethyl glycoside

• Debasish Pal and
• Balaram Mukhopadhyay

Beilstein J. Org. Chem. 2019, 15, 2563–2568, doi:10.3762/bjoc.15.249

• + 2] strategy where the required monosaccharide building blocks are prepared from commercially available sugars through rational protecting group manipulation. The NIS-mediated activation of thioglycosides was used extensively for the glycosylation reactions throughout. Keywords: 2-aminoethyl

• and Galf. In this communication we report on the total synthesis of this pentasaccharide repeating unit of the O-specific polysaccharide in the form of its 2-aminoethyl glycoside (Figure 1) through a [3 + 2] converging strategy. The building blocks were prepared by suitable protecting group

• , the disaccharide donor 16 may be prepared from monosaccharide acceptor 15 and donor 14. The monosaccharide building blocks can be prepared from commercially available ᴅ-glucose, ᴅ-galactose, ᴅ-glucosamine hydrochloride and ʟ-rhamnose through rational protecting group manipulations (Figure 2

A review of the total syntheses of triptolide

• Xiang Zhang,
• Zaozao Xiao and
• Hongtao Xu

Beilstein J. Org. Chem. 2019, 15, 1984–1995, doi:10.3762/bjoc.15.194

• were employed to successfully achieve Berchtold’s tetracyclic C-5,C-6 olefin intermediate 45 in only 7 steps with 8.1% overall yield in a protecting-group-free synthesis. However, we know the conversion of Berchtold’s C-5,C-6 tetracyclic olefin intermediate 45 to triptophenolide methyl ether (8) is a

• and reacted with 3,3-dimethylallyl bromide, followed by changing the protecting group from MOM ether to methyl ether to provide olefin 86. Allylic oxidation of 86 followed by nucleophilic bromination of the resulting allylic alcohol gave bromide 87. Dianion displacement of the bromide of 87 gave ester

Design, synthesis and biological evaluation of immunostimulating mannosylated desmuramyl peptides

• Rosana Ribić,
• Ranko Stojković,
• Lidija Milković,
• Mariastefania Antica,
• Marko Cigler and
• Srđanka Tomić

Beilstein J. Org. Chem. 2019, 15, 1805–1814, doi:10.3762/bjoc.15.174

• racemic Boc-protected (adamant-1-yl)glycine [32] 2 using the carbodiimide EDC/HOBt method [21]. The obtained mixture of BocAdGly-ʟ-Ala-ᴅ-isoGlnOBn diastereoisomers was treated with trifluoroacetic acid in order to remove the Boc protecting group while the diastereoisomer 4 with ᴅ-ʟ-ᴅ amino acid sequence

Recent advances on the transition-metal-catalyzed synthesis of imidazopyridines: an updated coverage

• Gagandeep Kour Reen,
• Ashok Kumar and
• Pratibha Sharma

Beilstein J. Org. Chem. 2019, 15, 1612–1704, doi:10.3762/bjoc.15.165

Synthesis and conformational preferences of short analogues of antifreeze glycopeptides (AFGP)

• Małgorzata Urbańczyk,
• Michał Jewgiński,
• Joanna Krzciuk-Gula,
• Jerzy Góra,
• Rafał Latajka and
• Norbert Sewald

Beilstein J. Org. Chem. 2019, 15, 1581–1591, doi:10.3762/bjoc.15.162

• the resin. After two minutes the diisopropyl azodicarboxylate (DIAD) solution was added dropwise to the reaction mixture. Once the reaction was complete, the o-NBS protecting group was removed by using 2-mercaptoethanol and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU). The Kaiser test did not reveal any

• diisopropyl azodicarboxylate (DIAD) in THF was introduced dropwise to the reaction vessel, in order to control exothermic reaction. The reaction was carried out for 2 hours and repeated. The resin was washed with THF and NMP. Finally, the o-NBS protecting group was removed by using 2-mercaptoethanol and 1,8

Anomeric sugar boronic acid analogues as potential agents for boron neutron capture therapy

• Daniela Imperio,
• Erika Del Grosso,
• Silvia Fallarini,
• Grazia Lombardi and
• Luigi Panza

Beilstein J. Org. Chem. 2019, 15, 1355–1359, doi:10.3762/bjoc.15.135

• protecting group gave the intermediate 3 in good yield. Standard substitution of the hydroxy group gave the 1-deoxy-1-iododerivative 4. Base-promoted dehydroiodination, followed by Zémplen removal of the benzoate gave the desired enol ether 6, which was selected as precursor for the preparation of the first

Alkylation of lithiated dimethyl tartrate acetonide with unactivated alkyl halides and application to an asymmetric synthesis of the 2,8-dioxabicyclo[3.2.1]octane core of squalestatins/zaragozic acids

• Herman O. Sintim,
• Hamad H. Al Mamari,
• Hasanain A. A. Almohseni,
• Younes Fegheh-Hassanpour and
• David M. Hodgson

Beilstein J. Org. Chem. 2019, 15, 1194–1202, doi:10.3762/bjoc.15.116

• sequence of oxidation and judicious protecting group manipulation. Base-induced epimerisation of the monoalkylated tartrates favours cis-disposition of the ester groups on the five-membered ring, thereby accessing the predominant stereochemistry found in several substituted tartaric acid-containing natural

• irretrievable five-membered lactol formation would be expected [39]. Unfortunately, various reagents (TBAF/AcOH [40], NaH/HMPA [41], Bu4OH/DMF [40], NaOMe/MeOH) failed to selectively deprotect the secondary TBDPS ether in α-diazo ester 23 in the presence of the tertiary TBS ether. Reassessment of the protecting

• group strategy led us to TES protection at both alcohols, on the basis that this group should be robust enough to withstand the enolate manipulation chemistry, that desilylation of the secondary TES ether during acetonide removal could be restored in the subsequent tertiary alcohol silylation step, that

Electrophilic oligodeoxynucleotide synthesis using dM-Dmoc for amino protection

• Shahien Shahsavari,
• Dhananjani N. A. M. Eriyagama,
• Bhaskar Halami,
• Vagarshak Begoyan,
• Marina Tanasova,
• Jinsen Chen and
• Shiyue Fang

Beilstein J. Org. Chem. 2019, 15, 1116–1128, doi:10.3762/bjoc.15.108

• electrophilic oligodeoxynucleotides (ODNs) was achieved using dimethyl-Dmoc (dM-Dmoc) as amino protecting group. Due to the high steric hindrance of the 2-(propan-2-ylidene)-1,3-dithiane side product from deprotection, the use of excess nucleophilic scavengers such as aniline to prevent Michael addition of the

• thioester. Using the technology, the sensitive groups can be installed at any location within the ODN sequences without using any sequence- or functionality-specific conditions and procedures. Keywords: Dmoc; electrophilic; oligonucleotides; protecting group; solid-phase synthesis; Introduction After over

• ]. Considering that the widely used Fmoc protecting group, of which the H-9 has a pKa of ≈22 [42], can be readily removed with a weak base such as piperidine, we hypothesized that the oxidized Dmoc groups and linkers could be cleaved under weakly basic and non-nucleophilic conditions via β-elimination. Indeed

Diaminoterephthalate–α-lipoic acid conjugates with fluorinated residues

• Leon Buschbeck,
• Aleksandra Markovic,
• Gunther Wittstock and
• Jens Christoffers

Beilstein J. Org. Chem. 2019, 15, 981–991, doi:10.3762/bjoc.15.96

• trifluoromethylated benzaldehyde was accomplished as described for compound 2 and furnished product 6 in 91% yield. The Alloc-protecting group was then cleaved (95% yield of product 8) in a palladium-catalyzed allylic substitution reaction with morpholine as a scavenger of the allylic cation [45][46]. Finally, the

Synthesis of (macro)heterocycles by consecutive/repetitive isocyanide-based multicomponent reactions

• Angélica de Fátima S. Barreto and
• Carlos Kleber Z. Andrade

Beilstein J. Org. Chem. 2019, 15, 906–930, doi:10.3762/bjoc.15.88

• fragment of the molecule, called tubuvaline (50); and finally an Ugi reaction was used to couple them. Initial attempts to use tubuvaline 50 led to an undesirable product due to water attack at the reaction intermediate before Mumm rearrangement. This was circumvented by changing the protecting group of 50

Photochemical generation of the 2,2,6,6-tetramethylpiperidine-1-oxyl (TEMPO) radical from caged nitroxides by near-infrared two-photon irradiation and its cytocidal effect on lung cancer cells

• Ayato Yamada,
• Manabu Abe,
• Yoshinobu Nishimura,
• Shoji Ishizaka,
• Masashi Namba,
• Taku Nakashima,
• Kiyofumi Shimoji and
• Noboru Hattori

Beilstein J. Org. Chem. 2019, 15, 863–873, doi:10.3762/bjoc.15.84

• -responsive photo-labile protecting group [56][57][58] with simple cyclic stilbene structures such as 2-(4-nitrophenyl)benzofuran (NPBF) that absorb in the NIR region of 710–760 nm for the uncaging of bioactive substances such as glutamate and Ca2+ [59][60][61][62][63][64]. Herein, we report the synthesis of

Synthesis of acylglycerol derivatives by mechanochemistry

• Karen J. Ardila-Fierro,
• Andrij Pich,
• Marc Spehr,
• José G. Hernández and
• Carsten Bolm

Beilstein J. Org. Chem. 2019, 15, 811–817, doi:10.3762/bjoc.15.78

• synthetic alternative involves multiple preparative steps in organic solvents (e.g., CH2Cl2, THF, Et2O). These considerations led us to explore a mechanochemical multistep route for the synthesis of protected DAGs 5 starting from glycidol (1) through the installation of a hydroxy protecting group, followed

• the mechanosynthesis of DAGs 5 was established, we turned our efforts towards the conjugation of DAG 5a with 7-hydroxycoumarin (9) (Scheme 5). Initially, removal of the TBDMS protecting group of 5a was attempted by milling. However, reacting DAG 5a with a mixture of BF3·CH3CN and silica gel followed

• DAGs; PG = protecting group. Protection of glycidol (1) with TBDMSCl in the ball mill. MM = mixer mill, PBM = planetary ball mill. Cobalt-catalyzed epoxide ring-opening in the ball mill. Mechanosynthesis of DAGs 5. Conjugation of DAG 5a with 7-hydroxycoumarin (9). Supporting Information Supporting

Tuning the stability of alkoxyisopropyl protection groups

• Zehong Liang,
• Henna Koivikko,
• Mikko Oivanen and
• Petri Heinonen

Beilstein J. Org. Chem. 2019, 15, 746–751, doi:10.3762/bjoc.15.70

• only the 2-methoxypropan-2-yl protecting group (MIP) has been adopted in use [2] and the alternative, 2-benzyloxypropan-2-yl, introduced by Mukaiyama in the 1980’s [6] has not gained popularity. The MIP group has been used, e.g., in solution-phase oligonucleotide synthesis for the primary 5’-hydroxy

• more electron-withdrawing groups than trifluoroethanol. Nevertheless, our interest was in studying the protecting group abilities, and the studied compounds fit the most relevant reactivity area in that sense. As mentioned above, enol ether derivatives (as 8a) were formed under more acidic conditions

• . The vinyl ether hydrolysis has earlier shown to be even a subject of general acid catalysis [13][14]. It is useful to compare the stabilities of the acetal protections to those of the 4,4’-dimethoxytrityl protecting group used in oligonucleotide synthesis. Directly comparable data are hard to find

Synthesis of functionalized diazocines for application as building blocks in photo- and mechanoresponsive materials

• Widukind Moormann,
• Daniel Langbehn and
• Rainer Herges

Beilstein J. Org. Chem. 2019, 15, 727–732, doi:10.3762/bjoc.15.68

• step the hydroxy groups in 8a and 8b were protected as tert-butyl ethers (Scheme 2) to prevent oxidation in the following oxidative C–C coupling [31]. The tert-butyl ether was chosen as the protecting group because it is stable towards the oxidizing conditions of the C–C coupling reactions and the

Efficient synthesis of 4-substituted-ortho-phthalaldehyde analogues: toward the emergence of new building blocks

• Clémence Moitessier,
• Ahmad Rifai,
• Pierre-Edouard Danjou,
• Isabelle Mallard and
• Francine Cazier-Dennin

Beilstein J. Org. Chem. 2019, 15, 721–726, doi:10.3762/bjoc.15.67

• protecting group described in the literature for 4,5-dihydroisobenzofuran-5-ol (3) is acetyl [19]. Thus, beside this former, several protecting groups such as: methyl (Me), benzyl (Bn), tert-butyldimethylsilyl (TBDMS) and trimethylsilyl (TMS) were tested (Scheme 2). As summarized in Table 1, major disparity

• key intermediate 4,5-dihydroisobenzofuran-5-ol (3) before reaching the oxidation step. The methoxy protecting group and the DDQ oxidation reagent were found to be the most efficient. Moreover, deprotection of 4-methoxy-ortho-phthalaldehyde (5b) was successfully achieved using [Bmim]Br and p-TsOH on

Design and synthesis of multivalent α-1,2-trimannose-linked bioerodible microparticles for applications in immune response studies of Leishmania major infection

• Chelsea L. Rintelmann,
• Tara Grinnage-Pulley,
• Kathleen Ross,
• Daniel E. K. Kabotso,
• Angela Toepp,
• Anne Cowell,
• Christine Petersen,
• Balaji Narasimhan and
• Nicola Pohl

Beilstein J. Org. Chem. 2019, 15, 623–632, doi:10.3762/bjoc.15.58

• these conditions. Therefore, future applications to automated syntheses will exclude this nitrogen protecting group. The light chain fluorous CbzF tag was advantageous in reducing the number of steps to a readily conjugateable molecule for particle functionalization compared to that of our previously

Synthesis of the polyketide section of seragamide A and related cyclodepsipeptides via Negishi cross coupling

• Jan Hendrik Lang and
• Thomas Lindel

Beilstein J. Org. Chem. 2019, 15, 577–583, doi:10.3762/bjoc.15.53

• separate the diastereomers of product 13 by column chromatography. The use of DMEAD (di-2-methoxyethyl azodicarboxylate) [38] was inferior (33%). The PMP protecting group was envisioned to be stable during the following steps and to be selectively cleavable with ceric ammonium nitrate (CAN). Reduction of

• ). For the synthesis of organozinc homoenolate 8, the MnBr2/CuCl-catalyzed reaction of diethylzinc with β-bromopropionic acid ester 19 in DMPU proved to be the best choice [42]. Racemization was avoided. The PMP protecting group was removed (CAN) affording methyl ester 7 (82%, Scheme 3). For comparison

Synthesis and biological investigation of (+)-3-hydroxymethylartemisinin

• Toni Smeilus,
• Farnoush Mousavizadeh,
• Johannes Krieger,
• Xingzhao Tu,
• Marcel Kaiser and
• Athanassios Giannis

Beilstein J. Org. Chem. 2019, 15, 567–570, doi:10.3762/bjoc.15.51

• 24% and 16% yield, respectively. Protection of the free hydroxy group of 16 as a silyl ether and methylation of the obtained lactone in α-position (LDA/MeI/HMPA) afforded derivative 17. After removal of the TES protecting group (+)-3-hydroxymethyl-9-epi-artemisinin (18, Scheme 3) was obtained

Selectivity in multiple multicomponent reactions: types and synthetic applications

• Ouldouz Ghashghaei,
• Francesca Seghetti and
• Rodolfo Lavilla

Beilstein J. Org. Chem. 2019, 15, 521–534, doi:10.3762/bjoc.15.46

• antitumor peptidomimetics (Scheme 16) [53]. The convergent approach employs three different isocyanide-MCRs, efficiently prepares the building blocks and combines them, intercalating protecting group cleavages. Conclusion The MMCRs approach represents the most efficient way to build chemical complexity and

Syntheses and chemical properties of β-nicotinamide riboside and its analogues and derivatives

• Mikhail V. Makarov and
• Marie E. Migaud

Beilstein J. Org. Chem. 2019, 15, 401–430, doi:10.3762/bjoc.15.36

• the corresponding protected derivative 30 was low (Scheme 15). Yet, this particular protecting group is easily removed under mild acidic conditions, such as diluted HCl in organic solvents (THF/MeOH) or 90% aqueous trifluoroacetic acid or hydrogenolysis. 3.3. Reduction of the pyridinium core of NR

Sigmatropic rearrangements of cyclopropenylcarbinol derivatives. Access to diversely substituted alkylidenecyclopropanes

• Guillaume Ernouf,
• Jean-Louis Brayer,
• Christophe Meyer and
• Janine Cossy

Beilstein J. Org. Chem. 2019, 15, 333–350, doi:10.3762/bjoc.15.29

• (TBS) ether of propargyl alcohol by a rhodium-catalyzed cyclopropanation with an aryldiazoacetate followed by reduction of the ester moiety and protecting group manipulation. Phosphinite 6a, generated from alcohol 5a under standard conditions, did not undergo a [2,3]-sigmatropic rearrangement into the

• (7d/7’d = 52:48) were present. An inversion of the face selectivity was detected in favor of diastereomer 7’e (7e/7’e = 43:57) arising from the rearrangement of phosphinite 6e possessing a p-trifluoromethylphenyl substituent. Replacement of the acetal protecting group of the hydroxymethyl substituent