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

• ], published in 2007, Kishi and co-workers increased the overall efficiency of the synthesis by reorganizing the assembly of the principal fragments and by optimizing the key C(sp2)–C(sp3) Negishi cross-coupling reactions as well as the choice of protecting groups. The 3rd generation approach [123], published

• secondary TES and the primary TBS ether protecting groups was followed by selective oxidation of the ensuing primary alcohol to deliver seco acid 27. The crucial macrolactonization was performed under Yamaguchi conditions [135] in 70% yield and subsequent cleavage of the secondary TBS ether under mildly

Effect of uridine protecting groups on the diastereoselectivity of uridine-derived aldehyde 5’-alkynylation

• Raja Ben Othman,
• Mickaël J. Fer,
• Laurent Le Corre,
• Sandrine Calvet-Vitale and
• Christine Gravier-Pelletier

Beilstein J. Org. Chem. 2017, 13, 1533–1541, doi:10.3762/bjoc.13.153

• -Paris), 45 rue des Saints Pères, 75270 Paris 06, France 10.3762/bjoc.13.153 Abstract The 5’-alkynylation of uridine-derived aldehydes is described. The addition of alkynyl Grignard reagents on the carbonyl group is significantly influenced by the 2’,3’-di-O-protecting groups (R1): O-alkyl groups led to

• ; nucleoside; protecting groups; uridine; Introduction Nucleoside and nucleotide derivatives or analogues are biologically active compounds of major interest [1][2]. Their widespread applications span from therapeutic agents, such as antibacterial [3][4][5], antiviral [6] or antitumor [7][8] drugs, to

• organometallic reagents onto nucleoside aldehyde (Table 1), we decided to investigate the influence of the protecting groups of the uridine aldehyde on the stereochemical outcome of the nucleophilic addition of a Grignard reagent and we wish to report herein the results of our study. Results and Discussion We

A new member of the fusaricidin family – structure elucidation and synthesis of fusaricidin E

• Marcel Reimann,
• Louis P. Sandjo,
• Luis Antelo,
• Eckhard Thines,
• Isabella Siepe and
• Till Opatz

Beilstein J. Org. Chem. 2017, 13, 1430–1438, doi:10.3762/bjoc.13.140

• single signal set, so the fate of the assumed minor stereoisomer remains unclear and it was probably lost during HPLC purification. The analysis also revealed that the acylation with the GHPD side chain was selective for the amine and no O-acylated product was formed. Side chain protecting groups were

Synthesis of oligonucleotides on a soluble support

• Harri Lönnberg

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

• oligonucleotide. Since the phosphate protecting groups are normally base-labile and the repeatedly removable 5´-O protecting group is acid-labile, the 2´-O-protection should preferably be removable under orthogonal conditions. For this purpose, numerous protecting groups have been proposed [18][19], the fluoride

Construction of highly enantioenriched spirocyclopentaneoxindoles containing four consecutive stereocenters via thiourea-catalyzed asymmetric Michael–Henry cascade reactions

• Yonglei Du,
• Jian Li,
• Kerong Chen,
• Chenglin Wu,
• Yu Zhou and
• Hong Liu

Beilstein J. Org. Chem. 2017, 13, 1342–1349, doi:10.3762/bjoc.13.131

• diastereoselectivity (3:97 dr). To further extend the reaction scope, we attempted to exchange the N-Boc group of the 3-substituted oxindoles with other protecting groups, such as Bn, CH3 or an acetyl group. The results demonstrated that only an acetyl protecting group proved to be well tolerated, providing for the

Strategies toward protecting group-free glycosylation through selective activation of the anomeric center

• A. Michael Downey and
• Michal Hocek

Beilstein J. Org. Chem. 2017, 13, 1239–1279, doi:10.3762/bjoc.13.123

• Abstract Glycosylation is an immensely important biological process and one that is highly controlled and very efficient in nature. However, in a chemical laboratory the process is much more challenging and usually requires the extensive use of protecting groups to squelch reactivity at undesired reactive

• review, we showcase the methods available for the selective activation of the anomeric center on the glycosyl donor and the mechanisms by which the glycosylation reactions take place to illustrate the power these techniques. Keywords: glycosides; glycosylation; oligosaccharides; protecting groups

• result, in synthetic chemistry, this process of glycosylation is very often cumbersome and can involve the use of highly toxic reagents [5][6][7][8]. The idealized scenario would be a glycosylation strategy that can occur in the complete absence of protecting groups under mild, neutral conditions. The

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

• practical synthetic methods for the selective synthesis of precursor dialkynes bearing different substituents (alkyl, aryl) at the triple bonds, based on ketals or an imine as protecting groups. We show for isomeric dialkynes that the reaction cascade induced by Pt(II) includes ring annulation, sulphur

An eco-compatible strategy for the diversity-oriented synthesis of macrocycles exploiting carbohydrate-derived building blocks

• Sushil K. Maurya and
• Rohit Rana

Beilstein J. Org. Chem. 2017, 13, 1106–1118, doi:10.3762/bjoc.13.110

• and 2c) irrespective of the position of the propargyl group on the primary OH (1e) or secondary OH group (1d). Next we thought of exploring the effect of protecting groups on the feasibility of the reaction and the yields and various building blocks with free OH groups were selected. It is worth

A concise and practical stereoselective synthesis of ipragliflozin L-proline

• Shuai Ma,
• Zhenren Liu,
• Jing Pan,
• Shunli Zhang and
• Weicheng Zhou

Beilstein J. Org. Chem. 2017, 13, 1064–1070, doi:10.3762/bjoc.13.105

• was purified by recrystallization from methanol, and the desired product in 65.3% yield with HPLC purity 99.79% was obtained; the diastereomer 5’ was not detected. The protecting groups of 5 were removed in presence of sodium methoxide in refluxing methanol, and then recrystallized to give

• derivative in situ, and the latter coupled with pivaloyl-protected 1,2-anhydroglucal 7 [20] to get the α-C-arylglucoside 8. After removing the protecting groups in the presence of sodium methoxide, the α-anomer 6’ of ipragliflozin was obtained. The hydroxy group in 2-position of 8 was protected by pivaloyl

A strategic approach to [6,6]-bicyclic lactones: application towards the CD fragment of DHβE

• Tue Heesgaard Jepsen,
• Emil Glibstrup,
• François Crestey,
• Anders A. Jensen and
• Jesper Langgaard Kristensen

Beilstein J. Org. Chem. 2017, 13, 988–994, doi:10.3762/bjoc.13.98

• intramolecular Mizoroki–Heck cross-coupling reaction and a 6π-electrocyclization as key steps. Results and Discussion First strategy with Ts and Cbz protecting groups As depicted in Scheme 1, our first strategy featured a late stage installation of the lactonic D ring by a 6π-electrocyclization and formation of

Total synthesis of TMG-chitotriomycin based on an automated electrochemical assembly of a disaccharide building block

• Yuta Isoda,
• Norihiko Sasaki,
• Kei Kitamura,
• Shuji Takahashi,
• Sujit Manmode,
• Naoko Takeda-Okuda,
• Jun-ichi Tamura,
• Toshiki Nokami and
• Toshiyuki Itoh

Beilstein J. Org. Chem. 2017, 13, 919–924, doi:10.3762/bjoc.13.93

• -chitotriomycin using an automated electrochemical synthesizer for the assembly of carbohydrate building blocks is demonstrated. We have successfully prepared a precursor of TMG-chitotriomycin, which is a structurally-pure tetrasaccharide with typical protecting groups, through the methodology of automated

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

• as for the non-methylated derivative [21]. Then, the 1,3-dipolar cycloaddition reaction of 6 with benzyl azide in toluene at 70 °C led to a mixture of regioisomeric triazoles 7 in a 42:58 ratio. The removal of all protecting groups was achieved by treatment of compounds 7 with ammonia followed by

Exploring endoperoxides as a new entry for the synthesis of branched azasugars

• Svenja Domeyer,
• Mark Bjerregaard,
• Henrik Johansson and
• Daniel Sejer Pedersen

Beilstein J. Org. Chem. 2017, 13, 644–647, doi:10.3762/bjoc.13.63

• was encouraging and gave access to a variety of novel protected azasugar precursors. We conclude that the choice of amine and dihydroxy protecting groups can have an impact on the success of the endoperoxide synthesis and its thermal stability, and that employing phthalimide and acetonide groups for N

Revaluation of biomass-derived furfuryl alcohol derivatives for the synthesis of carbocyclic nucleoside phosphonate analogues

• Bemba Sidi Mohamed,
• Christian Périgaud and
• Christophe Mathé

Beilstein J. Org. Chem. 2017, 13, 251–256, doi:10.3762/bjoc.13.28

• afforded the carbocyclic phosphonate (+/−)-10. Subsequently, the phosphonoester protecting groups were cleaved in the presence of TMSCl and NaI in a CH3CN/DMF mixture to give (+/−)-12 in 61% yield. The treatment of (+/−)-9 with K2CO3 in methanol at room temperature gave compound (+/−)-11 which upon

• treatment in acidic medium, the synthesis of the target compounds (+/−)-26 and (+/−)-27 was envisaged through the use of precursors without acid-labile protecting groups. Thus, reaction of (+/−)-7 with N6-Bz-adenine [14] or 2-amino-6-chloropurine in the presence of PPh3 and DIAD in THF provided the

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

• vaccines is the assembly of the trisaccharide β-D-GalpNAc-(1→4)-[α-D-Glcp-(1→3)]-β-D-ManpNAcA, in which the branching points are equipped with orthogonal protecting groups. A linear approach relying on the sequential assembly of monosaccharide building blocks proved superior to a convergent [3 + 3

• with steric bulk around the acceptor. Trisaccharides 2 and 3 can be derived from differentially protected common building blocks that carry tert-butyldimethylsilyl (TBS), benzoate (Bz) or acetate (Ac) ester and 2-naphthylmethyl (NAP) protecting groups that can be removed sequentially to allow for

• poor. Apparently, the “nitrile effect” [37][38] is partially overruled by the participating nature of the C3 ester protecting groups Ac/Bz that leads to a preference for the cis-glycosidic α-linked product. Linear total synthesis of 12F repeating unit hexasaccharide 1. The failure of the convergent [3

A new class of organogelators based on triphenylmethyl derivatives of primary alcohols: hydrophobic interactions alone can mediate gelation

• Wangkhem P. Singh and
• Rajkumar S. Singh

Beilstein J. Org. Chem. 2017, 13, 138–149, doi:10.3762/bjoc.13.17

• reflected in its higher MGC and lower Tgel values. Generally, triphenylmethyl protecting groups of alcohols are easily removed under acidic conditions in solution [29]. We wanted to see if this is still true for triphenylmethyl derivatives present in the gel state (e.g., gels obtained from triphenylmethyl

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

• synthesis of Garner’s aldehyde (4a) and its analogues. Results and Discussion Our synthetic route is shown in Scheme 1. We planned to synthesize 4a with various protecting groups from a commercially available amino ester through a three-step procedure utilizing the automated synthesizer, ChemKonzert (Figure

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

• observed. Therefore, the glycosylation of methyl selenol using the mixture of donors 9/10 was performed first. After Zemplén deprotection of the acetate protecting groups, separation of the unprotected pyranose/furanose isomers was achieved and seleno pyranosides 3 (3α/3β = 1:18, Scheme 2) as well as one

Orthogonal protection of saccharide polyols through solvent-free one-pot sequences based on regioselective silylations

• Serena Traboni,
• Emiliano Bedini and
• Alfonso Iadonisi

Beilstein J. Org. Chem. 2016, 12, 2748–2756, doi:10.3762/bjoc.12.271

• Serena Traboni Emiliano Bedini Alfonso Iadonisi Department of Chemical Sciences, University of Naples Federico II, Via Cinthia 4, 80126, Naples, Italy 10.3762/bjoc.12.271 Abstract tert-Butyldimethylsilyl (TBDMS) and tert-butyldiphenylsilyl (TBDPS) are alcohol protecting groups widely employed in

• experimentally simple tool for the straightforward access to saccharide building-blocks useful in organic synthesis. Keywords: carbohydrates; one-pot synthesis; regioselective protection; silyl protecting group; solvent-free reaction; Introduction The application of an orthogonal set of protecting groups

• to a broad range of conditions and feasible removal under conditions compatible with many other used alcohol protecting groups [1][2][3]. For this reason, silyl protecting groups are often serving as temporary protecting groups with polyol and saccharide substrates. The most robust and adopted silyl

β-Amino functionalization of cinnamic Weinreb amides in ionic liquid

• Yi-Ning Wang,
• Guo-Xiang Sun and
• Gang Qi

Beilstein J. Org. Chem. 2016, 12, 2372–2377, doi:10.3762/bjoc.12.231

• reaction conditions required for the removal of the N-protecting groups. With the aminochlorination developed in the past few years [31], we found that when the aminochlorination reactions of α,β-unsaturated ketones 3 were carried out in ionic liquid, [BMIM][NTf2] (1-n-butyl-3-methylimidazolium bis

• -protecting groups is relatively easier than those shown above; and 3) the ionic liquids are environmentally friendly and can be readily recycled. Results and Discussion The first attempt was to conduct the aminochlorination reaction of N-methoxy-N-methylcinnamoylamide (5a) in acetonitrile by using 2-NsNCl2

• achieved by the aminochlorination of α,β-unsaturated Weinreb amides. The new process has the advantages that the starting materials can be easily achieved and the N-protecting groups simply removed. Additionally, the reactions can be readily performed in the ionic liquid [BMIM][NTf2] at room temperature

Useful access to enantiomerically pure protected inositols from carbohydrates: the aldohexos-5-uloses route

• Felicia D’Andrea,
• Giorgio Catelani,
• Lorenzo Guazzelli and
• Venerando Pistarà

Beilstein J. Org. Chem. 2016, 12, 2343–2350, doi:10.3762/bjoc.12.227

• precursors are employed as starting materials. As an example of application of the method, the indirect selective protection of secondary inositols’ hydroxy functions, by placing specific protecting groups on the aldohexos-5-ulose precursor has been presented. Keywords: aldohexos-5-uloses; inositols

• group (position 6). This 2,3,6-cis arrangement of the aldol products was observed irrespective to the stereochemistry of the other two positions (4 and 5), corresponding to the C-2 and C-3 of the parent dicarbonyl derivative. To determine the effect of additional protecting groups on the reaction, the

• stereoselectivity in accordance with the predicted stereo-outcome. In this way, the orthogonal protecting groups (allyl and naphthalenylmethyl) installed on aldohexos-5-ulose 20, differentiated the two 1,2-cis hydroxy couples (2,3 and 4,5 positions) of 22 which can be easily transformed further in a selective

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

• -hydroxyenduracididine 52 using the same procedure. The new route proved more efficient than the previous report and provided access to both diastereomers suitably armed with orthogonal protecting groups. Synthesis of (±)-enduracididine and (±)-allo-enduracididine by Du Bois et al.: The synthesis of (±)-enduracididine

• protected linear precursor 115. Cleavage of the TBS and methyl ester protecting groups afforded seco-acid 116. However, during the hydrolysis step, two of the three Cbz groups were cleaved from the enduracididine residue, and the position of the remaining Cbz and CO2H could not be determined. It was decided

• that final deprotection of the remaining enduracididine protecting groups would take place after formation of the macrocycle. Treatment of linear precursor 116 with modified Shiina macrolactonisation conditions reported by Batey et al. [74] of 2-methyl-6-nitrobenzoic anhydride (MNBA), DMAP and Dy(OTf)3

The direct oxidative diene cyclization and related reactions in natural product synthesis

• Juliane Adrian,
• Leona J. Gross and
• Christian B. W. Stark

Beilstein J. Org. Chem. 2016, 12, 2104–2123, doi:10.3762/bjoc.12.200

• protecting groups. The first total synthesis of membrarollin (62, Scheme 13) was finally disclosed by Brown and co-workers in 2009 [107]. Similarly starting from 1-dodecyne (56), triene system 61 was selectively oxidized using a permanganate-mediated oxidative cyclization affording two separable

Synthesis of the C8’-epimeric thymine pyranosyl amino acid core of amipurimycin

• Pramod R. Markad,
• Navanath Kumbhar and
• Dilip D. Dhavale

Beilstein J. Org. Chem. 2016, 12, 1765–1771, doi:10.3762/bjoc.12.165

• including solvent, Lewis acid, and protecting groups on the nucleobase or sugar; we thought of synthesizing the peracylated anhydrosugar to alter its reactivity towards glycosylation [22]. In this regard, anhydrosugar 15 was subjected to 10% Pd/C and Et3SiH (for deprotection of the benzyl functionality and

Beta-hydroxyphosphonate ribonucleoside analogues derived from 4-substituted-1,2,3-triazoles as IMP/GMP mimics: synthesis and biological evaluation

• Tai Nguyen Van,
• Audrey Hospital,
• Corinne Lionne,
• Lars P. Jordheim,
• Charles Dumontet,
• Christian Périgaud,
• Laurent Chaloin and
• Suzanne Peyrottes

Beilstein J. Org. Chem. 2016, 12, 1476–1486, doi:10.3762/bjoc.12.144

• -protected nucleotides 3a–o (Scheme 2) in moderate to good yields. Removal of the sugar protecting groups (acetyl and benzoyl) in basic conditions resulted in the formation of the nucleotides 4a–q (Scheme 2), which were then treated by trimethylsilyl bromide (TMSBr) to generate the corresponding phosphonic

• water and extracted with EtOAc, the organic layers were combined and dried over with MgSO4 and concentrated under reduced pressure. The crude material was purified by flash chromatography (CH2Cl2/EtOAc) to give the desired product. General procedure D for removal of sugar protecting groups: The