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

Automated glycan assembly of a S. pneumoniae serotype 3 CPS antigen

• Markus W. Weishaupt,
• Stefan Matthies,
• Mattan Hurevich,
• Claney L. Pereira,
• Heung Sik Hahm and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2016, 12, 1440–1446, doi:10.3762/bjoc.12.139

• step with the activator prior to each glycosylation cycle greatly increased the yields by neutralizing any residual base from deprotection steps in the synthetic cycle. This process improvement is applicable to AGA of many other oligosaccharides. Keywords: automation; glycosylation; protecting groups

Conjugate addition–enantioselective protonation reactions

• James P. Phelan and
• Jonathan A. Ellman

Beilstein J. Org. Chem. 2016, 12, 1203–1228, doi:10.3762/bjoc.12.116

• led to low conversion. The use of potassium tert-butoxide was found to be essential to achieve good reactivity and enantioselectivity. Other amino-protecting groups (Boc, phthalimido) or tertiary N-methylated variants rendered the 1,4-acceptor unreactive. Glorius and co-workers proposed that an

NeoPHOX – a structurally tunable ligand system for asymmetric catalysis

• Jaroslav Padevět,
• Marcus G. Schrems,
• Robin Scheil and
• Andreas Pfaltz

Beilstein J. Org. Chem. 2016, 12, 1185–1195, doi:10.3762/bjoc.12.114

• determined by X-ray diffraction and compared with known phosphinooxazoline complexes. We were interested to see whether the differences in steric shielding of the coordination sphere by the protecting groups on the tertiary alcohol function correlated with the hydrogenation results. From the obtained crystal

Chiral cyclopentadienylruthenium sulfoxide catalysts for asymmetric redox bicycloisomerization

• Barry M. Trost,
• Michael C. Ryan and
• Meera Rao

Beilstein J. Org. Chem. 2016, 12, 1136–1152, doi:10.3762/bjoc.12.110

• reaction for the synthesis of Tris-protected [3.1.0] pyrrolidines, it occurred to us that protecting groups other than Tris may be equally effective for the [3.1.0] system. The Tris group was chosen during our optimization of the six-membered ring system (Table 5), which may have significantly different

Catalytic asymmetric synthesis of biologically important 3-hydroxyoxindoles: an update

• Bin Yu,
• Hui Xing,
• De-Quan Yu and
• Hong-Min Liu

Beilstein J. Org. Chem. 2016, 12, 1000–1039, doi:10.3762/bjoc.12.98

• (Scheme 1) [14]. 3-Allyl-3-hydroxyoxindoles were obtained in 89–98% yield and with 32–86% ee when the reactions were carried out at −60 °C using 5 mol % of CNN pincer Pd complex (cat. 1). Substituents attached to the isatin aromatic ring and N-protecting groups were important in controlling the

One-pot synthesis of enantiomerically pure N-protected allylic amines from N-protected α-amino esters

• Gastón Silveira-Dorta,
• Sergio J. Álvarez-Méndez,
• Víctor S. Martín and
• José M. Padrón

Beilstein J. Org. Chem. 2016, 12, 957–962, doi:10.3762/bjoc.12.94

• is remarkable that this protocol avoids using O-protecting groups or the Garner aldehyde which have been used extensively in the synthesis of related compounds. Conclusion In summary, this simple protocol described herein enables a rapid access to a number of useful enantiopure allylic amines from

Muraymycin nucleoside-peptide antibiotics: uridine-derived natural products as lead structures for the development of novel antibacterial agents

• Daniel Wiegmann,
• Stefan Koppermann,
• Marius Wirth,
• Giuliana Niro,
• Kristin Leyerer and
• Christian Ducho

Beilstein J. Org. Chem. 2016, 12, 769–795, doi:10.3762/bjoc.12.77

• guanidinylation reagent 55. With the protected epicapreomycidine precursor 56 in hand, the Boc and acetonide protecting groups were removed. Urea formation with the valine derivative 57 with final oxidation of the primary hydroxy function afforded the desired dipeptide 58 [78] (Scheme 7). Furthermore, Ducho et al

• (5'S)-configuration, contrary to the results of MIC value determination. Further studies were then carried out with (5'R)-derivatives only, i.e., with 5'-epimers of the parent natural products. The influence of protecting groups was examined applying a strategy of stepwise deprotection. This led to

Synthesis and in vitro cytotoxicity of acetylated 3-fluoro, 4-fluoro and 3,4-difluoro analogs of D-glucosamine and D-galactosamine

• Štěpán Horník,
• Lucie Červenková Šťastná,
• Petra Cuřínová,
• Jan Sýkora,
• Kateřina Káňová,
• Roman Hrstka,
• Ivana Císařová,
• Martin Dračínský and
• Jindřich Karban

Beilstein J. Org. Chem. 2016, 12, 750–759, doi:10.3762/bjoc.12.75

• -anhydrohexopyranoses were then converted into the target fluoro analogs of D-glucosamine and D-galactosamine (Scheme 1). Dual protection of the anomeric and primary hydroxy groups in the form of the 1,6-anhydro bridge reduced the number of protecting groups, and the rigid bicyclic skeleton of 1,6-anhydrohexopyranoses