Preactivation-based chemoselective glycosylations: A powerful strategy for oligosaccharide assembly

• Weizhun Yang,
• Bo Yang,
• Sherif Ramadan and
• Xuefei Huang

Beilstein J. Org. Chem. 2017, 13, 2094–2114, doi:10.3762/bjoc.13.207

• disaccharide 7, which could be subjected to bromine-promoted glycosylation for further chain elongation. As an example, preactivation of a monosaccharide 8 with bromine was followed by the addition of a bifunctional disaccharide building block 10 and subsequent TMSOTf-promoted orthoester rearrangement

• transformations commonly encountered in building block preparation [41]. At the same time, mild promoters are available for thioglycoside activation. The anomeric reactivities of thioglycosides towards glycosylation can be significantly influenced by the protective groups on the glycan ring as well as the size

• prepare building blocks with the required anomeric reactivities. Furthermore, the relative anomeric reactivity values of a building block can vary depending on the structures of acceptors and reaction condition [44], presenting challenges in accurately predicting the reaction outcome. The aforementioned

Intramolecular glycosylation

• Xiao G. Jia and
• Alexei V. Demchenko

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

• activation of the S-ethyl leaving group in compound 55 was achieved with MeOTf and the glycosylation of the central building block took place with concomitant removal of the p-methoxybenzyl (PMB) group. The o-allylphenyl leaving group was activated with NIS/TfOH, and again the PMB group of the acceptor was

1,3-Dibromo-5,5-dimethylhydantoin as promoter for glycosylations using thioglycosides

• Fei-Fei Xu,
• Claney L. Pereira and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2017, 13, 1994–1998, doi:10.3762/bjoc.13.195

• building block 8 followed by UV-cleavage, disaccharide 16 was obtained in 63% isolated yield. Moreover, DBDMH performs as well as N-iodosuccinimide (NIS) in activating phenyl selenoglycoside 17 in the presence of water to furnish hemiacetal 18 en route to glycosyl imidate 19 (Scheme 2). Conclusion The

• compounds. Acknowledgements We gratefully acknowledge the Max Planck Society for financial support. We thank Dr. Martina Delbianco for help with automated glycan assembly, Ms. Priya Bharate for providing building block 8, Dr. Madhu Emmadi for building block 17, Dr. Lennart Lykke for building block 9 and Ms

Mechanochemical synthesis of small organic molecules

• Tapas Kumar Achar,
• Anima Bose and
• Prasenjit Mal

Beilstein J. Org. Chem. 2017, 13, 1907–1931, doi:10.3762/bjoc.13.186

• amines were safely controlled at maximum contacts (solvent-free) by the acid salt NaHSO4. Using 2.0 equiv of both NaHSO4 and PIDA, 72–92% of amides were isolated within 2 h (Scheme 17) [81]. Amino acids are one of the important biomolecules for example as building block of peptides and proteins [75][82

Pd(OAc)₂/Ph₃P-catalyzed dimerization of isoprene and synthesis of monoterpenic heterocycles

• Dominik Kellner,
• Maximilian Weger,
• Andrea Gini and
• Olga García Mancheño

Beilstein J. Org. Chem. 2017, 13, 1807–1815, doi:10.3762/bjoc.13.175

• ), 34.1 (C-7), 32.7 (C-8), 22.4 (Me-6), 21.4 (Me-16), 13.8 (Me-10); HRMS (ESI+): calcd. for [C17H24NO2S]+: 306.1528; found: 306.1529. Isoprene as chemical building block in nature and organic synthesis. Pd-catalyzed dimerization of isoprene. Putative mechanism for the Pd(OAc)2-catalyzed dimerization of

A novel approach to oxoisoaporphine alkaloids via regioselective metalation of alkoxy isoquinolines

• Benedikt C. Melzer and
• Franz Bracher

Beilstein J. Org. Chem. 2017, 13, 1564–1571, doi:10.3762/bjoc.13.156

• alkaloids one common building block, (4-methoxy-2-(methoxycarbonyl)phenyl)boronic acid pinacol ester (9) [24], could be applied, since the alkaloids of interest all bear the methoxy group at C-9. Suzuki cross-coupling reaction of the iodinated isoquinolines 8a–c with this boronate under Pd(PPh3)4 catalysis

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

• devoted to the synthesis of new MraY inhibitors [49][50], we were interested in developing a more efficient access to 5’-ethynyluridine, a crucial building block for the further synthesis of triazole-containing compounds [49]. Intrigued by the moderate diastereomeric ratio reported for the addition or

• reagent, we manage to obtain an excellent diastereoselectivity. Indeed, by using the most bulky 2’,3’-O-TIPS protecting groups and TIPS-ethynylmagnesium bromide, the 5’-ethynylation was achieved in a 99:1 ratio in favor of the 5’S-isomer. The resulting building block with a broad potential in nucleos(t

Photocatalyzed synthesis of isochromanones and isobenzofuranones under batch and flow conditions

• Manuel Anselmo,
• Lisa Moni,
• Hossny Ismail,
• Davide Comoretto,
• Renata Riva and
• Andrea Basso

Beilstein J. Org. Chem. 2017, 13, 1456–1462, doi:10.3762/bjoc.13.143

• conditions [7], in this case the results were not significantly better, as shown in Table 3. Having set up the conditions for the synthesis of isochromanones, we moved to explore the possibility to obtain isobenzofuranones 13 by introducing an ester functional group in the alkene building block, according to

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

• should be generated by nucleophilic addition of an allyl anion equivalent to the resulting aldehyde 5. Guanidine formation and ozonolysis with subsequent oxidation to the carboxylic acid would then furnish the protected GHPD side chain building block 3 which can then be coupled to the cyclodepsipeptide

• chain [12]. In order to reduce the number of linear steps, the protected guanidino group was included in the side chain building block in our case. This strategy would allow to assemble the complete peptide core in a solid-phase synthesis and to perform the solution-phase coupling without a large excess

• of the GHPD side chain building block. Thus, Cudic’s SPPS approach should be combined with the advantages of the late stage coupling employed by Jolliffe. Synthesis The C13-fragment was prepared starting from erucamide (6) in three simple operations. Reduction of the amide with lithium aluminium

Synthesis of oligonucleotides on a soluble support

• Harri Lönnberg

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

• has been regarded as an approach that could combine the advantageous features of both the solution and solid-phase syntheses. The critical step of this approach is the separation of the support-anchored oligonucleotide chain from the monomeric building block and other small molecular reagents and

• order by esterification of phosphoric acid with the 3´-OH of one and the 5´-OH of the other nucleoside. Usually, the 3´-OH is first esterified with an appropriate derivative of phosphoric acid and the resulting building block is then reacted with the 5´-OH (Figure 1). Either a linear or a convergent

• the nucleobases are usually protected with acyl groups and the 5´-OH of the monomeric building block with a 4,4’-dimethoxytrityl group (DMTr), or sometimes with its monomethoxytrityl analog (MMTr) [4][5]. To achieve coupling, phosphoramidites are activated with azoles [6], such as tetrazole [7], its

BODIPY-based fluorescent liposomes with sesquiterpene lactone trilobolide

• Ludmila Škorpilová,
• Silvie Rimpelová,
• Michal Jurášek,
• Miloš Buděšínský,
• Jana Lokajová,
• Roman Effenberg,
• Petr Slepička,
• Tomáš Ruml,
• Eva Kmoníčková,
• Pavel B. Drašar and
• Zdeněk Wimmer

Beilstein J. Org. Chem. 2017, 13, 1316–1324, doi:10.3762/bjoc.13.128

• , containing Tb, ChL and BODIPY, represents a well-defined traceable system with a potentiated ability to assemble into liposomal systems. Results and Discussion Chemistry In this work, Tb was connected to a pegylated BODIPY building block containing ChL. This way obtained construct 6 was used as a component

• for liposomal formulation. The syntheses of some of the employed molecules were previously described [24][27][28], their structures are shown in Figure 1. The synthesis of a BODIPY-based building block is displayed in Scheme 1, part A. Methyl 4-iodo-L-phenylalaninate hydrochloride was prepared by the

• hydrolysis of methyl ester 1 with aqueous LiOH in THF and subsequent Suzuki cross-coupling with BODIPY-BA [34] catalyzed by Pd(PPh3)4 and K2CO3 in a mixture of toluene/MeOH/water provided the fluorescent building block 3 in 88% yield. Sequential connection of other functional components of the target

Total synthesis of elansolids B1 and B2

• Liang-Liang Wang and
• Andreas Kirschning

Beilstein J. Org. Chem. 2017, 13, 1280–1287, doi:10.3762/bjoc.13.124

• . Results and Discussion The improved synthesis utilizes the Suzuki–Miyaura cross-coupling reaction to merge the western fragment derived from ketone 9 with the newly designed eastern building block 13. This fragment was obtained in very good yield from vinyl iodide 12 [9] by a Stille protocol using doubly

• elansolid B1 (2). The improvements are mainly associated with the preparation of the triene unit at C10–C15 by utilizing the Stille and the Suzuki–Miyaura cross-coupling reactions as well as the highly versatile difunctionalized building block 14. In principal, the synthesis sheds light on how such (Z,E,Z

Aqueous semisynthesis of C-glycoside glycamines from agarose

• Juliana C. Cunico Dallagnol,
• Alexandre Orsato,
• Diogo R. B. Ducatti,
• Miguel D. Noseda,
• Maria Eugênia R. Duarte and
• Alan G. Gonçalves

Beilstein J. Org. Chem. 2017, 13, 1222–1229, doi:10.3762/bjoc.13.121

• , there is no available methodology to obtain this building block using chemical hydrolysis. We produced compound 9 by hydrolysis of the previously synthesized glycamine 7. In addition, we conducted a stepwise sequence of hydrolysis and reduction reactions, followed by periodate cleavage of the 1,2

Strategies in megasynthase engineering – fatty acid synthases (FAS) as model proteins

• Manuel Fischer and
• Martin Grininger

Beilstein J. Org. Chem. 2017, 13, 1204–1211, doi:10.3762/bjoc.13.119

• importantly suggesting ACP to dock with different faces during intra- and intermodular acyl-chain delivery [39][40]. Strategies for megasynthase engineering The concept of one multienzyme module being responsible for the incorporation of one building block in modular systems has inspired chemists and

Towards open-ended evolution in self-replicating molecular systems

• Herman Duim and
• Sijbren Otto

Beilstein J. Org. Chem. 2017, 13, 1189–1203, doi:10.3762/bjoc.13.118

• , chosen such that the IGS of one pair is matched to the target sites of the next pair. In this way one ribozyme, say E1, can catalyze the formation of the next ribozyme, E2, from its non-covalently bound building blocks I2. This ribozyme can in turn catalyze the formation of E3 from its building block and

• building blocks consist of an aromatic core that is functionalized with two thiol groups and a peptide chain (Figure 12a). Building block 1 and 2 are very closely related to each other and differ only in a single amino acid of the peptide chain. These peptide building blocks can then be oxidized to form

• doubled, leading to an exponential self-replication. In previous work it was already shown that the less hydrophobic building block 2 tends to form larger octameric macrocycles than the more hydrophobic building block 1 which forms hexamers [54]. This is reasonable, since a weaker hydrophobic interaction

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

• sequence of protection-deprotection-functionalization reactions at appropriate position (Figure 1). D-glucose, D-xylose and L-arabinose were used as the key starting materials for the DOS protocol. It was expected that each given sugar building block (generated in the building phase of the DOS) could be

• ratio of integration of the terminal alkyne proton in the propargyl building block and the characteristic triazole–alkene proton in the cyclo-adducts. The click reaction proceeds under various conditions with a plenty of sources of Cu(I) [19]. We have selected copper iodide (CuI) as Cu(I) source for the

• ether group on the primary OH group (1a and 1c) or xylose derived building block containing a propargyl group on the secondary OH group (1b). Further, a comparatively lower yield for the cycloaddition reaction (3c) was obtained when both building blocks used contain a secondary azide group (2b) and a

Total syntheses of the archazolids: an emerging class of novel anticancer drugs

• Stephan Scheeff and
• Dirk Menche

Beilstein J. Org. Chem. 2017, 13, 1085–1098, doi:10.3762/bjoc.13.108

• , a procedure that was further studied by the group [71]. The two vicinal Z-alkenes were then installed by two consecutive Still–Gennari olefinations [72] with aldehydes 15 and 18. In both cases coupling with the Still–Gennari reagent 16 gave 17 and after reduction the final building block 5 was

• . Notably, they had to switch the halide/organometallic functionality of each building block after an unsuccessful coupling between the stannane synthesized by reduction and methylation of ketone 67 and the iodine derived from fragment 62. They assume that the steric hindrance of the methyl group in C10

• position possibly lowers the reactivity of the iodine in the oxidative addition step in the catalytic cycle. For the synthesis of stannane 56 the authors could benefit from the previous fragment synthesis. In 2010 they first published an approach to an eastern building block through an allylation

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

• electrochemical solution-phase synthesis developed by us. The synthesis of structurally well-defined TMG-chitotriomycin has been accomplished in 10-steps from a disaccharide building block. Keywords: automated synthesis; electrochemical oxidation; glycosylation; glucosamine; total synthesis; Introduction

• linkage [26]. Here we report the total synthesis of TMG-chitotriomycin (1) as a single stereoisomer, which was prepared by automated electrochemical assembly started from a disaccharide building block. Results and Discussion To synthesize the potential precursor 7 of TMG-chitotriomycin (1

• lack of neighboring group participation [27]. 4-Fluorophenyl 3,4,6-tri-O-acetyl-2-deoxy-2-azido-β-D-thioglucoside (2a) afforded the corresponding disaccharide α-isomer 5aα exclusively by the reaction with building block 4 via the glycosyl triflate intermediate 3a (Scheme 1). On the other hand, 4

First total synthesis of kipukasin A

• Chuang Li,
• Haixin Ding,
• Zhizhong Ruan,
• Yirong Zhou and
• Qiang Xiao

Beilstein J. Org. Chem. 2017, 13, 855–862, doi:10.3762/bjoc.13.86

• of aroyl building block 9 (Scheme 1). Vilsmeier formylation of 1,3-dihydroxy-5-methylbenzene (5) gave 2,4-dihydroxy-6-methylbenzaldehyde (6) in 75% yield [25][26]. Then compound 6 could react with methyl iodine in acetone by using K2CO3 as base. The obtained 2,4-dimethoxy-6-methylbenzaldehyde (7) was

• -6-methylbenzoyl chloride (9) was used directly in the next step without further purification. Then we started to synthesize glycosylation donor 16 as the key building block (Scheme 2). In previous reports, 3,5-O-diacetyl-1,2-O-isopropylidene-D-ribofuranose (11) was prepared either from D-xylose [29

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

• aldol/hemiketalization reaction of a C4 aldehyde with a C3 ketone provides the differentially protected ketoheptose building block, which can be further reacted to furnish target D-manno-heptulose. Keywords: aldol reaction; cascade reaction; D-manno-heptulose; higher-carbon sugar; ketoheptose

• protected ketoheptose building block is still attractive due to the versatile functionalization possibilities of the building block into various derivatives of D-manno-heptulose. A de novo synthesis has proved to be an attractive strategy to produce orthogonally protected carbohydrate building blocks from

• of the differentially protected ketoheptose building block 2. The ketoheptose 2 can be further divided into C4 aldehyde 3 and C3 ketone 4 via a cascade aldol/hemiketalization pathway. Results and Discussion The synthesis of the C4 aldehyde commenced with commercially available D-lyxose (5, Scheme 2

Fast and efficient synthesis of microporous polymer nanomembranes via light-induced click reaction

• Qi An,
• Youssef Hassan,
• Xiaotong Yan,
• Peter Krolla-Sidenstein,
• Tawheed Mohammed,
• Mathias Lang,
• Stefan Bräse and
• Manuel Tsotsalas

Beilstein J. Org. Chem. 2017, 13, 558–563, doi:10.3762/bjoc.13.54

• the substrates with an alkyne terminated self-assembled monolayer, which presents initial groups for the stepwise growing of the CMPs using the TYC reaction. In the first step, we immersed the functionalized surface in a solution of the tetra-topic thiol building block (tetrakis(4-sulfanylphenyl

• substrate in a solution of the tetra-topic alkyne building block (tetrakis(4-ethynylphenyl)methane, TPM-alkyne), again with a small amount of photoinitiator. Then we irradiated the substrate for 3 minutes and rinsed the substrate thoroughly with absolute THF. Figure 1 shows the LbL synthesis procedure as

Effect of the ortho-hydroxy group of salicylaldehyde in the A³ coupling reaction: A metal-catalyst-free synthesis of propargylamine

• Sujit Ghosh,
• Kinkar Biswas,
• Suchandra Bhattacharya,
• Pranab Ghosh and
• Basudeb Basu

Beilstein J. Org. Chem. 2017, 13, 552–557, doi:10.3762/bjoc.13.53

• invented an unprecedented effect of salicylaldehyde, one of the A3 coupling partners, which could lead to the formation of propargylamine, an important pharmaceutical building block, in the absence of any metal catalyst and under mild conditions. The role of the hydroxy group in ortho position of

Polyketide stereocontrol: a study in chemical biology

• Kira J. Weissman

Beilstein J. Org. Chem. 2017, 13, 348–371, doi:10.3762/bjoc.13.39

• (i.e., formation of the methylmalonyl-O-AT intermediate) [30]. Substrate preference can be rationalized, at least in part, by bioinformatics which has revealed several sequence motifs correlating with building block choice (whether for starter or extender units, malonyl or branching extender units) [31

• numbering) capable of forming salt bridges with the carboxyl group of the building block, while these are non-polar amino acids in starter-unit specific ATs. The choice of methylmalonyl-CoA over malonyl-CoA is correlated with a YASH motif some 100 residues downstream of the active site serine, whereas

Regiochemistry of cyclocondensation reactions in the synthesis of polyazaheterocycles

• Patrick T. Campos,
• Leticia V. Rodrigues,
• Andrei L. Belladona,
• Caroline R. Bender,
• Juliana S. Bitencurt,
• Fernanda A. Rosa,
• Davi F. Back,
• Helio G. Bonacorso,
• Nilo Zanatta,
• Clarissa P. Frizzo and
• Marcos A. P. Martins

Beilstein J. Org. Chem. 2017, 13, 257–266, doi:10.3762/bjoc.13.29

• , followed by aromatization finally generates product 5 (Scheme 1). The trichloromethyl (CCl3) substituent as a leaving group in β-alkoxyvinyl trichloromethyl ketones has been previously used by us for the synthesis of similar heterocycles [27][28]. Products 5–7 are considered to be very attractive building

• block in the synthesis of heterocycles, because they have three different electrophilic carbonyl groups. This is expected to lead to different reaction pathways and thus, diverse products. However, the amide carbonyl of these compounds is considered to be less reactive, as its modification results in

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

• sources for the future and can be used to produce a range of chemical building blocks. The latter products can further be transformed to value-added compounds that are suitable for supplement or replacement to oil-derived chemicals. One such building block is furfuryl alcohol which is obtained through the