Co-reporter:Scott J. Hasty;Mithila D. Bandara;Nigam P. Rath;Alexei V. Demchenko
The Journal of Organic Chemistry February 17, 2017 Volume 82(Issue 4) pp:1904-1911
Publication Date(Web):January 30, 2017
DOI:10.1021/acs.joc.6b02478
This article describes the development of S-benzimidazolyl (SBiz) imidates as versatile building blocks for oligosaccharide synthesis. The SBiz imidates have been originally developed as a new platform for active-latent glycosylations. This article expands upon the utility of these compounds. The application to practically all common concepts for the expeditious oligosaccharide synthesis including selective, chemoselective, and orthogonal strategies is demonstrated. The strategy development was made possible thanks to our enhanced understanding of the reaction mechanism and the modes by which SBiz imidates interact with various promoters of glycosylation.
Co-reporter:Swati S. Nigudkar;Tinghua Wang;Salvatore G. Pistorio;Jagodige P. Yasomanee;Keith J. Stine;Alexei V. Demchenko
Organic & Biomolecular Chemistry 2017 vol. 15(Issue 2) pp:348-359
Publication Date(Web):2017/01/04
DOI:10.1039/C6OB02230H
Previously we communicated 3,3-difluoroxindole (HOFox) – mediated glycosylations wherein 3,3-difluoro-3H-indol-2-yl (OFox) imidates were found to be key intermediates. Both the in situ synthesis from the corresponding glycosyl bromides and activation of the OFox imidates could be conducted in a regenerative fashion. Herein, we extend this study with the main focus on the synthesis of various OFox imidates and their investigation as glycosyl donors for chemical 1,2-cis and 1,2-trans glycosylation.
Co-reporter:Mithila D. Bandara;Jagodige P. Yasomanee;Nigam P. Rath;Christian M. Pedersen;Mikael Bols;Alexei V. Demchenko
Organic & Biomolecular Chemistry 2017 vol. 15(Issue 3) pp:559-563
Publication Date(Web):2017/01/18
DOI:10.1039/C6OB02498J
A new series of superarmed glycosyl donors has been investigated. It was demonstrated that the S-ethyl leaving group allows for high reactivity, which is much higher than that of equally equipped S-phenyl glycosyl donors that were previously investigated by our groups. The superarmed S-ethyl glycosyl donors equipped with a 2-O-benzoyl group gave complete β-stereoselectivity. Utility of the new glycosyl donors has been demonstrated in a one-pot one-addition oligosaccharide synthesis with all of the reaction components present from the beginning.
Co-reporter:Papapida Pornsuriyasak, Xiao G. Jia, Sophon Kaeothip, and Alexei V. Demchenko
Organic Letters 2016 Volume 18(Issue 9) pp:2316-2319
Publication Date(Web):April 26, 2016
DOI:10.1021/acs.orglett.6b01102
A new method for intramolecular oligosaccharide synthesis that is conceptually related to the general molecular clamp approach is introduced. Exceptional α-selectivity has been achieved in a majority of applications. Unlike other related concepts, this approach is based on the bisphenol A template, which allows one to connect multiple building blocks to perform templated oligosaccharide synthesis with complete stereoselectivity. This principle was demonstrated by the synthesis of an α,α-linked trisaccharide.
Co-reporter:Jagodige P. Yasomanee, Archana R. Parameswar, Papapida Pornsuriyasak, Nigam P. Rath and Alexei V. Demchenko
Organic & Biomolecular Chemistry 2016 vol. 14(Issue 11) pp:3159-3169
Publication Date(Web):12 Feb 2016
DOI:10.1039/C6OB00107F
2-O-Picolinyl protected glycosyl donors lead to the formation of 1,2-trans glycosides with complete stereoselectivity. This is due to the participatory effect of the picolinyl nitrogen that is able to block the bottom face of the ring via a six-membered cyclic intermediate. Herein we demonstrate that if the nitrogen atom of the O-picolinyl moiety is temporarily blocked by coordination to the metal center (Pd), it becomes unavailable to participate in glycosylation and hence the stereoselectivity of 2-O-picolinyl-assisted glycosylations can be “switched”.
Co-reporter:Xiao G. Jia, Papapida Pornsuriyasak, and Alexei V. Demchenko
The Journal of Organic Chemistry 2016 Volume 81(Issue 24) pp:12232-12246
Publication Date(Web):November 29, 2016
DOI:10.1021/acs.joc.6b02151
We previously communicated that high α-selectivity that can be achieved in intramolecular glycosylations using a rigid bisphenol A template supplemented with linkers of various lengths. Herein, we present our investigation of the mechanistic aspects of the templated synthesis that helped to design an improved template-linker combination. We demonstrate that bisphenol A as the template in combination with phthaloyl linker allows for superior stereoselectivity and yields in glycosylations. Several mechanistic studies explore origins of the enhanced stereoselectivity and yields achieved using the phthaloyl linker.
Co-reporter:Salvatore G. Pistorio, Swati S. Nigudkar, Keith J. Stine, and Alexei V. Demchenko
The Journal of Organic Chemistry 2016 Volume 81(Issue 19) pp:8796-8805
Publication Date(Web):August 30, 2016
DOI:10.1021/acs.joc.6b01439
The development of a useful methodology for simple, scalable, and transformative automation of oligosaccharide synthesis that easily interfaces with existing methods is reported. The automated synthesis can now be performed using accessible equipment where the reactants and reagents are delivered by the pump or the autosampler and the reactions can be monitored by the UV detector. The HPLC-based platform for automation is easy to setup and adapt to different systems and targets.
Co-reporter:Jagodige P. Yasomanee, Satsawat Visansirikul, Papapida Pornsuriyasak, Melissa Thompson, Stephen A. Kolodziej, and Alexei V. Demchenko
The Journal of Organic Chemistry 2016 Volume 81(Issue 14) pp:5981-5987
Publication Date(Web):June 15, 2016
DOI:10.1021/acs.joc.6b00910
The chemical synthesis of the repeating unit of S. aureus capsular polysaccharide type 5 equipped with capping methyl groups at the points of propagation of the polysaccharide sequence is described. This model compound was designed to study activation of the full length polysaccharide for conjugation to a carrier protein.
Co-reporter:Swati S. Nigudkar and Alexei V. Demchenko
Chemical Science 2015 vol. 6(Issue 5) pp:2687-2704
Publication Date(Web):06 Mar 2015
DOI:10.1039/C5SC00280J
Recent developments in stereoselective 1,2-cis glycosylation that have emerged during the past decade are surveyed herein. For detailed coverage of the previous achievements in the field the reader is referred to our earlier reviews: A. V. Demchenko, Curr. Org. Chem., 2003, 7, 35–79 and Synlett, 2003, 1225–1240.
Co-reporter:Satsawat Visansirikul, Jagodige P. Yasomanee, Papapida Pornsuriyasak, Medha N. Kamat, Nikita M. Podvalnyy, Chase P. Gobble, Melissa Thompson, Stephen A. Kolodziej, and Alexei V. Demchenko
Organic Letters 2015 Volume 17(Issue 10) pp:2382-2384
Publication Date(Web):April 30, 2015
DOI:10.1021/acs.orglett.5b00899
The first synthesis of the repeating unit of S. aureus capsular polysaccharide type 8 is described. The repeating unit is an unusual trisaccharide sequence of three uncommon sugars, all connected via 1,2-cis linkages. The synthetic trisaccharide was equipped with capping methyl groups at the points of propagation of the polysaccharide sequence.
Co-reporter:Abhijeet K. Kayastha, Xiao G. Jia, Jagodige P. Yasomanee, and Alexei V. Demchenko
Organic Letters 2015 Volume 17(Issue 18) pp:4448-4451
Publication Date(Web):September 9, 2015
DOI:10.1021/acs.orglett.5b02110
Remote 6-O-picolinyl or 6-O-picoloyl substituents often provide high β-selectivity due to H-bond-mediated aglycone delivery (HAD). Herein it has been demonstrated that if the nitrogen atom of the 6-O-picolinyl or picoloyl moiety is temporarily blocked by coordination to a metal center (Pd), it cannot engage in HAD-mediated β-glycosylation. Hence, the stereoselectivity of 6-O-picolinyl/picoloyl-assisted glycosylations can be “switched” to α-selectivity.
Co-reporter:Sneha C. Ranade, Alexei V. Demchenko
Carbohydrate Research 2015 Volume 403() pp:115-122
Publication Date(Web):11 February 2015
DOI:10.1016/j.carres.2014.06.025
•Direct versus remote activation mode of leaving groups.•Reactivity tuning of glycosyl donors.•Selective activation of carbohydrate building blocks.Structural modifications of the leaving group of S-glycosyl O-methyl phenylcarbamothioates (SNea) involving change of substituents that express different electronic effects led to a better understanding of how the reactivity of these glycosyl donors can be modified by changing the structure of their leaving groups. Mechanistic studies involving the isolation of departed aglycones were indicative of the direct activation of both p-methoxy-SNea and p-nitro-SNea leaving groups via the anomeric sulfur rather than the remote nitrogen atom. The presence of an electron donating substituent (p-methoxy) has a strong effect on the nucleophilicity of the sulfur atom that becomes more susceptible toward the attack of thiophilic reagents, in particular. This key observation allowed to differentiate the reactivity levels of p-methoxy-SNea versus p-nitro-SNea and even unmodified SNea leaving groups. The reactivity difference observed in the series of SNea leaving groups is sufficient to be exploited in expeditious oligosaccharide synthesis via selective activation strategies.
Co-reporter:S. Visansirikul;J. P. Yasomanee;A. V. Demchenko
Russian Chemical Bulletin 2015 Volume 64( Issue 5) pp:1107-1118
Publication Date(Web):2015 May
DOI:10.1007/s11172-015-0987-2
Described herein is the synthesis and evaluation of a series of glycosyl donors equipped with halobenzoyl substituents at O(4) and O(6) to study their properties in glycosylations. Among possible effects that may include carbonyl participation or H-bond mediated aglycone delivery, our results indicate that halobenzoyls act via a different mode.
Co-reporter:Dr. Jagodige P. Yasomanee ; Alexei V. Demchenko
Chemistry - A European Journal 2015 Volume 21( Issue 17) pp:
Publication Date(Web):
DOI:10.1002/chem.201406589
Abstract
Described herein is the expansion of the picoloyl protecting-group assisted H-bond mediated aglycone delivery (HAD) method recently introduced by our laboratory. At first it was noticed that high α-stereoselectivity is only obtained with S-ethyl glycosyl donors and only in the presence of dimethyl(methylthio)sulfonium trifluoromethanesulfonate (DMTST), in high dilution, and low temperature. Combining the mechanistic studies of the HAD reaction and bromine-promoted glycosylations allowed a very effective method to be devised that allows for highly stereoselective α-glycosidation of practically all common leaving groups (S-phenyl, S-tolyl, S/O-imidates) at regular concentrations and ambient temperature.
Co-reporter:Swati S. Nigudkar ; Keith J. Stine ;Alexei V. Demchenko
Journal of the American Chemical Society 2014 Volume 136(Issue 3) pp:921-923
Publication Date(Web):January 6, 2014
DOI:10.1021/ja411746a
This article describes 3,3-difluoroxindole (HOFox)-mediated glycosylation. The uniqueness of this approach is that both the in situ synthesis of 3,3-difluoro-3H-indol-2-yl (OFox) glycosyl donors and activation thereof can be conducted in a regenerative fashion as is a typical reaction performed under nucleophilic catalysis. Only a catalytic amount of the OFox imidate donor and a Lewis acid activator are present in the reaction medium. The OFox imidate donor is constantly regenerated upon its consumption until glycosyl acceptor has reacted.
Co-reporter:Salvatore G. Pistorio, Jagodige P. Yasomanee, and Alexei V. Demchenko
Organic Letters 2014 Volume 16(Issue 3) pp:716-719
Publication Date(Web):January 28, 2014
DOI:10.1021/ol403396j
O-Picoloyl groups at remote positions can mediate the course of glycosylation reactions by providing high facial selectivity for the H-bond-mediated attack of the glycosyl acceptor. A new practical method for the stereoselective synthesis of β-mannosides at ambient temperature is presented.
Co-reporter:Jagodige P. Yasomanee ; Alexei V. Demchenko
Angewandte Chemie International Edition 2014 Volume 53( Issue 39) pp:10453-10456
Publication Date(Web):
DOI:10.1002/anie.201405084
Abstract
A Hydrogen bond mediated aglycone delivery (HAD) method was applied to the synthesis of α-glucans, which are abundant in nature, but as targets represent a notable challenge to chemists. The synthesis of linear oligosaccharide sequences was accomplished in complete stereoselectivity in all glycosylations. The efficacy of HAD may diminish with the increased bulk of the glycosyl acceptor, and may be an important factor for the syntheses of oligomers beyond pentasaccharides. The synthesis of a branched structure proved more challenging, particularly with bulky trisaccharide acceptors.
Co-reporter:Jagodige P. Yasomanee ; Alexei V. Demchenko
Angewandte Chemie 2014 Volume 126( Issue 39) pp:10621-10624
Publication Date(Web):
DOI:10.1002/ange.201405084
Abstract
A Hydrogen bond mediated aglycone delivery (HAD) method was applied to the synthesis of α-glucans, which are abundant in nature, but as targets represent a notable challenge to chemists. The synthesis of linear oligosaccharide sequences was accomplished in complete stereoselectivity in all glycosylations. The efficacy of HAD may diminish with the increased bulk of the glycosyl acceptor, and may be an important factor for the syntheses of oligomers beyond pentasaccharides. The synthesis of a branched structure proved more challenging, particularly with bulky trisaccharide acceptors.
Co-reporter:Mads Heuckendorff, Hemali D. Premathilake, Papapida Pornsuriyasak, Anders Ø. Madsen, Christian M. Pedersen, Mikael Bols, and Alexei V. Demchenko
Organic Letters 2013 Volume 15(Issue 18) pp:4904-4907
Publication Date(Web):September 5, 2013
DOI:10.1021/ol402371b
A novel glycosyl donor that combines the concepts of both conformational and electronic superarming has been synthesized. The reactivity and selectivity of the donor have been tested in competition experiments.
Co-reporter:Swati S. Nigudkar, Archana R. Parameswar, Papapida Pornsuriyasak, Keith J. Stine and Alexei V. Demchenko
Organic & Biomolecular Chemistry 2013 vol. 11(Issue 24) pp:4068-4076
Publication Date(Web):23 Apr 2013
DOI:10.1039/C3OB40667A
Herein, we report a new class of glycosyl donors, benzoxazolyl imidates, for chemical glycosylation. The O-benzoxazolyl (OBox) leaving group was designed with an aim to compare the relative reactivity and stability of similarly structured S-benzoxazolyl (SBox) glycosides (thioimidates) developed in our lab and glycosyl trichloroacetimidates (TCAI, O-imidates) developed by Schmidt. Novel OBox donors can be activated under catalytic conditions and provided excellent yields in glycosylation. The OBox imidates were found to be more reactive than either SBox or TCAI donors. The high reactivity profile was confirmed in direct competitive experiments and was found beneficial for HPLC-assisted solid-phase synthesis.
Co-reporter:N. Vijaya Ganesh, Kohki Fujikawa, Yih Horng Tan, Swati S. Nigudkar, Keith J. Stine, and Alexei V. Demchenko
The Journal of Organic Chemistry 2013 Volume 78(Issue 14) pp:6849-6857
Publication Date(Web):July 3, 2013
DOI:10.1021/jo400095u
Comparative study of Surface-Tethered Iterative Carbohydrate Synthesis (STICS) using HPLC-assisted experimental setup clearly demonstrates benefits of using longer spacer-anchoring systems. The use of mixed self-assembled monolayers helps provide the required space for glycosylation reaction around the immobilized glycosyl acceptor. Both extension of the spacer length and using mixed self-assembled monolayers help promote the reaction, and the beneficial effects may include moving the glycosyl acceptor further out into solution and providing additional conformational flexibility. It is possible that surface-immobilized glycosyl acceptors with a longer spacer (C8–O–C8)-lipoic acid have a higher tendency to mimic a solution-phase reaction environment than acceptors with shorter spacers.
Co-reporter:Jagodige P. Yasomanee ;Alexei V. Demchenko
Journal of the American Chemical Society 2012 Volume 134(Issue 49) pp:20097-20102
Publication Date(Web):November 20, 2012
DOI:10.1021/ja307355n
O-Picolinyl and O-picoloyl groups at remote positions (C-3, C-4, and C-6) can mediate glycosylation reactions by providing high or even complete facial selectivity for the attack of the glycosyl acceptor. The set of data presented herein offers a strong evidence of the intermolecular H-bond tethering between the glycosyl donor and glycosyl acceptor counterparts while providing a practical new methodology for the synthesis of either 1,2-cis or 1,2-trans linkages. Challenging glycosidic linkages including α-gluco, β-manno, and β-rhamno have seen obtained with high or complete stereocontrol.
Co-reporter:N. Vijaya Ganesh, Kohki Fujikawa, Yih Horng Tan, Keith J. Stine, and Alexei V. Demchenko
Organic Letters 2012 Volume 14(Issue 12) pp:3036-3039
Publication Date(Web):May 30, 2012
DOI:10.1021/ol301105y
A standard HPLC was adapted to polymer supported oligosaccharide synthesis. Solution-based reagents are delivered using a software-controlled solvent delivery system. The reaction progress and completion can be monitored in real time using a standard UV detector. All steps of oligosaccharide assembly including loading, glycosylation, deprotection, and cleavage can be performed using this setup.
Co-reporter:Sophon Kaeothip, Jagodige P. Yasomanee, and Alexei V. Demchenko
The Journal of Organic Chemistry 2012 Volume 77(Issue 1) pp:291-299
Publication Date(Web):December 4, 2011
DOI:10.1021/jo2019174
Elaborating on previous studies by Lemieux for highly reactive “armed” bromides, we discovered that β-bromide of the superdisarmed (2-O-benzyl-3,4,6-tri-O-benzoyl) series can be directly obtained from the thioglycoside precursor. When this bromide is glycosidated, α-glycosides form exclusively; however, the yields of such transformations may be low due to the competing anomerization into α-bromide that is totally unreactive under the established reaction conditions.
Co-reporter:Laurel K. Mydock, Medha N. Kamat, and Alexei V. Demchenko
Organic Letters 2011 Volume 13(Issue 11) pp:2928-2931
Publication Date(Web):May 12, 2011
DOI:10.1021/ol2009818
It is reported that stable glycosyl sulfonium salts can be generated via direct anomeric S-methylation of ethylthioglycosides. Mechanistically, this pathway represents the first step in the activation of thioglycosides for glycosidation; however, it can further allow for the synthesis and isolation of quasi-stable sulfonium ions, representing a new approach for studying these key intermediates.
Co-reporter:Kohki Fujikawa, N. Vijaya Ganesh, Yih Horng Tan, Keith J. Stine and Alexei V. Demchenko
Chemical Communications 2011 vol. 47(Issue 38) pp:10602-10604
Publication Date(Web):05 Sep 2011
DOI:10.1039/C1CC13409D
Herein, we report the invention of a novel expeditious concept for oligosaccharide synthesis. Unlike the classic orthogonal strategy based on leaving groups, the reverse approach is based on orthogonal protecting groups, herein p-methoxybenzyl and 4-pentenoyl, which allows for efficient oligosaccharide assembly in the reverse direction.
Co-reporter:Sophon Kaeothip, Geeta Paranjape, Shana E. Terrill, Aileen F. G. Bongat, Maria L. D. Udan, Teerada Kamkhachorn, Hope L. Johnson, Michael R. Nichols and Alexei V. Demchenko
RSC Advances 2011 vol. 1(Issue 1) pp:83-92
Publication Date(Web):18 Jul 2011
DOI:10.1039/C1RA00145K
Sepsis is a serious medical condition characterized by bacterial infection and a subsequent massive systemic inflammatory response. The release of proinflammatory products and mediators from responding innate immune cells, such as mononuclear phagocytes, directly contributes to the pathogenesis of sepsis. The primary bacterial trigger of inflammation is lipopolysaccharide (LPS), which interacts with the germline-encoded macrophage receptor cluster of differentiation 14 (CD14) via its Lipid A moiety. In an effort to identify compounds that block LPS-induced inflammation we investigated a series of Lipid A analogs that lack a disaccharide core yet still possess potent antagonistic activity against LPS. We found it beneficial to develop molecules that contain the following: a glucopyranoside core, hydrophobic ether substituents, and an amino acid to provide an ionic character to the constructs. Here we report an efficient synthesis of molecules of this type and the ensuing biological studies thereof.
Co-reporter:Sophon Kaeothip, Alexei V. Demchenko
Carbohydrate Research 2011 Volume 346(Issue 12) pp:1371-1388
Publication Date(Web):6 September 2011
DOI:10.1016/j.carres.2011.05.004
Traditional strategies for oligosaccharide synthesis often require extensive protecting and/or leaving group manipulations between each glycosylation step, thereby increasing the total number of synthetic steps while decreasing the efficiency of the synthesis. In contrast, expeditious strategies allow for the rapid chemical synthesis of complex carbohydrates by minimizing extraneous chemical manipulations. Oligosaccharide synthesis by selective activation of one leaving group over another is one such expeditious strategy. Herein, the significant improvements that have recently emerged in the area of the selective activation are discussed. The development of orthogonal strategy further expands the scope of the selective activation methodology. Surveyed in this article, are representative examples wherein these excellent innovations have been applied to the synthesis of various oligosaccharide sequences.
Co-reporter:Scott J. Hasty;Matthew A. Kleine ;Dr. Alexei V. Demchenko
Angewandte Chemie International Edition 2011 Volume 50( Issue 18) pp:4197-4201
Publication Date(Web):
DOI:10.1002/anie.201007212
Co-reporter:Sophon Kaeothip and Alexei V. Demchenko
The Journal of Organic Chemistry 2011 Volume 76(Issue 18) pp:7388-7398
Publication Date(Web):July 28, 2011
DOI:10.1021/jo201117s
Discrimination among S-thiazolinyl (STaz), S-benzoxazolyl (SBox), and S-ethyl anomeric leaving groups was achieved by fine-tuning activation conditions. Preferential glycosidation of a certain leaving group is determined neither by the strength of the activating reagent nor by the stability of the leaving group itself; instead, the type of activation plays the key role. The activation conditions established herein were applied to a sequential five-step synthesis of a hexasaccharide using six monosaccharide building blocks equipped with six different leaving groups.
Co-reporter:Scott J. Hasty;Matthew A. Kleine ;Dr. Alexei V. Demchenko
Angewandte Chemie 2011 Volume 123( Issue 18) pp:4283-4287
Publication Date(Web):
DOI:10.1002/ange.201007212
Co-reporter:Teerada Kamkhachorn, Archana R. Parameswar and Alexei V. Demchenko
Organic Letters 2010 Volume 12(Issue 13) pp:3078-3081
Publication Date(Web):June 7, 2010
DOI:10.1021/ol101089u
A very elegant Fraser-Reid armed−disarmed approach recently expanded to the building blocks of the superarmed and superdisarmed series shows very high utility in chemoselective oligosaccharide synthesis. Although a number of studies dedicated to the chemoselective activation of 2-amino-2-deoxysugars have emerged, little remains known about how the reactivity of the armed/disarmed building blocks of the neutral sugars directly compares to that of their 2-aminosugar counterparts. A preliminary study of this comparative reactivity is presented.
Co-reporter:Sneha C. Ranade, Sophon Kaeothip, and Alexei V. Demchenko
Organic Letters 2010 Volume 12(Issue 24) pp:5628-5631
Publication Date(Web):November 18, 2010
DOI:10.1021/ol1023079
It is reported that S-glycosyl O-methyl phenylcarbamothioates (SNea carbamothioates) have a fully orthogonal character in comparison to S-benzoxazolyl (SBox) glycosides. This complete orthogonality was revealed by performing competitive glycosylation experiments in the presence of various promoters. The results obtained indicate that SNea carbamothioates have a very similar reactivity profile to that of glycosyl thiocyanates, yet are significantly more stable and tolerate selected protecting group manipulations. These features make the SNea carbamothioates new promising building blocks for further utilization in oligosaccharide synthesis.
Co-reporter:Cornelia Vetter, Papapida Pornsuriyasak, Jürgen Schmidt, Nigam P. Rath, Tobias Rüffer, Alexei V. Demchenko and Dirk Steinborn
Dalton Transactions 2010 vol. 39(Issue 27) pp:6327-6338
Publication Date(Web):01 Jun 2010
DOI:10.1039/B927058B
Reactions of fac-[PtMe3(4,4′-R2bpy)(Me2CO)][BF4] (R = H, 1a; tBu, 1b) and fac-[PtMe3(OAc-κ2O,O′)(Me2CO)] (2), respectively, with thioglycosides containing thioethyl (ch-SEt) and thioimidate (ch-STaz, Taz = thiazoline-2-yl) anomeric groups led to the formation of the carbohydrate platinum(IV) complexes fac-[PtMe3(4,4′-R2bpy)(ch*)][BF4] (ch* = ch-SEt, 8–14; ch-STaz, 15–23) and fac-[PtMe3(OAc-κ2O,O′)(ch*)] (ch* = ch-SEt, 24–28; ch-STaz = 29–35), respectively. NMR (1H, 13C, 195Pt) spectroscopic investigations and a single-crystal X-ray diffraction analysis of 19 (ch-STaz = 2-thiazolinyl 2,3,4,6-tetra-O-benzoyl-1-thio-β-D-galactopyranose) revealed the S coordination of the ch-SEt glycosides and the N coordination of the ch-STaz glycosides. Furthermore, X-ray structure analyses of the two decomposition products fac-[PtMe3(bpy)(STazH-κS)][BF4] (21a) and 1,6-anhydro-2,3,4-tri-O-benzoyl-β-D-glucopyranose (23a), where a cleavage of the anomeric C–S bond had occurred in both cases, gave rise to the assumption that this decomposition was mediated due to coordination of the thioglycosides to the high electrophilic platinum(IV) atom, in non-strictly dried solutions. Reactions of fac-[PtMe3(Me2CO)3][BF4] (3) with ch-SEt as well as with ch-SPT and ch-Sbpy thioglycosides (PT = 4-(pyridine-2-yl)-thiazole-2-yl; bpy = 2,2′-bipyridine-6-yl), having N,S and N,N heteroaryl anomeric groups, respectively, led to the formation of platinum(IV) complexes of the type fac-[PtMe3(ch*)][BF4] (ch* = ch-SEt, 36–40, ch-SPT 42–44, ch-Sbpy 45, 46). The thioglycosides were found to be coordinated in a tridentate κS,κ2O,O′, κS,κN,κO and κS,κ2N,N′ coordination mode, respectively. Analogous reactions with ch-STaz ligands succeeded for 2-thiazolinyl 2,3,4-tri-O-benzyl-6-O-(2,2′-bipyridine-6-yl)-1-thio-β-D-glucopyranoside (5h) resulting in fac-[PtMe3(ch-STaz)][BF4] (41, ch-STaz = 5h), having a κ3N,N′,N′′coordinated thioglycoside ligand.
Co-reporter:Laurel K. Mydock and Alexei V. Demchenko
Organic & Biomolecular Chemistry 2010 vol. 8(Issue 3) pp:497-510
Publication Date(Web):2009/11/12
DOI:10.1039/B916088D
The main focus of this perspective lies in the discussion of the recent mechanistic theories and supporting experimental evidences that have been put forth in an attempt to advance our understanding of the factors affecting chemical glycosylation.
Co-reporter:Archana R. Parameswar;Jacqueline A. Hawkins;Laurel K. Mydock;Mark S. Ss;Alexei V. Demchenko
European Journal of Organic Chemistry 2010 Volume 2010( Issue 17) pp:3269-3274
Publication Date(Web):
DOI:10.1002/ejoc.201000024
Abstract
The accumulation of psychosine (galactosyl sphingosine) has been associated with the pathogenesis of Krabbe disease; however, the exact mechanism of its cytotoxicity remains unclear. Herein, we describe the synthesis of the unnatural enantiomer of erythro-sphingosine, psychosine, and related derivatives thereof that would allow for the mechanistic elucidation of the toxicity of psychosine.
Co-reporter:Sophon Kaeothip, Steven J. Akins, Alexei V. Demchenko
Carbohydrate Research 2010 Volume 345(Issue 15) pp:2146-2150
Publication Date(Web):13 October 2010
DOI:10.1016/j.carres.2010.08.003
Comparative side-by-side glycosylation studies demonstrated that glycosyl thiocyanates, thioimidates, and thioglycosides provide comparative stereoselectivities in glycosylations. Very high α-stereoselectivity that was previously recorded for glycosyl thiocyanates can be achieved, but only if glycosyl acceptors are equipped with electron-withdrawing acyl substituents. Partially benzylated glycosyl acceptors provided relatively modest stereoselectivity, which was on a par with other common glycosyl donors. Accordingly, thioimidates and thioglycosides showed high stereoselectivity similarly to that of thiocyanates with different classes of acylated primary and secondary glycosyl acceptors.
Co-reporter:Papapida Pornsuriyasak, Sneha C. Ranade, Aixiao Li, M. Cristina Parlato, Charles R. Sims, Olga V. Shulga, Keith J. Stine and Alexei V. Demchenko
Chemical Communications 2009 (Issue 14) pp:1834-1836
Publication Date(Web):18 Feb 2009
DOI:10.1039/B817684A
A new surface-tethered iterative carbohydrate synthesis (STICS) technology is presented in which a surface functionalized ‘stick’ made of chemically stable high surface area porous gold allows one to perform cost efficient and simple synthesis of oligosaccharide chains; at the end of the synthesis, the oligosaccharide can be cleaved off and the stick reused for subsequent syntheses.
Co-reporter:Papapida Pornsuriyasak, Cornelia Vetter, Sophon Kaeothip, Michael Kovermann, Jochen Balbach, Dirk Steinborn and Alexei V. Demchenko
Chemical Communications 2009 (Issue 42) pp:6379-6381
Publication Date(Web):24 Sep 2009
DOI:10.1039/B903942B
This study clearly demonstrates that a multi-dentate metal coordination to the leaving group, along with O-5 and/or a protecting group at O-6, has a strong effect on the stereoselectivity of chemical glycosylation.
Co-reporter:Archana R. Parameswar Dr.;In Ho Park Dr.;Rina Saksena Dr.;Pavol Ková&x10d; Dr.;Moon H. Nahm ;Alexei V. Demchenko
ChemBioChem 2009 Volume 10( Issue 18) pp:2893-2899
Publication Date(Web):
DOI:10.1002/cbic.200900587
Abstract
The first synthesis of the newly discovered oligosaccharide of pneumococcal serotype 6C and its spacer-containing analogue is reported. Conjugation of the spacer-containing oligosaccharides of pneumococcal saccharides 6A, 6B, 6C and derivatives thereof with bovine serum albumin (BSA) protein carrier was carried out by using squaric-acid approach to obtain the oligosaccharide–protein conjugates in excellent yields. The conjugates have been tested with a rabbit antiserum pool (Pool B) used for pneumococcal serotyping. The results showed that synthetic carbohydrate conjugates express epitopes found in native capsular polysaccharides of serotypes 6A, 6B, and 6C.
Co-reporter:Papapida Pornsuriyasak, Nigam P. Rath and Alexei V. Demchenko
Chemical Communications 2008 (Issue 43) pp:5633-5635
Publication Date(Web):01 Oct 2008
DOI:10.1039/B810569C
This study focusses on a new concept for oligosaccharide synthesis based on 4-(pyridin-2-yl)thiazol-2-yl thioglycosides that can either act as effective glycosyl donors or can be deactivated by stable bidentate complexation with palladium(II) bromide.
Co-reporter:Papapida Pornsuriyasak;Alexei V. Demchenko Dr.
Chemistry - A European Journal 2006 Volume 12(Issue 25) pp:
Publication Date(Web):26 JUN 2006
DOI:10.1002/chem.200600262
In the aim of developing new procedures for efficient oligosaccharide assembly, a range of S-thiazolinyl (STaz) glycosides have been synthesized. These novel derivatives were evaluated against a variety of reaction conditions and were shown to be capable of being chemoselectively activated in the armed–disarmed fashion. Moreover, the S-thiazolinyl moiety exhibited a remarkable propensity for selective activation over other common leaving groups. Conversely, a variety of leaving groups could be selectively activated over the STaz moiety, which, in turn, allowed STaz/S-ethyl and STaz/S-phenyl orthogonal approaches. To demonstrate versatility of novel STaz derivatives, a number of oligosaccharide targets have been synthesized in a convergent selective, orthogonal, and chemoselective fashion.
Co-reporter:James T. Smoot;Papapida Pornsuriyasak;Alexei V. Demchenko Dr.
Angewandte Chemie 2005 Volume 117(Issue 43) pp:
Publication Date(Web):13 OCT 2005
DOI:10.1002/ange.200502694
Unterstützung gewährt: Eine neuartige Glycosylierungsstrategie (siehe Bild) ermöglicht es, eine 1,2-trans-glycosidische Bindung chemoselektiv vor anderen Verknüpfungen einzuführen, indem eine 2-O-Picolyleinheit genutzt wird. Diese Nachbargruppe kann über einen sechsgliedrigen Übergangszustand effizient an der Reaktion teilnehmen und zugleich den Glycosyldonor im aktivierten Zustand erhalten. Bn=Benzyl, Bz=Benzoyl, Tf=Trifluormethansulfonyl, Pic=Picolyl.
Co-reporter:Papapida Pornsuriyasak, Alexei V. Demchenko
Tetrahedron: Asymmetry 2005 Volume 16(Issue 2) pp:433-439
Publication Date(Web):24 January 2005
DOI:10.1016/j.tetasy.2004.11.029
Application of two classes of thioimidoyl derivatives, S-benzoxazolyl (SBox) and S-thiazolyl (STaz) glycosides to selective activation over thioglycosides is described. These results allowed us to synthesize a tetrasaccharide derivative using a leaving group differentiated one-pot strategy in 73% yield over three sequential glycosylation steps.Methyl O-(2,3,4,6-tetra-O-benzoyl-β-d-glucopyranosyl)-(1→6)-O-(2,3,4-tri-O-benzoyl-β-d-galactopyranosyl)-(1→6)-O-(2,3,4-tri-O-benzoyl-β-d-glucopyranosyl)-(1→6)-2,3,4-tri-O-benzyl-β-d-glucopyranosideC116H102O31[α]D27=+153.0 (c 0.7, CHCl3)Ethyl 2,3,4-tri-O-benzoyl-6-O-(2,3,4,6-tetra-O-benzoyl-β-d-glucopyranosyl)-1-thio-β-d-glucopyranosideC63H54O17[α]D27=+17.0 (c 0.9, CHCl3)Ethyl 4-O-(3,4,6-tri-O-acetyl-2-O-benzyl-α-d-glucopyranosyl)-2,3,6-tri-O-benzyl-1-thio-α-d-mannopyranosideC48H56O13[α]D25=+72.8 (c 1.0, CHCl3)
Co-reporter:James T. Smoot, Papapida Pornsuriyasak,Alexei V. Demchenko
Angewandte Chemie International Edition 2005 44(43) pp:7123-7126
Publication Date(Web):
DOI:10.1002/anie.200502694
Co-reporter:Alexei V. Demchenko Dr.;Papapida Pornsuriyasak;Cristina De Meo Dr.;Nelli N. Malysheva Dr.
Angewandte Chemie International Edition 2004 Volume 43(Issue 23) pp:
Publication Date(Web):1 JUN 2004
DOI:10.1002/anie.200454047
Donating with a difference: Thiazolyl (Taz) substituted thioglycosides have been successfully used in the synthesis of both 1,2-trans- and 1,2-cis-glycosides and also have found application in convergent oligosaccharide synthesis. In addition, this study has demonstrated that STaz and SEt moieties are fully orthogonal (see scheme, Bn=benzyl; X=STaz, Y=SEt or X=SEt, Y=STaz).
Co-reporter:Alexei V. Demchenko Dr.;Papapida Pornsuriyasak;Cristina De Meo Dr.;Nelli N. Malysheva Dr.
Angewandte Chemie 2004 Volume 116(Issue 23) pp:
Publication Date(Web):1 JUN 2004
DOI:10.1002/ange.200454047
1,2-trans- und 1,2-cis-Glycoside konnten mithilfe von Thiazolyl(Taz)-substituierten Thioglycosiden erhalten werden. Des Weiteren eignen sich diese Reagentien für die konvergente Oligosaccharidsynthese. Es konnte gezeigt werden, dass STaz- und SEt-Einheiten vollständig orthogonal sind (siehe Schema, Bn=Benzyl; X=STaz, Y=SEt oder X=SEt, Y=STaz).
Co-reporter:Swati S. Nigudkar, Tinghua Wang, Salvatore G. Pistorio, Jagodige P. Yasomanee, Keith J. Stine and Alexei V. Demchenko
Organic & Biomolecular Chemistry 2017 - vol. 15(Issue 2) pp:NaN359-359
Publication Date(Web):2016/10/27
DOI:10.1039/C6OB02230H
Previously we communicated 3,3-difluoroxindole (HOFox) – mediated glycosylations wherein 3,3-difluoro-3H-indol-2-yl (OFox) imidates were found to be key intermediates. Both the in situ synthesis from the corresponding glycosyl bromides and activation of the OFox imidates could be conducted in a regenerative fashion. Herein, we extend this study with the main focus on the synthesis of various OFox imidates and their investigation as glycosyl donors for chemical 1,2-cis and 1,2-trans glycosylation.
Co-reporter:Papapida Pornsuriyasak, Cornelia Vetter, Sophon Kaeothip, Michael Kovermann, Jochen Balbach, Dirk Steinborn and Alexei V. Demchenko
Chemical Communications 2009(Issue 42) pp:NaN6381-6381
Publication Date(Web):2009/09/24
DOI:10.1039/B903942B
This study clearly demonstrates that a multi-dentate metal coordination to the leaving group, along with O-5 and/or a protecting group at O-6, has a strong effect on the stereoselectivity of chemical glycosylation.
Co-reporter:Jagodige P. Yasomanee, Archana R. Parameswar, Papapida Pornsuriyasak, Nigam P. Rath and Alexei V. Demchenko
Organic & Biomolecular Chemistry 2016 - vol. 14(Issue 11) pp:NaN3169-3169
Publication Date(Web):2016/02/12
DOI:10.1039/C6OB00107F
2-O-Picolinyl protected glycosyl donors lead to the formation of 1,2-trans glycosides with complete stereoselectivity. This is due to the participatory effect of the picolinyl nitrogen that is able to block the bottom face of the ring via a six-membered cyclic intermediate. Herein we demonstrate that if the nitrogen atom of the O-picolinyl moiety is temporarily blocked by coordination to the metal center (Pd), it becomes unavailable to participate in glycosylation and hence the stereoselectivity of 2-O-picolinyl-assisted glycosylations can be “switched”.
Co-reporter:Kohki Fujikawa, N. Vijaya Ganesh, Yih Horng Tan, Keith J. Stine and Alexei V. Demchenko
Chemical Communications 2011 - vol. 47(Issue 38) pp:NaN10604-10604
Publication Date(Web):2011/09/05
DOI:10.1039/C1CC13409D
Herein, we report the invention of a novel expeditious concept for oligosaccharide synthesis. Unlike the classic orthogonal strategy based on leaving groups, the reverse approach is based on orthogonal protecting groups, herein p-methoxybenzyl and 4-pentenoyl, which allows for efficient oligosaccharide assembly in the reverse direction.
Co-reporter:Swati S. Nigudkar and Alexei V. Demchenko
Chemical Science (2010-Present) 2015 - vol. 6(Issue 5) pp:NaN2704-2704
Publication Date(Web):2015/03/06
DOI:10.1039/C5SC00280J
Recent developments in stereoselective 1,2-cis glycosylation that have emerged during the past decade are surveyed herein. For detailed coverage of the previous achievements in the field the reader is referred to our earlier reviews: A. V. Demchenko, Curr. Org. Chem., 2003, 7, 35–79 and Synlett, 2003, 1225–1240.
Co-reporter:Swati S. Nigudkar, Archana R. Parameswar, Papapida Pornsuriyasak, Keith J. Stine and Alexei V. Demchenko
Organic & Biomolecular Chemistry 2013 - vol. 11(Issue 24) pp:NaN4076-4076
Publication Date(Web):2013/04/23
DOI:10.1039/C3OB40667A
Herein, we report a new class of glycosyl donors, benzoxazolyl imidates, for chemical glycosylation. The O-benzoxazolyl (OBox) leaving group was designed with an aim to compare the relative reactivity and stability of similarly structured S-benzoxazolyl (SBox) glycosides (thioimidates) developed in our lab and glycosyl trichloroacetimidates (TCAI, O-imidates) developed by Schmidt. Novel OBox donors can be activated under catalytic conditions and provided excellent yields in glycosylation. The OBox imidates were found to be more reactive than either SBox or TCAI donors. The high reactivity profile was confirmed in direct competitive experiments and was found beneficial for HPLC-assisted solid-phase synthesis.
Co-reporter:Papapida Pornsuriyasak, Nigam P. Rath and Alexei V. Demchenko
Chemical Communications 2008(Issue 43) pp:NaN5635-5635
Publication Date(Web):2008/10/01
DOI:10.1039/B810569C
This study focusses on a new concept for oligosaccharide synthesis based on 4-(pyridin-2-yl)thiazol-2-yl thioglycosides that can either act as effective glycosyl donors or can be deactivated by stable bidentate complexation with palladium(II) bromide.
Co-reporter:Papapida Pornsuriyasak, Sneha C. Ranade, Aixiao Li, M. Cristina Parlato, Charles R. Sims, Olga V. Shulga, Keith J. Stine and Alexei V. Demchenko
Chemical Communications 2009(Issue 14) pp:
Publication Date(Web):
DOI:10.1039/B817684A
Co-reporter:Mithila D. Bandara, Jagodige P. Yasomanee, Nigam P. Rath, Christian M. Pedersen, Mikael Bols and Alexei V. Demchenko
Organic & Biomolecular Chemistry 2017 - vol. 15(Issue 3) pp:NaN563-563
Publication Date(Web):2016/11/29
DOI:10.1039/C6OB02498J
A new series of superarmed glycosyl donors has been investigated. It was demonstrated that the S-ethyl leaving group allows for high reactivity, which is much higher than that of equally equipped S-phenyl glycosyl donors that were previously investigated by our groups. The superarmed S-ethyl glycosyl donors equipped with a 2-O-benzoyl group gave complete β-stereoselectivity. Utility of the new glycosyl donors has been demonstrated in a one-pot one-addition oligosaccharide synthesis with all of the reaction components present from the beginning.
Co-reporter:Laurel K. Mydock and Alexei V. Demchenko
Organic & Biomolecular Chemistry 2010 - vol. 8(Issue 3) pp:NaN510-510
Publication Date(Web):2009/11/12
DOI:10.1039/B916088D
The main focus of this perspective lies in the discussion of the recent mechanistic theories and supporting experimental evidences that have been put forth in an attempt to advance our understanding of the factors affecting chemical glycosylation.
Co-reporter:Cornelia Vetter, Papapida Pornsuriyasak, Jürgen Schmidt, Nigam P. Rath, Tobias Rüffer, Alexei V. Demchenko and Dirk Steinborn
Dalton Transactions 2010 - vol. 39(Issue 27) pp:NaN6338-6338
Publication Date(Web):2010/06/01
DOI:10.1039/B927058B
Reactions of fac-[PtMe3(4,4′-R2bpy)(Me2CO)][BF4] (R = H, 1a; tBu, 1b) and fac-[PtMe3(OAc-κ2O,O′)(Me2CO)] (2), respectively, with thioglycosides containing thioethyl (ch-SEt) and thioimidate (ch-STaz, Taz = thiazoline-2-yl) anomeric groups led to the formation of the carbohydrate platinum(IV) complexes fac-[PtMe3(4,4′-R2bpy)(ch*)][BF4] (ch* = ch-SEt, 8–14; ch-STaz, 15–23) and fac-[PtMe3(OAc-κ2O,O′)(ch*)] (ch* = ch-SEt, 24–28; ch-STaz = 29–35), respectively. NMR (1H, 13C, 195Pt) spectroscopic investigations and a single-crystal X-ray diffraction analysis of 19 (ch-STaz = 2-thiazolinyl 2,3,4,6-tetra-O-benzoyl-1-thio-β-D-galactopyranose) revealed the S coordination of the ch-SEt glycosides and the N coordination of the ch-STaz glycosides. Furthermore, X-ray structure analyses of the two decomposition products fac-[PtMe3(bpy)(STazH-κS)][BF4] (21a) and 1,6-anhydro-2,3,4-tri-O-benzoyl-β-D-glucopyranose (23a), where a cleavage of the anomeric C–S bond had occurred in both cases, gave rise to the assumption that this decomposition was mediated due to coordination of the thioglycosides to the high electrophilic platinum(IV) atom, in non-strictly dried solutions. Reactions of fac-[PtMe3(Me2CO)3][BF4] (3) with ch-SEt as well as with ch-SPT and ch-Sbpy thioglycosides (PT = 4-(pyridine-2-yl)-thiazole-2-yl; bpy = 2,2′-bipyridine-6-yl), having N,S and N,N heteroaryl anomeric groups, respectively, led to the formation of platinum(IV) complexes of the type fac-[PtMe3(ch*)][BF4] (ch* = ch-SEt, 36–40, ch-SPT 42–44, ch-Sbpy 45, 46). The thioglycosides were found to be coordinated in a tridentate κS,κ2O,O′, κS,κN,κO and κS,κ2N,N′ coordination mode, respectively. Analogous reactions with ch-STaz ligands succeeded for 2-thiazolinyl 2,3,4-tri-O-benzyl-6-O-(2,2′-bipyridine-6-yl)-1-thio-β-D-glucopyranoside (5h) resulting in fac-[PtMe3(ch-STaz)][BF4] (41, ch-STaz = 5h), having a κ3N,N′,N′′coordinated thioglycoside ligand.
![α-D-Glucopyranoside, methyl 6-O-[2,3,4,6-tetrakis-O-(phenylmethyl)-α-D-glucopyranosyl]-, 2,3,4-tribenzoate](/data/chemimg/121100/130050-85-0.png)
![α-D-Glucopyranoside, methyl 6-O-[2,3,4,6-tetrakis-O-(phenylmethyl)-α-D-glucopyranosyl]-, 2,3,4-tribenzoate](/data/chemimg/121100/130050-85-0_b.png)
![Ethanethioic acid, S-[2-[2-(2-hydroxyethoxy)ethoxy]ethyl] ester](http://img.cochemist.com/ccimg/153900/153870-20-3.png)
![Ethanethioic acid, S-[2-[2-(2-hydroxyethoxy)ethoxy]ethyl] ester](http://img.cochemist.com/ccimg/153900/153870-20-3_b.png)
![α-D-Glucopyranoside, methyl 2,3,6-tris-O-(phenylmethyl)-4-O-[2,3,4,6-tetrakis-O-(phenylmethyl)-β-D-glucopyranosyl]-](/data/chemimg/3739400/77117-44-3.png)
![α-D-Glucopyranoside, methyl 2,3,6-tris-O-(phenylmethyl)-4-O-[2,3,4,6-tetrakis-O-(phenylmethyl)-β-D-glucopyranosyl]-](/data/chemimg/3739400/77117-44-3_b.png)
![α-D-Glucopyranoside, methyl 2,3,6-tris-O-(phenylmethyl)-4-O-[2,3,4,6-tetrakis-O-(phenylmethyl)-α-D-glucopyranosyl]-](/data/chemimg/3739400/64694-18-4.png)
![α-D-Glucopyranoside, methyl 2,3,6-tris-O-(phenylmethyl)-4-O-[2,3,4,6-tetrakis-O-(phenylmethyl)-α-D-glucopyranosyl]-](/data/chemimg/3739400/64694-18-4_b.png)
METHANONE](http://img.cochemist.com/ccimg/3100/3006-48-2.png)
METHANONE](http://img.cochemist.com/ccimg/3100/3006-48-2_b.png)
![α-D-Glucopyranoside, methyl 2,3,4-tris-O-(phenylmethyl)-6-O-[2,3,4,6-tetrakis-O-(phenylmethyl)-β-D-glucopyranosyl]-](/data/chemimg/3739400/56632-57-6.png)
![α-D-Glucopyranoside, methyl 2,3,4-tris-O-(phenylmethyl)-6-O-[2,3,4,6-tetrakis-O-(phenylmethyl)-β-D-glucopyranosyl]-](/data/chemimg/3739400/56632-57-6_b.png)
![α-D-Glucopyranoside, methyl 2,3,4-tris-O-(phenylmethyl)-6-O-[2,3,4,6-tetrakis-O-(phenylmethyl)-α-D-glucopyranosyl]-](/data/chemimg/3739400/55094-26-3.png)
![α-D-Glucopyranoside, methyl 2,3,4-tris-O-(phenylmethyl)-6-O-[2,3,4,6-tetrakis-O-(phenylmethyl)-α-D-glucopyranosyl]-](/data/chemimg/3739400/55094-26-3_b.png)
