Expeditious oligosaccharide synthesis via selective, semi-orthogonal, and orthogonal activation

Abstract

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.

S-Benzimidazolyl (SBiz) Imidates as a Platform for Oligosaccharide Synthesis via Active–Latent, Armed–Disarmed, Selective, and Orthogonal Activations

“…Selective activation, wherein one leaving group is activated over another with no protecting group manipulations in between, offers a streamlined access to oligosaccharides. 22 However, aligning multiple leaving groups is not always feasible and syntheses involving sequential activations of three or more different leaving groups are still rare. 23 In this respect, the orthogonal strategy that relies on only two leaving groups that can be orthogonally activated one over another offers a significant advantage.…”

“…It should be mentioned that AgOTf-mediated activation of thioimidates in general and SBiz in particular also offers a convenient and reliable entry into oligosaccharide synthesis via selective activation over alkyl/aryl thioglycosides. 22 To illustrate the viability of this statement, we conducted a AgOTf-mediated activation of SBiz donor 1 over S -ethyl acceptor 25 . 43 This selective activation led to the formation of disaccharide 26 in 92% yield.…”

“…In our opinion, the set of the competition experiments presented in Schemes and is clearly indicative of the completely orthogonal character of the SBiz-H and SBiz-An leaving groups. Selective activation, wherein one leaving group is activated over another with no protecting group manipulations in between, offers a streamlined access to oligosaccharides . However, aligning multiple leaving groups is not always feasible and syntheses involving sequential activations of three or more different leaving groups are still rare .…”

“…As a result, disaccharide 24 was produced in 10 min in 67% yield ultimately confirming the electronic (arming-disarming) effects of O -protecting groups on the reactivity of differentially protected SBiz-H imidates (Scheme ). It should be mentioned that AgOTf-mediated activation of thioimidates in general and SBiz in particular also offers a convenient and reliable entry into oligosaccharide synthesis via selective activation over alkyl/aryl thioglycosides . To illustrate the viability of this statement, we conducted a AgOTf-mediated activation of SBiz donor 1 over S -ethyl acceptor 25 .…”

S-Benzimidazolyl (SBiz) Imidates as a Platform for Oligosaccharide Synthesis via Active–Latent, Armed–Disarmed, Selective, and Orthogonal Activations

“…Selective activation, wherein one leaving group is activated over another with no protecting group manipulations in between, offers a streamlined access to oligosaccharides. 22 However, aligning multiple leaving groups is not always feasible and syntheses involving sequential activations of three or more different leaving groups are still rare. 23 In this respect, the orthogonal strategy that relies on only two leaving groups that can be orthogonally activated one over another offers a significant advantage.…”

“…It should be mentioned that AgOTf-mediated activation of thioimidates in general and SBiz in particular also offers a convenient and reliable entry into oligosaccharide synthesis via selective activation over alkyl/aryl thioglycosides. 22 To illustrate the viability of this statement, we conducted a AgOTf-mediated activation of SBiz donor 1 over S -ethyl acceptor 25 . 43 This selective activation led to the formation of disaccharide 26 in 92% yield.…”

“…In our opinion, the set of the competition experiments presented in Schemes and is clearly indicative of the completely orthogonal character of the SBiz-H and SBiz-An leaving groups. Selective activation, wherein one leaving group is activated over another with no protecting group manipulations in between, offers a streamlined access to oligosaccharides . However, aligning multiple leaving groups is not always feasible and syntheses involving sequential activations of three or more different leaving groups are still rare .…”

“…As a result, disaccharide 24 was produced in 10 min in 67% yield ultimately confirming the electronic (arming-disarming) effects of O -protecting groups on the reactivity of differentially protected SBiz-H imidates (Scheme ). It should be mentioned that AgOTf-mediated activation of thioimidates in general and SBiz in particular also offers a convenient and reliable entry into oligosaccharide synthesis via selective activation over alkyl/aryl thioglycosides . To illustrate the viability of this statement, we conducted a AgOTf-mediated activation of SBiz donor 1 over S -ethyl acceptor 25 .…”

Total synthesis of tetraacylated phosphatidylinositol hexamannoside and evaluation of its immunomodulatory activity

“…Our planned sugar assembly towards the tetramannoside 3 hinges on the chemoselective activation of a trichloroacetimidate donor in the presence of a thioglycoside acceptor 55 ( Fig. 5 ).…”

S-Benzimidazolyl (SBiz) Imidates as a Platform for Oligosaccharide Synthesis via Active–Latent, Armed–Disarmed, Selective, and Orthogonal Activations

“…Selective activation, wherein one leaving group is activated over another with no protecting group manipulations in between, offers a streamlined access to oligosaccharides. 22 However, aligning multiple leaving groups is not always feasible and syntheses involving sequential activations of three or more different leaving groups are still rare. 23 In this respect, the orthogonal strategy that relies on only two leaving groups that can be orthogonally activated one over another offers a significant advantage.…”

“…It should be mentioned that AgOTf-mediated activation of thioimidates in general and SBiz in particular also offers a convenient and reliable entry into oligosaccharide synthesis via selective activation over alkyl/aryl thioglycosides. 22 To illustrate the viability of this statement, we conducted a AgOTf-mediated activation of SBiz donor 1 over S -ethyl acceptor 25 . 43 This selective activation led to the formation of disaccharide 26 in 92% yield.…”

“…In our opinion, the set of the competition experiments presented in Schemes and is clearly indicative of the completely orthogonal character of the SBiz-H and SBiz-An leaving groups. Selective activation, wherein one leaving group is activated over another with no protecting group manipulations in between, offers a streamlined access to oligosaccharides . However, aligning multiple leaving groups is not always feasible and syntheses involving sequential activations of three or more different leaving groups are still rare .…”

“…As a result, disaccharide 24 was produced in 10 min in 67% yield ultimately confirming the electronic (arming-disarming) effects of O -protecting groups on the reactivity of differentially protected SBiz-H imidates (Scheme ). It should be mentioned that AgOTf-mediated activation of thioimidates in general and SBiz in particular also offers a convenient and reliable entry into oligosaccharide synthesis via selective activation over alkyl/aryl thioglycosides . To illustrate the viability of this statement, we conducted a AgOTf-mediated activation of SBiz donor 1 over S -ethyl acceptor 25 .…”

Total synthesis of tetraacylated phosphatidylinositol hexamannoside and evaluation of its immunomodulatory activity

“…Our planned sugar assembly towards the tetramannoside 3 hinges on the chemoselective activation of a trichloroacetimidate donor in the presence of a thioglycoside acceptor 55 ( Fig. 5 ).…”

S-Benzimidazolyl (SBiz) Imidates as a Platform for Oligosaccharide Synthesis via Active–Latent, Armed–Disarmed, Selective, and Orthogonal Activations

“…Selective activation, wherein one leaving group is activated over another with no protecting group manipulations in between, offers a streamlined access to oligosaccharides. 22 However, aligning multiple leaving groups is not always feasible and syntheses involving sequential activations of three or more different leaving groups are still rare. 23 In this respect, the orthogonal strategy that relies on only two leaving groups that can be orthogonally activated one over another offers a significant advantage.…”

“…It should be mentioned that AgOTf-mediated activation of thioimidates in general and SBiz in particular also offers a convenient and reliable entry into oligosaccharide synthesis via selective activation over alkyl/aryl thioglycosides. 22 To illustrate the viability of this statement, we conducted a AgOTf-mediated activation of SBiz donor 1 over S -ethyl acceptor 25 . 43 This selective activation led to the formation of disaccharide 26 in 92% yield.…”

“…In our opinion, the set of the competition experiments presented in Schemes and is clearly indicative of the completely orthogonal character of the SBiz-H and SBiz-An leaving groups. Selective activation, wherein one leaving group is activated over another with no protecting group manipulations in between, offers a streamlined access to oligosaccharides . However, aligning multiple leaving groups is not always feasible and syntheses involving sequential activations of three or more different leaving groups are still rare .…”

“…As a result, disaccharide 24 was produced in 10 min in 67% yield ultimately confirming the electronic (arming-disarming) effects of O -protecting groups on the reactivity of differentially protected SBiz-H imidates (Scheme ). It should be mentioned that AgOTf-mediated activation of thioimidates in general and SBiz in particular also offers a convenient and reliable entry into oligosaccharide synthesis via selective activation over alkyl/aryl thioglycosides . To illustrate the viability of this statement, we conducted a AgOTf-mediated activation of SBiz donor 1 over S -ethyl acceptor 25 .…”

Total synthesis of tetraacylated phosphatidylinositol hexamannoside and evaluation of its immunomodulatory activity

“…Our planned sugar assembly towards the tetramannoside 3 hinges on the chemoselective activation of a trichloroacetimidate donor in the presence of a thioglycoside acceptor 55 ( Fig. 5 ).…”