Linker, loading, and reaction scale influence automated glycan assembly

• Marlene C. S. Dal Colle,
• Manuel G. Ricardo,
• Nives Hribernik,
• José Danglad-Flores,
• Peter H. Seeberger and
• Martina Delbianco

Beilstein J. Org. Chem. 2023, 19, 1015–1020, doi:10.3762/bjoc.19.77

• Universität Berlin, Arnimallee 22, 14195 Berlin, Germany 10.3762/bjoc.19.77 Abstract Automated glycan assembly (AGA) affords collections of well-defined glycans in a short amount of time. We systematically analyzed how parameters connected to the solid support affect the AGA outcome for three different

• purification steps. Keywords: automated glycan assembly; photocleavable linker; polysaccharides; solid-phase synthesis; Introduction Automated glycan assembly (AGA) is a solid-phase method that enables the rapid synthesis of complex oligo- and polysaccharides from protected monosaccharide building blocks

Progress and challenges in the synthesis of sequence controlled polysaccharides

• Giulio Fittolani,
• Theodore Tyrikos-Ergas,
• Denisa Vargová,
• Manishkumar A. Chaube and
• Martina Delbianco

Beilstein J. Org. Chem. 2021, 17, 1981–2025, doi:10.3762/bjoc.17.129

• approach (also known as fragment coupling) allows connecting pre-assembled oligosaccharide blocks. To decrease the synthetic time required for the chemical synthesis of polysaccharides, automated techniques have been developed [28][29][30][31]. Automated glycan assembly (AGA) connects monosaccharide BBs on

Automated glycan assembly of arabinomannan oligosaccharides from Mycobacterium tuberculosis

• Alonso Pardo-Vargas,
• Priya Bharate,
• Martina Delbianco and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2019, 15, 2936–2940, doi:10.3762/bjoc.15.288

• the understanding of these polysaccharides and the development of novel therapeutical and diagnostic agents. Automated glycan assembly (AGA) was employed to prepare the core structure of AM from MTB, containing α-(1,6)-Man, α-(1,5)-Ara, and α-(1,2)-Man linkages. The introduction of a capping step

• after each glycosylation and further optimized reaction conditions allowed for the synthesis of a series of oligosaccharides, ranging from hexa- to branched dodecasaccharides. Keywords: arabinomannan; automated glycan assembly; capping; Introduction Bacterial infections caused by MTB killed 1.7

• Mai Hoang for the proofreading of the manuscript. This work used Dr. Bharate’s thesis “Automated Glycan Assembly of Oligomannose Glycans for Sensing Applications” as a source.

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

• trimethylsilyl trifluoromethanesulfonate (TMSOTf) were employed as co-promoters in solution or automated glycan assembly on solid phase. Keywords: automated glycan assembly; 1,3-dibromo-5,5-dimethylhydantoin; glycosylation; promoter; thioglycosides; Introduction Thioglycosides are versatile glycosylating

• donors [3][6][7][8][9][10][11][12][13][14][15][16][17][18]. However, most of those activators are expensive and toxic [5][17][19]. Poor solubility complicates the use of some promoters during automated glycan assembly [20][21][22][23], while the instability of some activators in solution requires them to

• acetonitrile [45] was used as co-solvent. With all these donors, the α-stereoselectivity increased at higher temperature [46]. Donor 13, containing a remote participating group, produced the disaccharide with better α-selectivity [22][42]. Automated glycan assembly is the most rapid means to access complex

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

• participation groups and solvent effects. It lends further credence to the linear assembly concept in which one monosaccharide unit at a time is incorporated, and which serves as the basis for automated glycan assembly [43]. With the synthetically sourced hexasaccharide repeating unit in hand detailed

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

• variability. Herein, we report the first iterative automated glycan assembly (AGA) of a conjugation-ready S. pneumoniae serotype 3 CPS trisaccharide. This oligosaccharide was assembled using a novel glucuronic acid building block to circumvent the need for a late-stage oxidation. The introduction of a washing

• ]. Automated glycan assembly builds on monomeric building blocks that are incorporated during iterative glycosylations [28][29]. Here, a set of building blocks was identified that can be employed interchangeably in the automated syntheses of a wide variety of biologically relevant glycans. To minimize the post

• using Pd(OH)2/C in methanol/water/acetic acid (50:25:1 v/v/v) afforded the fully deprotected S. pneumoniae serotype 3 CPS antigen 11 in 71% yield over three steps (Scheme 5). Conclusion The first automated glycan assembly of a conjugation-ready S. pneumoniae serotype 3 trisaccharide 11 using glucuronic

Automated solid-phase synthesis of oligosaccharides containing sialic acids

• Chian-Hui Lai,
• Heung Sik Hahm,
• Chien-Fu Liang and
• Peter H. Seeberger

Beilstein J. Org. Chem. 2015, 11, 617–621, doi:10.3762/bjoc.11.69

• carbohydrate antigens (TACAs) such as the sialyl-Tn antigen (sTn) [2]. Neu5Ac is often the terminal residue and is usually linked via an α-(2,3) or α-(2,6) linkage to galactose (Gal) (Figure 1) [3]. Automated glycan assembly enables rapid access to structurally defined oligosaccharides [4][5] including

• incorporation of sialic acid–galactose disaccharide building blocks [5][11]. Here, we describe a sialic acid building block that can be utilized for automated glycan assembly. Results and Discussion Sialylating oligosaccharides in high yield and α-selectivity was challenging since the presence of a C-1 carboxyl

• these considerations sialyl phosphate building blocks 4 and 5 [14] were selected for automated glycan assembly using monosaccharides (Scheme 1). The synthesis of building block 4 commenced with the placement of a C-9 Fmoc protecting group on thioglycoside 1 [14] to produce 2. Installation of O