Linear Synthesis of De novo Oligo‐Iduronic Acid

Abstract

L‐Iduronic acid (IdoA) plays a pivotal role in glycosaminoglycan (GAG) protein interactions. However, the structural microheterogeneity of GAG appears to impede the systematic investigation of IdoA functions. Under such conditions, oligo‐Iduronic acid (Oligo‐IdoA) are ideal and straightforward heparin mimetics to unravel the relationship between IdoA structure and functions. Herein, we report for the first‐time linear synthesis of rare oligo‐IdoA precursor utilizing anhydrous β‐L‐idopyranosyl and IdoA thiophenol building block. After screening various synthetic strategies, we have Installed successive IdoA by 5 step reactions with 25–26 % overall yield. These oligo‐IdoA are expected to be excellent probes to understand conformational plasticity of IdoA and fine tune carbohydrate–protein interactions.

Discovery of rare sulfated N-unsubstituted glucosamine based heparan sulfate analogs selectively activating chemokines

“…13 r Disaccharides ( 21 and 18 ) and monosaccharide precursors were synthesized from glucosamine and iduronic acid building blocks 14 , 16 , 19 & 20 , as previously described. 13h , 14 Next, we adopted [2 + 2] glycosylation approach with 21 (glycosyl donor) and 18 (glycosyl acceptor) to obtain 1,6 anhydrous tetrasaccharide 22 in excellent yield. Acetolysis of the reducing end IdoA residue of 22 with the aid of acetic anhydride and copper trifluoromethanesulfonate as catalyst followed by phenyl trimethylsulfide and ZnI 2 treatment afforded 24 as a thiophenol glycosyl donor.…”

Rational designing of glyco-nanovehicles to target cellular heterogeneity

“…The disaccharide donor 15 was obtained by acetolysis of 14 using acetic anhydride and copper( ii ) trifluoromethanesulfonate as a catalyst followed by phenyl trimethylsilyl sulphide and ZnI 2 treatment to generate corresponding thioglycoside in excellent yield. 10 Finally, glycosylation of donor 15 and acceptor 16 by utilizing N -iodosuccinimide (NIS) and the trimethylsilyl trifluoromethanesulfonate (TMSOTf) promoter resulted in 90% of tetrasaccharide 17 ( Scheme 1 ).…”

Developments in the Chemical Synthesis of Heparin and Heparan Sulfate

“…At a basic level, HS consists of a repeating disaccharide unit of either (‐ l ‐IdoA‐α‐1,4‐ d ‐GlcN‐α‐1,4‐) or (‐ d ‐GlcA‐β‐1,4‐ d ‐GlcN‐α‐1,4‐). Consequently, efforts in HS synthesis usually focus first on the provision of appropriate disaccharide building blocks, [21] for subsequent iterative oligosaccharide assembly. Additionally, de novo syntheses of mimetic fragments containing just one monosaccharide component (e. g., l ‐IdoA) have been completed [22] .…”

“…Consequently, efforts in HS synthesis usually focus first on the provision of appropriate disaccharide building blocks, [21] for subsequent iterative oligosaccharide assembly. Additionally, de novo syntheses of mimetic fragments containing just one monosaccharide component (e. g., l-IdoA) have been completed.…”