Fluorous-Assisted Chemoenzymatic Synthesis of Heparan Sulfate Oligosaccharides

Abstract

The chemoenzymatic synthesis of heparan sulfate tetrasaccharide (1) and hexasaccharide (2) with a fluorous tag attached at the reducing end is reported. The fluorous tert-butyl dicarbonate (FBoc) tag did not interfere with enzymatic recognition for both elongation and specific sulfation, and flash purification was performed by standard fluorous solid-phase extraction (FSPE). Based on an FBoc attached disaccharide as acceptor, a series of partial N-sulfated, 6-O-sulfated heparan sulfate oligosaccharides were successfully synthesized employing fluorous techniques.

A Dilemma in the Glycosaminoglycan‐Based Therapy: Synthetic or Naturally Unique Molecules?

“…Protocols for synthesizing HS oligosaccharide on the basis of chemoenzymatic reactions have been established . Comprehensive reviews in the area have been published .…”

“…Another example is the 2‐ O ‐sulfated GlcA‐containing HS hexasaccharides recently produced by Hsieh and co‐workers . As seen for the modular‐based synthesis of HS oligosaccharides, fluorous tag can be also fruitfully used in chemoenzymatic‐based synthesis of HS tetrasaccharide and hexasaccharide . It has been reported that this tag besides facilitating purification steps via FSPE does not interfere with any enzyme involved in the elongation and further modification of HS chains …”

Synthetic Oligosaccharide Libraries and Microarray Technology: A Powerful Combination for the Success of Current Glycosaminoglycan Interactomics

“…In glycosaminoglycanomics, for example, GAG‐like molecules (mostly oligosaccharides of well‐defined structures and sizes) have been successfully synthesized . GAG synthesis can be accomplished either by chemoenzymatic routes– or based on modular assembly of pre‐synthesized building blocks –––. Module‐based synthesis is sometimes used in conjunction with additional chemical and/or enzymatic steps to increase yield and diversity of sulfation patterns .…”

“…Protocols to synthesize HS oligosaccharide on the bases of chemoenzymatic reactions have been established . Comprehensive reviews in the area have been published .…”

“…Another example is the 2‐O‐sulfated GlcA‐containing HS hexasaccharides recently produced by Hsieh et al . As seen for the modular‐based synthesis of HS oligosaccharides, fluorous tag can also be fruitfully used in chemoenzymatic‐based synthesis of HS tetrasaccharide and hexasaccharide . Besides facilitating purification steps via FSPE, it has been reported that this tag does not interfere with any enzyme involved in the elongation and modification of HS chains .…”