The Road to Structurally Defined β-Glucans

Abstract

β-glucans are polymers of glucose that have been isolated from a variety of organisms. Isolated β-glucans have been used for medical purposes for centuries; however, efforts to define the biological activities of β-glucans experimentally were initiated in the 1940's. The diversity of structure associated with isolated β-glucans has impeded said investigations, and efforts to leverage the biological activity of β-glucans for clinical applications. In recognition of the need for defined β-glucans that retain the biological activity of isolated β-glucans, considerable investment has been made to facilitate the synthesis of structurally defined β-glucans. Here, we review the different approaches that have been applied to prepare β-glucans. In addition, we summarize the approaches that have been utilized to conjugate β-glucans to proteins.

Keywords: carbohydrate chemistry; glycomimetics; polysaccharides; β-glucans.

Scheme 1.

Kitamura synthesis of linear β-(1,3)-glucans.

Scheme 2.

Takahashi synthesis of linear and branched β-(1,3)-glucans.

Scheme 3.

Vetvicka synthesis of β-(1,3)-glucans.

Scheme 4.

Bundle synthesis of β-(1,3)-glucans.

Scheme 5.

A) Liu and B) Costantino synthesis of β-(1,3)-glucans.

Scheme 6.

A) Mechanistic rationalization for ADMB β-selectivity. B) Ensley synthesis of β-(1,3)-glucans.

Scheme 7.

Li ionic liquid mediated synthesis of β-(1,3)-glucans.

Scheme 8.

Seeberger first generation solid phase synthesis of β-(1,3)-glucans. A) Proof of concept synthesis of β-(1,3)-glucans and B) synthesis of decasaccharide.

Scheme 9.

Seeberger second generation solid phase synthesis of β-(1,3)-glucans.

Scheme 10.

Enzymatic synthesis of linear β-(1,3)-glucans.

Scheme 11.

Enzymatic synthesis of branched β-(1,3)-glucans.

Scheme 12.

Bertozzi’s glycopolymer based β-(1,3)-glucan mimetics.

Scheme 13.

Carbocycle based β-(1,3)-glucans mimetic. A) hydroxyamine derivatives and B) thioether mimetics of β-(1,3)-glucans.

Scheme 14.

Conjugation of β-(1,3)-glucans to proteins via lysine residues

Scheme 15.

Protein conjugation of Protein conjugation of β-(1,3)-glucans through lysine residues via tyrosine residues.

Scheme 16.

Protein conjugation of naturally isolated laminarin via A) oxidative cleavage and B) reductive amination.