Multigram Synthesis of Isobutyl-β-C-galactoside as a Substitute of Isopropylthiogalactoside for Exogenous Gene Induction in Mammalian Cells

Abstract

Herein we report that isobutyl-β-C-galactoside (IBCG) is also a promising inducer of gene expression in mammalian cells and report a new synthetic route to the compound that should make obtaining the multigram quantities of material required for animal studies more feasible. A convenient synthesis of IBCG, an inducer of genes controlled by the lac operon system in bacterial cells, was achieved in 5 steps from galactose in 81% overall yield without any chromatographic separation steps. An optimized microwave-assisted reaction at high concentration was key to making the C-glycosidic linkage. A Wittig reaction on a per-O-silylated rather than per-O-acetylated or -benzylated substrate proved most effective in installing the final carbon atom.

Silane- and peroxide-free hydrogen atom transfer hydrogenation using ascorbic acid and cobalt-photoredox dual catalysis

“…The catalytic hydrogenation was readily applicable to C-glycosides derived from ribofuranose (2af) and galactose (2ag). Importantly, the present protocol is even suitable for the hydrogenation of an unprotected galactose derivative and afforded the gene inducer isobutyl-β-C-galactoside (IBCG, 2ah) 66 in 89% yield.…”

Designing sugar mimetics: non-natural pyranosides as innovative chemical tools

“…Substitution of the glycosidic oxygen atom with sulfur [35–37] or carbon [38,39] is a now common method to enhance stability of glycosides. Substitution of the pyranose oxygen, such as in 5- S glycosides, can possibly minimize structural changes [40] and such sugar mimics have shown increased cytotoxic activity towards cancer cell lines compared to their O counterpart [41].…”

Regioselective Benzylation of 2‐Deoxy‐2‐aminosugars using Crown Ethers: Application to a Shortened Synthesis of Hyaluronic Acid Oligomers

“…[2] For example, we recently demonstrated that the protecting groups greatly influence the reactivity of intermediates in the synthesis a carba-sugar. [3] The protecting groups on the donor and acceptors also play key roles in determining outcomes in glycosylation reactions. [4] For example, we recently noted that a fluorous phosphate protecting group could change the stereochemical out of a glycosylation unexpectedly.…”

“…The chosen protecting groups are much more than inert groups in carbohydrates synthesis, since they can also have a profound impact on the reactivity in glycosylation of the substrate 2. For example, we recently demonstrated that the protecting groups greatly influence the reactivity of intermediates in the synthesis a carba‐sugar 3. The protecting groups on the donor and acceptors also play key roles in determining outcomes in glycosylation reactions 4.…”