Disaccharides: Synthetic Methods

This set covers techniques for disaccharide synthesis, including selective protecting group strategies for different hydroxyl positions and the properties of various glycosyl donors and activators.

Glycosyl donor

An electrophilic species with a leaving group at the anomeric position that reacts to form a glycosyl cation.

Glycosyl acceptor

A nucleophilic species that has a hydroxyl group available to donate an electron pair and form a glycosidic bond.

Fischer glycosidation

A reaction that converts an anomeric $-OH$ to $-OR$ using a Lewis acid and an alcohol solvent, such as anhydrous $SOCl_2$, $AcCl$, or $ZnCl_2$.

Primary Hydroxyl ($C6$)

The least hindered position on a sugar backbone which can be selectively protected using sterically hindered or bulky protecting groups.

Anomeric Centre ($C1$)

The only hemiacetal $-OH$ in a free monosaccharide, possessing reactivity distinct from secondary alcohols.

Cyclic benzylidene

A stable 6-membered ring in a chair conformation formed by the reaction of benzaldehyde and an acid catalyst to protect $C4$ and $C6$.

Acetonides

Cyclic acetals formed from acetone and an acid catalyst that specifically target and protect $1,2$-cis diols.

Ring-chain tautomerism

The process where a hemiacetal sugar interconverts between furanose, open-chain, and pyranose forms, which is stopped when the sugar is 'locked' as an acetal.

5-membered ring formation

The outcome favoured by kinetics when ketones react with diols to form cyclic acetals.

6-membered ring formation

The outcome favoured by thermodynamics when aldehydes react with diols to form cyclic acetals.

PTSA

A strong organic acid with a $pKa hickapprox -3$ used in the selective protection of $1,2$-trans diols.

Glycosyl bromides

Unstable glycosyl donors that must be prepared shortly before use and were the first known donors used in disaccharide synthesis.

Halophilic metal activator

A metal salt such as $AgOTf$, $AgClO_4$, $HgBr_2$, or $Hg(CN)_2$ used to promote the leaving of a halide from a glycosyl donor via an $SN1$-type pathway.

Thioglycosides

Glycosyl donors formed by treating an anomeric acetate with a thiol and a Lewis acid; they are more stable than bromides and do not react until activated by a soft electrophile.

N-iodosuccinimide ($NIS$)

A soft electrophile used as an activator for thioglycoside donors because sulfur acts as a soft nucleophile.

DAST

Diethylaminosulfur trifluoride, a reagent used to provide a source of nucleophilic fluoride when synthesizing glycosyl fluorides from thioglycosides.

Glycosyl fluorides

Donors more stable than corresponding bromides or chlorides that are typically activated with hard Lewis acids like $BF_3 hickcdot Et_2O$ or $SnCl_2$.

Global protecting groups

Protection strategies for all hydroxyl types (primary, secondary, and anomeric) using esters like acetates or benzoyls, and ethers like benzyl or methyl groups.