5. chemical synthesis of oligosaccharides

why is glycosidic bond formation between 2 glucose residues challenging

reactivity: OH- is a poor LG, needs activating first

regioselectivity: what positions the two sugars are linked

stereoselectivity: alpha or beta anomer

what needs to be done for efficient and selective coupling between 2 monosaccharides

1. increase donor reactivity: activate anomeric hydroxyl group by turning it into a better LG

2. accomplish regioselectivity by installing appropriate PGs

3. encourage stereoselectivity for alpha or beta anomeric products by selecting appropriate reaction conditions and PGs

what is the key to achieving selectivity in glycosidic bond formation

selective protection and deprotection of specific hydroxyl groups

what PG is selectively added onto the least hindered OH

triphenyl methyl ether (trityl)

Trityl structure

C(Bn3)Cl

tritryl protection and deprotection conditions

protection: titryl-Cl (TRCl) and base

deprotection: mild acid, AcOH

what are the non-selective PGs for hydroxyl groups

acetyl esters (Ac)

benzoyl esters (Bz)

protection and deprotection conditions for acetyl esters

protection: Ac2O and pyridine (base)

deprotection: NaOMe

protection and deprotection conditions for benzoyl esters

protection: Bz2O or BzCl and pyridine

deprotection: NaOMe

what PGs are for the anomeric hydroxyl group

fisher glycosylation to produce OMe on anomeric carbon

deprotection of anomeric acetyl or benzoyl ester

fisher glycosylation

MeOH and H+ (HCl), produces an alkyl glyocisde

deprotection of anomeric acetyl or benzoyl ester

H2N-NH2 (hydrazine) or PhCNH2 (benzyl amine)

what PG is used for selective protection of 1,3-diols

benzylidene acetal, adds onto C4 and C6

protection and deprotection conditions for benzylidene acetal

protection: PhCH(OMe2) and acid

deprotection: H2, Pd/C

selective cleavage of benzylidene from one of the two hydroxyl groups is possible through

reducing agents, NaBH4 (C4 free) and LiAlH4 (C6 free)