Level III Lectures

Contents

1 Monosaccharides

Natural products -digitoxin, kanamycin, salicin, glucose, sucrose, mannose

1.1 Nomenclature

a simplest sugar glyceraldehyde

b L and D stereochemistry

c keto-aldo-ose - pyranoses, furanoses

1.2 Structure and conformation of monosaccharides

a Mutarotation of hemi-acetals, reasons and mechanism

b Preferrred chair conformation of pyranoses

Level I Tutorial recap - dimethylcyclohexanes

c Anomeric effect - evidence, explaination

alpha-D-Glucose

2 Protecting Groups

What is a protecting group?

2.1 For alcohols

a Esters - Acetyl (Ac), Benzoyl (Bz)

b Ethers - Methyl (Me), Benzyl (Bn), Silyl (TIPS, TBDMS etc), MOM

2.2 For thiols

BOC, Cbz, allyl carbamate, Fmoc

Acetonides, Dispiroketals, Carbonates

2.5 For amino alcohols

2.6 For carbonyls

Acetonides - 1,2 and 1,3 Diols and Dithiols

2.7 For carboxylates

Esters - Methyl (Me), Benzyl (Bn)

3 Reactivity

3.1 Alcohols

b Conversion to halides

c Mitsunobu inversion

d Barton deoxygenation

3.2 Carbonyls

a Oxidation - halogens, Ag+, to aldonic acids (lactones)

b Reduction to alditols

c Condenstions- Killiani-Fischer extension, Wohl degradation

3.3 Glycoside formation - 4 x 1,2 regioisomers

a Formation of 1,2 trans glycosides - paricipating neighboring group

b Formation of cis a-(axial)-glycoside - in situ anomerisation

c Formation of cis b-(equatorial) glycoside - special methods required

3.4 Formation of 'stable' activated glycosides and their use in Glycoside formation

a Glycosyl trichloroacetimidate

b Glycosyl phenylsulfide

c Armed/Disarmed Glycoside donors

d w-pentenyloxy glycoside

4.0 Synthetic Examples

4.1 Synthesis of glycosidic portion of Calicheamicin

Calicheamicin Binding to DNA

a Calicheamicin

b The Synthetic Target

c Construction of DC Rings

d Construction of BAE Rings and final DCBAE Rings

4.2 Library synthesis of Di and Tri-saccharides

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