Solid Phase Peptide Synthesis

Solid Phase Peptide Synthesis

CH

Br Cl

H

Fischer Projections revisited

CH

Br Cl

H

CH

Cl

H Br

(R)

Remember that 3 group rotations are always allowed

CH₃ Br Cl

H

CH₃ Cl H

Br

CH₃

Cl

H Br

(R)

CH₃

Br

Cl H

(R)

180° rotations of entire molecule are allowed

CH₃ Br Cl

H

H Cl Br

CH₃

CH₃

Cl

H Br

(R)

H

Br H₃C

Cl (R) 180°

90° rotations of entire molecule are NOT allowed CH₃

Br Cl

H

Cl CH₃ H

Br

CH₃

Cl

H Br

(R)

Cl

H Br CH₃

(S) 90°

x

x

mirror images are enantiomers

CH

Br Cl

H

CH

Cl Br

H

CH

Cl

H Br

( R )

CH

Cl Br H

( S )

identification of meso compounds by a horizontal mirror plane

CH

OH H

H CH

(R)

OH

mirror plane

CH₃ OH H

H HO

CH₃ OH H

(R) (S)

CH₃

H OH

HO H

HO H

H OH

CH₃

MESO compounds

CH₃ Br Cl

H

a Helpful way to assign stereochemistry

CH₃ Br Cl

H

CH₃

Cl

H Br

(R) 2 1

3

4

4 3

2 1

notice that

lowest priority group (H) is in the back

lowest priority group on bottom

(

S

notice that

lowest priority group (H) is in the front

CH₃ Br H

Cl

CH₃ Br H

Cl

CH₃

H

Cl Br

4 1 3

2

2 3

4 1

lowest priority group on side

If the lowest priority group is on the top or bottom: assign 'as normal'

CH₃ Br Cl

H 2 1

3

4

clockwise = R H

Cl F

Br 3 2

4

1

counterclockwise = S

BUT If the lowest priority group is on the SIDE: make the OPPOSITE ASSIGNMENT

CH3 H Cl

Br 2 4

3

1

clockwise =

S

(opposite of the 'normal assignment)

CH₃ F H

Br 4 2

3

1

counterclockwise =

R

(

R

S

CH

OH H

H HO

CH

OH

H

CHO

H OH

HO H

H OH

H OH

CH2OH

D-glucose: an aldohexose

all of the natural sugars have R configuration at this stereo- center.

aldehyde six carbon sugar

(R)

Carbohydrates: C

H

O

Dextrorotatory = D

• (R) configuration for sugars Levorotatory = L

•(S)-configuration for sugars

CH2OH O

HO H

H OH H OH CH₂OH

D-fructose: a ketohexose

D-ribose: an aldopentose CHO

H OH

H OH

CH₂OH

H OH

Open chain sugars can equilibrate with cyclic hemiacetals

O O H H mech

Cyclic hemiacetal formation

OH O

O OH

CHO

H OH

HO H

H OH

H OH

CH₂OH glucose

H OH

HO H

H OH

H OH

HO

O

OK, so this is how they drew it back in the 1800’s

Haworth Projections

For glucose

CHO

H OH

HO H

H OH

H OH

CH₂OH

CHO

H OH

HO H

H OH

H OH 90° turn

HO

1 2 3 4 5

OH O H⁺

5

OH OH

4 OH

3

OH

2 1

O OH

5

OH OH

4 OH

3

OH

2

1 O

OH

5

OH OH

4 OH

3

OH

2

+ 1

! anomer

" anomer

For ribose

CHO

H OH

H OH

H OH

CH₂OH 90° turn

CHO

H OH

H OH

H HO OH

OH OH

HO O

OH squiggly line represents mixture of ! and " anomers

Converting Haworth Projections to Chair Projections

For glucose

O

OH

5

OH OH

4 OH

3

OH

2 1

! anomer

O

HO HOHO

OH OH

4 5

3 2

1 6 6

axial O OH

5

OH OH

4 OH

3

OH

2 1

! anomer

O

HO

HOHO OH

OH

4 5

3 2

1 6 6

equatorial

Mutarotation of glucose

!

= +112

!

= +52

H₂O O

HO HOHO

OH OH

OH

HO HOHO

O cat H⁺ OH

or OH^– O

HO

HOHO OH

OH

starch: two components

O

HO OHO

OH

O

HO OHO

O

!

!

amylose

O

HO OHO

HO

O

HO OHO

!

!

amylopectin

O

HO HO

O OH

!

O O

HO HO

O OH

!

O

a disaccharide

Oligosaccharides and Polysaccharides

O

HO OHO

OH

O

HO

OHO O

OH

cellulose : a glucose polymer highly linear strucrture: very effective for intrastrand H-bonding insoluble: cell walls

! !

etc O

HO HOHO

OH

O

HO HO

O OH

OH

maltose (beer): a glucose dimer

!

(~20%)

‘soluble starch’ (~80%)

‘insoluble starch’

Amylose is highly helical

Oligosaccharides and Polysaccharides

end view

O

HO OHO

OH

O

HO OHO

O

!

!

amylose

Some reactions of sugars

Kiliani Fischer Synthesis

CHO HO H H OH

CH₂OH H OH

arabinose an aldopentose

1) NaCN

separable

HO H

H OH

CH₂OH H OH H OH CHO

glucose an aldohexose

HO H H OH

CH₂OH H OH HO H

CHO

Mannose an aldohexose 2) H₂/Pd

BaSO₄ 3) H₃O⁺

+

HO H H OH

CH2OH H OH H OH

C

Intermediate from reduction

step N

HO H H OH

CH₂OH H OH H OH HC NH H₃O⁺

H₂/Pd BaSO₄ NaCN

a cyanohydrin

Some reactions of sugars

Wohl Degradation

CHO

HO H

H OH

CH2OH

H OH

arabinose an aldopentose 1) H2N-OH

HO H

H OH

CH2OH

H OH

H OH

CHO

glucose an aldohexose

2) Ac₂O; NaOMe 3) H3O⁺

HO H

H OH

CH₂OH

H OH

H OH

N OH H

AcO H

H OAc

CH₂OAc

H OAc

H OAc

N OAc H

H2N-OH

Ac2O NaOMe

–OAc

AcO H

H OAc

CH₂OAc

H OAc

H OAc

N

HO H

H OH

CH₂OH

H OH

H OH

N H₃O⁺

(retro cyanohydrin)

H⁺

HNO₃

HO H

H OH

CH₂OH

H OH

H OH

CHO

HO H

H OH

CO₂H

H OH

H OH

CO₂H

glucose optically active

HNO3

HO H

CH₂OH

H OH

H OH

CHO

xylose meso

optically inactive

HO H

CH2OH

H OH

H OH

CO2H

mirror plane

Oxidation of sugars

The Fischer Proof

The Fischer Proof

H OH

CO₂H

H OH

H OH

CO₂H

H OH

CO₂H

H OH

HO H

CO₂H

HO H

CO₂H

H OH

H OH

CO₂H

HO H

CO₂H

H OH

HO H

CO₂H

HNO₃ HNO₃ HNO₃ HNO₃

meso optically active meso optically active

The Fischer Proof

H OH

CO₂H

H OH

H OH

CO₂H

H OH

CO₂H

H OH

HO H

CO₂H

HO H

CO₂H

H OH

H OH

CO₂H

HO H

CO₂H

H OH

HO H

CO₂H

HNO₃ HNO₃ HNO₃ HNO₃

meso optically active meso optically active HNO₃

optically active

H OH

CO2H

HO H

CO₂H

H OH CO₂H H OH CO₂H

HNO₃

meso

The Fischer Proof

H OH

CO₂H

H OH

H OH

CO₂H

H OH

CO₂H

H OH

HO H

CO₂H

HO H

CO₂H

H OH

H OH

CO₂H

HO H

CO₂H

H OH

HO H

CO₂H

HNO₃ HNO₃ HNO₃ HNO₃

meso optically active meso optically active HNO₃

optically active

H OH

CO2H

HO H

CO₂H

H OH CO₂H H OH CO₂H

HNO₃

meso

It is arabinose

The Fischer Proof: Fischer used this type of analysis for all of the Sugars, starting from a good guess for glyceraldehyde

H OH

CO₂H

H OH

H OH

CO₂H

H OH

CO₂H

H OH

HO H

CO₂H

HO H

CO₂H

H OH

H OH

CO₂H

HO H

CO₂H

H OH

HO H

CO₂H

HNO₃ HNO₃ HNO₃ HNO₃

meso optically active meso optically active HNO₃

optically active

H OH

CO2H

HO H

CO₂H

H OH CO₂H H OH CO₂H

HNO₃

meso

It is arabinose