Transcript Projections - McMaster University

Projections
O
H
OH
1
H
OH
2
HO
O
1
OH
2
3
HO
4
OH
5
OH
HO
3
O
OH
4
OH
5
CH2OH
OH
CH2OH
6
OH
6
HO
4
OH
HO
6
5
H
O
OH
OH

OH
O
OH
3
Haworth of ribose
convential Fischer
turn on
side
1
2
OH
OH
OH

Haworth
OH
More Reactions of Sugars
1)
Reactions of OH group(s):
a)
Esterification:
O
O
OAc
OH
HO
HO
O
O
O
AcO
AcO
OH
HO
AcO
O
acetic anhydride:
reactive acid derivative
b)
O
penta-O-acetyl--D-glucopyranose
Ethers:
SN2
R-OH
+
Ph
Br
R-Ph
Benzyl ethers
b) Ethers (con’t)
HO
O
Ph3CBr
OH
TrO
O
OH
S N1
OH
via stable
carbocation
OH
OH
OH
(cf malachite
green)
**SELECTIVE: steric hinderance
only 1o reacts
Tr = trityl =
c) Acetals
O
TrO
O
TrO
OH
O
OH
H+
OH
OH
(eg. TsOH)
Acetonide: best for 5 - membered rings
requires cis OH groups
O
O
c) Acetals (con’t)
HO
O
O
O
Ph
H
OH
TsOH
OMe
OH
OH
H
O
Ph
OH
OMe
O
OH
Benzaldehyde: prefers 6-membered ring
the 2 OH's can be cis or trans (provide they are diequatorial)
WHY?
Me2CO: requires R2 (Me) to be axial in 6membered ring
R1
R2
O
O
O
PhCHO: can have R2 = H & Ph can be
equatorial
* new stereocentre
These reactions are used for selective protection of one
alcohol & activation of another (protecting group chemistry)
HO
O
TrO
T
O
TrCl
OH
T
OH
1° alcohol is most
reactive protect
first
TrO
O
TrO
T
O
H2 O
OH
activate 2o
alcohol
CH3SO2Cl
inverts stereochemistry
at C3
O
T
O
S
O
reactivate
MeSO2Cl
AZT
TrO
O
T
+
TrO
O
N N N
OMs
SN2
N3
HO
T
O
HCl
remove Tr
N3
T
e.g, synthesis of sucrose (Lemieux, Alberta)
OPG
OPG
OPG
OH
O
PGO
PGO
OPG
OH
PGO
O
PGO
Activate anomeric
centre as oxonium
ion
• Can only couple one way—if we don’t protect, get all
different coupling patterns
• Yet nature does this all of the time: enzymes hold
molecules together in the correct orientation, BUT the
mechanism still goes through an oxonium ion (more on
this later)
Selectivity of Anomer Formation in Glycosides
• Oxonium ion can often be attacked from both Re & Si
faces to give a mixture of anomers.
+
Si face
O
Re face
• How do we control this?
HO
HO
HO
O
HO
Ac2O
OH
(Cf Exp 2)
AcO
AcO
AcO
O
OAc
AcO
HBr/AcOH
AcO
-anomer is favored
due to strongly ewithdrawing Br
AcO
AcO
O
AcO
Br
-bromide
AcO
AcO
AcO
MeOH
O
AcO
Br
Ag2CO3
AcO
AcO
AcO
AcO
+
O
O
O
O
AcO
AcO
O
O
+
cis-fused dioxolenium ion--must be axial!
MeOH
AcO
AcO
AcO
O
OMe
AcO
-glycoside activity
This reaction provides a clue to how an enzyme might
stabilize an oxonium ion (see later)
Examples of Naturally Occurring di- & oligoSaccharides
Maltose:
2 units of glucose
a β sugar
α glycoside
1,4-linkage
Lactose (milk):
galactose + glucose
a β sugar
β glycoside
1,4-linkage
OH OH
O
HO
OH
OH
O
HO
O
OH
OH
HO
Sucrose (sugar):
glucose + fructofuranose
a β sugar
α glycoside
1,2-glycosidic bond
HO
HO
O
OH OH
O
CH2OH
OH
O
CH2OH
α-1,6-glycosidic bond
Amylopectin (blood cells):
an oligosaccharide
α-1,4-glycosidic bond
Structure Determination of Sugars
• The following is an example to review & expand your
knowledge of NMR
– Consider the question of glycoside formation:
HO
HO
HO
HO
O
HO
H3O+
OH
MeOH
HO
HO
O
OMe
HO
 or  anomer?
See NMR spectra of both anomers:
They are different-diastereomers have different spectra,
but which is which?
-methyl glucopyranose
HO
HO
HO
O
HO
OMe
H
-methyl glucopyranose
HO
HO
HO
O
HO
H
OMe
These spectra are rich in independent information:
1) Chemical shift, :
•
Reveals functional groups (see chart)
•
Depends on inductive effects, # of EWGs &  bonds
Inductive effects
Cl CH3
CH3
Si CH3
e.g.
+
Chemical
shift (ppm)
-

0
0

-
+

# of EWGs
e.g. glucose– anomeric H is most downfield since 2 O atoms
attached to C have more of an effect that 1 atom.  we can
assign the anomeric proton in the both spectra of α and β
methyl glucoside
 bonds –alkenes, aromatics, C=O, etc
2)
Integrals
•
3)
NMR is quantitative e.g. glycosides—area under anomeric
signal = 1; area under the signal at  3.3 = 3x bigger,  3
protons, must be a CH3 group
Multiplicity
•
Protons communicate their spins over 1, 2 or 3 bonds—
reveals # of neighbors
e.g. CH3-O group: a singlet, one line, no neighbors—nearst
neighbor is 4 bonds away
e.g. anomeric proton: a doublet, 2 peaks, one neighbor that is
3 bonds away (recall n neighbors, n +1 peaks)
4)
Coupling Constant
•
Distance between peaks in a multiplet is J, coupling
constant—depends on geometry
(con’t)
4)
•
•
e.g. α glycoside: 2 peaks are 4.650-4.632 = 0.018 ppm apart
spectrometer frequency = 200 MHz
J = 0.018 ppm x 200 MHz = 3.6 Hz
For the β-glycoside, J = 8.0 Hz
Different J values reflect different geometries:
 H1 – C1 – C2 – H2 = 60° in α, = 180° in β
J depends on geometry according to Karplus curve:
At 60°, J is small
180°, J is large
 J reveals the geometry, i.e., the
stereochemistry of the glycoside
dihedral H-X-X-H
• But, looking at the spectra, note that the CHOH protons
at C-2, C-3, C-4, C-5 & C-6 are all overlapping.
•  hard to measure each J value—How to use NMR to
get a complete structure?
• What about a very complex case, i.e., sucralose, the
sweetener in splenda:
HO
HO
HO
O
HO
HO
Cl2
O
O
HO
OH
Cl
HO
O
Cl
O
HO
HO
OH
OH
SUCROSE
Cl
O
OH
SUCRALOSE
• Where are the chlorines? Which anomer is formed?
Pyranose &/or furanose ring?
A challenging structure—need advanced NMR methods