Super Armed Glycosyl Donors in Glycosylation Chemistry

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Super Armed Glycosyl Donors in Glycosylation
Chemistry
1C4
4C1

• Jensen, H.H. Pedersen, C.M. Bols, M. Chem.
  Eur. J.,2007, 13, 7576.
• Pedersen, C.M. Nordstrm, L.U. Bols, M. J. Am.
  Chem. Soc., 2007, 129, 9222.

TalineBoghossianApril 8, 2009
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Recall General GlycosylationChemistry
Glycosyl Acceptor

• Donor Leaving Group
• Acceptor Reactive Hydroxyl
• Promoter Activate Glycosyl Donor LG

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Armed, Disarmed and Super Armed Donors
4C1
R TBS, TIPS
Disarmed Donor
Less Reactive
1C4
Armed Donor
Super Armed Donor Axial OR more reactive
More Reactive
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Reactivity of Donor Hydroxyl Groups
Acid Hydrolysis Slow
Equatorial
Rel. rate 1
Axial
Acid Hydrolysis Fast
Rel. rate 248
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Why are Axial Hydroxyls More Reactive?

• Basicity increases with axial OH
• Differences in charge-dipole interactions

pKa 8.4
pKa 9.4
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First Super Armed Glycosyl Donor Synthesized
Super Armed Donor
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Super Armed Donor Glucose Derivative
ß Super Armed Donor
a Super Armed Donor
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Glycosylation Super Armed and Armed
NIS, TfOH (cat) CH2Cl2, ms 4 Å - 85C

ß 65
a
NIS, TfOH (cat) CH2Cl2, ms 4 Å - 85C

ß 51
ß
Very fast activation of super armed donor ?
approx. 15 mins High reactivity of twisted donor
does not depend on 1C4 conformation
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Why Beta Selectivity?
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Enhanced Reactivity - Conformation or Silicon
Effect?

NIS/TfOHCH2Cl2, - 85C
- ß selectivity - Not necessary to have Silyl
groups for ß selectivity or for
reactivity. - Conformational effect
Only ß 51
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Enhanced Reactivity - Conformation or Silicon
Effect?

7 ß product
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Competition Experiment Suggests High Reactivity
of Super Armed Donors

NIS, TfOH (cat) CH2Cl2, ms 4 Å - 85C
Acceptor
Super Armed Donor
Armed Donor
75 , aß 14
No Coupling Between Acceptor and Armed Donor
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One Pot Synthesis of a Trisaccharide

Super Armed
2.1 equiv NIS, TfOH CH2Cl2, 4 Å MS - 88 to -50 C
Armed
Disarmed
64 Trisaccharide
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Rhamnose Derivative - a Selectivity
-85 C
-65 C
100 C
1C4
4C1
Fast
Slow
Acceptor
Acceptor
a
ß
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Glycosylation with Rhamnose Donor a Selectivity
NIS, TfOH (cat) CH2Cl2, 4 Å MS
- 60 C
Only a90
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Conclusion

• Bulky PG (TBS, TIPS) at axial position force
  pyranose ring to take a boat conformation
• Minimized dipoles
• Super armed donors gt armed donors
• Selectively make a or ß depending on the
  glycoside derivative and temperature