Sugars and Their Use in Synthesis
Matthew M. Kreilein
Wednesday, January 11th, 2006
I believe it was George Bernard Shaw who was asked if he knew that “sugar” was the
only word in the English language where “su” was pronounced “sh”. He replied, “Sure”.
Carbohydrates have often been relegated to the sidelines of chemistry, one example
being the complete omission of essential and challenging sugar portions from many
papers on “natural product synthesis”. One can almost hear the collective sigh, “Difficult
chemistry, difficult biology, difficult analysis, I don’t want to see another protecting group,
let’s leave the sugar off”.
Carbohydrates - A Hostile Scientific Frontier Becomes Friendlier, Chem. Rev., 100, 2000
What is a Carbohydrate (Sugar)?
- It’s like defining a compound as “organic” or not. I’ve heard a definition of an “organic”
compound to be one that must have at least one C-C and/or one C-H bond. So does
that make CCl4 inorganic?
- Get their name, carbohydrate, because the simplest form of them (reducing sugars)
can be expressed as “hydrates of carbon”. For example…
-This doesn’t really work all that well as a definition of a carbohydrate as methyl Dglucopyranoside would be called a carbohydrate by chemists, but can’t be expressed as
a “hydrate of carbon”.
What is a Carbohydrate (Sugar)?
- Perhaps the United States Supreme Court can help. Justice Potter Stewart in
Jacobellis v. Ohio, 378 U.S. 184, 197 (1964) regarding what was “obscene” wrote…
"I shall not today attempt further to define the kinds of material I understand to be
embraced . . . but I know it when I see it . . .”
Sugars are everywhere with a huge number of possibilities as far as structure
1,6-dichloro-1,6-dideoxy-β-D-fructofuranosyl
4-chloro-4-deoxy-α-D-galactopyranoside
[a.k.a. sucralose or Splenda®]
- 1000 ways of linking three of the same D-hexopyranosides via glycosidic bonds in
contrast to only one way of peptide bonding three identical α-amino acids.
- this leads to a huge amount of possible unique structures when sugars are involved.
For example, there are over 2,000,000 possible pentasaccharides using D-sugars.
Incredibly important in biological functions…
Why use sugars?
- Cheap and readily available
- Lactose ~$0.10/lb on commercial scale about
1 penny per mole for 10 chiral centers.
…most of the time.
- Can set five stereocenters with a purchase order
- Ability to isolate oxygens, protect, and manipulate in a myriad of ways
(more on this later)
How long have chemists been messing with them?
“Method for the Detection of Artificial or Dextro Glucose in Cane Sugar, and the Exact
Determination of Cane Sugar by the Polariscope” de P. Ricketts, P. J. Am. Chem. Soc.,
1879, 1, 1-6.
“The Mechanism of Carbohydrate Oxidation. XVIII. The Oxidation of Certain Sugars with
Silver Oxide in the Presence of Postassium Hydroxide” Busch, K.G.A.; Clark, J.W.;
Genung, L.B.; Schroeder, E.F.; Evans, W.L. J. Org. Chem., 1936, 1, 1-16.
Sugar problems to deal with/consider when using:
You will burn steps/time protecting and deprotecting with the “right” condition in order to
avoid bad things like “peeling” (more on this later as well).
Show how this happens:
And why it happens:
Using the Lipták method, the following is observed…
Show how this happens:
And why it happens:
One of the most common ways to use a sugar you’ll see
Capon, B. Chem. Rev. 1969, 69, 407-498
Is this an efficient way?
25 atoms, 18 sugar bits, 7 other, 21 of 29 steps sugar route, 8 of 29 other.
72% of synthetic steps to get 72% of the atoms…not too bad really.
A Sweet Use of Symmetry