Sugar in the primordial soup

The formose reaction and the origin of life

 Content
• Life from the Soup
• Proteins versus RNA
• Prebiotic syntheses of amino acids &
nucleobases
• Prebiotic synthesis of sugars
• Sugar in space
• Conclusion
 Life on Earth
Now 
 0.7109 yrs ago – Multicellular organisms
 1.2109 yrs ago – Eukaryotic organisms

 3.5109 yrs ago – Prokaryotic organisms

Prebiotic

 4.6109 yrs ago – Formation of Earth

 What started life?

What compounds were

present in the beginning?

What compounds/reactions
are required now?
 The primordial ”soup”
CH3CN N2
CH2O CH4

CO2 CH2CHCN HCCCN

CO NH3
NCCN
SO2 H2O HCN

Note: no photosynthesis - no O2!

 Natural products
Steroids Purines Polyketides

Lipids
Terpenes Aminoacids

Alkaloids
Pyrimidines Carbohydrates
 Some are more important!
Steroids Purines Polyketides

Lipids
Terpenes Aminoacids

Alkaloids
Pyrimidines Carbohydrates
The essentials of (modern) life
Proteins
composed of amino acids
catalyse reactions

RNA
composed of nucleobases,
ribose and phosphate
carry genetic information
Which was first, RNA or proteins?

Proteins
– superior catalysts, simple building blocks, stable

RNA
– can be catalysts, complex building blocks, unstable
but can replicate themselves
 OH

O
Protein

HN

aminoacid
NH

O OH

H2N
Prebiotic amino acid syntheses

alanine 1,7%
glycine 2,1%

S.L. Miller
Science 117 (1952) 528-529
J. Am. Chem. Soc. 77 (1955) 2351-2361
 RNA
phosphodiester
NH2
O

O P O N
N

O
nucleobase
N
N
O

O OH

ribose
Prebiotic nucleobase syntheses

J. Oró, Nature 191 (1961) 1193-1194

Common monosaccharides
aldopentoses aldohexoses ketohexose
ribose glucose
CHO CHO

H OH H OH
H OH HO H
H OH H OH
fructose
CH2OH H OH
CH2OH
CH2OH
O
HO H

arabinose mannose H OH
H OH
CHO CHO
CH2OH
HO H HO H

H OH HO H

H OH H OH

CH2OH H OH
CH2OH
Prebiotic carbohydrate synthesis:

The Formose reaction

OH
CH2O (CH2O)n

A. Butlerow, Liebigs Ann. Chem. 53 (1861) 295-298

O. Leow, J. prakt. Chem. 33 (1886) 321-351
Some of the reactions involved

Cannizzaro
de Bruyn-van Ekenstein
Aldol condensation
Retro-aldol
 Cannizzaro reaction

OH
O
OH HO O  H H O

+
 H
 H  O  H

Cannizzaro, Ann. 88 (1853) 129-

 de Bruyn-van Ekenstein
rearrangement
D-Glucose 66% D-Mannose 3%
HO
HO OH
O
HO O
HO OH HO
HO
OH
OH

OH

OH
O
OH

HO
OH D-Fructose 31%

de Bruyn, Rec. Trav. Chim. 14 (1895) 150-

Evans, Chem. Rev. 31 (1942) 537-559
de Bruyn-van Ekenstein mechanism
Glucose Mannose Fructose
CHO CHO CH2OH

H OH HO H O

HO H HO H HO H

H OH H OH H OH

H OH H OH H OH

CH2OH CH2OH CH2OH

H OH

OH

HO H
1,2-Enediol
H OH

H OH

CH2OH
 The first step...
O

HO O O H H
H H +
H H H O H OH

formate methanol

glycolaldehyde
O
O
HO OH
HO
OH OH
H H O
H H
H
H H H H
 Aldol condensation

O
O
O O

OH H H
H OH
OH OH
H H
OH

glyceraldehyde
 de Bruyn-van Ekenstein

O OH OH

OH OH
H OH H OH OH

OH OH O

glyceraldehyde dihydroxyacetone
 C3+C1  C2+C2
O
O
O
HO
H H
HO OH OH

OH

OH
OH

H H
H
OH
OH

O O
O OH
 very slow

Autocatalytic C1 C1
cycle
C2 C2 C1

fast
C4 C3

C1
The result:
 Sugars in formose
(55% total yield of sugars)

Aldopentoses 7%
(1.4% ribose)

Ketopentoses 8%

Aldohexoses 18%

Ketohexoses 18%
 Open chain forms
aldoses ketoses

tetroses 11-16% 100%

pentoses 0.1-0.2% 8-22%

hexoses 0.002-0.1% 0.3-0.7%

 Tautomers of D-ribose
Cyclic forms (99,9%)
OH OH

O O
OH Acyclic forms (0,1%)
OH
HO OH HO OH HO OH O H

-furanose -furanose H OH H OH

H OH H OH

O O H OH H OH
HO HO
OH CH2OH CH2OH
OH OH
OH OH OH hydrate aldehyde
-pyranose -pyranose
 Problems

Much more hexoses than pentoses

Very little ribose

Racemic mixture of sugars

dihydroxyacetone
CH2OH

O CH2OH CH2OH

CH2OH O O

OH HO
OH +
HO OH

OH OH
O

CH2OH CH2OH
OH

CH2OH
D-sorbose D-fructose
D-glyceraldehyde 26% 34%

H.O.L. Fischer & E. Baer, Helv. Chim. Acta 19 (1936) 519-532

Glycolaldehyde phosphate 1
CHO CHO

CH2OPO3 CHOPO3

CHO CHOH

CH2OPO3 CHOPO3

CHO CHOH

CH2OPO3 CH2OPO3

Müller et al., Helv. Chim. Acta 73 (1990) 1410

Glycolaldehyde phosphate 2
CHO CHO

CH2OPO3 CHOPO3

CHO CHOH

CH2OPO3 CHOPO3

CH2O CH2OH
Extraterrestial compounds

Aminoacids 60 ppm
Carbohydrates 60
Pyrimidines 0.06
Purines 1.2
 Aminoacids
Gly Glu Pro

Ala Val Leu

Asp

+12 not found in proteins

 Carbohydrates

Glucose Mannose

Arabinose Xylose

Dihydroxyacetone

+ aldonic acids & alditols

 Conclusion
The basic building blocks of proteins and RNA can be
prepared from compounds expected to be present on
early Earth.

The conditions to make them are incompatible, i.e. they

can not be formed under the same reaction conditions
and in the same place.

The strongest proof that they could have been formed

prebiotically is their presence in extraterrestrial matter.