Sugar in the primordial soupThe 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

4.6109 yrs ago – Formation of Earth

3.5109 yrs ago – Prokaryotic organisms

Now

1.2109 yrs ago – Eukaryotic organisms 0.7109 yrs ago – Multicellular organisms

Prebiotic

What started life?

What compounds were present in the beginning?

What compounds/reactions are required now?

The primordial ”soup”

CO2

N2

CO

SO2

CH2O CH4

Note: no photosynthesis - no O2!

NH3

HCN

CH3CN

CH2CHCN HCCCN

NCCNH2O

Aminoacids

Natural products

Steroids

TerpenesLipids

Purines Polyketides

CarbohydratesAlkaloidsPyrimidines

Aminoacids

Some are more important!

Steroids

TerpenesLipids

Purines Polyketides

CarbohydratesAlkaloidsPyrimidines

The essentials of (modern) life

Proteinscomposed of amino acidscatalyse reactions

RNAcomposed of nucleobases,ribose and phosphatecarry 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

H2N

NH

HN

O

O

O

OH

OH

Protein

aminoacid

Prebiotic amino acid syntheses

S.L. MillerScience 117 (1952) 528-529J. Am. Chem. Soc. 77 (1955) 2351-2361

glycine 2,1%

alanine 1,7%

O

O OH

O

P O

O

O N

NN

N

NH2

RNA

ribose

nucleobase

phosphodiester

Prebiotic nucleobase syntheses

J. Oró, Nature 191 (1961) 1193-1194

Common monosaccharides

H

CHO

OH

HHO

OHH

OHH

CH2OH

glucose

HO

CHO

H

HHO

OHH

OHH

CH2OH

mannose

H

CHO

OH

OHH

OHH

CH2OH

ribose

HO

CHO

H

OHH

OHH

CH2OH

arabinose

CH2OH

O

HHO

OHH

OHH

CH2OH

fructose

aldopentoses aldohexoses ketohexose

Prebiotic carbohydrate synthesis:

The Formose reaction

A. Butlerow, Liebigs Ann. Chem. 53 (1861) 295-298O. Leow, J. prakt. Chem. 33 (1886) 321-351

CH2O (CH2O)nOH

Some of the reactions involved

Cannizzaro

de Bruyn-van Ekenstein

Aldol condensation

Retro-aldol

Cannizzaro reaction

Cannizzaro, Ann. 88 (1853) 129-

H

O OH

H

OHO H

O

O

OH

+ H

OH

de Bruyn-van Ekenstein rearrangement

de Bruyn, Rec. Trav. Chim. 14 (1895) 150-Evans, Chem. Rev. 31 (1942) 537-559

OHO

HO

OH

HO

OHO

HO

HO OH

O

OHHO

OH

OH

OH

OH

OH

D-Glucose 66% D-Mannose 3%

D-Fructose 31%

de Bruyn-van Ekenstein mechanismGlucose Mannose Fructose

1,2-Enediol

CHO

OHH

HHO

H OH

OHH

CH2OH

CHO

HHO

HHO

H OH

OHH

CH2OH

CH2OH

O

HHO

H OH

OHH

CH2OH

OH

HHO

H OH

OHH

CH2OH

H OH

H H

HO O

H H

O

H O

O

H OH

H H

+

H

HOOH

H H

O

H

HO OH

O

H

HOH

H

O

H H

The first step...

formate methanol

glycolaldehyde

Aldol condensation

H

O

OHOH

H

O

OHH H

O

H

O

OH

OH

glyceraldehyde

de Bruyn-van Ekenstein

OHH

O

OH

OH OHOH

H

OH

OH

OH

O

OH

glyceraldehyde dihydroxyacetone

C3+C1 C2+C2

HO OH

O

H H

O

HO

O

OH

OH

H

OH

OH

OH

O

H

OH

O

OH

O

H

Autocatalyticcycle

C2C2

C3C4

C1C1

C1

C1

very slow

fast

The result:

Sugars in formose(55% total yield of sugars)

Aldopentoses 7%(1.4% ribose)

Aldohexoses 18%

Ketopentoses 8%

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

OHO

OH OH

OH

OHO

OH

OHOH

H OH

OHH

OHH

CH2OH

O H

H OH

OHH

OHH

CH2OH

HO OHOH

HO OH

O

OH

HO OH

O

OHOH

Cyclic forms (99,9%)

Acyclic forms (0,1%)

-furanose -furanose

-pyranose-pyranose

hydrate aldehyde

Problems

Much more hexoses than pentoses

Very little ribose

Racemic mixture of sugars

OH

CH2OH

O

CH2OH

O

OH

CH2OH

CH2OH

O

OH

HO

OH

CH2OH

CH2OH

O

OH

CH2OH

HO

OH+

D-glyceraldehyde

dihydroxyacetone

D-sorbose26%

D-fructose34%

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

Glycolaldehyde phosphate 1CHO

CH2OPO3

CHO

CHOPO3

CHOH

CHOPO3

CH2OPO3

CHOH

CHO

CH2OPO3

CHO

CH2OPO3

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

Glycolaldehyde phosphate 2CHO

CH2OPO3

CHO

CHOPO3

CHOH

CHOPO3

CH2OH

CHO

CH2OPO3

CH2O

Extraterrestial compounds

AminoacidsCarbohydratesPyrimidinesPurines

60 ppm60 0.06 1.2

Aminoacids

Gly

Ala

Glu

Val

Pro

Asp

Leu

+12 not found in proteins

Carbohydrates

+ aldonic acids & alditols

Mannose

Xylose

Glucose

Arabinose

Dihydroxyacetone

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.