Sugar in the primordial soup - Stenutz · Sugar in the primordial soup The formose reaction and the origin of life. Content ... Extraterrestial compounds Aminoacids Carbohydrates

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

← 4.6×109 yrs ago – Formation of Earth

← 3.5×109 yrs ago – Prokaryotic organisms

Now →

← 1.2×109 yrs ago – Eukaryotic organisms← 0.7×109 yrs ago – Multicellular organisms

Prebiotic

What started life?

What compounds were present in the beginning?

What compounds/reactions are required now?

The primordial ”soup”

N2CH2O CCH3CN H4

HCCCNCO2 CH2CHCNNH3CONCCN

H2O HCNSO2

Note: no photosynthesis - no O2!

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

glycine 2,1%

alanine 1,7%

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

RNA

O

O OH

O

P O

O

O N

NN

N

NH2

ribose

phosphodiester

nucleobase

Prebiotic nucleobase syntheses

J. Oró, Nature 191 (1961) 1193-1194

Common monosaccharidesaldohexoses ketohexosealdopentoses

H

CHO

OH

OHH

OHH

CH2OH

ribose

HO

CHO

H

OHH

OHH

CH2OH

arabinose

H

CHO

OH

HHO

OHH

OHH

CH2OH

glucose

HO

CHO

H

HHO

OHH

OHH

CH2OH

mannose

CH2OH

O

HHO

OHH

OHH

CH2OH

fructose

Prebiotic carbohydrate synthesis:

The Formose reaction

CH2O (CH2O)nOH

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

Some of the reactions involved

Cannizzaro

de Bruyn-van Ekenstein

Aldol condensation

Retro-aldol

Cannizzaro reaction

ϕ H

O OH

ϕ H

OHO ϕ H

O

ϕ O

OH

+ϕ H

OH

Cannizzaro, Ann. 88 (1853) 129-

de Bruyn-van Ekensteinrearrangement

OHO

HO

OH

HOO

HOHO

HO OH

O

OHHO

OH

OH

OH

OH

OH

D-Glucose 66% D-Mannose 3%

D-Fructose 31%

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

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

The first step...

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

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

very slow

Autocatalyticcycle

C2

C3C4

C1C1

C1

C1

fast

C2

The result:

Sugars in formose(55% total yield of sugars)

Aldopentoses 7%(1.4% ribose)

Ketopentoses 8%

Aldohexoses 18%

Ketohexoses 18%

Open chain forms

0.3-0.7%0.002-0.1%hexoses

8-22%0.1-0.2%pentoses

100%11-16%tetroses

ketosesaldoses

Tautomers of D-riboseCyclic forms (99,9%)

OHO

OH OHOH

OHO

OHOH

OH

OHHO OH

O

OH

HO OH

O

OHOH

α-furanose β-furanose

β-pyranoseα-pyranose

Acyclic forms (0,1%)

H OH

OHH

OHH

CH2OH

O H

H OH

OHH

OHH

CH2OH

HO OH

hydrate aldehyde

Problems

Much more hexoses than pentoses

Very little ribose

Racemic mixture of sugars

dihydroxyacetone

OH

CH2OH

O

CH2OH

O

OH

CH2OH

CH2OH

O

OH

HO

OH

CH2OH

CH2OH

O

OH

CH2OH

HO

OH+

D-sorbose26%

D-fructose34%D-glyceraldehyde

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 ppm600.061.2

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.