Toward higher polyprenols under 'prebiotic' conditions

Article abstract of DOI:10.1016/S0040-4039(03)01624-1

Geraniol and isomers (C₁₀) can be obtained by the condensation of C₅ monoprenols at room temperature in the presence of montmorillonite K-10. It is also possible to obtain farnesol (C₁₅) and isomers by condensation of geraniol with isopentenol. Despite the low yields achieved, these findings support the hypothesis that polyprenyl phosphates may have been formed in prebiotic conditions, and served as constituents of primitive membranes.

Full text of DOI:10.1016/S0040-4039(03)01624-1

TETRAHEDRON
LETTERS
Pergamon
Tetrahedron Letters 44 (2003) 6959–6961
Toward higher polyprenols under ‘prebiotic’ conditions
Laurent De´saubry,* Yoichi Nakatani and Guy Ourisson
UMR 7509, Universite´ Louis Pasteur, CNRS, Centre de Neurochimie, 5 rue Blaise Pascal, F-67084 Strasbourg, France
Received 16 May 2003; revised 18 June 2003; accepted 27 June 2003
Abstract—Geraniol and isomers (C10) can be obtained by the condensation of C5 monoprenols at room temperature in the
presence of montmorillonite K-10. It is also possible to obtain farnesol (C15) and isomers by condensation of geraniol with
isopentenol. Despite the low yields achieved, these findings support the hypothesis that polyprenyl phosphates may have been
formed in prebiotic conditions, and served as constituents of primitive membranes.
© 2003 Elsevier Ltd. All rights reserved.
simulation of prebiotic reactions.14–17 It has been used
in particular in the synthesis of branched polyprenols
by Nagano et al.18
Living cells are surrounded by lipidic membranes that
universally contain polyprenoids.1 The difficulty of
identifying any reasonable prebiotic mechanism for the
formation of n-acyl phospholipids had led us to postu-
late that primitive membranes were constituted of the
simplest possible amphiphiles derived from polyprenols,
the polyprenyl phosphates, which we have shown to
self-organise into vesicles, provided they contain at least
15 carbons in their lipophilic part (two C10 chains, or
one C]15 chain).2–6 Leaving aside provisionally the
vexing problem of the abiotic origin of the C5 unit,
isopentenol or dimethylallyl alcohol, it was easy to
formulate in simplistic terms the reaction leading to
homologation as an acid-catalysed alkylation of isopen-
tenol 3 by the dimethylallyl cation derived from
dimethylallyl alcohol 1, or from dimethyl vinyl carbinol
2. We have now shown that it is indeed possible to
achieve this homologation and to obtain, from these C5
units, C10 isomers containing geraniol 4, and from
geraniol C15 homologues containing farnesol 13.
The reaction conditions were simple: prenol 1 or
dimethyl vinyl carbinol 2 and isopentenol 3 (10 equiv.)
were stirred for 9 days in the presence of montmoril-
lonite K10 at room temperature. Apolar olefins and
ethers were removed by chromatography on silica gel.
The mixture of alcohols was benzoylated and analyzed
by GC–MS, and the identification of peaks was based
on the retention time and the mass spectrum of authen-
tic samples.
Using prenol 1 as a substrate afforded alcohols 4–8 in
57% yield. With dimethyl vinyl carbinol 2, the yield was
42%. Replacing prenol 1 by 2 did not affect signifi-
cantly the ratio of the alcohols 4–8 (Table 1). Geraniol
4 represented only 3% of these alcohols; the major
products were homoallylic, with a predominance of
trans-isogeraniol 6. Such a trend in the regioselectivity
Many simulations of prebiotic reactions have involved
clays as acidic catalysts, including amino acid forma-
tion and amino acid polymerisation, RNA and DNA
oligomerisation.7–11 It has also been suggested that
clays were involved in the apparition of the genetic
code.12 This implication of clays in the origin of life was
first suggested by Bernal, half a century ago.13 This
choice was justified by the likely presence of clays on
primitive earth and by the variety of reactions that they
can catalyze.14 Montmorillonite K10 is the clay most
frequently used, both in organic synthesis and in the
Table 1. Prenylation of isopentenol 3 by 1 or 2 catalyzed
by montmorillonite K10a
Substrate
Total yield (%)b,c
Ratio (%)c
4
5
6
7
8
1
2
57
42
3
3
24
19
46
52
12
10
15
16
a 1 ml of 1 or 2 reacted with 10 ml of 3 and 5 g of montmorillonite
K10.
* Corresponding author. Fax: 33 (0)3 88 60 76 20; e-mail: desaubry@
chimie.u-strasbg.fr
b Yields are relative to substrates 1 or 2.
c Percentages determined by GC of the corresponding benzoate esters.
0040-4039/$ - see front matter © 2003 Elsevier Ltd. All rights reserved.
doi:10.1016/S0040-4039(03)01624-1

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L. De´saubry et al. / Tetrahedron Letters 44 (2003) 6959–6961
Authentic samples of alcohols 5, 7 and 9–11 were
of the proton elimination has been reported by Julia et
al. in their studies on biomimetic prenylation reac-
tions.19 Products 9 and 10 were also formed in 10 and
0.2% yields, respectively, by self-condensation of
isopentenol 3 (Scheme 1). Nagai and colleagues have
described the same reaction using BF3·Et2O, instead of
montmorillonite K10, as an acid.20
prepared according to described procedures.20–22
The synthesis of trans-b-isogeraniol 6 and trans-b-iso-
farnesol trans-12 involved Negishi’s Zr-catalyzed car-
boalumination of protected 3-butyn-1-ol with AlMe3
followed by a palladium-catalyzed coupling reaction
with prenyl acetate or geranyl acetate (Scheme 3).23
We also checked that geraniol 4 reacts like 1 or 2 to
afford C15 homoallylic alcohols 11 and 12 as well as a
small amount of farnesol 13 in about 15% overall yield
(Scheme 2). As previously, the crude mixture was ana-
lyzed by GC–MS using authentic benzoyl esters of 11,
trans-12 and 13 as references.
Our data constitute the first evidence that a clay can
catalyze an isoprenic condensation. The predominance
of homoallylic alcohols 5–7 over geraniol 4 may be
important in a prebiotic context, because phosphate
esters of homoallylic alcohols 5–7 would obviously be
Scheme 1. Condensation of 3 with 1 or 2 in the presence of montmorillonite K10.
Scheme 2. Condensation of geraniol 4 with isopentenol 3.
Scheme 3.

L. De´saubry et al. / Tetrahedron Letters 44 (2003) 6959–6961
6961
much more stable than the allylic phosphate esters of 4,
and might therefore be candidate primitive phospho-
lipids after further elongation.
6. Pozzi, G.; Birault, V.; Werner, B.; Dannenmuller, O.;
Nakatani, Y.; Ourisson, G. Angew. Chem., Int. Ed. Engl.
1996, 35, 177–180.
7. Ferris, J. P.; Hill, A. R., Jr.; Liu, R.; Orgel, L. E. Nature
1996, 381, 59–61.
8. Ertem, G.; Ferris, J. P. Nature 1996, 379, 238–240.
9. Ferris, J. P.; Ertem, G. O. Science 1992, 257, 1387–
1389.
The results described, together with the ability of mont-
morillonite K10 to catalyze phosphorylations,24 support
the hypothesis that clays may have played a role in the
genesis of primitive membranes.
10. Ertem, G.; Ferris, J. P. J. Am. Chem. Soc. 1997, 119,
7197–7201.
11. Prakash, C.; Pitsch, S.; Ferris, J. P. Chem. Commun.
2000, 2497–2498.
12. Hartman, H. J. Mol. Evol. 1995, 40, 541–544.
13. Bernal, J. D. The Physical Basis of Life; Routledge:
London, 1951.
Acknowledgements
We thank Dr. Franck Pinot for performing GC–MS
analysis.
14. Negron-Mendoza, A.; Albarran, G.; Ramos-Bernal, S. In
Chemical Evolution: Physics of the Origin and Evolution of
Life; Chela-Flores, J.; Raulin, F., Eds.; Clays as natural
catalysts in prebiotic processes; Kluwer Academic Publi-
cations: Dordrecht, 1996; pp. 97–106.
15. Laszlo, P. Science 1987, 235, 1473–1477.
16. Smith, K. Organic Chemistry Using Clays; Ellis Horwood
Ltd: New York, 1992.
References
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contain polyprenyl phospholipids as their membrane
matrix; dolichol phosphates are widely present in mem-
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proteins into membranes; eucaryotic phospholipidic
membranes are reinforced by cholesterol and procaryotic
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