INFIQC   05475
INSTITUTO DE INVESTIGACIONES EN FISICO- QUIMICA DE CORDOBA
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Synthesis of linear D-alt-L peptidomimetics starting from a carbohydrate precursor
Autor/es:
SOL C. PARAJÓN PUENZO; ADRIANA A. KOLENDER; SANDRA E. MARTÍN; OSCAR VARELA
Lugar:
Brasilia
Reunión:
Congreso; 14th Brazilian Meeting on Organic Synthesis (14th BMOS); 2011
Resumen:
Synthesis of linear d-alt-l
peptidomimetics starting from a carbohydrate precursor
Sol C. Parajón Puenzo, Adriana A. Kolender, Sandra E. Martín, Oscar
Varela*
Dpto. Química Orgánica,
CIHIDECAR-CONICET-UBA, Facultad de Ciencias Exactas y Naturales, Buenos Aires,
Argentina INFIQC, Departamento
de Química Orgánica, Facultad de Ciencias Químicas, Universidad Nacional de
Córdoba, Córdoba, Argentina
*e-mail varela@qo.fcen.uba.ar
Keywords: peptidomimetics, oligopeptides, carbohydrates
INTRODUCTION
Fundamental building blocks used by nature are amalgamated to produce
natural-like, yet unnatural, structural entities with multifunctional groups
anchored in a single ensemble. For example, hybrid molecules that maintain the
basic structure of a carbohydrate have been obtained. This hybrids include
amino and carboxyl functional groups, characteristic of amino acids. Diverse arrays
of peptidic templates have been employed for the construction of homo- and
heterooligomers that behave as peptidomimetics. These molecules are sometimes
able to associate themselves spontaneously (self-assembly process) to form
complex architectures.1 The novel materials find useful applications
as microelectronics, drug delivery and tissue engineering. The linear
oligopeptides are also precursor of cyclic peptoids (carbopeptoids) useful as
molecular receptors.2 We describe herein the synthesis of an amino acid
building block starting from inexpensive d-Glucono-1,5-lactone.
As the amino containing stereocenter possesses the S configuration, the molecule is combined with d-alanine (R configuration) to give d-alt-l
peptides to favor self-assembly processes.
RESULTS AND DISCUSSION
Treatment of d-Glucono-1,5-lactone (1) with 2,2-dimethoxypropane led to conversion
into the methyl ester and simultaneous protection as the 3,4:5,6-di-O-isopropylidene derivative (2). The free hydroxyl group was
substituted by azide to obtain 4,
via the triflate 3. Treatment of 4 with bis(tribultyltin) oxide [(Bu3Sn)2O]
gave the free carboxylic acid 5,
without racemization or elimination at C-2, as happened with other bases.
Coupling of 5 with d-alanine in the presence of 1-hydroxybenzotriazole
(HOBt), N,N-diisopropylethylamine (DIPEA) and a carbodiimide (EDCI) afforded
the dipeptide 6. This key
intermediate was used as precursor of both the acid 7 (by reaction with (Bu3Sn)2O) and the amine 8 (under Staudinger conditions).
Condensation of 7 and 8 gave the d-alt-l-tetrapeptide 9.
Additionally, dipeptide 6 was also used as the starting
material to prepare the sugar amino acid 10,
which was subjected to autocondensation with HOBt, DIPEA, EDCI.
Scheme 1. Synthesis of oligopeptides
6-10.
CONCLUSION
The sugar-based amino acid precursor 5 has been synthesized straightforward from d-Glucono-1,5-lactone. This building block was employed as
key intermediate in the stereocontrolled synthesis of linear d-alt-l oligopeptides.
ACKNOWLEDGEMENTS
We are indebted to ANPCyT, UBA, UNC and CONICET for financial support.
REFERENCES
[1] Börner, J.
C. Prog. Polym. Sci. 2009, 34, 811.
2 Driggers, E. M.; Hale, S. P.; Lee, J.; Terrett, N. K. Nat. Rev. Drug Discovery 2008, 7,
608.