Institut de Chimie Moléculaire et des Matériaux d'Orsay

Chimie Peptidomimétique Photochimie, Procédés Alternatifs - CP3A

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Synthesis of Small-ring homologated amino acids

For the last decade we have been developing synthetic methodologies aimed at expanding the inventory of homologated small ring amino acids and various derivatives. A key approach in our work has been to privilege strategies which are simple, convenient, and provide more than a few token milligrams of the target molecule – in other words, we seek practical syntheses! For four-membered rings, photochemical 2+2 cycloaddition approaches have been a regular theme: further details of studies in this are given on this page. Other approaches to selected four-membered ring targets have been considered too. For three-membered rings, we have used an adaptation of the Kulinkovich reaction or the Bull oxazolidinone methodology.

Selected Papers

4-rings by photochemistry

1- The [2+2] photocycloaddition of uracil derivatives with ethylene as a general route to cis-cyclobutane β-aminoacids. C. GAUZY, B. SABY, E. PEREIRA, S. FAURE, D. J. AITKEN, Synlett, 2006, 1394-1398.

2- [2+2] Photocycloadditions with chiral uracil derivatives: access to all four stereoisomers of 2 aminocyclobutanecarboxylic acid. C. FERNANDES, C. GAUZY, Y. YANG, O. ROY, E. PEREIRA, S. FAURE, D. J. AITKEN, Synthesis, 2007, 2222-2232.

3- Efficient synthesis of 3-hydroxymethylated cis- and trans-cyclobutane β-amino acids using an intramolecular photocycloaddition strategy A. MONDIÈRE, R. PENG, R. REMUSON, D. J. AITKEN, Tetrahedron, 2008, 64, 1088-1093.

4- Expedient preparation of all isomers of 2 aminocyclobutane-1-carboxylic acid in enantiomerically pure form. C. FERNANDES, E. PEREIRA, S. FAURE, D. J. AITKEN, J. Org. Chem., 2009, 74, 3217-3220.

5- N-Aminoazetidinecarboxylic acid: direct access to a small-ring hydrazino acid. V. DECLERCK, D. J. AITKEN, J. Org. Chem., 2011, 76, 708-711.

6- A refined synthesis of enantiomerically pure 2-aminocyclobutane carboxylic acids. V. DECLERCK, D. J. AITKEN, Amino Acids, 2011, 41, 587-595.

7- A unified synthesis of all stereoisomers of 2-(aminomethyl)cyclobutane-1-carboxylic acid. V. ANDRE, M. GRAS, H. AWADA, R. GUILLOT, S. ROBIN, D. J. AITKEN Tetrahedron, 2013, 69, 3571-3576.

8- Stereoselective intermolecular [2 + 2]-photocycloaddition reactions of maleic anhydride: stereocontrolled and regiocontrolled access to 1,2,3-trifunctionalized cyclobutanes. F. HERNVANN, G. RASORE, V. DECLERCK, D. J. AITKEN, Org. Biomol. Chem., 2014, 12, 8212-8222.

9- Practical syntheses of both enantiomers of the conformationally restricted GABA analogue cis-(2-aminocyclobutyl)acetic acid. H. AWADA, S. ROBIN, R. GUILLOT, O. YAZBECK, D. NAOUFAL, N. JABER, A. HACHEM, D. J. AITKEN, Eur. J. Org. Chem., 2014, 7148-7155.

4-rings by other methods

10- Evaluation of an aza-Michael approach for the synthesis of 3,3-dimethyl-2-aminocyclobutane-1-carboxylic acid. F. CHARNAY-POUGET, M. FRANK, J.-P. BALTAZE, E. PEREIRA, D. J. AITKEN, ARKIVOC, 2012, v, 80-93.

Cyclopropanes

11- An expedient asymmetric synthesis of N-protected (S,S)-2-aminomethyl-1-cyclopropanecarboxylic acid. D. J. AITKEN, S. D. BULL, I. R. DAVIES, L. DROUIN, J. OLLIVIER, J. PEED, Synlett, 2010, 2729-2732.

12- Stereoselective preparation of β,γ-methano-GABA derivatives. D. J. AITKEN, L. DROUIN, S. GORETTA, R. GUILLOT, J. OLLIVIER, M. SPIGA, Org. Biomol. Chem., 2011, 9, 7517-7524.