Abstract
The binding and stabilizing effect of arginine residues in certain aldolases served as inspiring source for the development of a family of amino acylguanidine organocatalysts. Screening and optimization led to identify the threonine derivative as the most suitable catalyst for the asymmetric aldol addition of hydroxyacetone, affording the syn diastereomer in high ee. In contrast, the proline derivative yielded the anti diasteromer. MMFF models suggest the presence of an extensive hydrogen bonding network between the acylguanidinium group and the reaction intermediates.
Highlights
An arginine residue is an additional important parameter in both aldolase classes, participating in the stabilization and orientation of the intermediates through its guanidine group [1,2,3]. This feature made me think that amino guanidines, and in particular, amino acid derived acylguanidines, could become convenient organocatalysts for the asymmetric aldol reaction, exploiting the enamine formation ability of class I aldolases and the intermediates stabilization ability provided by the arginine residue in some class I and II aldolases (Figure 1A,B)
Remarkable rate acceleration and stereoselectivity were obtained for the aldol reaction of cyclohexanone and aromatic aldehydes [9]
A novel family of amino acid derived acylguanidines for the asymmetric aldol reaction of hydroxyacetone have been synthesized, characterized, and optimized. These compounds were isolated as diprotonated species and the threonine derivative 3d afforded high levels of stereoselectivity for the syn aldol diasteromer, surpassing the characteristics of free threonine
Summary
An arginine residue is an additional important parameter in both aldolase classes, participating in the stabilization and orientation of the intermediates through its guanidine group [1,2,3] This feature made me think that amino guanidines, and in particular, amino acid derived acylguanidines, could become convenient organocatalysts for the asymmetric aldol reaction, exploiting the enamine formation ability of class I aldolases and the intermediates stabilization ability provided by the arginine residue in some class I and II aldolases (Figure 1A,B). Remarkable rate acceleration and stereoselectivity were obtained for the aldol reaction of cyclohexanone and aromatic aldehydes [9] In this communication, a novel family of bioinspired organocatalysts is presented [10].
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