1,2-Asymmetric induction in dianionic functionalization reactions of L-aspartic acid diesters 1

Asparagine Synthetase Chemotherapy

“…First, by analogy to the chemistry of aminoacyl tRNA synthetases, attack of the side-chain carboxylate of bound aspartate on the α-phosphate of ATP likely proceeds via in-line attack with inversion at the phosphorus atom (Scheme 2) (128). Second, studies with non-natural, conformationally constrained aspartate analogs, prepared using the diastereoselective alkylation of L-aspartate diester derivatives (129,130), demonstrated that the polar functional groups are located on one face in the bound conformation of aspartate (131). After refinement using constrained molecular dynamics (MD) simulations (132) in combination with simulated annealing algorithms (133), and subsequent energy minimization, the resulting model was then modified by connecting the side-chain carboxylate of aspartate to the α-phosphate of the ATP moiety to form the βAspAMP intermediate.…”

Tetrahydro-1,3-oxazin-6-ones as templates for the stereoselective synthesis of β-substituted L-aspartic acids

“…Direct alkylation of aspartic acid derivatives was first reported by Seebach in 1981, 2 and later by Baldwin and other workers. [3][4][5][6][7][8][9][10][11][12] Except for reports of stereospecific allylation, 10,11 these reactions gave mixtures of diastereoisomers. A recent study has indicated how the structural and experimental features in such reactions affect the diastereoselectivity.…”

“…A recent study has indicated how the structural and experimental features in such reactions affect the diastereoselectivity. 12 Single diastereoisomeric β-alkylaspartates have been synthesised indirectly using chiral βlactam esters as templates which are alkylated trans to the ester group. [13][14][15][16] We have developed a stereoselective method of preparing homochiral 4-substituted glutamic acids and prolines by using pyroglutamic acid as a chiral template.…”

Stereocontrolled routes to β,β′-disubstituted α-amino acids

“…Factors controlling the diastereoselectivity are: (i) the nature of the base: with LiHMDS the anti-products are obtained in high diastereoselectivities, 197,205 whereas using KHMDS the syn-products are the major ones (with however lower selectivities). 192,193,204 This selectivity reversal stems from a different complexation on the enolate intermediate; 206 (ii) the nature of the protecting groups: higher selectivities are observed with bulky protecting amino-and ester-groups; (iii) brominated compounds are usually the best electrophiles in these reactions; (iv) increased diastereoselectivities have been observed in the presence of additives such as HMPA or LiCl. 196,200 Representative examples are given in Scheme 62.…”