170642-23-6Relevant articles and documents
Antimalarial activity of a new family of analogues of manzamine A
Winkler, Jeffrey D.,Londregan, Allyn T.,Hamann, Mark T.
, p. 2591 - 2594 (2007/10/03)
Manzamine A represents an important lead structure for the development of novel antimalarial chemotherapies. The synthesis and biological evaluation of a group of simplified analogues of manzamine A, which were designed to examine the roles of the A and D
Enantioselective Synthesis of Non-Natural Aromatic α-Amino Acids
Krebs, Andreas,Ludwig, Verena,Pfizer, Jose,Duerner, Gerd,Goebel, Michael W.
, p. 544 - 553 (2007/10/03)
We present two complementary methods for the stereoselective synthesis of non-natural α-amino acids with aromatic or heteroaromatic side chains. One approach is based on the chemical transformation of methionine, whereas the other applies the stereoselective Myers alkylation of glycine. The resulting product types differ in the linker length between glycine and the aromatic substituent. Since methionine and pseudoephedrine are available in both absolute configurations, R- or S-configured enantiopure amino acids with either C2 or C3 linkers can be obtained on gram scales. In each case the key step of the synthesis is hydroboration of the unsaturated building blocks 9 and 17, followed by palladium-catalyzed Suzuki cross-coupling with aryl halides. Attention must in certain cases be paid to the stereochemical integrity when basic Suzuki conditions are applied. Our initial difficulties are reported as well as the final "racemization-proof" procedures. The protecting groups chosen for the α-amino acids should be compatible with solid-phase peptide synthesis. This was confirmed by the successful synthesis of a series of tripeptides.
The imine (+)-pseudoephedrine glycinamide: A useful reagent for the asymmetric synthesis of (R)-α-amino acids
Guillena, Gabriela,Najera, Carmen
, p. 181 - 183 (2007/10/03)
The new imine derived from Myers (+)-pseudoephedrine glycinamide can be diastereoselectively alkylated with alkyl halides at room temperature using NaOEt or LiO-tert-Bu as bases under phase transfer conditions. Hydrolysis to the corresponding alkylated products was easily achieved under mild conditions to afford (R)-α-amino acids.
Highly practical methodology for the synthesis of D- and L-α-amino acids, N-protected α-amino acids, and N-methyl-α-amino acids
Myers, Andrew G.,Gleason, James L.,Yoon, Taeyoung,Kung, Daniel W.
, p. 656 - 673 (2007/10/03)
Full details are provided for an exceedingly practical method to synthesize D- and L-α-amino acids, N-protected α-amino acids, and N-methyl-α-amino acids, employing as a key step the asymmetric alkylation of pseudoephedrine glycinamide (1) or pseudoephedrine sarcosinamide (2). Practical procedures for the synthesis of 1 and 2 from pseudoephedrine and glycine methyl ester or sarcosine methyl ester, respectively, are presented. Optimum protocols for the enolization and subsequent alkylation of 1 and 2 are described. Alkylation reactions of 1 and 2 are found to be quite efficient with a wide range of alkyl halide substrates, and the products are formed with high diastereoselectivity. The products of these alkylation reactions are hydrolyzed efficiently and with little to no racemization simply by heating in water or water-dioxane mixtures. This protocol provides an exceedingly practical method for the preparation of salt-free α-amino acids of high enantiomeric purity. Alternatively, the alkylation products may be hydrolyzed in high yield and with little to no racemization by heating with aqueous sodium hydroxide. The alkaline hydrolyzate can then be treated with an acylating reagent to provide directly highly enantiomerically enriched N-protected derivatives such as N-Boc and N-Fmoc. Key features necessary for the successful execution of these experimental procedures are identified.
