Xuejun Tang

Convenient, large-scale asymmetric synthesis of enantiomerically pure trans-cinnamylglycine and -α-alanine

Asymmetric syntheses of (S)-trans-cinnamylglycine and (S)-α-trans-cinnamyl-α-alanine via reactions of cinnamyl halides (Cl, Br) with Ni(II)-complexes of the chiral Schiff base of glycine or alanine with (S)-o-[N-(N-benzylprolyl)amino]benzophenone were developed. Inexpensive and readily available reagents and solvents were used, including an easily recyclable chiral auxiliary. The simplicity of the experimental procedures and the high stereochemical outcome make this method synthetically attractive for preparing the target amino acids on multi-gram scales.

Large-scale asymmetric synthesis of novel sterically constrained 2′,6′-dimethyl- and α,2′,6′-trimethyltyrosine and -phenylalanine derivatives via alkylation of chiral equivalents of nucleophilic glycine and alanine

Abstract Asymmetric synthesis of (S)-2′,6′-dimethyltyrosine (DMT), (S)-2′,6′-dimethylphenylalanine (DMP), (S)-α,2′,6′-trimethyltyrosine (α-TMT) and (S)-α,2′,6′-trimethylphenylalanine (α-TMP) via reactions of 4′-benzyloxy-2′,6′-dimethylbenzyl bromide or 2′,6′-dimethylbenzylbromide with Ni(II)-complexes of the chiral Schiff base of glycine or alanine with (S)-o-[N-(N-benzylprolyl)amino]benzophenone were developed. Inexpensive and readily available reagents and solvents, a recyclable chiral auxiliary, simplicity of the experimental procedures and high chemical yields make this method synthetically attractive for preparing the target amino acids on a multi-gram scale.

Convenient, asymmetric synthesis of enantiomerically pure 2′,6′-dimethyltyrosine (DMT) via alkylation of chiral equivalent of nucleophilic glycine

Abstract Asymmetric synthesis of ( S )-2′,6′-dimethyltyrosine (DMT) via reactions of 4′-benzyloxy-2′,6′-dimethylbenzyl bromide with Ni(II)-complexes of the chiral Schiff base of glycine with ( S )- o -[ N -( N -benzylprolyl)amino]benzophenone was developed. Inexpensive and readily available reagents and solvents involved, including recyclable chiral auxiliary, simplicity of the experimental procedures and high chemical yields, make this method synthetically attractive for preparing the target amino acids on a multi-gram scale.

A novel strategy toward [6,5]-bicyclic β-turn dipeptide

Abstract A novel strategy toward the syntheses of [6,5]-bicyclic β-turn dipeptides has been developed starting from δ,e-unsaturated amino acids. This is the first example showing that this scaffold can be synthesized from a terminal alkene using a trifluoroacetyl protected amino acid. Both enantiomers of the δ,e-unsaturated amino acid were synthesized by a modified method using Ni(II)-complexes.

First stereoselective synthesis of an optically pure β-substituted histidine: (2S,3S)-β-methylhistidine

We report the first example of the asymmetric synthesis of the β-substituted histidine, (2S,3S)-β-methylhistidine. A key in the synthesis is the use of the protecting group, 2-mesitylenesulfonyl (Mts-), for the imidazole ring to minimize epimerization during synthesis.

Synthesis of β-phenyl-δ,ε-unsaturated amino acids and stereoselective introduction of side chain groups into [4,3,0]-bicyclic β-turn dipeptides ☆

(2S,3S)- and (2R,3R)-2-amino-3-phenyl-5-hexenoic acids have been synthesized in large scale by using Ni(II)-complexes as a template. The amino acids were used in the synthesis of [4,3,0]-bicyclic β-turn mimetics by a convergent methodology. The unique advantage of this strategy is the convenience of introducing side chain groups with predetermined chiralities on both the five- and six-membered heterocyclic rings.

Design, Synthesis and Biological Evaluation of Novel Non-Peptide Opioid Ligands for Human Pain

To find therapeutics for human pain with efficacy but without the side effects which accompany morphine-related drugs is a critical need. Based on extensive structure-activity studies of cyclic enkaphalins, we have designed and synthesized a series of conformationally constrained peptide analogues such as [(2S,3R)-TMT1]-DPDPE, which are essentially specific for the δ-opioid receptor [1]. Aiming to transfer the pharmacophores in these peptide ligands to a non-peptide scaffold and to maintain the high binding affinity and biological activities at the δ-receptor, first and second generation non-peptide ligands were successfully designed with the aid of computer modeling [2,3]. In an effort to optimize these ligands, we present some newly designed ligands such as 6–11 that are based on computer modeling and our understanding of current successful examples like SL-3111.

Synthesis of Amino Acids with Novel Biophysical Properties

Amino acids with unique physical properties have been used to study the conformational interactions of peptides and proteins. Two such molecules are pyrenylalanine and ferro-cenylalkyl derivatives of amino acids. Pyrenylalanine has unique spectroscopic properties that can be exploited to understand conformations of peptides [1], Ferrocenylalkyl derivatives of amino acids combine the properties of ferrocene and amino acids to offer compounds that will intercalate with DNA and can be targeted towards cancerous cells [2]. This paper describes the synthesis of these compounds and presents preliminary data concerning the intercalation of the ferrocenylalkyl amino acids towards DNA.

An Efficient Method for Large-Scale Synthesis of Stereochemically Defined and Conformationally Constrained β-Substituted or α,β-Disubstituted Amino Acids

In our continuing efforts to design and synthesize conformationally constrained peptides to understand the interactions between receptors and ligands, a wide range of sterically constrained amino acids are needed [1]. As a part of our efforts in this area, we have developed a systematic practical method for preparation of conformationally constrained novel amino acids in gram quantities. Starting from chiral nickel (II) complexes containing a glycine or alanine moiety, which were prepared from commercially available materials, alkylations with the corresponding alkyl halides followed by routine work-up, provide the target amino acids in good overall yields and excellent optical purity [2–7].