192655-69-9

Upstream product

• 6525-53-7 L-glutamic acid dimethyl ester 
• 100-52-7 benzaldehyde 
• 23150-65-4 L-glutamic dimethyl ester hydrochloride 
• 56-86-0 L-glutamic acid 

Downstream Products

• 433285-17-7 dimethyl (S)-2-{N-benzyl-N-[2-(benzyloxycarbonylamino)acetyl]amino}pentanedioate 
• 269717-62-6 dimethyl (-)-(S)-2-[N-benzyl-N-(2-chloroacetyl)amino]pentanedioate 
• 1083424-92-3 C₁₇H₂₃NO₄ 
• 433285-21-3 methyl (-)-(S)-3-[1-benzyl-4-(4-methoxybenzyl)-3,6-dioxopiperazin-2-yl]propanoate 
• 433285-20-2 methyl (S)-3-(1-benzyl-4-butyl-3,6-dioxopiperazin-2-yl)propionate 
• 433285-19-9 dimethyl (S)-2-[N-(2-azidoacetyl)-N-benzylamino]pentanedioate 
• 433285-18-8 methyl (S)-3-(1-benzyl-3,6-dioxopiperazin-2-yl)propionate 

Relevant academic research and scientific papers

Rigidity versus Flexibility: Is This an Issue in σ1 Receptor Ligand Affinity and Activity?

Stereoisomeric 2,5-diazabicyclo[2.2.2]octanes 14 and 15 were prepared in a chiral-pool synthesis starting from (S)- or (R)-aspartate. The key step in the synthesis was a Dieckmann-analogous cyclization of (dioxopiperazinyl)acetates 8, which involved trapping of the intermediate hemiketal anion with Me3SiCl. The σ1 affinity was tested using membrane preparations from animal (Guinea pig) and human origin. The binding of bicyclic compounds was analyzed by molecular dynamics simulations based on a 3D homology model of the σ1 receptor. The good correlation between Ki values observed in the σ1 assays and calculated free binding energy, coupled with the identification of four crucial ligand/receptor interactions, allowed the formulation of structure-affinity relationships. In an in vitro antitumor assay with seven human tumor cell lines, the bicyclic compounds inhibited selectively the growth of the cell line A427, which is due to induction of apoptosis. In this assay, the compounds behave like the known σ1 receptor antagonist haloperidol.

Substituted azabicyclo[3.1.0]hexan-1-ols from aspartic and glutamic acid derivatives via titanium-mediated cyclopropanation

The Kulinkovich cyclopropanation reaction has been used to synthesize azabicyclo[3.1.0]hexanols from amino acid derivatives containing two ester moieties.

Synthesis of bicyclic σ receptor ligands with cytotoxic activity

All possible stereoisomeric alcohols (6-benzyl-8-(4-methoxybenzyl)-6,8- diazabicyclo[3.2.2]nonan-2-ol) and methyl ethers (6-benzyl-2-methoxy-8-(4- methoxybenzyl)-6,8-diazabicyclo[3.2.2]nonane) are prepared from (R)- and (S)-glutamate. A Dieckmann analogous cyclization, which makes use of trapping the primary cyclization product with Me3SiCl, generates the bicyclic framework. Stereoselective LiBH4 reduction and Mitsunobu inversion establish the configuration in position 2. Enantiomeric alcohols 15 (1S,2S,5R) and ent-15 (1R,2R,5S) as well as diastereomeric methyl ethers ent-17 (1R,2R,5S) and ent-22 (1R,2S,5S) display high σ1 receptor affinity. Cell growth inhibition of the stereoisomeric alcohols and methyl ethers against five human tumor cell lines is investigated. In particular, at a concentration of 20 μthe four methyl ethers stop completely the cell growth of the small cell lung cancer cell line A-427, indicating a specific target in this cell line. The IC50-values of methyl ethers ent-17 and ent-22 are in the range of the antitumor drugs cisplatin and oxaliplatin. Binding assays show that the investigated tumor cell lines express considerable amounts of σ1 and σ2 receptors.

Sodium borohydride: A versatile reagent in the reductive N-monoalkylation of α-amino acids and α-amino methyl esters

α-Amino acids and α-amino methyl esters are easily converted to their N-monoalkyl derivatives by a reductive condensation reaction using several carbonyl compounds in the presence of sodium borohydride. This reducing agent has shown a wide versatility with minor but essential procedural variations. The reaction allows the α-monodeuterium labeling of the new N-substituent by use of sodium borodeuteride.

Synthesis of chiral non-racemic 3-(dioxopiperazin-2-yl)propionic acid derivatives

Starting with the proteinogenic amino acid (S)-glutamate (3) a facile, high yielding synthesis of the chiral non-racemic 3-(dioxopiperazin-2-yl)propionates 6, 11, and 14 is presented. Key intermediates in the synthesis of N1-benzyl substituted (dioxopiperazin-2yl)propionates 11 and 14 are the N-monobenzylglutamate 8 and the chloroacetamide 12, which allow introduction of various substituents in position 4 of the piperazine ting. In receptor binding studies with radioligands the 3-(piperazin-2-yl)propanol 15 was found to have promising affinity for σ1-receptors (Ki=66.1 nM).