159380-98-0

Upstream product

• 92278-77-8 (2R,2'R)-dibenzyl 3,3'-disulfanediylbis(2-((tert-butoxycarbonyl)amino)propanoate) 
• 10389-65-8 di-t-butoxycarbonyl-L-cystine 
• 24424-99-5 di-tert-butyl dicarbonate 
• 159380-94-6 (2R)-(-)-benzyl 2-(tert-butoxycarbonylamino)-3-(2-hydroxyethylsulfanyl)propanoate 
• 245759-81-3 (R)-2-tert-Butoxycarbonylamino-3-(2-hydroxy-ethylsulfanyl)-propionic acid 
• 6367-98-2 (-)-(2R)-2-amino-3-(2-hydroxyethylsulfanyl)propanoic acid 

Downstream Products

• 159380-99-1 (2R)-(+)-benzyl 3-(2-azidoethylsulfonyl)-2-(tert-butoxycarbonylamino)propanoate 

Relevant academic research and scientific papers

Identification and immunological evaluation of novel TLR2 agonists through structure optimization of Pam3CSK4

Toll-like receptor 2 (TLR2) is a bridge between innate immunity and adaptive immunity. TLR2 agonists have been exploited as potential vaccine adjuvants and antitumor agents. However, no TLR2 agonists have been approved by FDA up to now. To discover drug-like TLR2 selective agonists, a novel series of Pam3CSK4 derivatives were designed based on the crystal structure of hTLR2-hTLR1-Pam3CSK4 complex, synthesized and evaluated for their immune-stimulatory activities. Among them, 35c was identified as a murine-specific TLR2 agonist, while 35f was a human-specific TLR2 agonist. Besides, 35d (human and murine TLR2 agonist) showed TLR2 agonistic activity comparable to Pam3CSK4, which included: elevated IL-6 expression level (EC50 = 83.08 ± 5.94 nM), up-regulated TNF-α and IL-6 mRNA expression and promoted maturation of DCs through activating the NF-κB signaling pathway. TLRs antibodies test showed that 35a and 35d were TLR2/1 agonists, while 35f was a TLR2/6 agonist.

Synthesis of Amino Acids with Modified Principal Properties 3: Sulfur-Containing Amino Acids

The synthesis and characterization of seven medium-sized, medium-polar, sulfur-containing amino acids are presented.The compounds were prepared with the objective of finding amino acids which possess physical and chemical properties such that their principal properties would be clearly different from those of previously known amino acids.The principal properties are determined as latent variables in principal component analysis of molecular property descriptors.The following amino acids were prepared in homochiral form from L-cysteine: (2R)-2-amino-3-(2-hydroxyethylsulfanyl)propanoic acid, (2R)-2-amino-3-(2-hydroxyethylsulfonyl)propanoic acid, (3R)-perhydro-1,4-thiazine-3-carboxylic acid and (3R)-1,1-dioxoperhydro-1,4-thiazine-3-carboxylic acid. (3R)-1-Oxoperhydro-1,4-thiazine-3-carboxylic acid was prepared in N,C protected form, but all attempts to obtain the free amino acid failed.The principal properties of this amino acid were determined on the racemic diastereomers obtained by oxidation of the racemic perhydro-1,4-thiazine-3-carboxylic acid prepared from 2-aminoethanethiol and ethyl 3-bromo-2-oxopropanoate.With the exception of (3R)-perhydro-1,4-thiazine-3-carboxylic acid for which the synthesis has been previously described, the amino acids described are new compounds.An improved synthesis of (3R)-perhydro-1,4-thiazine-3-carboxylic acid via the cyclization of (2R)-benzyl-2-amino-3-(2-hydroxyethylsulfanyl)propanoate under Mitsunobu conditions is presented.Full experimental details for the syntheses are given.The principal property scores of the synthesized sulfur-containing amino acids and of the structurally related 3-(2-aminoethyl)cysteine which was commercially available are given.