197727-97-2

Upstream product

• 2393-23-9 4-methoxy-benzylamine 
• 63-91-2 L-phenylalanine 
• 17462-25-8 C₂₅H₂₆N₂O₄ 
• 13734-34-4 N-tert-butoxycarbonyl-L-phenylalanine 
• 186581-53-3 diazomethane 
• 51537-64-5 (S)-tert-butyl (1-((4-methoxybenzyl)amino)-1-oxo-3-phenylpropan-2-yl)carbamate 

Downstream Products

• 808149-73-7 (S)-4-Benzyl-3-[(2S,4R)-4-benzyl-5-((3aS,8aR)-2,2-dimethyl-8,8a-dihydro-3aH-indeno[1,2-d]oxazol-3-yl)-2-hydroxy-5-oxo-pentyl]-1-(4-methoxy-benzyl)-imidazolidin-2-one 
• 194599-55-8 (2R,4S)-2-Benzyl-5-((S)-5-benzyl-2-oxo-imidazolidin-1-yl)-4-hydroxy-pentanoic acid ((1S,2R)-2-hydroxy-indan-1-yl)-amide 
• 808149-71-5 (S)-4-Benzyl-1-pyridin-4-ylmethyl-imidazolidin-2-one 
• 808149-70-4 (S)-4-Benzyl-1-pyridin-2-ylmethyl-imidazolidin-2-one 
• 808149-69-1 (S)-4-Benzyl-1-pyridin-3-ylmethyl-imidazolidin-2-one 
• 380649-10-5 (S)-4-Benzyl-imidazolidin-2-one 
• 808149-68-0 (S)-4-Benzyl-1-(4-methoxy-benzyl)-imidazolidin-2-one 

Relevant academic research and scientific papers

Protecting-Group-Free Amidation of Amino Acids using Lewis Acid Catalysts

Amidation of unprotected amino acids has been investigated using a variety of ‘classical“ coupling reagents, stoichiometric or catalytic group(IV) metal salts, and boron Lewis acids. The scope of the reaction was explored through the attempted synthesis of amides derived from twenty natural, and several unnatural, amino acids, as well as a wide selection of primary and secondary amines. The study also examines the synthesis of medicinally relevant compounds, and the scalability of this direct amidation approach. Finally, we provide insight into the chemoselectivity observed in these reactions.

1,4-Cyclohexadiene with Pd/C as a rapid, safe transfer hydrogenation system with microwave heating

A method for the rapid, safe hydrogenation of alkenes and deprotection of benzyl ethers and carboxybenzyl amides is described using catalytic transfer hydrogenation under microwave heating conditions. Commonly available Pd/C catalyst is extremely effective with 1,4-cyclohexadiene as the hydrogen transfer source. In general, the reactions are complete within five minutes at 100 °C.

Enantioselective nickel-catalyzed conjugate addition of dialkylzinc to chalcones using chiral α-amino amides

A series of α-amino amides derived from natural amino acids (alanine, valine, phenylalanine, isoleucine, and phenylglycine) have been synthesized and fully characterized. Their Ni(II) complexes prepared from Ni(acac)2 catalyze the enantioselective conjugate addition of diethylzinc to chalcones in high yields and in good enantioselectivities (up to 84%). The side chain of the amino acid and the substituents in the amide nitrogen govern the enantioselectivity of the catalytic process.

Potent inhibitors of the HIV-1 protease incorporating cyclic urea P1-P2 scaffold

We have developed an efficient synthetic approach to analogues of potent HIV-protease inhibitor (PI) 4. Key chemistry includes TFA-mediated deprotection of MOB-protected 16 to precursor 17. Alkylation of 17 enabled the synthesis of many PIs, as exemplified here by 13, 19-21, in excellent yields and purity, and thus overcoming bottlenecks of our prior synthetic approach to these PIs. These results allowed to rapidly evaluate the SAR in P1-P2 cyclic urea-based HIV-1 PIs as well as provided a strong rationale towards P1-P2 pyrrolidone scaffold-based PIs, ultimately leading to subnanomolar PIs (follow-up communication). We have developed synthetic approaches to novel analogues of 2-imidazolidinone scaffold 2, which was found to be an effective P1-P2 mimetic in HIV-1 protease inhibitor 4. This enabled a rapid synthesis of analogues of 4 and subsequently allowed us to evaluate and rationalize the SAR. Accordingly, trans relationship of P1 and P2 substituents in the P1-P2 mimetic, as found in a related 2-pyrrolidone-based scaffold 1, was found necessary for high potency against HIV-1 protease. Results of this study provided further rationale towards subsequent optimization of 2-pyrrolidone-based lead 3, which led us to potent and drug-like HIV-1 protease inhibitors described in a follow-on report (Bioorg. Med. Chem. Lett. 2004, 14, in press. doi:10.1016/j.bmcl.2004.08.039).

Synthesis of chiral α-amino-diazoketones on solid support: An access to β-homologated amino acid derivatives

Diazoketone derivatives were obtained on solid support from their corresponding α-amino acids anchored by their N-terminus to the resin. A complete study was performed to optimize the two steps process of this synthesis on solid support: activation of the carboxylic acid function followed by reaction with diazomethane. The obtained diazoketones were then submitted to Wolff rearrangement in the presence of an amine to yield the corresponding homologated amides or in the presence of water to yield the corresponding β-homologated amino acids.