4353-32-6Relevant articles and documents
Facile synthesis of α-hydroxy carboxylic acids from the corresponding α-amino acids
Stuhr-Hansen, Nicolai,Padrah, Shahrokh,Str?mgaard, Kristian
supporting information, p. 4149 - 4151 (2015/02/02)
An effective and improved procedure is developed for the synthesis of α-hydroxy carboxylic acids by treatment of the corresponding protonated α-amino acid with tert-butyl nitrite in 1,4-dioxane-water. The amino moiety must be protonated and located α to a carboxylic acid function in order to undergo initial diazotization and successive hydroxylation, since neither β-amino acids nor acid derivatives such as esters and amides undergo hydroxylations. The method is successfully applied for the synthesis of 18 proteinogenic amino acids.
The discovery, characterization and crystallographically determined binding mode of an FMOC-containing inhibitor of HIV-1 protease
Rutenber, Earl E.,De Voss, James J.,Hoffman, Lucas,Stroud, Robert M.,Lee, Kwan H.,Alvarez, Juan,McPhee, Fiona,Craik, Charles,Ortiz De Montellano, Paul R.
, p. 1311 - 1320 (2007/10/03)
A pharmacophore derived from the structure of the dithiolane derivative of haloperidol bound in the active site of the HIV-1 protease (HIV-1 PR) has been used to search a three-dimensional database for new inhibitory frameworks. This search identified an FMOC-protected N-tosyl arginine as a lead candidate. A derivative in which the arginine carboxyl has been converted to an amide has been crystallized with HIV-1 PR and the structure has been determined to a resolution of 2.5 A with a final R-factor of 18.5%. The inhibitor binds in an extended conformation that results in occupancy of the S2, S1', and S3' subsites of the active site. Initial structure-activity studies indicate that: (1) the FMOC fluorenyl moiety interacts closely with active site residues and is important for binding; (2) the N(G)-tosyl group is necessary to suppress protonation of the arginine guanidinyl terminus; and (3) the arginine carboxamide function is involved in interactions with the water coordinated to the catalytic aspartyl groups. FMOC-protected arginine derivatives, which appear to be relatively specific and nontoxic, offer promise for the development of useful HIV-1 protease inhibitors.
