165683-89-6Relevant academic research and scientific papers
Novel peptidyl aryl vinyl sulfones as highly potent and selective inhibitors of cathepsins L and B
Mendieta, Laura,Pico, Anna,Tarrago, Teresa,Teixido, Meritxell,Castillo, Marcos,Rafecas, Llorenc,Moyano, Albert,Giralt, Ernest
, p. 1556 - 1567 (2011/11/29)
Herein we present the design, synthesis, and evaluation of a structurally novel library of 20 peptidyl 3-aryl vinyl sulfones as inhibitors of cathepsins L and B. The building blocks, described here for the first time, were synthesized in a highly efficient and enantioselective manner, starting from 3-aryl-substituted allyl alcohols. The corresponding vinyl sulfones were prepared by a new approach, based on a combination of solid-phase peptide synthesis using the Fmoc/tBu strategy, followed by solution-phase coupling to the corresponding (R)-3-amino-3-aryl vinyl sulfones as trifluoroacetate salts. The inhibitory activity of the resulting compounds against cathepsins L and B was evaluated, and the compound exhibiting the best activity was selected for enzymatic characterization. Finally, docking studies were performed in order to identify key structural features of the aryl substituent.
Stereoselective synthesis of anti-N-protected 3-amino-1,2-epoxides by nucleophilic addition to N-tert-butanesulfinyl imine of a glyceraldehyde synthon
Harried, Scott S.,Croghan, Michael D.,Kaller, Matthew R.,Lopez, Patricia,Zhong, Wenge,Hungate, Randall,Reider, Paul J.
experimental part, p. 5975 - 5982 (2009/12/24)
(Chemical Equation Presented) A di-O-TBS protected glyceraldehyde synthon was condensed with Ellman's reagent to form a bench-stable N-tert-butanesulfinyl imine 6, which served as a common intermediate for the stereoselective introduction of various R groups. The Ellman adducts were converted to useful multifunctional intermediates 18a-i in one pot. The alcohols 18a-i were efficiently elaborated to both known and novel anti-N-protected-3-amino-1,2- epoxides in two steps. Compound 2a is a key intermediate toward HIV protease inhibitors.
Enantiodivergent, catalytic asymmetric synthesis of γ-amino vinyl sulfones
Pico, Anna,Moyano, Albert,Pericas, Miquel A.
, p. 5075 - 5083 (2007/10/03)
A set of diversely substituted N-Boc-γ-amino vinyl sulfones has been prepared by a four-step procedure from readily available, highly enantiopure anti-N-Boc-3-amino-1,2-alkanediols. This new route, which does not depend on the accessibility of α-amino acids as starting materials, is noteworthy for its efficiency, for its generality, and for the fact that both enantiomers of a given γ-amino vinyl sulfone can be obtained with equal ease.
Stereocontrolled synthesis of all four stereoisomers of fully protected 2-amino-3-hydroxypentanoic acid from imines derived from D-glyceraldehyde
Badorrey, Ramon,Cativiela, Carlos,Diaz-de-Villegas, Maria D.,Galvez, Jose A.
, p. 14145 - 14160 (2007/10/03)
N-Benzylimines derived from conveniently protected (R)-glyceraldehyde underwent diastereoselective phenylmagnesium bromide addition to afford the corresponding aminodiols, whose absolute configuration at the newly formed stereogenic carbon depends on the
Ready access to stereodefined β-hydroxy-γ-amino acids. Enantioselective synthesis of fully protected cyclohexylstatine
Castejon, Patricia,Moyano, Albert,Pericas, Miquel A.,Riera, Antoni
, p. 7063 - 7086 (2007/10/03)
A convenient entry to enantiopure syn or anti β-hydroxy-γ-amino acids is described. The starting compounds for the synthesis, anti 3-amino-1,2-diols, are readily available in high enantiomeric purity through catalytic asymmetric epoxidation of an allylic alcohol and titanium-promoted oxirane opening. After adequate protection of the nitrogen, a stereodivergent sequence leads to both anti and syn N-Boc aminoalkyl epoxides. Subsequent regioselective ring-opening with cyanide, protection of the resulting secondary alcohol and nitrile to carboxyl conversion afford, in good yields, protected β-hydroxy-γ-amino acid belonging to either the anti (erythro) or syn (threo) series. This methodology has been applied to the enantioselective preparation of cyclohexylstatine, a key component of several aspartyl protease inhibitors, in fully protected form.
A convenient, stereodivergent approach to the enantioselective synthesis of N-Boc-aminoalkyl epoxides
Castejon, Patricia
, p. 3019 - 3022 (2007/10/02)
An efficient, stereodivergent and enantioselective synthesis of N-Boc-aminoalkyl epoxides has been developed. Starting from enantiomerically enriched anti N-diphenylmethyl-3-amino-1,2-diols, and after a change in the nitrogen protecting group, an intramol
