144284-25-3Relevant articles and documents
Biocatalytic retrosynthesis approaches to d-(2,4,5-trifluorophenyl)alanine, key precursor of the antidiabetic sitagliptin
Parmeggiani, Fabio,Rué Casamajo, Arnau,Colombo, Danilo,Ghezzi, Maria Chiara,Galman, James L.,Chica, Roberto A.,Brenna, Elisabetta,Turner, Nicholas J.
, p. 4368 - 4379 (2019)
The integration of biocatalytic steps in retrosynthetic analysis of a target molecule offers multiple advantages, such as reduction of the environmental footprint of the process, viability of milder and safer reaction conditions, and accessibility of transformations that are challenging with traditional chemical synthesis. Herein, six chemo-enzymatic routes are described for the synthesis of a fluorinated d-phenylalanine derivative, precursor of the blockbuster antidiabetic drug sitagliptin. All routes start from the same aldehyde precursor and involve at least one biocatalytic step, including reductive amination, transamination, deracemisation, hydroamination, and alkene reduction. The target molecule was obtained in 2-5 steps from the aldehyde, with ee up to >99% and in 36-62% isolated yield. Furthermore, as part of one of the routes, the first example of a fully biocatalytic conversion of a cinnamic acid derivative to the corresponding d-phenylalanine (formal d-selective hydroamination) is reported.
Syntheses, antiproliferative activity and theoretical characterization of acitretin-type retinoids with changes in the lipophilic part
Magoulas, George E.,Bariamis, Stavros E.,Athanassopoulos, Constantinos M.,Haskopoulos, Anastasios,Dedes, Petros G.,Krokidis, Marios G.,Karamanos, Nikos K.,Kletsas, Dimitris,Papaioannou, Dionissios,Maroulis, George
experimental part, p. 721 - 737 (2011/03/20)
Acitretin analogs, incorporating changes in the lipophilic part, were efficiently synthesized from commercially available aromatic aldehydes or methyl ketones using the Wittig or Horner-Wadsworth-Emmons reaction. Their antiproliferative activity was evaluated against human breast MCF-7 epithelial cells. Analogs 3, 4, 8 and 11 exhibited strong, dose-dependent, antiproliferative activity on the tested cell line. Analog 3, incorporating three methoxy groups in the aromatic ring, exhibited the strongest inhibitory effect at 10 μM. High-level all electron conventional ab initio and density functional theory quantum chemical calculations were performed to obtain the molecular structure, electron charge distribution and polarization properties of all compounds of interest in this work. The most active analogs were planar and were characterized by larger dipole moments than the other synthesized molecules. Another factor of importance to the analysis of the activity of these molecules is the dipole polarizability.
