748128-33-8Relevant articles and documents
Iridium-catalysed C-H borylation of β-aryl-aminopropionic acids
MacDonald, Simon J. F.,Nortcliffe, Andrew,Robinson, Henry,Simelis, Klemensas,Stillibrand, Joe
supporting information, p. 6696 - 6701 (2020/09/21)
Iridium-catalysed catalytic, regioselective C-H borylation of β-aryl-aminopropionic acid derivatives gives access to 3,5-functionalised protected β-aryl-aminopropionic acid boronates. The synthetic versatility of these new boronates is demonstrated through sequential one-pot functionalisation reactions to give diverse building blocks for medicinal chemistry. The C-H borylation is also effective for dipeptide substrates. We have exemplified this methodology in the synthesis of a pan αv integrin antagonist.
Kinetic Resolution of Aromatic β-Amino Acids Using a Combination of Phenylalanine Ammonia Lyase and Aminomutase Biocatalysts
Weise, Nicholas J.,Ahmed, Syed T.,Parmeggiani, Fabio,Turner, Nicholas J.
, p. 1570 - 1576 (2017/05/05)
An enzymatic strategy for the preparation of (R)-β-arylalanines employing phenylalanine aminomutase and ammonia lyase (PAM and PAL) enzymes has been demonstrated. Candidate PAMs with the desired (S)-selectivity from Streptomyces maritimus (EncP) and Bacillus sp. (PabH) were identified via sequence analysis using a well-studied template sequence. The newly discovered PabH could be linked to the first ever proposed biosynthesis of pyloricidin-like secondary metabolites and was shown to display better β-lyase activity in many cases. In spite of this, a method combining the higher conversion of EncP with a strict α-lyase from Anabaena variabilis (AvPAL) was found to be more amenable, allowing kinetic resolution of five racemic substrates and a preparative-scale reaction with >98% (R) enantiomeric excess. This work represents an improved and enantiocomplementary method to existing biocatalytic strategies, allowing simple product separation and modular telescopic combination with a preceding chemical step using an achiral aldehyde as starting material. (Figure presented.).
Synthesis and biological evaluation of 3-phenyl-3-aryl carboxamido propanoic acid derivatives as small molecule inhibitors of retinoic acid 4-hydroxylase (CYP26A1)
Zhao, Dongmei,Sun, Bin,Ren, Jinhong,Li, Fengrong,Song, Shuai,Lv, Xuejiao,Hao, Chenzhou,Cheng, Maosheng
, p. 1356 - 1365 (2015/03/04)
All-trans-retinoic acid (ATRA), the biologically active metabolite of vitamin A, is used medicinally for the treatment of hyperproliferative diseases and cancers. However, it is easily metabolized. In this study, the leading compound S8 was found based on virtual screening. To improve the activity of the leading compound S8, a series of novel S8 derivatives were designed, synthesized and evaluated for their in vitro biological activities. All of the prepared compounds showed that substituting the 5-chloro-3-methyl-1-phenyl-1H-pyrazole group for the 2-tertbutyl-5-methylfuran scaffold led to a clear increase in the biological activity. The most promising compound 32, with a CYP26A1 IC50 value of 1.36 μM (compared to liarozole (IC50 = 2.45 μM) and S8 (IC50 = 3.21 μM)) displayed strong inhibitory and differentiation activity against HL60 cells. In addition, the study focused on the effect of β-phenylalanine, which forms the coordination bond with the heme of CYP26A1. These studies suggest that the compound 32 can be used as an appropriate candidate for future development.