131180-45-5Relevant academic research and scientific papers
Organocatalytic enantioselective α-hydroxymethylation of aldehydes: Mechanistic aspects and optimization
Boeckman, Robert K.,Biegasiewicz, Kyle F.,Tusch, Douglas J.,Miller, John R.
, p. 4030 - 4045 (2015/05/05)
Further studies of the direct enantioselective α-hydroxymethylation of aldehydes employing the α,α-diarylprolinol trimethylsilyl ether class of organocatalysts are described. This process has proven efficient for access to β-hydroxycarboxylic acids and δ-hydroxy-α,β-unsaturated esters from aldehydes in generally good yields, excellent enantioselectivity, and compatibility with a broad range of functional groups in the aldehyde. The goal of these studies was to identify the critical reaction variables that influence the yield and enantioselectivity of the α-hydroxymethylation process such as catalyst structure, pH of the medium, purity of the reactants and reagents particularly with respect to the presence of acidic impurities, and the nature of the buffer, along with the standard variables including solvent, time, temperature and mixing efficiency. The previously identified intermediate lactol has been further characterized and its reactivity examined. These studies have led to identification of the most critical variables translating directly into improved substrate scope, reproducibility, enantioselectivity, and yields.
Synthesis and discovery of N -carbonylpyrrolidine- or N -sulfonylpyrrolidine-containing uracil derivatives as potent human deoxyuridine triphosphatase inhibitors
Miyakoshi, Hitoshi,Miyahara, Seiji,Yokogawa, Tatsushi,Chong, Khoon Tee,Taguchi, Junko,Endoh, Kanji,Yano, Wakako,Wakasa, Takeshi,Ueno, Hiroyuki,Takao, Yayoi,Nomura, Makoto,Shuto, Satoshi,Nagasawa, Hideko,Fukuoka, Masayoshi
, p. 2960 - 2969 (2012/06/01)
Recently, deoxyuridine triphosphatase (dUTPase) has emerged as a potential target for drug development as part of a new strategy of 5-fluorouracil-based combination chemotherapy. We have initiated a program to develop potent drug-like dUTPase inhibitors based on structure-activity relationship (SAR) studies of uracil derivatives. N-Carbonylpyrrolidine- and N-sulfonylpyrrolidine- containing uracils were found to be promising scaffolds that led us to human dUTPase inhibitors (12k) having excellent potencies (IC50 = 0.15 μM). The X-ray structure of a complex of 16a and human dUTPase revealed a unique binding mode wherein its uracil ring and phenyl ring occupy a uracil recognition region and a hydrophobic region, respectively, and are stacked on each other. Compounds 12a and 16a markedly enhanced the growth inhibition activity of 5-fluoro-2′-deoxyuridine against HeLa S3 cells in vitro (EC50 = 0.27-0.30 μM), suggesting that our novel dUTPase inhibitors could contribute to the development of chemotherapeutic strategies when used in combination with TS inhibitors.
Asymmetric carbonyl reduction with borane catalyzed by chiral phosphinamides derived from L-amino acid
Li, Kangying,Zhou, Zhenghong,Wang, Lixin,Chen, Qifa,Zhao, Guofeng,Zhou, Qilin,Tang, Chuchi
, p. 95 - 100 (2007/10/03)
Two types of chiral phosphinamide catalysts 3a-d and 4a-c were prepared from L-phenylalanine and L-proline, respectively. Their applications in the asymmetric borane reduction of prochiral ketones were investigated. The chiral secondary alcohols were obtained with excellent chemical yields and moderate to high enantiomeric excesses.
A Practical Enantioselective Synthesis of α,α-Diaryl-2-pyrrolidinemethanol. Preparation and Chemistry of the Corresponding Oxazaborolidines
Mathre, David J.,Jones, Todd K.,Xavier, Lyndon C.,Blacklock, Thomas J.,Reamer, Robert A.,et al.
, p. 751 - 762 (2007/10/02)
A practical two-step enantioselective synthesis of α,α-diaryl-2-pyrrolidinemethanols (1) from proline, based on the addition of aryl Grignard reagents to proline-N-carboxanhydride (3), is reported.An investigation into the chemistry of the corresponding B-alkyl- and B-aryloxazaborolidines (2) led to the development of a reliable procedure for their preparation.
