40847-09-4Relevant academic research and scientific papers
Novel poly(2-oxazoline)s with pendant l-prolinamide moieties as efficient organocatalysts for direct asymmetric aldol reaction
Wang, Yao,Shen, Huifang,Zhou, Le,Hu, Fangyu,Xie, Shoulei,Jiang, Liming
, p. 6739 - 6749 (2016/09/03)
Poly(2-oxazoline)-supported bifunctional organocatalysts have been prepared through a bottom-up protocol, which involves synthesis of well-defined poly(2-oxazoline) precursors bearing amino groups in the side-chains followed by amide coupling with N-Boc-l-proline then deprotection. The resultant l-prolinamido-functionalized polymers have proven to be significantly more active than their monomeric counterparts for the aldolisation of cyclic ketones with several substituted benzaldehydes under neat conditions. By using 15 mol% of the polymer as a catalyst, the direct aldol reaction products were isolated in high yields and with good diastereo- and enantioselectivity. Based on circular dichroism spectrum analysis, the enhancement in catalytic activity is probably related to the conformational changes of the pseudo-peptide scaffold of poly(2-oxazoline)s. In addition, these soluble polymeric catalysts can be recovered and reused by precipitation in ether for five catalytic cycles without significantly diminishing their efficiency.
Chiral primary amine catalyzed asymmetric direct cross-aldol reaction of acetaldehyde
Hu, Shenshen,Zhang, Long,Li, Jiuyuan,Luo, Sanzhong,Cheng, Jin-Pei
, p. 3347 - 3352 (2011/08/03)
The first primary aminocatalytic direct cross-aldol reaction of acetaldehyde is presented. Among the various vicinal diamines screened, the L-tert-leucine derivative 1c in conjunction with (H4SiW 12O40)0.25 was identified as the optimal catalyst; good catalytic activity (up to 99% yield in 4 h), and high enantioselectivities (up to 92% ee) were achieved for a range of donors, including aromatic aldehydes and isatin derivatives. Aqueous acetaldehyde solution and paraldehyde can be conveniently applied in this system.
Aminocarbonyloxymethyl ester prodrugs of flufenamic acid and diclofenac: Suppressing the rearrangement pathway in aqueous media
Ribeiro, Lina,Silva, Nuno,Iley, Jim,Rautio, Jarkko,Jaervinen, Tomi,Mota-Filipe, Helder,Moreira, Rui,Mendes, Eduarda
, p. 32 - 40 (2007/10/03)
Aminocarbonyloxymethyl ester prodrugs are known to undergo rearrangement in aqueous solutions to form the corresponding N-acylamine side product via an O → N intramolecular acyl transfer from the carbamate conjugate base. Novel aminocarbonyloxymethyl esters of diclofenac and flufenamic acid containing amino acid amide carriers were synthesized and evaluated as potential prodrugs displaying less ability to undergo rearrangement. These compounds were prepared in reasonable yield by a four-step synthetic method that uses the appropriate N-Boc-protected amino acid N-hydroxysuccinimide ester and secondary amine and chloromethyl chloroformate as key reactants. Their reactivity in pH 7.4 buffer and 80% human plasma at 37°C was assessed by RP-HPLC. The aminocarbonyloxymethyl esters containing a secondary carbamate group derived from amino acids such as glycine or phenylalanine were hydrolyzed quantitatively to the parent drug both in non-enzymatic and enzymatic conditions, with no rearrangement product being detected. The oral bioavailability in rats was determined for selected diclofenac derivatives. These derivatives displayed a bioavailability of 25 to 68% relative to that of diclofenac, probably due to their poor aqueous solubility and lipophilicity. These results suggest that further optimization of aminocarbonyloxymethyl esters as potential prodrugs for non-steroidal anti-inflammatory drugs require the use of amino acid carriers with ionizable groups to improve aqueous solubility.
