1.Synthesis of (+)-Ipalbidine Based on 6-exo-trig Radical Cyclization of a β-Amino Radical.
Chea J1, Clive DL1. J Org Chem. 2015 Oct 16;80(20):10294-8. doi: 10.1021/acs.joc.5b01890. Epub 2015 Oct 7.
N-Boc (S)-proline was converted into (2S)-2-[(phenylselanyl)methyl]pyrrolidine, which was alkylated on nitrogen with 2-bromo-1-(4-methoxyphenyl)ethan-1-one. Reaction with vinyllithium, 6-exo-trig radical cyclization (Bu3SnH, AIBN, PhMe, 110 °C), dehydration (P2O5, H3PO4), and demethylation (BBr3) gave (+)-ipalbidine with ee >99%.
2.Intracellular accumulation of boceprevir according to plasma concentrations and pharmacogenetics.
Cusato J1, Allegra S2, De Nicolò A2, Boglione L2, Fatiguso G2, Abdi AM2, Cariti G2, Di Perri G2, D'Avolio A2. Int J Antimicrob Agents. 2015 Jun;45(6):657-61. doi: 10.1016/j.ijantimicag.2015.01.019. Epub 2015 Mar 14.
Boceprevir (BOC) is a directly-acting antiviral agent for the treatment of hepatitis C virus genotype 1 (HCV-1) infection. It is a mixture of two stereoisomers, the inactive R and the active S isomers. No data have previously been published on BOC intracellular accumulation. In this study, BOC isomer concentrations in peripheral blood mononuclear cells (PBMCs) and plasma were determined. The influence of various single nucleotide polymorphisms (SNPs) on plasma and intracellular drug exposure at Week 4 of triple therapy were also evaluated. Plasma and intracellular BOC concentrations were determined at the end of the dosing interval (C(trough)) using a UPLC-MS/MS validated method. Allelic discrimination was performed through real-time PCR. Median plasma concentrations were 65.97 ng/mL for the S isomer and 36.31 ng/mL for the R isomer; the median S/R plasma concentration ratio was 1.66. The median PBMC concentration was 2285.88 ng/mL for the S isomer; the R isomer was undetectable within PBMCs.
3.Diastereoselective Synthesis of 1-Deoxygalactonojirimycin, 1-Deoxyaltronojirimycin, and N-Boc-(2S,3S)-3-Hydroxypipecolic Acid via Proline Catalyzed α-Aminoxylation of Aldehydes.
Chacko S1, Ramapanicker R1. J Org Chem. 2015 May 1;80(9):4776-82. doi: 10.1021/acs.joc.5b00424. Epub 2015 Apr 17.
An efficient synthesis of deoxygalactonojirimycin and deoxyaltronojirimycin through the use of proline catalyzed asymmetric α-aminoxylation of a higher homologue of Garner's aldehyde, derived from l-aspartic acid, is reported. The method is also used for a highly diastereoselective synthesis of the N-Boc derivative of (2S,3S)-3-hydroxypipecolic acid. The configuration of the proline catalyst used for the asymmetric aminoxylation step ultimately controls the absolute configuration of three adjacent stereogenic centers in the final products.
4.Synergetic catalysis based on the proline tailed metalloporphyrin with graphene sheet as efficient mimetic enzyme for ultrasensitive electrochemical detection of dopamine.
Yan X1, Gu Y1, Li C1, Tang L1, Zheng B1, Li Y1, Zhang Z2, Yang M3. Biosens Bioelectron. 2016 Mar 15;77:1032-8. doi: 10.1016/j.bios.2015.10.085. Epub 2015 Oct 30.
In this paper, linking with the butoxycarbonyl (BOC) protection of proline, a new tailed metalloporphyrin with many useful active functions, nickel (II) 5-[4-N-(tert-Butoxycarbonyl)-l-prolinecoxylpropyloxy]phenyl-10,15,20-triphenylporphyrin (NiTBLPyP), was designed and synthesized. And the NiTBLPyP polymer (poly(NiTBLPyP)) was successfully obtained via a low-cost electrochemical method and exploited as an efficient mimic enzyme. Subsequently, a noncovalent nanohybrid of poly(NiTBLPyP) with graphene (rGO) sheet (rGO-poly(NiTBLPyP)) was prepared through π-π stacking interaction for the ultrasensitive and selective detection of DA. The nanohybrid was characterized by UV-vis spectroscopy, Fourier transform infrared spectra, Raman spectroscopy, scanning electron microscopy and electrochemical impedance spectroscopy. Due to the excellent electrocatalytic ability of poly(NiTBLPyP) film and aromatic π-π stacking interaction between poly(NiTBLPyP and rGO sheet, the obtained rGO-poly(NiTBLPyP) film exhibited a great synergistic amplification effect toward dopamine oxidation.