Publications by authors named "S J Kolis"
Article Synopsis
- The combination of ethyl (hydroxyimino)cyanoacetate (Oxyma) and diisopropylcarbodiimide (DIC) is effective for activating amino acids in peptide synthesis, but raises safety concerns due to the potential production of hydrogen cyanide (HCN) at 20 °C.
- A comprehensive study reveals two pathways for the formation of HCN from the Oxyma/DIC adduct, differing in the specific carbon atom targeted during the reaction process.
- The research suggests that one pathway, where the sp-nitrogen attacks the oxime carbon, is more favorable and aligns well with experimental data, potentially guiding strategies to reduce HCN generation in future applications.
Article Synopsis
- The aza-Henry reaction can be risky when scaling up due to hazards from peracids and nitroalkanes, leading to the need for safer alternatives.
- A new continuous and scalable platform was developed to create aliphatic nitroalkanes by oxidizing oximes using peracetic acid, which allows direct use of the nitroalkane in the aza-Henry reaction.
- The innovative pipe-in-series reactor improves safety and efficiency, enabling the production of purified nitroalkane solutions for enantioselective reactions while avoiding dangerous intermediate isolation.
A stereoselective aza-Henry reaction between an arylnitromethane and Boc-protected aryl aldimine using a homogeneous Brønsted acid-base catalyst was translated from batch format to an automated intermittent-flow process. This work demonstrates the advantages of a novel intermittent-flow setup with product crystallization and slow reagent addition which is not amenable to the standard continuous equipment: plug flow tube reactor (PFR) or continuous stirred tank reactor (CSTR). A significant benefit of this strategy was the integration of an organocatalytic enantioselective reaction with straightforward product separation, including recycle of the catalyst, resulting in increased intensity of the process by maintaining high catalyst concentration in the reactor.
View Article and Find Full Text PDFThe effect of saquinavir-boosted ritonavir at therapeutic (1000/100 mg twice daily [bid]) and supratherapeutic (1500/100 mg bid) doses was evaluated in a double-blind, placebo- and positive-controlled (moxifloxacin 400 mg) 4-way crossover thorough QT/QTc study. Least squares mean estimated study-specific QTc (QTcS) change from dense predose baseline (ddQTcS(dense)) was the primary endpoint. Greatest mean increase in ddQTcS(dense) occurred 12 hours postdose for the 1000/100-mg group (18.
View Article and Find Full Text PDFThe BRAF(V600E) mutation is common in several human cancers, especially melanoma. RG7204 (PLX4032) is a small-molecule inhibitor of BRAF(V600E) kinase activity that is in phase II and phase III clinical testing. Here, we report a preclinical characterization of the antitumor activity of RG7204 using established in vitro and in vivo models of malignant melanoma.
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