A Symmetric dihydroxylation in an approach to the enantioselective synthesis of 2-anylpropanoic and non-steroidal anti-inflammatory drugs

Available online 25 March 1998.Naproxen ((S)-2-(6-methoxy-2-naphthyl)propanoic acid) and flurbiprofen ((S)-2-(3-fluoro-4-phenylphenyl)propanoic acid) have been synthesised in high enantiomeric excess. The synthetic strategy employed was to introduce asymmetry into the molecules by Sharpless asymmetric dihydroxylation of the appropriate methyl styrenes. The resultant diols were then converted into optically active epoxides and the required stereogenic centre was assembled by catalytic hydrogenolysis of the introduced benzylic epoxide oxygen bond, followed by oxidation of the derived optically active primary alcohol.Robert C. Griesbach, David P.G. Hamon and Rebecca J. Kenned

Toward in silico CMC: An industrial collaborative approach to model‐based process development

The Third Modeling Workshop focusing on bioprocess modeling was held in Kenilworth, NJ in May 2019. A summary of these Workshop proceedings is captured in this manuscript. Modeling is an active area of research within the biotechnology community, and there is a critical need to assess the current state and opportunities for continued investment to realize the full potential of models, including resource and time savings. Beyond individual presentations and topics of novel interest, a substantial portion of the Workshop was devoted toward group discussions of current states and future directions in modeling fields. All scales of modeling, from biophysical models at the molecular level and up through large scale facility and plant modeling, were considered in these discussions and are summarized in the manuscript. Model life cycle management from model development to implementation and sustainment are also considered for different stages of clinical development and commercial production. The manuscript provides a comprehensive overview of bioprocess modeling while suggesting an ideal future state with standardized approaches aligned across the industry

Environmental regulation of leaf colour in red 35S : PAP1 Arabidopsis thaliana

High-temperature, low-light (HTLL) treatment of 35S:PAP1 Arabidopsis thaliana over-expressing the PAP1 (Production of Anthocyanin Pigment 1) gene results in reversible reduction of red colouration, suggesting the action of additional anthocyanin regulators. High-performance liquid chromatography (HPLC), liquid chromatography mass spectrometry (LCMS) and Affimetrix®-based microarrays were used to measure changes in anthocyanin, flavonoids, and gene expression in response to HTLL.\ud \ud \ud HTLL treatment of control and 35S:PAP1 A. thaliana resulted in a reversible reduction in the concentrations of major anthocyanins despite ongoing over-expression of the PAP1 MYB transcription factor. Twenty-one anthocyanins including eight cis-coumaryl esters were identified by LCMS. The concentrations of nine anthocyanins were reduced and those of three were increased, consistent with a sequential process of anthocyanin degradation. Analysis of gene expression showed down-regulation of flavonol and anthocyanin biosynthesis and of transport-related genes within 24 h of HTLL treatment. No catabolic genes up-regulated by HTLL were found.\ud \ud Reductions in the concentrations of anthocyanins and down-regulation of the genes of anthocyanin biosynthesis were achieved by environmental manipulation, despite ongoing over-expression of PAP1. Quantitative PCR showed reduced expression of three genes (TT8, TTG1 and EGL3) of the PAP1 transcriptional complex, and increased expression of the potential transcriptional repressors AtMYB3, AtMYB6 and AtMYBL2 coincided with HTLL-induced down-regulation of anthocyanin biosynthesis.\ud \ud HTLL treatment offers a model system with which to explore anthocyanin catabolism and to discover novel genes involved in the environmental control of anthocyanins