Development and validation of ion-pairing HPLC-CAD chromatography for measurement of Islatravir’s phosphorylated intermediates

Gunsch, Matthew J.; Schwalm, Erica L.; Ouimet, Claire M.; Halsey, Holst M.; Hamilton, Simon; Bernardoni, Frank; Jo, Junyong

doi:10.1016/j.jpba.2022.114684

Cited by 6 publications

(1 citation statement)

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“…Consequently, reduction of the total protein content in the aqueous reaction stream was a critical factor for ensuring development of a robust process capable of delivering high-quality API. [34][35][36][37] Decreasing the overall enzyme loading was required to enable an efficient final API filtration after the aldol-glycosylation step. 34,38 Reduced protein levels also minimizes side reactions catalyzed by host cell proteins, namely phosphate hydrolysis by endogenous E. coli phosphatases (Scheme 2).…”

Section: Enzyme Developmentmentioning

confidence: 99%

Development of a Biocatalytic Aerobic Oxidation for the Manufacturing Route to Islatravir

Shaw,

Fryszkowska,

Alvizo

et al. 2023

Preprint

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Biocatalytic oxidations have the potential to address many synthetic chemistry challenges, enabling the selective synthesis of chiral intermediates such as carbonyl compounds, alcohols, or amines. The use of oxygen-dependent enzymes can dramatically reduce the environmental footprint of redox transformations at manufacturing scale. Here, as part of the biocatalytic cascade to an anti-HIV investigational drug islatravir 1, we describe the development of an aerobic oxidation process delivering (R)-ethynylglyceraldehyde 3-phosphate 3 using an evolved galactose oxidase enzyme. Integrated enzyme and reaction engineering were critical for achieving a robust, high-yielding oxidation performed at pilot plant scale (>20 kg, 90% yield).

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Section: Enzyme Developmentmentioning

confidence: 99%