Development of an Improved Process for Doxercalciferol via a Continuous Photochemical Reaction

Abstract

Doxercalciferol (1α-hydroxyvitamin D2) is a commercially approved vitamin D derivative used to treat chronic kidney disease (CKD) patients whose kidneys cannot metabolically introduce a hydroxyl group at C1. A new process for the production of doxercalciferol from ergocalciferol was developed using a continuous photoisomerization of a known vitamin D intermediate as the key step, thus circumventing the limitations of batch photoisomerization processes. Doxercalciferol is produced in an overall yield of about 10% from ergocalciferol.

Photochemical Transformations Accelerated in Continuous‐Flow Reactors: Basic Concepts and Applications

“…Researchers from Genzyme Corporation have developed a new synthetic route towards doxercalciferol (1a-hydroxyvitamin D2). [84] A key step in this process was the photoisomerization with 9-acetylanthracene as a photocatalyst (Scheme 11B). A FEP capillary (1.59 mm ID, 15.24 m length) was wrapped around a cooled immersion well with a pyrex sleeve.…”

Flow photochemistry: Old light through new windows

“…As part of a new route to the therapeutic vitamin D derivative doxercalciferol, the sensitized photoisomerisation of 104 to 105 was investigated (Scheme 36) [94]. A continuous-flow photochemical reactor was constructed by using the Booker-Milburn/Berry configuration in the hope that flow conditions would overcome the inherent difficulties in scaling up a batch process.…”

Batch versus Flow Photochemistry: A Revealing Comparison of Yield and Productivity

“…The FEP reactor concept has now been used and adapted for a number of reactions, resulting in the synthesis of a wide range of complex, photochemically derived products. [19][20][21][22][23][24][25][26][27][28] Perhaps the most striking of these has been the use of an FEP flow reactor in the scaled-up continuous synthesis of the frontline anti-malarial drug artemisinin described by Seeberger and co-workers. [29,30] Many groups have now reported the advantages of flow photochemistry over previously reported batch results.…”