An Efficient Multigram Synthesis of Hypericin Improved by a Low Power LED Based Photoreactor

Abstract

In this work, an improved synthesis process was developed for the multigram production of hypericin. An inexpensive and efficient low power Light Emission Diode (LED) based photoreactor was designed and employed to perform the protohypericin photocyclization reaction allowing its photoconversion in hypericin. This closed system overcomes safety issues related to scale-up hypericin preparation typically described in the literature which combines the use of open systems, organic solvents, and high-power light sources. The photoreactor designed allows a solution to, mainly, the intrinsic effect of hypericin photobleaching inherent to the protohypericin photocyclization reaction, implying an increase in the yield of the final product and consequently the final cost. Using a red-LED based photoreactor, a safety protocol was carried out in a 5-g scale hypericin preparation with quantitative yield.

From Protohypericin to Hypericin: Photoconversion Analysis Using a Time-Resolved Thermal Lens Technique

“…The linear increase of the photoreaction rate with the concentration of pHyp indicates the presence of possible extra steps in the photoconversion processes of pHyp to Hyp, which could involve sub-products in the photocyclization process. 18,55…”

“…The pHyp samples were prepared as the methodology described in the reference Gonçalves. 18 Four concentrations of pHyp (100 nM, 200 nM, 300 nM, and 400 nM) in ethanol were prepared and stored in amber flasks. TL measurements were performed in each sample using four different optical excitation powers at 25 ℃.…”

“…The pHyp samples were prepared as the methodology described in the reference Gonçalves. 18 Four concentrations of pHyp (100 nM, 200 nM, 300 nM, and 400 nM) in ethanol were prepared and stored in amber flasks. TL measurements were performed in each sample using four different optical excitation powers at 25 C. In addition, the ultraviolet-visible (UV-Vis) optical absorbance spectra of pHyp and Hyp were measured by a spectrophotometer (PerkinElmer, model Lambda 1050) in a quartz cuvette (L ¼ 1 cm) from 400 nm to 700 nm.…”

“…14 Recently, the synthesis of Hyp was significantly improved by substituting the multifrequency light source (mercury vapor lamp) in the photoconversion of pHyp to Hyp by a narrow-band light emission diode (LED) with a maximum emission at 530 nm. 18 According to the authors, the longtime illumination of Hyp with a mercury vapor-based multifrequency light source during the photocyclization process induces the photobleaching of Hyp, a collateral negative effect that reduces the yielding of Hyp synthesis.…”

Reactor Technology Concepts for Flow Photochemistry

“…In the second example Gonçalves et al . describe the multigram synthesis of hypericin 23 , a natural product rarely available by direct extraction from St. John's Wort as main herbal source . The photocyclisation of protohypericin 22 is the final step in the synthesis of 23 yielding a compound with strong light absorption in the orange region at λ max =596 nm (Figure ).…”