Issue 36, 2023

Concise synthesis of (R)-reticuline and (+)-salutaridine by combining early-stage organic synthesis and late-stage biocatalysis

Abstract

Efficient access to the morphinan scaffold remains a major challenge in both synthetic chemistry and biotechnology. Here, a biomimetic chemo-enzymatic strategy to synthesize the natural promorphinan intermediate (+)-salutaridine is demonstrated. By combining early-stage organic synthesis with enzymatic asymmetric key step transformations, the prochiral natural intermediate 1,2-dehydroreticuline was prepared and subsequently stereoselectively reduced by the enzyme 1,2-dehydroreticuline reductase obtaining (R)-reticuline in high ee and yield (>99% ee, up to quant. conversion, 92% isol. yield). In the final step, membrane-bound salutaridine synthase was used to perform the selective ortho-para phenol coupling to give (+)-salutaridine. The synthetic route shows the potential of combining early-stage advanced organic chemistry to minimize protecting group techniques with late-stage multi-step biocatalysis to provide an unprecedented access to the medicinally important compound class of promorphinans.

Graphical abstract: Concise synthesis of (R)-reticuline and (+)-salutaridine by combining early-stage organic synthesis and late-stage biocatalysis

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Article information

Article type
Edge Article
Submitted
05 May 2023
Accepted
10 Aug 2023
First published
24 Aug 2023
This article is Open Access

All publication charges for this article have been paid for by the Royal Society of Chemistry
Creative Commons BY license

Chem. Sci., 2023,14, 9863-9871

Concise synthesis of (R)-reticuline and (+)-salutaridine by combining early-stage organic synthesis and late-stage biocatalysis

E. Cigan, J. Pletz, S. A. Berger, B. Hierzberger, M. Grilec-Zlamal, A. Steiner, I. Oroz-Guinea and W. Kroutil, Chem. Sci., 2023, 14, 9863 DOI: 10.1039/D3SC02304D

This article is licensed under a Creative Commons Attribution 3.0 Unported Licence. You can use material from this article in other publications without requesting further permissions from the RSC, provided that the correct acknowledgement is given.

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