Regiodivergent Synthesis of ortho- and para-Cannabinoquinones

TY - JOUR

T1 - Regiodivergent Synthesis of ortho- and para-Cannabinoquinones

AU - Mattoteia, Daiana

AU - Taglialatela-Scafati, Orazio

AU - Muñoz, Eduardo

AU - de la Vega, Laureano

AU - Caprioglio, Diego

AU - Appendino, Giovanni

N1 - Funding Information: We are grateful to MIUR Italy (PRIN2017, Project 2017WN73PL, bioactivity‐directed exploration of the phyto‐cannabinoid chemical space) for financial support. Publisher Copyright: © 2020 Wiley-VCH GmbH Copyright: Copyright 2020 Elsevier B.V., All rights reserved.

PY - 2020/12/31

Y1 - 2020/12/31

N2 - Spurred by the remarkable biological profile of cannabinoquinoids, we have systematically investigated the periodinane oxidation of their resorcinolic precursors, discovering that the regiochemistry of oxidation, a critical maneuver for bioactivity, depends not only on the nature of the oxidant (λ3- vs. λ5-iodanes), but also on post-oxidative prototropic- and valence tautomeric equilibria that isomerize ortho-quinones to para-quinones. By complementary selection of the periodinane oxidant and by freezing prototropic equilibration with O-methylation, isomeric ortho- and para-quinones could be obtained from mono- and diphenolic cannabinoids, setting the stage for the exploration of novel areas of the biological space, and establishing a blueprint for the extension of this strategy to other classes of bioactive alkylresorcinols.

AB - Spurred by the remarkable biological profile of cannabinoquinoids, we have systematically investigated the periodinane oxidation of their resorcinolic precursors, discovering that the regiochemistry of oxidation, a critical maneuver for bioactivity, depends not only on the nature of the oxidant (λ3- vs. λ5-iodanes), but also on post-oxidative prototropic- and valence tautomeric equilibria that isomerize ortho-quinones to para-quinones. By complementary selection of the periodinane oxidant and by freezing prototropic equilibration with O-methylation, isomeric ortho- and para-quinones could be obtained from mono- and diphenolic cannabinoids, setting the stage for the exploration of novel areas of the biological space, and establishing a blueprint for the extension of this strategy to other classes of bioactive alkylresorcinols.

KW - Iodanes

KW - Oxidation

KW - Phytocannabinoids

KW - Quinones

KW - Tautomerism

UR - https://www.scopus.com/pages/publications/85096697112

U2 - 10.1002/ejoc.202001258

DO - 10.1002/ejoc.202001258

M3 - Article

AN - SCOPUS:85096697112

SN - 1434-193X

VL - 2020

SP - 7429

EP - 7434

JO - European Journal of Organic Chemistry

JF - European Journal of Organic Chemistry

IS - 48

ER -