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 - http://www.scopus.com/inward/record.url?scp=85096697112&partnerID=8YFLogxK
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 -