RT Journal Article
T1 Efficient Asymmetric Synthesis of an A-Ring Synthon for Pd-Catalyzed Preparation of 1α-Hydroxyvitamin D Metabolites and Analogs
A1 Loureiro Martínez, Julián
A1 Kattner, Lars
A1 Mouriño Mosquera, Antonio
K1 A-Ring synthons
K1 Carbonyl-ene reaction
K1 Chiral β-hydroxy ketones
K1 1α-Hydroxyvitamin D
K1 Palladium
AB An efficient Lewis acid-assisted asymmetric carbonyl-ene reaction to set the 1α-hydroxyl functionality of enol-triflate, precursor of the A-ring of the hormone calcitriol and its 1α-hydroxyderivatives, is described. The secondary parallel hypercalcemic effects associated with the treatment of several hyperproliferative diseases with the natural hormone 1α,25-dihydroxyvitamin D3 (calcitriol) and/or known active vitamin D metabolites and analogs, demand the development of efficient and rapid methods for the preparation of vitamin D receptor (VDR) ligands as new selective and non-calcemic agonists. Here we describe an efficient and adaptable multigram-scale synthetic sequence to access an A-ring synthon as useful precursor of the vitamin D triene system of 1α-hydroxylated vitamin D derivatives via Pd-catalyzed carbocyclization/Suzuki–Miyaura cross-coupling reactions in a protic medium. The key step is an asymmetric Lewis acid-promoted carbonyl-ene reaction to a chiral glyosylate ester to establish the 1α-hydroxyl group of 1α,25-dihydroxyvitamin D3 and its derivatives
PB Wiley
SN 1434-193X
YR 2022
FD 2022
LK http://hdl.handle.net/10347/29237
UL http://hdl.handle.net/10347/29237
LA eng
NO Eur. J. Org. Chem. 2022, e202200314
NO This research was funded by ENDOTHERM GmbH, Xunta de Galicia (GRC/ED431B/20) and the University of Santiago de Compostela (Spain)
DS Minerva
RD 24 abr 2026