01666nas a2200169   4500008004100000022001400041245011200055210006900167260000800236300001400244490000600258520103600264100002401300700002501324700002301349856012401372       2019                        eng d  a2470-134300aTotal synthesis of (+/-)-quinagolide: a potent D-2 receptor agonist for the treatment of hyperprolactinemia0 aTotal synthesis of quinagolide a potent D2 receptor agonist for   cMAY  a8231-82380 v43 a<p>A potent dopamine (D-2) receptor agonist (+/-)-quinagolide, which is used for the treatment of hyperprolactinemia, was synthesized using the ring closing metathesis (RCM) approach from meta-hydroxybenzaldehyde as the starting material. The key features of this synthesis are pyrolytic elimination, late-stage expedient synthesis of functionalized trans-fused tetrahydropyridine-3-carboxylates from olefin 6, via conjugate addition-elimination upon acetate 11, followed by RCM and phenyliodine bis(trifluoroacetate) (PIFA)-mediated Hofmann rearrangement of piperidine-3-carboxamide, which enables the synthesis of 3-aminopiperidine skeleton of quinagolide. For the total synthesis of natural products such as ergot alkaloids, late-stage synthesis of functionalized trans-fused tetrahydropyridine-3-carboxylates using RCM and PIFA-mediated Hofmann rearrangement of piperidine-3-carboxamide, which allows quick access to the synthetically challenging 3-aminopiperidine skeleton, are the main achievements of the present work.</p>
1 aChavan, Subhash, P.1 aKadam, Appasaheb, L.1 aKawale, Sanket, A.  uhttps://library.ncl.res.in/content/total-synthesis-quinagolide-potent-d-2-receptor-agonist-treatment-hyperprolactinemia