Total synthesis and isolation of citrinalin and cyclopiamine congeners

Abstract

It is said that carbon, the most abundant element in organic matter, supplies life’s quantity, whereas nitrogen supplies its quality. It is therefore unsurprising that many natural products that contain basic nitrogens (alkaloids) are coveted for their benefit to human health. However, nitrogen is known to mire many chemical syntheses because of its basicity and susceptibility to oxidation. This challenge may be heightened by the presence of more than one nitrogen atom in a targeted complex alkaloid, but can be met by the selective introduction and removal of functional groups that mitigate basicity, as highlighted herein with the first chemical syntheses of citrinalin B and cyclopiamine B. The chemical connections that have been realized as a result of these syntheses, in addition to the isolation of both 17-hydroxycitrinalin B and citrinalin C through 13C feeding studies, supports the existence of a common bicyclo[2.2.2]diazaoctane containing biogenetic precursor to these compounds as has been proposed previously.

Mitragynine/Corynantheidine Pseudoindoxyls As Opioid Analgesics with Mu Agonism and Delta Antagonism, Which Do Not Recruit β-Arrestin-2

“…39,43 To better understand the pharmacology of this template, SAR studies were carried out by modifying the C-9 and N-1 (indole nitrogen) positions. Six analogs with various substituents in the C-9 positions and 2 analogs at N-1 were synthesized.…”

Synthetic Applications of the Parkins Nitrile Hydration Catalyst [PtH{(PMe2O)2H}(PMe2OH)]: A Review

“…The same group also described the synthesis of different psymberin analogues from primary amide 44, which was also accessed though a nitrile hydration reaction promoted by 1 [56,57]. The total syntheses of the prenylated indole alkaloids citrinalin B (47) and cyclopiamine (48) has been recently accomplished for the first time by Mercado-Marin, García-Reinada, and co-workers (Scheme 12) [60]. In their work, the key carbamate intermediate 46 was generated through a two-step sequence from tricyclic nitrile 45 via initial hydration of the C≡N catalyzed by complex [PtH{(PMe2O)2H}(PMe2OH)] (1), followed by Hofmann rearrangement of the resulting carboxamide (not isolated) promoted by PIFA in MeOH.…”

Recent Advances in Substrate-Controlled Asymmetric Induction Derived from Chiral Pool α-Amino Acids for Natural Product Synthesis

“…Cycloaddition reactions have also been adapted for the proline-derived total synthesis of natural products. Sarpong et al completed the impressive syntheses of ent-citrinalin B (15) and cyclopiamine B (16) as shown in Scheme 3 [13][14][15]. The authors utilized the chirality of D-proline for the stereoselective construction of a cis-fused ring system within final products 15 and 16.…”