26057-57-8Relevant academic research and scientific papers
Structural characterization of EasH (Aspergillus japonicus)-an oxidase involved in cycloclavine biosynthesis
Jakubczyk, Dorota,Caputi, Lorenzo,Stevenson, Clare E. M.,Lawson, David M.,O'Connor, Sarah E.
, p. 14306 - 14309 (2016)
Aj_EasH is a non-heme iron- and α-keto-glutarate-dependent oxidase that is responsible for an unusual cyclopropyl ring formation in the biosynthesis of the fungal ergot alkaloid cycloclavine. The three dimensional structure of Aj_EasH (2.2 ? resolution) reported here provides insight into the mechanism of this unusual and complex reaction.
Enantioselective Formal Synthesis of (+)-Cycloclavine and Total Synthesis of (+)-5- epi-Cycloclavine
Wang, Wei,Mi, Yang,Cao, Xiao-Ping,Shi, Zi-Fa
, p. 6603 - 6607 (2019)
Starting from the commercially available 4-bromoindole, a concise and efficient enantioselective formal synthesis of (+)-cycloclavine (1) in 13 steps with 2.0% overall yield and a total synthesis of (+)-5-epi-cycloclavine (2) in 14 steps with 3.3% overall yield were achieved. Key features of the syntheses include the addition of a Grignard reagent to the C-N/Heck reaction sequence to construct the fused 6-5-6 ring systems, cyclopropanation, an ester aminolysis reaction, and the first example of the construction of a 3-azabicyclo[3,1,0]hexane through an intramolecular [3 + 2] cycloaddition/nitrogen extrusion.
Discovery and Reconstitution of the Cycloclavine Biosynthetic Pathway - Enzymatic Formation of a Cyclopropyl Group
Jakubczyk, Dorota,Caputi, Lorenzo,Hatsch, Ana?lle,Nielsen, Curt A. F.,Diefenbacher, Melanie,Klein, Jens,Molt, Andrea,Schr?der, Hartwig,Cheng, Johnathan Z.,Naesby, Michael,O'Connor, Sarah E.
, p. 5117 - 5121 (2015)
The ergot alkaloids, a class of fungal-derived natural products with important biological activities, are derived from a common intermediate, chanoclavine-I, which is elaborated into a set of diverse structures. Herein we report the discovery of the biosynthetic pathway of cycloclavine, a complex ergot alkaloid containing a cyclopropyl moiety. We used a yeast-based expression platform along with in vitro biochemical experiments to identify the enzyme that catalyzes a rearrangement of the chanoclavine-I intermediate to form a cyclopropyl moiety. The resulting compound, cycloclavine, was produced in yeast at titers of >500 mg L-1, thus demonstrating the feasibility of the heterologous expression of these complex alkaloids.
Asymmetric Total Synthesis and Biological Evaluation of (+)-Cycloclavine
McCabe, Stephanie R.,Wipf, Peter
, p. 213 - 224 (2019/01/04)
The first total synthesis of natural (+)-cycloclavine uses a catalytic asymmetric cyclopropanation of allene, a regiospecific Pd-catalyzed enone formation, and two intramolecular Diels-Alder reactions for indole/indoline annulations. The binding properties of natural (+)- and unnatural (-)-cycloclavine on 16 CNS receptors revealed significant stereospecificity and unique binding profiles in comparison to LSD, psilocin, and DMT. Differential 5-HT affinities, as well as novel sigma1 receptor properties bode well for potential therapeutic developments of clavine alkaloid scaffolds.
