Enantioselective syntheses of coronaridine and 18-methoxycoronaridine

Selective Syntheses of Planar-Chiral Ferrocenes

“…In the last few decades it has been found that Ugi’s approach is applicable to related substrates, revealing almost the same stereoselectivities regarding ortho-directed lithiation and nucleophilic substitution of the amine moiety. This includes utilization of N , N -dimethyl-1-ferrocenylalkylamines and -benzylamines ( 85 ), ,− homoannularly bridged N , N -α-dimethylamino-1,2-tetramethylene ferrocenes ( 86 ), − heteroannularly bridged [3] ( 87 , ,− 88 , )- and [5]ferrocenophanes ( 89 ) , as well as bisferrocenyldiamines ( 90 ) (Chart ). The enantiopure starting materials 85 – 90 have been made available among others by resolution, ,, asymmetric reductions of ferrocenyl ketones ,,,,,,, and imines, , asymmetric alkylation/arylation of ferrocenealdehydes, , and the use of enantiomerically pure cyclopentadienes or cyclopentadienyl ligands. ,,, …”

Recent Advances in Natural Product Synthesis by Using Intramolecular Diels−Alder Reactions

“…In addition to the above-mentioned examples of the total synthesis of the indole alkaloids, the potential of an IMDA reaction has been strengthened through the total synthesis of other indole alkaloids such as (+)- cis -trikentrin B, (±)-eburnamonine, (±)-albifloranine, (−)-vindoline, (±)-alloyohimbane, (−)-normalidine, (−)-coronaridine, (−)-suaveoline, and natural minovine …”

Efficient Preparation of the 18-Methoxycoronaridine Side-Chain Precursor

“…Scheme 1] is a congener of ibogaine that has shown promise as an agent for the treatment of drug abuse. 1 Syntheses of racemic 2,3 and enantiopure 4 18-MC have been published, as well as a communication from our group for the chemical resolution of enantiomers 5 for evaluation in rat models of addiction. In order to prepare kilogram amounts of racemic 3 for ongoing biological studies, however, we required some process modifications to the published syntheses to improve the overall chemical throughput.…”

“…Our initial large-scale preparation of 18-MC (3) adhered closely to the literature procedures, 3,4 requiring an eighteen-step synthesis, including the seven-step synthesis of the side-chain precursor 1 as depicted in Scheme 2. This preparation of side chain component 1 began with the aalkylation of commercially available dimethyl allylmalonate (5) with 2-chloroethyl methyl ether to provide the bissubstituted malonate 6.…”

“…The chemistry route developed 3,4 for the initial side chain synthesis was applied to carry the bisalkylated malonate 14 forward to the requisite benzyl-protected acetal 18 (Scheme 4). During this phase of the research effort, only a few process modifications were necessary to apply the procedures to large-scale manipulation.…”