Vincorine

Three dimeric indole alkaloids of a new type, peceyline, peceylanine, and pelankine, have been isolated from a Sri Lankan apocynaceous plant, Petchia ceylanica Wight.876 The structures of these bases were determined mainly by n.m.r. spectroscopy. In their H spectra, all three alkaloids exhibit four aromatic singlets, one olefinic hydrogen multiplet, two methoxycarbonyl singlets, two N-methyl singlets, and two C-methyl doublets. One half of the non-aromatic carbon resonances in the 13C spectra show that one monomer unit is common to all three alkaloids, and inspection reveals that this unit must be based on vincorine... 

The non-aromatic portion of the second monomer unit in peceyline and peceylanine is also identical (13C spectra), and is based on vincorine epoxide. Since peceyline contains no methoxy-groups other than those in the ester functions, and its H aromatic resonances are consistent with an unsymmetrical dibenzofuran system, a possible structure for peceyline is (186). 

C45H54N4O7 142795-96-8 81 1 l-Methoxy-10-(l I -vincorinyl)- A Istonia pittleri vincamajine = Tonduzia pittieri 11-[10-(11-Methoxyvincamajinyl)]-vincorine 144... 

Methoxy-I0-(11 -vincoiinyl)- A Istonia pittieri vincamedine Tonduzia pittieri (-)-11 -(10-( 11 -Methoxy vincamedinyl)]-vincorine 144... 

Peceyline (183), C42H48N406, mp 310°C (decomp.), [a]D -355°, and pec-eylanine (184), C44H54N4O7, mp 157-158°C, [a]D -237°, are two other vincorine-vincorine types of bisindole alkaloids isolated from Petchia cey-... 

Minfiensine (99) [43] exemplifies a variety of indole alkaloids containing the novel l,2,3,4-tetrahydro-9a,4a-(iminoethano)-9/7-carbazole ring skeleton. These include minfiensine (99), vincorine (100) [44], corymine (101) [45], and echitamine (102) [46] (Fig. 4). They exhibit a number of impressive biological activities, including significant anticancer activity [47]. Since the first characterization of the first akuammiline alkaloid member echitamine (102), more than 80 years ago, only a few successful syntheses of this challenging tetracyclic system have been reported. 

Pleiocraline (236) occurs with pleiocorine in Alstonia deplanchei, and shares many of the latter s structural features. Thus, the n.rn.r. spectrum reveals that pleiocraline also contains a 2,7-dihydropleiocarpamine unit, but, in place of the vincorine unit present in pleiocorine, pleiocraline contains a component closely related to Na-methyl-deacetyldeformo-l,2/8//-dihydroakuammiline. The n.rn.r. data also indicate that the nature and positions of attachments of the two monomeric components are the same in pleiocorine and pleiocraline. 

The first part of this section will address studies directed toward the synthesis of alkaloids with an N4—C2 bond connectivity resulting in the l,2,3,4-tetrahydro-9a,4a-(iminoethano)-9H-carbazole core 82 embedded within echitamine (3) and vincorine (18) (Figure 3). 

Qin and coworkers were next able to prepare vinyl iodide 118 in five steps from the Nl-methylindole congener of tetracycle 117, but were unable to complete the total synthesis of vincorine (18) from this intermediate (Scheme 6). 

In particular, the disconnection between vincorine (18) and indoline 118 comprises the seemingly simple formation of a carbon—carbon bond, reminiscent of work performed by Rawal to install the ethyhdene moiety into Strychnos alkaloids. Unfortunately, multiple attempts including various reductive Heck coupHng protocols, Michael conditions, and radical... 

An additional six steps consisting of deprotections, oxidations, and meth-ylations completed the first total synthesis of an akuammiline alkaloid, ( )-vincorine (18). This racemic synthesis took a total of 31 steps and proceeded with a 1% overall yield. 

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