Carbolines, rearrangement synthesis

A new simple oxindole alkaloid, (-)-horsfiline (57) was obtained from Horsfieldia superba (Myristicaceae), in addition to the known alkaloids 6-methoxy-2-methyl-l,2,3,4-tetrahydro-P-carboline (58) and 5-methoxy-A, -dimethyltryptamine [59]. Horsfiline is a simple spiro-pyrrolidinyloxindole, its structure was deduced from spectral data (MS NMR) as well as by partial synthesis from 58 via oxidation with Pb(OAc)4 to the acetoxyindolenine 59, followed by acid catalysed rearrangement (MeOH/AcOH) to ( )-horsfiline (Scheme 2) [59]. 

The ability to rearrange substituted tetrahydro-)3-carbolines into indolenines under appropriate acidic conditions has led to a synthesis of 16-methylaspidospermidine from an intermediate in another total synthesis of the eburnamine-type alkaloids (Chart III). This route to d -eburnamine is an interesting variant of an eax lier synthesis of eburn-amonine (7). The boron trifluoride-etherate rearrangement and ring closure of the tetracyclic intermediate appeared to have given an entirely homogeneous product and the subsequent lithium aluminum hydride... 

Synthesis of left-hand segment began with 7-benzyloxyindole 197. A Vilsmeier-Haack formylation followed by condensation afforded nitroalkene 198. Reduction, acylation with succinic anhydride, and subsequent Bischler-Napieralski cyclization provided dihydro-p-carboline 199. Noyori asymmetric reduction of 199, further treatment with A-iodosuccinimide, followed by activation with silver triflate in the presence of dimethoxy-N,N-diallylaniline furnished the desired coupling product 200. Subsequent saponification and cyclization via a ketene intermediate gave the rearrangement precursor 201. Oxidative skeletal rearrangement initiated by m-CPBA followed by removal of the Fmoc group and conversion of the aniline to the hydrazine furnished Fischer indole precursor 202 (Scheme 35). 

At about the same time, Nicolaou and Chen et al. independently reported the synthesis of haplophytine [85]. Retrosynthetically, haplophytine was envisioned by a sequence of Suzuki-Miyaura Coupling, Vilsmeier-Haack reaction, and radical cyclization from indole 205 and vinyl iodide 206. The left-hand domain 205 could arise through the oxidative skeletal rearrangement of enamine 207, which could be obtained from the oxidative coupling of tetrahydro-jS-carboline 208 and diphenol 209 (Scheme 37). 

Further studies with P. citrinum VKM FW-800 obtained from the permafrost region of Northern Russia, led to the isolation of the alkaloids (+)-quinocitrinine A and (—)-quinocitrinine B, which are diastereomers at the C-1 and C-9 stereocenters (186). These alkaloids were the first pyrrolo[3,4-lr]quinoline-type representatives isolated from microbial sources. Their structures are unique in that a quinolone skeleton is conjugated with a y-lactam ring. A biomimetic total S3mthesis of quinolactacin B was reported by Tatsuta s group (215). A new enantioselective synthesis of quinolactacins A2 and B, via the skeletal rearrangement of a p-carboline to the pyrrolo[3,4- ]quinolin-4(lf-D-one system by an... 

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