Indole alkaloids pentacyclic

The pyrrolonaphthyridines 208 and 209 can be prepared from rearrangement of the pentacycle 207 upon treatment with trifluoroacetic acid (TFA) (Scheme 52). These products are of interest as they have the same structural skeleton as the indole alkaloid (—)-goniomitine, isolated from the root bark of Gonioma Malagasy <1995JOC3282>. Compound 208 has since been used in the synthesis of further derivatives which show cytotoxic activity against leukemia cells <2001BML79>. 

The Aspidosperma family of indole alkaloids has inspired many synthetic strategies for the construction of their pentacyclic framework of the parent compound aspidospermidine (366), since the initial clinical success of two derivatives, vinblastine (10) and vincristine, as anticancer agents. The alkaloids such as (-)-rhazinal (369) and (-)-rhazinilam (6) have been identified as novel leads for the development of new generation anticancer agents [10,11]. Bis-lactams (-)-leucunolam (370) and (-t-)-epi-leucunolam (371) have bio-genetic and structural relationships with these compounds [236]. Recently, enantioselective or racemic total syntheses of some of the these natural product were achieved. One successful synthesis was the preparation of the tricyclic ketone 365, an advanced intermediate in the synthesis of aspidospermidine (366), from pyrrole (1) (Scheme 76) [14]. The key step is the construction of the indolizidine 360, which represents the first example of the equivalent intramolecular Michael addition process [14,237,238]. The DIBAL-H mediated reduction product was subject to mesylation under the Crossland-... 

Bosch, J., Amat, M., Sanfeliu, E., and Miranda, M.A. (1985) Studies on the synthesis of pentacyclic strychnos indole alkaloids. Photocydization of N-chloroacetyl-1,2,3,4,5,6-hexahydr o-l,5-methanoazocino[4,3-b]indole derivatives. Tetrahedron, 41, 2557-2566. 

The key step of this synthesis is a sequential asymmetric Heck-N-acyliminium ion cyclization of dienyl carbamate triflate 13 to provide enantiopure 3,4-dihydro-9a,4a-(iminoethano)-9/f-carbazole 16. This intermediate and related structures containing a 2,3-double bond should represent versatile precursors for constructing a variety of pentacyclic indole alkaloids containing the (hydroiminoethano)-carba-zole fragment. 

The usefulness of aminosiloxy diene Diels-Alder chemistry to the preparation of different substituted cyclohexenones is demonstrated in Table 11.3 The functionality at the 4 and 5-positions of the cyclohexenones can be easily controlled by the substitution pattern in the dienophile. The differing endo-exo selectivity found in the initial cycloadducts does not impact the usefulness of this route to cyclohexenones, since the amino group is eliminated in the last step. Chiral versions of aminosiloxy dienes provide the opportunity for asymmetric synthesis. Indeed, the diphenylpyrrolidine-substituted diene allows the synthesis of a variety of cyclohexenones, with good to excellent ee s 2b The usefulness of aminosiloxy diene Diels-Alder reactions to natural product synthesis is exemplified through the stereocontrolled synthesis of the pentacyclic indole alkaloid tabersonine 2c... 

Indo-Pacific sponges of the genus Fascaplysinopsis produce a series of bis-indole alkaloids known as the fascaplysins (51) and reticulatines (52), some of which are p-carbolinium ion alkaloid salts of terpene carboxylates. Fascaplysin (44), which was reported by Ireland and coworkers, at the University of Utah, from a Fijian collection of Fascaplysinopsis sp., is a fused pentacyclic pigment exhibiting antimicrobial and cytotoxic properties. Crews... 

A pentacyclic indole alkaloid isolated from the leaves of Hunteria zeylanica was identified as pleiocarpamine (167) by Arambewela and Khuong-Huu (78). 

The pentacyclic oxindoles are true oxindole analogs of the heteroyo-himbane alkaloids. Their structure is based on chemical and physical data supported, in many instances, by their synthesis from the corresponding indole alkaloids. Some physical properties of members of this... 

In a study on biomimetic alkaloid synthesis the pentacyclic indole alkaloid vincadifformin (1) was synthesized in two steps starting from tryptamine hydrochloride (X) ... 

The Aspidosperma alkaloids are a group of more than 100 monomeric and dimeric monoterpene indole alkaloids with aspidospermidine (228) representing a key member of the class and sometimes considered to be the parent [68]. Numerous total syntheses of this pentacyclic compound have been reported. Our own contributions in the area were prompted by the discovery of a new method for preparing indoles via a palladium-catalysed Ullmann cross-coupling reaction that proceeds especially efficiently at close to room temperature [69] and which we felt could serve as the centrepiece in developing a new synthesis of compound 228 and, in the longer term, syntheses of dimeric members of the indole alkaloid class such as the clinically significant alkaloids vinblastine and vincristine. 

More recently, Kalaus and Szantay have made use of a similar approach to synthesize a variety of pentacyclic indole alkaloids containing the aspidospermane, ibophyUidine, and iboxyphylline core structures. In one approach, featured in the formal total synthesis of ( )-12-demethoxy-N(l)-acetylcylindrocarine (188) [73], a benzyl-protected tryptamine derivative 183 was treated with an appropriately substituted aldehyde (184) to form the enamine species 185a-b, which then underwent... 

The total synthesis of several members of the vinca and tacaman class of indole alkaloids has also been accompHshed using push-pull dipoles in the critical cycloaddition step (2007OL3249, 2008JOC2792). The central step in the synthesis consists of an intramolecular [3-F2]-cycloaddition reaction of an a-diazo indoloamide (i.e., 19), which delivers the pentacyclic skeleton of the natural product in excellent yield (Scheme 6). The acid lability of... 

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