Studies on the synthesis and biosynthesis of the fungal alkaloid necatorone

An alternative pathway for the biosynthesis of the fungal alkaloid necatorone has been studied using fluorine-labeled 3-(2-carboxyphenylamino)-l-tyrosine. Although no incorporation of this compound could be detected in feeding experiments with young specimens of Lactarius necator, an analogous 3-aminotyrosine derivative could be converted synthetically into the oxopyridoacridine core structure of necatorone. In experiments aimed at the synthesis of aaptamine-type alkaloids, an unprecedented cyclization of a 3-aminotyrosine-methyl propiolate adduct to a methyl isoquinoline-3-carboxylate was observed. A mechanism is proposed, in which C3 of the propiolate delivers C1 of the isoquinoline nucleus.     

Studies of new indole alkaloid coupling methods for the synthesis of haplophytine

[reaction: see text] The two novel bisindole alkaloid structures shown can be synthesized in a few steps from the canthiphytine derivative 9.     

Structural biology in plant natural product biosynthesis--architecture of enzymes from monoterpenoid indole and tropane alkaloid biosynthesis

Several cDNAs of enzymes catalyzing biosynthetic pathways of plant-derived alkaloids have recently been heterologously expressed, and the production of appropriate enzymes from ajmaline and tropane alkaloid biosynthesis in bacteria allows their crystallization. This review describes the architecture of these enzymes with and without their ligands.     

Fungal indole alkaloid biosynthesis: genetic and biochemical investigation of the tryptoquialanine pathway in Penicillium aethiopicum

Tremorgenic mycotoxins are a group of indole alkaloids which include the quinazoline-containing tryptoquivaline (2) that are capable of eliciting intermittent or sustained tremors in vertebrate animals. The biosynthesis of this group of bioactive compounds, which are characterized by an acetylated quinazoline ring connected to a 6-5-5 imidazoindolone ring system via a 5-membered spirolactone, has remained uncharacterized. Here, we report the identification of a gene cluster (tqa) from P. aethiopicum that is involved in the biosynthesis of tryptoquialanine (1), which is structurally similar to 2. The pathway has been confirmed to go through an intermediate common to the fumiquinazoline pathway, fumiquinazoline F, which originates from a fungal trimodular nonribosomal peptide synthetase (NRPS). By systematically inactivating every biosynthetic gene in the cluster, followed by isolation and characterization of the intermediates, we were able to establish the biosynthetic sequence of the pathway. An unusual oxidative opening of the pyrazinone ring by an FAD-dependent berberine bridge enzyme-like oxidoreductase has been proposed based on genetic knockout studies. Notably, a 2-aminoisobutyric acid (AIB)-utilizing NRPS module has been identified and reconstituted in vitro, along with two putative enzymes of unknown functions that are involved in the synthesis of the unnatural amino acid by genetic analysis. This work provides new genetic and biochemical insights into the biosynthesis of this group of fungal alkaloids, including the tremorgens related to 2.     

Thermal rearrangements of some indole alkaloid derivatives

Under both static and flow thermolysis conditions, several compounds with an “aspidosperma” framework rearranged to “vinca” derivatives. Thus (-)1,2-dehydroaspidospermidine ($\text{4}$) rearranged to (-) gave vincane $\text{14}$. Compound $\text{6}$ rearranged to vincamine ($\text{13a}$) and 16-epi vincamine ($\text{13b}$) under either condition ; increasing the temperature resulted in formation of apovincamine ($\text{19}$) (pyrolysis) or vincamone thermolysis).     

A cage-monoterpene indole alkaloid from Alstonia scholaris

An unprecedented cage-like alkaloid, scholarisine A was isolated from the leaves of Alstonia scholaris and its structure determined on the basis of 1D and 2D NMR, FTIR, UV, and high-resolution mass spectroscopic data. This alkaloid might be derived from picrinine via oxygenation, rearrangement, and lactonization.     

Enantioselective synthesis of marine indole alkaloid hamacanthin B

An enantioselective total synthesis of hamacanthin B (1) is described. This synthesis is based on the asymmetric synthesis of (S)-2-azido-(indol-3-yl)ethylamine 7, which is coupled with the 3-indolyl-alpha-oxoacetyl chloride 8 and subsequently used in a successful intramolecular Staudinger-aza Wittig cyclization to form the central dihydropyrazinone ring. The stereochemistry of naturally isolated hamacanthin B is revealed as the (S)-configuration.     

Foundations for directed alkaloid biosynthesis

In this issue of Chemistry & Biology, Bernhardt and coworkers [1] assay the functional plasticity of strictosidine synthase, a gateway enzyme in the biosynthetic pathways of monoterpene indole alklaloids, and the downstream operability of the products of strictosidine synthase variants in the larger context of the plant biosynthetic pathways.     

Crystal structure of salts of indole alkaloid norfluorocurarine

Single crystal XRD is used to study the crystals of salts of indole alkaloid norfluorocurarine: hydrochloride recrystallized from absolute alcohol, dihydrate hydrochloride recrystallized from water, methochloride monohydrate recrystallized from water, solvate form of methochloride obtained from ethanol, and methobromide monohydrate. Intra- and intermolecular hydrogen bonds are analyzed in these crystals. The crystal structures of norfluorocurarine methochloride and methobromide monohydrates are isomorphic. In norfluorocurarine salts, the orientation of the carbonyl group is determined by the intramolecular C19=O…H-N1 hydrogen bond that is absent in the solvate form with ethanol.     

A new monoterpenoid indole alkaloid from Rauvolfia yunnanensis

One new monoterpenoid indole alkaloid, 11-methoxyburnamine-17-O-3′,4′,5′-trimethoxybenzoate (1), was isolated from Rauvolfia yunnanensis Tsiang. Its structure was identified by spectroscopic evidences.     

Synthesis of 12-epi-ent-polyalthenol an antitumour indole sesquiterpene alkaloid

The synthesis of 12-epi-ent-polyalthenol, 10, and its epimer at C-19, 11, from ent-halimic acid as starting material has been carried out. The structure of the natural product polyalthenol 1 is confirmed in this way. The synthesized indole sesquiterpenes 10 and 11 and their acetylderivatives 32 and 33 inhibited cellular proliferation of a number of human leukaemic and solid tumour cell lines.     

Aristomakine,a novel indole alkaloid from aristotelia serrata

The isolation and structural determination of aristomakine (I), an unusual indole alkaloid with an N-isopropyl group, is reported.