Montanine alkaloids

Kokas OJ, Banwell MG, Willis AC (2008) Chemoenzymatic Approaches to the Montanine Alkaloids A Total Synthesis of (+)-Nangustine. Tetrahedron 64 6444... 

Montanine alkaloids are members of the alkaloids of the plant family of Amarylli-daceae. They represent a relatively small class of compounds with the typical methanomorphanthridine skeleton exhibiting some anxiolytic, anti-depressive and anti-convulsive activities [135, 136]. The total syntheses of the natural (-)-mon-tanine enantiomers are only mentioned, not described, here (for these (—(-enantiomers see, e.g. literature cited in [137]). 

The total chemo-enzymatic synthesis of three of the (-l-)-montanine alkaloids, namely (+)-brunsvigine [138], (-l-)-nangustine [139] and (-l-)-montabuphine [140], has been reported in the last 3 years. These non-natural enantiomers have been prepared from monochiral 3-halo-m-1,2-dihydrocatechols precursors. A total of over 17-20 reaction steps are needed for their syntheses (Fig. 22). 

We have extended the chemistry shown in Scheme 10 to the preparation of e f-nangustine (ent-99) and to the synthesis of compound 119 that corresponds to the structure assigned to montabuphine [51]. Montabuphine has attracted considerable attention because its isolation suggested that both enantiomeric forms of the montanine alkaloid framework occur in nature. In the event, and by employing a reaction sequence similar to that shown above, we were able to prepare target 119 from cis-l,2-dihydrocatechol 100. However, a comparison of the physical and spectral data recorded on the synthesised form of amine 119 with those reported for (+)-montabuphine suggests that they are different compounds. 

Scheme 11 Synthesis of the basic pentacyclic framework, 103, associated with the montanine alkaloids...

Castilhos TS, Giordani RB, Henriques AT, Menezes FS, Zuanazzi JAS (2007) hr vitro evaluation of the antiinflammatory, antioxidant and antimicrobial activities of the montanine alkaloid. Rev Bras Farm 17 209... 

The alkaloids related to crinine (359), which possess the 5,10b-ethanophen-anthridine nucleus, have been the subject of extensive synthetic investigations (190). Alkaloids of this family bearing oxygen functionality at C-ll occupy a special position since they are possible biosynthetic and chemical precursors of the subgroups that incorporate a 2-benzopyrano[3,4-c]indole ring such as those alkaloids related to pretazettine (395), tazettine (397), and macronine (401) and the methanomorphanthridines such as montanine (584). 

Although the alkaloids of the montanine type have not stimulated a high degree of synthetic interest, several approaches to montanine (584) have been... 

Fig. 22 Chemo-enzymatic, enantio-selective total synthesis of three non-natural montanine type alkaloids, (+)-brunsvigine, (+)-nangustine and (+)-montabuphine (TD toluene dioxygenase)...

Amaryllidaceae Alkaloids.—Detail has been added to the fairly thoroughly delineated pathways to the Amaryllidaceae alkaloids.75 76 11-Hydroxyvittatine (94), previously shown to be a precursor for narciclasine (96),76 has been proposed as an intermediate in the biosynthesis of haemanthamine (92) and montanine (95) following the observed specific incorporation of vittatine (93) into the two... 

Galanthamine-type alkaloids derived from a dibenzofuran ring Crinine-type alkaloids derived from 5,10b-ethanophenanthridine Montanine-type alkaloids derived from 5, 11b-... 

Representative examples of Amatyllidaceae alkaloids are lyeorine 1, lycorenine 2, crinine 3, cheiylline 4, galanthamine 5, montanine 6, nareielasine 7, and tazettine 8. 

Although synthetic approaches toward the montanine-type alkaloids had been made by intramolecular cyclization of 3-(3,4-methylenedioxy)phenyl-hexahydroindoline derivatives (176), these attempts were thus far unsuccessful. The 5,11-methanomorphanthridine ring systems 341-343 (Fig. 21)... 

The intramolecular acylation of the vinyl lithium derivative of 63, prepared by exchange of iodine with lithium (chapter 8) with the Weinreb amide on the side chain gives the five-membered heterocyclic ring in 64, an intermediate on the way to (-)-brunsvigine 65, an alkaloid of the montanine group.14... 

The molecular structures and absolute configurations of two 5,10-ethano-phenanthridine alkaloids, 6-hydroxybuphanidrine (22) methiodide and haeman-thamine p-bromobenzoate (23), have been determined by J -ray analysis.19 An important first paper on the 13C n.m.r. spectral analysis of several Amaryllidaceae alkaloids (among them buphanamine, lycorenine, tazettine, deoxy-tazettine, montanine, and galanthine) using sophisticated proton decoupling techniques requires the careful attention of alkaloid chemists.20 The XH n.m.r. 

Total synthesis of montanine-type Amaryllidaceae indole alkaloids 00PAC1773. 

Narcissus alkaloid structures. Narciclasine and Montanine types. 

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