Meloscine

Recent interest in the use of N-unsubstituted 2-quinolones stems from the fact, that they coordinate effectively to chiral lactam-based templates via two hydrogen bonds. The prototypical template to be used in photochemical reactions is compound 115, which can be readily prepared from Kemp s triacid [108]. The template is transparent at a wavelength X > 290 nm, and can be nicely used in stoichiometric amounts for enantioselective photochemical and radical reactions [109]. Conditions which favor hydrogen bonding (nonpolar solvent, low temperature) are required to achieve an efficient association of a given substrate. The intramolecular [2 + 2]-photocycloaddition of 4-alkylquinolone 114 proceeded in the presence of 115 with excellent enantioselectivity, and delivered product 116 as the exclusive stereoisomer (Scheme 6.41) [110]. Application of the enantiomer ent-115 ofcomplexing agent 115 to the reaction 111 —> 112 depicted in Scheme 6.40 enabled enantioselective access to (+ )-meloscine [111]. 

Selig, P. and Bach, T. (2008) Enantioselective total synthesis of the melodinus alkaloid (+ )-meloscine. Angewandte Chemie, International Edition, 47, 5082-5084. 

The meloscine group of alkaloids has been added to the list of those whose n.m.r. spectra have been thoroughly analysed by a French-American collabora-tion as example, the assignments for meloscine (190) are quoted. Details have been given,in a Russian paper, of the A-ray determination of the structureof pseudokopsinine. 

It is of interest to compare the alkaloidal composition of the Indonesian L eugenefolia which gave besides leuconolam, 21-O-methylleuconolam and rhazinilam-N-oxide, yohimbine, P-yohimbine, and the diazaspiroleuconolam compound, leuconoxine (17S) [136], which has since then also been obtained from the North Borneo species, Kopsia tenuis [19], A similar diazaspiroleuconolam derivative 176 has been obtained via a facile acid-induced ring-reclosure reaction of leuconolam, while the base-induced reaction gave the meloscine-type derivative 177 [127,128]. 

Markownikov addition of HQ to the 6,7-double bond (82.206). The resulting chlorolactams possess the same ring system as leuconoxine (74), from Leuconotis eugemfoUus. The structure of275was confirmed by X-ray crystal structure determination (207). A second reaction of considerable interest is that of leuconolam with potassium hydroxide in methanol, which involves the removal of a proton from C-16, followed by internal Michael addition to the 6,7-double bond. The product is the pentacyclic dilactam 277, which contains the meloscine ring system (82). 

The formation of the tricyclic 9a-arylhydrolilolidine ring system is exemplified in the conversion of (154) to (155).114 Wolff ring contraction of the ketonic ring of (155) and further functional group modifications provided the Melodinus alkaloid (i)-meloscine. (Scheme 55). 

The stereocontrolled total synthesis of the structurally unusual pentacyclic Melodinus alkaloid ( )-meloscine (29a) and ( )-epimeloscine (29b) was achieved starting from the aza-Cope precursor 231139. 

In a previous discussion of the genus Melodinus (Volume XI, p. 242), the isolation and structure elucidation of meloscine (238) and 16-epimeloscine (239) were discussed. The Hoffmann-La Roche group has subsequently published a full presentation of the structure elucidation of these novel alkaloids (110). 

A third alkaloid, isolated with the others from M. scandens Forst. (Ill), on acid hydrolysis underwent decarboxylation to give meloscine (238), and was ascribed the structure 240. In the more recent publication (110), the alkaloid is assigned the name scandine and its structure is conclusively demonstrated. 

The diamagnetic anisotropic effect of the carbomethoxyl group indicated it to be a and the B/C ring junction trans. Because (+)-scandine gave rise to (-t-)-meloscine (238), it was assigned the structure and absolute stereochemistry shown in 241 (110). 

Hz) at 2.23 ppm. The long-range coupling of H-4a is with H-19 (by double irradiation) and establishes the 21 proton to be a. The circular dichroism of meloscandinone was almost identical with that of the previously isolated meloscine alkaloids therefore, 248 also represents the absolute stereochemistry of meloscandinone (112,113). 

Oberhansli (286) has examined the crystal structure of the metho-bromide of meloscine and confirmed the structure and stereochemistry deduced by chemical and spectroscopic methods. 

The interval since the last review was written has seen the isolation of a number of new alkaloids but of few fundamentally new skeletal types. Meloscine (I) (1) and related alkaloids represent a completely novel group, whereas aspidodasycarpine (II) (2) is a new variation of the akuammigine type. 

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