Indolo quinolizidines, synthesis

CiqHi Nj, Mr 272.35, mp. 258-260 C, an indolo-quinolizidine alkaloid from the Gelsemium species G. sempervirens and G. elegans (Loganiaceae). For synthesis, see Lit.. S. has antitumor activity and shows a tendency for DNA intercalation (cytotoxicity). 

The intramolecular Pummerer reaction has been applied to the synthesis of simple quinolizidine alkaloids like lupinine <2000JOC2368>, and also to arenoquinolizine alkaloids. Thus, the 2-(2-piperidyl)indole 284 was converted to indolo[2,3- ]quinolizidine 287 following a protocol that has as the key step the regioselective cyclization onto the indole 3-position of a thionium ion generated by Pummerer reaction from the appropriately substituted compound... 

A series of papers have been published by Lounasmaa et al. (122-128) on the synthesis of different alkaloid-like indolo[2,3-a]quinolizidine derivatives by means of reduction and subsequent cyclization of A-[2-(indol-3-yl)ethyl]piridi-nium salts, developed as a general method for indole alkaloid synthesis by Wenkert and co-workers (129, 130). Aimed at the total synthesis of vallesiachotamine (9), valuable model studies were reported (131-133). Reduction of pyridinium salts 183 and 184 with sodium dithionite and subsequent acid-induced cyclization represents a convenient method for preparing val-lesiachotamine-type derivatives 185 and 186, respectively. 

Padwa and co-workers (232,233) adapted their thioisomiinchnone generation-cycloaddition strategy to the synthesis of several tetrahydroisoquinoline alkaloids and the indolo[2,3-a]quinolizidine alkaloid alloyohimbane 333 (Scheme 10.44). 

In some convenient and efficient syntheses reported, annelation of the terminal six-membered ring with the formation of C—N bond was involved <60AC(R)75, 68JHC799, 730PP55, 84AJC367>. One example demonstrated in Scheme 33, is the synthesis of indolo[2,3-u]quinolizidine (131) which has been obtained in 74% overall yield from amide (186) <75CPB304>. 

Progress in total synthesis of marine alkaloids, aaptamines 99H(50)549. Racemic and chiral syntheses of some indolo[2,3-a]quinolizidine alkaloids through a lactim ether route 98H(47)525. 

The reduction of several indolo[2,3-a]quinolizidines by BY gave novel products resulting from reduction of the indole double bond, cleavage of the C-D ring junction, or reduction of a lactame to a carbinol amine [371]. The known reduction of aromatic nitro compounds has been used as a key step in the synthesis of 2-aryl-2/f-benzotriazoles. Thus, treatment of the o-nitrophenylazo dye 342 gave the 2-aryl-2/7-benzotriazole-l-oxides 343 in good yields [513]. 

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