Quinocarcins

Azomethine yhdes have also been subjected to reactions with 165 (Scheme 12.52). Gamer and Ho (288) developed the reaction of the photogenerated azomethine ylide 173 with 165 for the synthesis of quinocarcin. The reaction gave 174 with complete endo/exo selectivity and with more than 90% de. Other types of azomethine ylides have also been used in reactions with 165 and its derivatives (289,290). 

Garner et al. [49] have synthesized the 6-exo-substituted 3,8-diazabicydo [3.2.1] octane core of DNA reactive quinocarcin alkaloid 99 by cydoaddition of the azomethine ylide 101, generated by irradiation (A. — 254 nm) of the corresponding aziridine 100, with Oppolzer s chiral acryloyl sultam (102). This produced 6-exo-subs tituted cycloadducts 103 104 in 25 1 diastereoselectivity (Scheme 8.30). 

The synthetic utility of the photolytic decomposition pathway of pyrrolo[3,4-J]-1,2,3-triazole derivatives has been realised in the asymmetric synthesis of (—)-quinocarcin. Thus, the triazine (62) was irradiated using a mercury light source to give aziridine (63) in 90% yield via loss of nitrogen <93JA10742>. 

However, the synthesis of (—)-quinocarcin required a suitably substituted maleimide precursor which incorporated a chiral auxiliary moiety that could subsequently form part of the target molecule. Consequently, the maleimide (169) was reacted with methyl azide to give the triazoline (62) in 99% yield <93JA10742>. 

Katoh, T., Kirihara, M., Yoshino, T., Tamura, O., Ikeuchi, F., Nakatani, K., Matsuda, F., Yamada, K., Gomi, K., Ashizawa, T., Terashima, S. Synthetic studies on quinocarcin and its related compounds. 5. Synthesis and antitumor activity of various structural types of quinocarcin congeners. Tetrahedron 1994, 50, 6259-6270. 

Cytotoxic activities of quinocarcin derivatives (XXI) against HeLa cells were reported by Saito et aL (47). From their data Eq. 25 was obtained [33] ... 

In this chapter, an attempt has been made to present a total of 30 QSAR models on 17 different heterocyclic compound series (acridine, benzimidazole, benzothiazole, camptothecin, flavonoid, indole, isatin, isoquinoUne, oncodazole, paclitaxel, phenanthridine, phenazine, podophyllotoxin, pyrrole, quinocarcin, quinoline, and quinolone) for their cytotoxic activities against various cancer cell lines. The QSARs have been found to be well correlated with a number of physicochemical and structural parameters. The most important parameter for these correlations is hydrophobicity, which is one of the most important determinants for the activity. 

Two more complex examples of this reaction type are used in work on the total synthesis of quinocar-cin and gelsemine. A vinyl sulfide is employed as nucleophile in an Af-acyliminium cyclization to produce the bridged substructure of quinocarcin (equation 96).A genuine equivalent of the Mannich reaction is put to practice in a synthetic approach to gelsemine (equation 97). The iminium intermediate, simply generated by protonation of the enecarbamate, apparently reacts only with the enol shown in (128). 

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