Alantrypinone, etc.

Novel spiro-type pyrazinoquinazoline alkaloids such as spiroquinazoline from Aspergillus flavipes [93], (+)-alantrypinone (24) [94], and (-)-seran-trypinone (25) [95], both from Penicillium thymicola possess a tricyclic pyrazinoquinazolinedione base bridged by a 3-methyleneoxindole substructure. The unusual structural feature and biological property [93] lead to efforts of two groups toward their total synthesis. Hart et al. fulfilled total synthesis of ent-24 via N-acyliminium ion cyclization that converts enamide 103 [255] to bridged indole 104 (Scheme 25) [256,257]. Subsequent NBS-mediated oxidative rearrangement of the bridged indole 104 to the oxindole led to the spirocyclic structure of ent-24 in 12% overall yield from isatoic anhydride by 10 steps. However, ent-17-epi-alantrypinone 105 was formed in 50: 50 to 40 : 60 ratio to ent-24 [256]. On the other hand, Kende et al. has fulfilled a concise total synthesis of (±)-alantrypinone 24 by unique hetero Diels-Alder route (Scheme 26) [268,269].

The Diels-Alder reaction of azadiene 106 prepared from 1-methyl-2,4-dihydro-1ff-pyrazino[2,1-fr]quinazoline-3,6-dione [255] with 3-methylene-oxindole 107 proceeds smoothly in chloroform at rt to afford exo- (108) and endo-isomer (109) in 55 and 18% yields, respectively. Mild hydrolysis of

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