Total syntheses of fumiquinazolines A, B, C, E, H, and I: Studies on the syntheses of fumiquinazoline D, fiscalin A and C.

摘要

A variety of 2,3-disubstitued quinazolin-4-ones (2.5 a--h ) were synthesized from iminobenzoxazines (2.3 a--h) formed by dehydrative cyclization of anthranilic diamides (2.2 a--h ) via intermediate amidines (2.4 a--h). The reaction conditions are modified for compatibility with the functional groups of fumiquinazolines.;We have completed the first syntheses of (-)-fumiquinazolines A (1.1), B (1.2), and I (1.14) which proceed in 16 steps from protected tryptophan, leucine and alanine in 7% overall yield making this family of compounds and a wide variety of analogues readily available. The oxidation of 3.4a with the saccharine-derived oxaziridine for fumiquinazoline A and B and the oxidation of 3.4b with dimethyldioxirane for fumiquinazoline I selectively form the appropriate imidazoindolone stereoisomers.;The syntheses of (-)-fumiquinazolines C (1.10), E (1.3), and H (1.15) were accomplished efficiently in 13 steps. N-FmocNHCH(CH2SePh)CO2H (4.3b) was used to introduce the key double bond of Cbz-dehydrofumiquinazolines A (4.1b). Cyclization of 4.1b formed the 7-member ether ring of Cbz-fumiquinazoline C (4.42) stereo specifically. Cyclization of dehydrofumiquinazoline I (4.61b) afforded fumiquinazoline H (1.15) under neutral conditions.;We have successfully prepared model 5.37 for fiscalin A with the anti H and OH by PtO2 catalyzed hydrogenation of imine. However, this procedure failed to work with the fully functionalized substrate for fiscalin A. Buchi's method and Nakagawa's method were also examined to prepare fiscalins A and C, but no desired products were obtained.