Total synthesis of (-)-fumiquinazolines A, B, C, E, H, and I. Approaches to the synthesis of fiscalin A.
The first syntheses of (-)-fumiquinazolines A, B, and I, which proceed in 14 steps from protected tryptophan, anthranilic acid, leucine, and alanine in 7% overall yield, are described. Tricycle 30 was formed by a palladium-catalyzed cyclization. Oxidation of 30a with saccharine-derived oxaziridine 21 for fumiquinazolines A and B and oxidation of 30b with dimethyldioxirane for fumiquinazoline I selectively formed the appropriate imidazoindolone stereoisomers. Application of the Ganesan-Mazurkiewicz cyclization completed the syntheses. Efficient 14-step syntheses of (-)-fumiquinazolines C (7) and E (3) and a 15-step synthesis of (-)-fumiquinazoline H (8) using FmocNHCH(CH2SePh)CO2H as a dehydroalanine precursor that spontaneously eliminated benzeneselenol without oxidation under the cyclization conditions are also reported. Model 86 for fiscalins A with the H and OH anti to each other has been prepared, but the procedure that worked for the model failed with the fully functionalized side chain.
Snider
Barry B
BB
Department of Chemistry, MS015, Brandeis University, Waltham, Massachusetts 02454-9110, USA. snider@brandeis.edu
Zeng
Hongbo
H
D002384:Catalysis; D003500:Cyclization; D007202:Indicators and Reagents; D007211:Indoles / Q000138:chemical synthesis*; D008958:Models, Molecular; D015394:Molecular Structure; D010084:Oxidation-Reduction; D011799:Quinazolines / Q000138:chemical synthesis*; D013237:Stereoisomerism
D007202:Indicators and Reagents; D007211:Indoles; D011799:Quinazolines; C081407:fiscalin A; C419468:fumiquinazoline A; C419467:fumiquinazoline B; C454622:fumiquinazoline C; C454623:fumiquinazoline E; C454624:fumiquinazoline H; C419466:fumiquinazoline I