The first total synthesis of discorhabdin A.
The first stereoselective total synthesis of a potent antitumor alkaloid, discorhabdin A (1), which is a unique sulfur-containing pyrroloiminoquinone alkaloid, is described. The key step in the stereocontrolled total synthesis of 1 involves both a diastereoselective oxidative spirocyclization using a hypervalent iodine(III) reagent and an efficient construction of the labile and highly strained N,S-acetal skeleton. These methodologies provide a breakthrough in the total syntheses of these promising new antitumor agents, discorhabdins and their analogues, which should serve as valuable probes for structure-activity studies.
Tohma
Hirofumi
H
Graduate School of Pharmaceutical Sciences, Osaka University, 1-6 Yamada-oka, Suita, Osaka 565-0871, Japan.
Harayama
Yu
Y
Hashizume
Miki
M
Iwata
Minako
M
Kiyono
Yorito
Y
Egi
Masahiro
M
Kita
Yasuyuki
Y
D000080:Acetals / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D009285:Naphthoquinones / Q000138:chemical synthesis / Q000737:chemistry; D010084:Oxidation-Reduction; D011809:Quinones / Q000138:chemical synthesis* / Q000737:chemistry*; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry*; D013237:Stereoisomerism; D013455:Sulfur / Q000737:chemistry; D013841:Thiazepines / Q000138:chemical synthesis* / Q000737:chemistry*
D000080:Acetals; D000970:Antineoplastic Agents; D009285:Naphthoquinones; D011809:Quinones; D013141:Spiro Compounds; D013841:Thiazepines; C471812:discorhabdin A; D013455:Sulfur