Sequential electrophilic trifluoromethanesulfanylation-cyclization of tryptamine derivatives: synthesis of C(3)-trifluoromethanesulfanylated hexahydropyrrolo[2,3-b]indoles.
A practical and efficient synthesis of C(3)-trifluoromethanesulfanylated hexahydropyrrolo[2,3-b]indoles 5 from tryptamine derivatives was described. The features of this synthesis included electrophilic activation of C(3) of tryptamine derivatives with "CF(3)S(+)" and cascade ring cyclization by carbamate nucleophile attacking at C(2). Surprisingly, when Lewis acid (BF(3)·OEt(2)) was used as activator instead of proton acid (TsOH·H(2)O) for the electrophilic trifluoromethanesulfanylation of tryptamine derivatives, the uncyclized product 6 was formed preferentially. This sequential trifluoromethanesulfanylation-cyclization protocol was used to synthesize several pyrrolidinoindolinic alkaloid analogues. The cytotoxicity activities of these trifluoromethanesulfanylated alkaloid analogues were evaluated against three cancer cell lines (K562, HeLa, L929).
Key Laboratory of Organofluorine Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Science, 345 Lingling Lu, Shanghai 200032, China.
Yi
Y
Yang
Xueliang
X
Jiang
Feng-Ling
FL
Qing
D005617:Chlorofluorocarbons, Methane / Q000138:chemical synthesis* / Q000737:chemistry; D003500:Cyclization; D007211:Indoles / Q000138:chemical synthesis* / Q000737:chemistry; D015394:Molecular Structure; D011758:Pyrroles / Q000138:chemical synthesis* / Q000737:chemistry; D013237:Stereoisomerism; D013438:Sulfhydryl Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D014363:Tryptamines / Q000737:chemistry*
D005617:Chlorofluorocarbons, Methane; D007211:Indoles; D011758:Pyrroles; D013438:Sulfhydryl Compounds; D014363:Tryptamines; C511200:hexahydropyrrolo(2,3-b)indole; C030820:tryptamine; C009554:fluoroform