Brief total synthesis of the cell cycle inhibitor tryprostatin B and related preparation of its alanine analogue.
Tryprostatin B was synthesized in 32% overall yield from the readily available dipeptide anhydride cyclo-(l-Trp-l-Pro). Its tandem C-3 prenylation/cyclization gave the corresponding pentacyclic pyrroloindole systems bearing a prenyl group at the indole C-3 position. These compounds were then submitted to acid-catalyzed opening of the newly formed ring, with concomitant migration of the prenyl group to the indole C-2 position. The alanine analogue of tryprostatin B was also prepared using a similar sequence. The successful implementation of this strategy strengthens the case for a biosynthetic route for the tryprostatins along similar lines.
Caballero
Esmeralda
E
Departamento de Química Orgánica y Farmacéutica, Facultad de Farmacia, Universidad Complutense, 28040 Madrid, Spain.
Avendaño
Carmen
C
Menéndez
J Carlos
JC
D000409:Alanine / Q000737:chemistry*; D000903:Antibiotics, Antineoplastic / Q000138:chemical synthesis*; D001230:Aspergillus / Q000737:chemistry; D002384:Catalysis; D002453:Cell Cycle / Q000187:drug effects; D003500:Cyclization; D006868:Hydrolysis; D007202:Indicators and Reagents; D026121:Indole Alkaloids / Q000138:chemical synthesis*; D007211:Indoles / Q000737:chemistry; D013058:Mass Spectrometry; D008968:Molecular Conformation; D010879:Piperazines / Q000138:chemical synthesis*; D013237:Stereoisomerism
D000903:Antibiotics, Antineoplastic; D007202:Indicators and Reagents; D026121:Indole Alkaloids; D007211:Indoles; D010879:Piperazines; C097859:tryprostatin B; D000409:Alanine