Structural reassignment, absolute configuration, and conformation of hypurticin, a highly flexible polyacyloxy-6-heptenyl-5,6-dihydro-2H-pyran-2-one.
The structural reassignment, absolute configuration, and conformational behavior of the highly flexible natural product hypurticin (pectinolide E), 6S-[3'S,5'R,6'S-triacetoxy-1Z-heptenyl]-5S-acetoxy-5,6-dihydro-2H-pyran-2-one (1), were ascertained by a molecular modeling protocol, which includes extensive conformational searching, geometry optimization by DFT B3LYP/DGDZVP calculations, and comparison between the theoretical (DFT) and experimental (1)H-(1)H NMR coupling constants. Hyptolide (2), a related cytotoxic 5,6-dihydro-2H-pyran-2-one that increased the S phase of the HeLa cell cycle, was employed as a reference substance to validate the theoretical protocol designed to characterize the 3D properties of compound 1. The related synthetic derivative, tri-O-acetyl-3,6-dideoxy-d-glucose diphenyldithioacetal (14), was prepared by a six-step reaction sequence starting from d-glucose and served as an enantiopure building block to reinforce the structural and configurational assignment of 1. This protocol proved to be an important tool for the structural characterization of highly flexible bioactive polyoxygenated natural products.
Mendoza-Espinoza
José Alberto
JA
Departamento de Química y Programa de Posgrado en Farmacología, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, DF, Mexico.
López-Vallejo
Fabian
F
Fragoso-Serrano
Mabel
M
Pereda-Miranda
Rogelio
R
Cerda-García-Rojas
Carlos M
CM
D000465:Algorithms; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005947:Glucose / Q000737:chemistry; D006367:HeLa Cells; D006801:Humans; D008958:Models, Molecular; D008968:Molecular Conformation; D015394:Molecular Structure; D011753:Pyrones / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D013237:Stereoisomerism
D011753:Pyrones; C540546:hypurticin; D005947:Glucose