Molecular simplification in bioactive molecules: formal synthesis of (+)-muconin.
The concept of molecular simplification as a drug design strategy to shorten synthetic routes, while keeping or enhancing the biological activity of the lead drug, has been applied to (+)-muconin, an acetogenin with remarkable cytotoxicity. A novel approach that enables the stereoselective synthesis of such a natural compound or its enantiomer from a common precursor is described. An additional advantage of the method is complete stereochemical control and the decrease in the number of chemical steps required, thus providing an enhancement of the overall yield. Antiproliferative studies against the human solid tumor cell lines showed that the aliphatic chain-THF/THP fragment of (+)-muconin has modest cytotoxic activity. The strategy opens the way to preparing novel bioactive acetogenin analogues by shorter synthetic routes.
Pinacho Crisóstomo
Fernando R
FR
Instituto Universitario de Bio-Organica Antonio Gonzalez, Universidad de La Laguna, Astrofísico Astrofísico Francisco Sanchez 2, 38206 La Laguna, Tenerife, Islas Canarias, Spain.
Carrillo
Romen
R
León
Leticia G
LG
Martín
Tomas
T
Padrón
José M
JM
Martín
Víctor S
VS
D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D005233:Fatty Alcohols / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D007783:Lactones / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D008968:Molecular Conformation; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D005233:Fatty Alcohols; D007783:Lactones; C485515:muconin