Semisynthesis of new sarcophine derivatives with chemopreventive activity.
The natural cembranolide sarcophine (3) and its lactone ring-opened analogue (10) were oxidized using selenium dioxide under different reaction temperatures to prepare hydroxylated derivatives. Nine new compounds were obtained, six of them targeted hydroxylated derivatives. The determination of regio- and stereochemistry as well as the mechanistic considerations on the selectivity observed in these reactions are discussed on the basis of 2D NMR and molecular modeling. In preliminary in vitro tests on inhibition of EBV-EA activation, compounds 10 and 12-15 have shown higher activity than the known chemopreventive agent sarcophytol A.
Katsuyama
Isamu
I
Department of Pharmacognosy and National Center for Natural Products Research, Research Institute of Pharmaceutical Sciences, School of Pharmacy, The University of Mississippi, University, MS 38677-1848, USA.
Fahmy
Hesham
H
Zjawiony
Jordan K
JK
Khalifa
Sherief I
SI
Kilada
Raouf W
RW
Konoshima
Takao
T
Takasaki
Midori
M
Tokuda
Harakuni
H
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D037421:Anthozoa; D016588:Anticarcinogenic Agents / Q000737:chemistry / Q000145:classification / Q000302:isolation & purification* / Q000494:pharmacology; D000956:Antigens, Viral / Q000378:metabolism; D018890:Chemoprevention / Q000379:methods; D004305:Dose-Response Relationship, Drug; D004534:Egypt; D006900:Hydroxylation; D019156:Indian Ocean; D008958:Models, Molecular; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D010084:Oxidation-Reduction; D018036:Selenium Compounds; D064588:Selenium Oxides; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D016588:Anticarcinogenic Agents; D000956:Antigens, Viral; C033305:Epstein-Barr virus early antigen; D018036:Selenium Compounds; D064588:Selenium Oxides; C014804:sarcophine; D015107:4-Butyrolactone