Bioactive rearranged and halogenated semisynthetic derivatives of the marine natural product sarcophine.
Cembranoids are natural diterpenes with 14-membered macrocyclic rings. The simplest natural cembranoid, (+)-cembrene, was isolated from pine oleoresin. Sarcophytols A and B are known cembranoids that inhibit tumor promotion. Sarcophine is a related cembranoid isolated from the Red Sea soft coral Sarcophyton glaucum. Sarcophine and its bioconversion products and semisynthetic derivatives are reported to possess cancer chemopreventive activity. Oxymercuration-demercuration of sarcophine using Hg(OAc)2 and NaBH4 afforded four new rearranged and hydroxylated products. Bromination of sarcophine with N-bromosuccinimide (NBS) furnished two new brominated and rearranged products. Reaction with iodine gave the known iso-sarcophinone and (+)-sarcophytoxin B. Structure elucidation was based on a combination of transition state modeling, molecular dynamics, mechanistic considerations, and 2D NMR data. The antiproliferative activity of the new products is also reported.
Sawant
Swapnali S
SS
Department of Basic Pharmaceutical Sciences, School of Pharmacy, University of Louisiana at Monroe, 700 University Avenue, Monroe, Louisiana 71209, USA.
Sylvester
Paul W
PW
Avery
Mitchell A
MA
Desai
Prashant
P
Youssef
Diaa T A
DT
El Sayed
Khalid A
KA
D015107:4-Butyrolactone / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D037421:Anthozoa / Q000737:chemistry*; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D018360:Crystallography, X-Ray; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006842:Hydrocarbons, Brominated / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D019156:Indian Ocean; D015394:Molecular Structure; D019906:Nuclear Magnetic Resonance, Biomolecular; D013237:Stereoisomerism; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D004224:Diterpenes; D006842:Hydrocarbons, Brominated; C037071:cembrane; C058761:sarcophytol A; C014804:sarcophine; C058762:sarcophytol B; D015107:4-Butyrolactone