ABSTRACT
Two new compounds 2ß-acetoxy-15-phenyl-(22,25-acetoxy)-ent-labda-8(17), 13(E)-diene (9) and 2ß-hydroxy-15-phenyl-(22,24,26-trimethoxy)-ent-labda-8(17),13(E)-diene (10) have been prepared by an Electrophilic Aromatic Substitution (EAS) reaction between diterpenyl allylic alcohols and 1,4-hydroquinone or 1,3,5-trimethoxybenzene using BF(3).Et(2)O as a catalyst. These compounds, along with a series of natural ent-labdanes 3-8, have been evaluated for their in vitro cytotoxic activities against cultured human cancer cells of PC-3 and DU-145 human prostate cancer, MCF-7 and MDA-MB-231 breast carcinoma and dermal human fibroblasts (DHF). Some compounds displayed inhibition at µM IC(50 )values.
Subject(s)
Antineoplastic Agents/chemical synthesis , Diterpenes/chemistry , Hydroquinones/chemical synthesis , Hydroquinones/pharmacology , Antineoplastic Agents/pharmacology , Breast Neoplasms/drug therapy , Cell Death/drug effects , Cell Line, Tumor , Female , Fibroblasts/drug effects , Humans , Inhibitory Concentration 50 , Male , Prostatic Neoplasms/drug therapyABSTRACT
The synthesis and structural determination of two new diterpenylhydroquinones: 2beta-acetoxy-15-phenyl-(22,25-dihydroxy)-ent-labda-8(17),13(E)-diene(1) and 2beta-hydroxy-15-phenyl-(22,25-dihydroxy)-ent-labda-8(17),13(E)-dieneis reported (2). These compounds were obtained by coupling via Electrophilic Aromatic Substitution (EAS) of 1,4-hydroquinone with primary or tertiary allyl alcohol derivatives of the natural ent-labdanes 3 and 4. With this new method, the best results were observed when mixtures of the primary alcohol derivatives 5-6 (26% yield of compound 1) and diol derivatives 9-10 (28% yield of compound 2) were used.
Subject(s)
Diterpenes/chemistry , Diterpenes/chemical synthesis , Hydroquinones/chemistry , Hydroquinones/chemical synthesis , Magnetic Resonance Spectroscopy , Molecular StructureABSTRACT
A route for the degradation of the side chain of ent-labdane derivatives has been devised, giving the useful synthon 2beta,12-dihydroxy-13,14,15,16,17-pentanor-ent-labdane-8-one (8). The use of this compound in the preparation of terpenylquinone derivatives shall be reported elsewhere. In addition we have synthesized the compound 2beta,12-diacetoxy-8beta,17-epoxy-13,14,15,16-tetranor-ent-labdane (10), which upon catalytic epoxide ring opening in alkaline or acid media gave rise in all cases to the formation of tricyclicc ompounds.
