Synthesis of Two New Hemisynthetic Diterpenylhydroquinones from Natural Ent-Labdanes

Abstract

The synthesis and structural determination of two new diterpenylhydroquinones: 2β-acetoxy-15-phenyl-(22,25-dihydroxy)-ent-labda-8(17),13(E)-diene (1) and 2β-hydroxy-15-phenyl-(22,25-dihydroxy)-ent-labda-8(17),13(E)-diene is 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.

Synthesis and Antiproliferative Activity of New Cyclodiprenyl Phenols against Select Cancer Cell Lines

“…The new cyclodiprenyl phenols 2 – 7 were synthesized from perillyl alcohol 1 by alkylation with the corresponding phenol in acetonitrile in the presence of boron trifluoride diethyl etherate as catalyst ( Scheme 1 ) [ 27 ].…”

Synthesis and Antitumor Activity of Diterpenylhydroquinone Derivatives of Natural Ent-Labdanes

“…Previously we reported the isolation and structural determination of the mixture of ent -labdanes 1 - 2 from Calceolaria inamoena and the preparation of derivatives 3 and 8 [ 13 , 14 ]. In the saponification reaction used for preparation of diterpenyl synthon 4 , a new compound 11 was obtained when acidic conditions were used, presumably due to a transesterification reaction and the presence of ethyl acetate in the workup procedure, nevertheless the target diol 4 could be obtained under partial neutralization conditions ( Scheme 1 ).…”

“…The next step was the coupling reaction between compound 4 and 1,4-hydroquinone to give diterpenylhydroquinone 8 , using the synthetic protocol recently reported by us [ 13 ]. A subsequent acetylation reaction, under standard conditions, gave the new compound 9 ( Scheme 1 ).…”

“…Recently we reported the synthesis and the structural determination of a series of natural ent -labdane derivatives 3 - 6 ( Figure 2 ) and the diterpenylhydroquinones 7 and 8 ( Figure 2 ) using Electrophilic Aromatic Substitution ( EAS ) reactions between an arene nucleus and an allylic alcohol as diterpenyl synthon [ 13 ].…”

Bioactive Prenyl- and Terpenyl-Quinones/Hydroquinones of Marine Origin †

“…Several ent -labdanes isolated from Calceolaria inamoena (Fam. Scrophulariaceae) were used by Catalan et al for the synthesis of drimane-quinones [ 164 ], and ent -halimic acid, isolated from Halimium viscosum (Fam. Cistaceae), was used by Marcos et al for the synthesis of several TQs with aureane skeleton ( Figure 50 ) [ 165 ].…”