Novel, racemic or nearly‐racemic antibacterial bromo‐ and chloroquinols and γ‐lactams of the verongiaquinol and the cavernicolin type from the marine sponge Aplysina (= Verongia) cavernicola

Abstract

AbstractButanolic extracts of the Mediterranean sponge Aplysina (= Verongia) cavernicola have given, by reverse‐phase HPLC, the antibacterial quinols (±)‐3‐bromoverongiaquinol (= (±)‐3‐bromo‐1‐hydroxy‐4‐oxo‐2,5‐cyclohexadine‐1‐acetamide; 1d) and (±)‐3‐bromo‐5‐chloroverongiaquinol (= (±)‐3‐bromo‐5‐chloro‐1‐hydroxy‐4‐oxo‐2,5‐cyclohexadine‐1‐acetamide; 1c) besides the products of their formal cyclization 5‐chlorohexadiene‐1‐acetamide; 1c) besides the products of their formal cyclization 5‐chlorocavernicolin (= 5‐cloro‐3,3a,7,7aβ‐tetrahydro‐3aβ‐hydroxy‐2,6(1H)‐indoledione; 6), the C(7)‐epimerizing 7β‐bromo‐5‐chlorocavernicolin (=7 β‐bromo‐5‐chloro‐3,3a,7,7aβ‐tetrahydro‐3aβ‐hydroxy‐2,6(1H)‐indoledione; 4a and 7α‐bromo‐5‐chlorocavernicolin (4b), and the C(7)‐epimerizing 5‐bromo‐7β‐chlorocavernicolin ( = 5‐bromo‐7β‐chloro‐3,3a,7,7aβ‐tetrahydro‐3aβ‐hydroxy‐2,6(1H)‐indoledione; 5a) and 5‐bromo‐7α‐chlorocavernicolin (5b). The latter four were isolated as mixtures of C(7)‐epimerizing monoacetates 4a′/4b′ and 5a′/5b′. Both 1 and 1c proved to be racemic from NMR examination of their esterification products with (–)‐methyl‐oxyacetic acid, whilst 6 had a ca. 6% enantiomeric purity as shown by a 1H‐NMR study of its monoacetate 6′ in the presence of a chiral shift reagent. These chiroptical data of the first chiral quinols from the Verongida and of 6 suggest phenol oxidative routes from tyrosine precursors for their formation. In view of their bioactivities, 1d and 1c have been synthesized from (p‐hydroxyphenyl)acetic acid byt phenol oxidative routes.