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New Types of Potentially Antimalarial Agents: Epidioxy‐substituted norditerpene and norsesterpenes from the marine sponge Diacarnus levii
Author(s) -
D'Ambrosio Michele,
Guerriero Antonio,
Deharo Eric,
Debitus Cécile,
Munoz Victoria,
Pietra Francesco
Publication year - 1998
Publication title -
helvetica chimica acta
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.74
H-Index - 82
eISSN - 1522-2675
pISSN - 0018-019X
DOI - 10.1002/hlca.19980810539
Subject(s) - chemistry , moiety , acetic acid , yield (engineering) , peroxide , enone , stereochemistry , labdane , proton nmr , organic chemistry , terpenoid , materials science , metallurgy
Natural free carboxylic acids from the hadromerid sponge Diacarnus levii (Kelly‐Borges and Vacelet) were esterified to yield the new cyclic norditerpene peroxides ent ‐muqubilin benzyl ester (= (α R ,3 S ,6 R )‐α,6‐dimethyl‐6‐[( E )‐4‐methyl‐6‐(2,6,6‐trimethyl‐cyclohex‐1‐en‐1‐yl)hex‐3‐enyl]‐1,2‐dioxan‐3‐acetic acid benzyl ester; 6 , diacarnoate B methyl ester(= (α S ,3 R ,6 R )‐α,6‐dimethyl‐6‐{2‐(4a S ,8a S )‐3,4,4a,5,6,7,8,8a‐octahydro‐3‐oxo‐2,5,5,8a‐tetramethylnaphthalen‐1‐yl)ethyl}‐1,2‐dioxan‐3‐acetic acid methyl ester; 9 ), and deoxydiacarnoate B benzyl ester (= (α S ,3 R ,6 R )‐α,6‐dimethyl‐6‐{2‐[(4a S ,8a S )‐3,4,4a,5,6,7,8,8a‐octahydro‐2,5,5,8a‐tetramethyl‐1‐naphthalenyl]ethyl}‐1,2‐dioxan‐3‐acetic acid benzyl ester; 10 ), which were isolated following extensive chromatography. The relative configuration of the peroxide/α‐methylacetate moiety of 6 , 9 , and 10 , was directly determined from their NMR spectra. The absolute configurations of the peroxide/α‐methylacetate moiety was deduced from comparative 1 H‐NMR data of the ( S )‐ and ( R )‐phenylglycine methyl ester derivatives 7 and 8 as well as 11 / 13 and 12 / 14 , all obtained from a mixture of the precursors of 3 , 6 , and 10 . The absolute configuration at the carbobicyclic moiety of enone 9 and of 10 , is identical, as established by chemical interconversion, 9 and 10 belong to the normal labdane series according to empirical CD rules, applied either directly to 9 or to the parent (+)‐sclareolide‐derived enone 20 . In contrast, molar rotation additivity rules suggest the ent ‐labdane configuration for 9 and 10 . The epidioxides 1 – 3 , 6 , and 10 proved active in vitro against the malaria parasite Plasmodium falciparum ; especially the previously isolated methyl 3‐epinuapapuanoate ( 2 ) was active against a chloroquine‐resistant strain, and this with a good security index.