Synthesis of enantio-manoyl oxides: modifiers of the activity of adenylatecyclase enzyme.
Cyclization of methyl ent-8 alpha-hydroxylabd-13(16),14-dien-18-oate with m-chloroperbenzoic acid gave methyl (13S)-ent-16-hydroxy-8 alpha,13-epoxylabd-14-en-18-oate and its epimer at C-13. Biotransformation of the former (which exhibits antileishmania activity) with Rhizopus nigricans cultures produced the methyl (13S)-ent-11 beta,16-dihydroxy-8 alpha,13-epoxilabd-14-en-18-oate (carbomanoyl, which inhibits the activity of the adenylatecyclase enzyme), methyl (13S)-ent-3 beta,16-dihydroxy-8 alpha,13-epoxilabd-14-en-18-oate, methyl (13S)-ent-3 beta,11 beta,16-trihydroxy-8 alpha,13-epoxilabd-14-en-18-oate and the (14S)-ent-3 beta-hydroxy-14,15-epoxy derivative that cyclized spontaneously to a spiran compound. Biotransformation of methyl (13S)-ent-16-hydroxy-3-oxo-8 alpha,13-epoxilabd-14-en-18-oate with R. nigricans produced ent-11 beta-hydroxylation, reduction of the keto group at C-3 (to give 3S-alcohol) and 14(S),15-epoxidation, which also rearranged to a spiro compound.
García-Granados
A
A
Departamento de Química Orgánica, Facultad de Ciencias, Universidad de Granada, Spain.
Liñán
E
E
Martínez
A
A
Onorato
M E
ME
Parra
A
A
Arias
J M
JM
D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000187:drug effects* / Q000378:metabolism; D000818:Animals; D001578:Benzopyrans / Q000138:chemical synthesis* / Q000493:pharmacokinetics / Q000494:pharmacology*; D001711:Biotransformation; D004789:Enzyme Activation; D007893:Leishmania donovani / Q000187:drug effects; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D012233:Rhizopus / Q000378:metabolism; D013237:Stereoisomerism
D000067956:Adenylyl Cyclase Inhibitors; D001578:Benzopyrans; D000262:Adenylyl Cyclases