Regioselective enzymatic acylations of polyhydroxylated eudesmanes: semisynthesis, theoretical calculations, and biotransformation of cyclic sulfites.
Different lipase enzymes have been tested in order to perform regioselective acetylations on the eudesmane tetrol from vulgarin. High yields (95%) of 1,12-diacetoxy derivative (4) were achieved in 1 h with Candida antarctica lipase (CAL). However, only the 12-acetyl derivative (6) was obtained in similar yield with Mucor miehei (MML) or Candida cylindracea (CCL) lipases. The enzymatic protection at C-1 and C-12 has been used to form eudesmane cyclic-sulfites between C-6 and C-4 atoms. The R/S-sulfur configuration has been assigned by means of the experimental and theoretical (13)C and (1)H NMR chemical shifts. The theoretical shifts were calculated using the GIAO method, with a MM+ geometry optimization followed by a single-point calculation at the B3LYP/6-31G(*) level (B3LYP/6-31G(*)//MM+). Moreover, B3LYP/6-31G(*) geometry optimizations were carried out to test the B3LYP/6-31G(*)//MM+ results, for the deacetylated sulfites (12 and 15). In addition to the delta(C) and delta(H) shifts, the (3)J(HH) coupling constants were also calculated and compared with the experimental values when available. Finally, different reactivities have been checked in both sulfites by biotransformation with Rhizopus nigricans. While the R-sulfite gave 2 alpha- and 11 beta-hydroxylated metabolites, the S-sulfite yielded only regioselective deacetylations. Furthermore, both sulfites showed different reactivities in redox processes.
García-Granados
A
A
Departamento de Química Orgánica, Facultad de Ciencias, Universidad de Granada, 18071-Granada, Spain. agarcia@ugr.es
Melguizo
E
E
Parra
A
A
Simeó
Y
Y
Viseras
B
B
Dobado
J A
JA
Molina
J
J
Arias
J M
JM
D000215:Acylation; D001711:Biotransformation; D003640:Dealkylation; D008049:Lipase / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D008968:Molecular Conformation; D009281:Naphthalenes / Q000138:chemical synthesis* / Q000737:chemistry; D012233:Rhizopus / Q000737:chemistry; D012717:Sesquiterpenes; D045787:Sesquiterpenes, Eudesmane; D013447:Sulfites / Q000737:chemistry*
D009281:Naphthalenes; D012717:Sesquiterpenes; D045787:Sesquiterpenes, Eudesmane; D013447:Sulfites; C015872:eudesmane; D008049:Lipase