Regioselective Enzymatic Acylations of Polyhydroxylated Eudesmanes:  Semisynthesis, Theoretical Calculations, and Biotransformation of Cyclic Sulfites

Abstract

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.

The influence of sulfur configuration in 1H NMR chemical shifts of diasteromeric five‐membered cyclic sulfites

“…More recent reports have demonstrated the importance of the differential reactivity of epimeric cyclic sulfites in organometallic additions, oxidations, and reactions with enzymes …”

1,3‐Dipolar Cycloaddition of 4‐Chlorobenzonitrile Oxide with Some Dipolarophiles: Theoretical Analysis of Regioselectivity

“…For instance, several treatments of 1,3-DC reactions of nitrile oxides with various dipolarophiles can be found in the literature [7][8][9]. Finally, the gauge-invariant atomic orbital (GIAO) method [10] was used to calculate NMR chemical shifts, to help the experimental cycloadduct determination, because it has shown to yield data comparable to those of the experiment [11]. 1).…”

NMR assignment in regioisomeric hydroquinones

“…[16,17] Among the wide range of DFT methods reported in the literature, the O3LYP [18,19] is a GGA hybrid class of functional that has demonstrated to be appropriate in reproducing the NMR properties, not only spin-spin coupling constants [20] but also chemical shifts of carbon, hydrogen and other atoms. [21 -23] In the present study, we report the two-step synthesis of a series of hydroquinones (Scheme 1) that fulfill the key structural features of the parent hydroquinone 1.…”