Abstract
The straightforward synthesis of phenylacetylrinvanyl (PhAR),
an ultrapotent capsaicinoid is described. The process starts with
the quantitative synthesis of methyl ricinoleate (MeRic) by castor
oil methanolysis. Afterwards, two alternative routes are possible:
a) chemoselective vanillylamine aminolysis of MeRic catalyzed by Candida antarctica lipase-B (CaLB) to
yield rinvanil, which after reaction with phenylacetic acid and
DCC-DMAP followed by a regioselectively pyrrolidine deacylation
results in PhAR with a 51% global yield, b) methyl 12-phenylacetylricinoleate
synthesis by reaction of MeRic with phenylacetic acid and DCC-DMAP,
followed by a chemoselective vanillylamine aminolysis catalyzed
by CaLB to obtain PhAR with a 70% global yield.
Key words
chemoselective synthesis - solvent effects - enzymes -
Candida antarctica B
- ultrapotent
capsaicinoid
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¹ H and ¹³ C
NMR spectroscopy was carried out on a JEOL Eclipse instrument at
300 and 400 MHz (¹ H NMR operating frequency),
with TMS as an internal standard and CDCl3 as solvent.
The IR spectra were carried out on a Bruker spectrophotometer Tensor
27. The [a]D
²0 values
were determined on a 341 Perkin Elmer polarimeter, at 1 dm cell length.
HRMS was determined on a JEOL JMS-SX102A instrument. Silica gel
chromatography: 70-230 mesh. Multiplicity keys: s = singlet,
d = doublet, t = triplet, c = quartet,
q = quintet, m = multiplet, br = broad,
dd = doublet of doublets.
