882
Notes
Chem. Pharm. Bull. 57(8) 882—884 (2009)
Vol. 57, No. 8
Regioselective Enzymatic Acylation and Deacetylation of Secoiridoid
Glucosides
José Andrés PÉREZ,*,a Juan Manuel TRUJILLO,a,b Hermelo LÓPEZ,a Zulma ARAG Ó N,a and
a
Carlos BOLUDA
a Instituto Universitario de Bioorgánica, Universidad de La Laguna; Carretera de la Esperanza, 2, 38205 La Laguna,
Tenerife, Canary Islands, Spain: and b Instituto de Productos Naturales y Agrobiología, CSIC; Avda. Astrofísico Francisco
Sánchez, 3, 38205 La Laguna, Tenerife, Canary Islands, Spain.
Received March 13, 2009; accepted April 24, 2009; published online May 19, 2009
Candida antarctica lipase (CAL) catalyses the regioselective cinnamoylation and benzoylation of the agly-
cone moiety of 10-hydroxyoleoside dimethyl ester a secoiridoid glucoside. This enzyme catalyses as well regiose-
lective deacetylation of the aglycone moiety of 10,2ꢀ,3ꢀ,4ꢀ,6ꢀ-pentaacetoxyoleoside dimethyl ester. Further action
of the enzyme results in deacetylation at C-6ꢀ and C-4ꢀ of the glucoside moiety.
Key words lipase; secoiridoid; regioselectivity; acylation; deacetylation
Iridoids and secoiridoids are compounds widely distrib- compound. 13C-NMR (Table 1), correlation spectroscopy
uted in the vegetal kingdom, whose varied biological activi- (COSY), heteronuclear multiple bond coherence (HMBC)
ties are extensively reported.1,2) These activities could be en- and heteronuclear single quantum coherence (HSQC) experi-
hanced by the presence or absence of certain functional ments provided additional information which supported the
groups in the molecule. Hydrolases regioselectivity regarding proposed structure. If these two times of reaction between
the modification of natural glycosides has been amply used.3) themselves and with those already published3) for acetylation
In a previous work,4) we reported about the regioselective of 1a are compared, it seems evident that the size of the acyl
acetylation catalyzed by lipase from Candida antarctica in group has an influence on the rate of reaction, though the
the aglycone moiety of 10-hydroxyoleoside dimethyl ester as amount of enzyme used in each process is the same.
well as the obtainment of two new secoiridoids glucosides by
Nevertheless, it is important to observe that these three
means of this enzymatic route. In this work we describe the processes of acylation were produced in the aglycone moiety,
cinnamoylation and the benzoylation of the aglycone moiety which means not a very common regioselectivity4,6,7) in en-
of 10-hydroxyoleoside dimethyl ester (1a), catalyzed by Can- zymatic reactions of this type in natural glucosides. Figure 1
dida antarctica lipase (CAL) in tetrahydrofuran (THF) where shows both processes of acylation.
the acyl group is provided by vinyl cinnamate or vinyl ben-
Deacetylation of 1b and 4 Deacetylation of 1b to ren-
1
zoate. Cinnamoylation yielded the already described natural der 4 (Fig. 1) took place in 48 h and 90% yield. H-NMR
product 2.5) Benzoylation produced the derivative 3, whose spectrum of 4 (Table 1) showed signal for the protons H-10a
structure unknown as of yet, was established by spectro- and H-10b at d 4.37 and 4.18, which correspond to the dia-
scopic methods.
magnetic shifted signals at d 4.81 and 4.74, respectively, for
Furthermore, we give herein, an account of the regioselec- the starting pentaacetate (1b), which indicates that the
tive enzymatic deacetylation of 10-hydroxyoleoside dimethyl deacetylation occurred at the site C-10. The chemical shifts
ester pentaacetate (1b) by the action of the same enzyme. for the rest of the protons, along with 13C-NMR (Table 1),
The deacetylation occurred at the C-10 position, that is in the COSY, HMBC and HSQC studies, strongly supported the
aglycone moiety, to give the tetraacetate derivative 4. Further structure given for this compound. The aglycone moiety is
deacetylation of the tetraacetate in the same conditions again the chosen site for the enzyme to react. The preference
yielded the diacetate 5. Compounds 4 and 5 have not been of this deacetylation and acylations for the site C-10, may be
previously described and their structures were determined by due to the rotation of the double bond 8—9 is restricted.
spectroscopic studies.
Deacetylation of 4 to 5 is slower; it needed 96 h and was car-
1
Acylation of 1a Cinnamoylation of 1a was carried out ried out only with 50% yield. H-NMR spectrum (Table 1)
with 80% yield after 7 d of reaction and a great excess of showed diamagnetic shifts for the protons H-4ꢂ, H-6ꢂa and
vinyl cinnamate. The product of reaction 2 was identified by H-6ꢂb from values of d 5.09—5.15, 4.29 and 4.14, respec-
comparison with an authentic sample.5) On the other hand, tively, for the original tetraacetate to the corresponding val-
benzoylation took place in 3 d with 90% yield and not so ues 3.80, 3.92 and 3.84, which allowed us to conclude that
1
great excess of vinyl benzoate. H-NMR spectrum (Table 1) deacetylations were produced at the C-4ꢂ and C-6ꢂ positions.
of 3 shows signals at d 4.98 and 4.92 of the protons H-10a This conclusion was supported by 13C-NMR (Table 1),
and H-10b, which means paramagnetic shifts with respect to COSY, HMBC and HSQC. In this case, the enzyme did not
the corresponding values in the starting compound 1a, those discriminate the sites C-6ꢂ and C-4ꢂ of the glucoside ring.
being at d 4.15 and 4.28, respectively. Signals for the aro- Comparison of these results with those of acetylation of 1a,
matic protons of the benzoyl group are also observed at d already published, allowed us to observe that the site C-2ꢂ of
7.97, 7.38 and 7.50 corresponding to H-2ꢀꢁH-6ꢀ, H-3ꢀꢁH- the glucoside ring remained unchanged, both in acetylation
5ꢀ and H-4ꢀ, respectively. The rest of the signals in this spec- and deacetylation processes, suggesting that this site is far
trum were in the same range from those for the starting from the active centre of the enzyme.
∗ To whom correspondence should be addressed. e-mail: japerez@ull.es
© 2009 Pharmaceutical Society of Japan
Perez, Jose Andres
