Prunus armeniaca hydroxynitrile lyase (ParHNL) catalyzed asymmetric synthesis of δ,ε-unsaturated cyanohydrins

Article abstract of DOI:10.1055/s-0029-1216732

Hydroxynitrile lyases (HNL) are one of the key enzymes in cyanogenic plants, catalyzing the final step in the biodegradation pathway of cyanogenic glycosides releasing HCN and the corresponding carbonyl components. We have been able to find some new plant

Full text of DOI:10.1055/s-0029-1216732

LETTER
1237
Prunus Armeniaca Hydroxynitrile Lyase (ParHNL) Catalyzed Asymmetric
Synthesis of d,e-Unsaturated Cyanohydrins
A
symmetric Syn
a
d
,
e
j
-Unsat
i
urated
bCyanohydrins Bhunya, Nandan Jana, Tapas Das, Samik Nanda*
Department of Chemistry, Indian Institute of Technology (IIT), Kharagpur 721302, India
E-mail: snanda@chem.iitkgp.ernet.in
Received 8 December 2008
termediates for accessing various small organic molecules
Abstract: Hydroxynitrile lyases (HNL) are one of the key enzymes
in cyanogenic plants, catalyzing the final step in the biodegradation
pathway of cyanogenic glycosides releasing HCN and the corre-
sponding carbonyl components. We have been able to find some
in asymmetric fashion as described by Marcus et al.6 w-
Unsaturated chiral nitrones have been synthesized from
d,e-unsaturated cyanohydrins and dipolar cycloaddition
new plant HNL from drupe available in the northern part of the reactions afford highly substituted carbocyclic analogues
Indian subcontinent. Asymmetric cyanohydrin synthesis from g,d-
unsaturated aldehydes by applying those new HNL is reported in
this communication.
in a stereoselective manner. The synthesized cyanohy-
drins from g,d-unsaturated aldehydes can also lead to var-
ious interesting small carbocyclic molecules by functional
group modification.
Key Words: hydroxynitrile lyase, cyanohydrins, asymmetric syn-
thesis
The required g,d-unsaturated aldehydes can be synthe-
sized by a three-step method starting from allylic alcohols
(Scheme 1). The allylic alcohols for accessing 1, 2, and 5
are commercially available; whereas the others were syn-
thesized from the respective ketones by a two step method
(Wittig–Horner–Emmons olefination with triethyl
phosphonoacetate followed by reduction with LiAlH4 and
AlCl3). The allylic alcohols are subjected to Johnson
orthoester Claisen rearrangement to yield the correspond-
ing g,d-unsaturated esters in good yield.7 Reduction of the
ester functionality followed by oxidation under Swern
conditions afforded the g,d-unsaturated aldehydes in good
yield.8
Enantiomerically pure cyanohydrins have attracted the at-
tention of organic chemists, as well as enzymologists, due
to their immense potential as chiral building blocks and
interesting biological properties.1 Enantiopure cyano-
hydrins serve as intermediates for several industrially use-
ful chemicals, and the use of chiral cyanohydrins as
building blocks for the production of important chemicals
is likely to continue growing, as it avoids problems asso-
ciated with the optical resolution of or asymmetric synthe-
sis of certain products.2 One of the most promising and
interesting ways to obtain enantiomerically pure cyanohy-
drins is the HNL-catalyzed addition of cyanide to the req-
uisite carbonyl compound.3 The chemistry and biology of
HNL have been extensively explored over the past two
decades,4 and active research to find new HNL with inter-
esting catalytic properties is still ongoing. Hydroxynitrile
lyase has been reckoned as an efficient industrial biocata-
lyst for the production of active pharmaceutical ingredi-
ents (APIs), chiral building blocks, and agrochemicals.
Both the alcohol and the nitrile parts of the cyanohydrin
functionality can undergo transformation to a range of
groups. These are general methods that proceed via race-
mization-free process so that the optical purity is retained.
Pioneering work by Effenberger, Griengl, and others
opened a new era in the area of asymmetric cyanohydrin
synthesis by HNL,4 readily available from the kernels of
almond, apple, cherry, apricots, and plums.
As part of our ongoing HNL screening program from sev-
eral cyanogenic plant species, we have been successful in
finding new HNL from various stone fruits collected from
the state of Himachalpradesh (Northern territory of India).
We mainly focused our attention on fruits from members
of the Rosaceae family (genus: Prunus). The fruits col-
lected comprised peach (Prunus persica), wild cherry
(Prunus avium), Red Indian plum (Prunus domestica),
Himalayan plum (Prunus americana), apricot (Prunus ar-
meniaca) and shakarpara (white apricot, a hybrid culti-
var). The enzymes isolated from the seed portion of all the
above collected fruit exhibit HNL activity as measured by
chiral HPLC based HNL assay method.9 All of the plant
materials produced (R)-mandelonitrile by Si-facial attack
as detected by chiral HPLC measurements when benz-
aldehyde was used as the standard assay substrate. Among
the plant HNL we screened, HNL from shakarpara (white
apricot, Prunus armeniaca) is superior in terms of
enantioselection (Table 1); whereas HNL from wild cher-
ry (Prunus avium) and apricot (Prunus armeniaca) also
exhibit good enantioselection under the standard assay
conditions. The partially purified enzyme solution can be
stored at 4 °C for 2–3 months without significant loss of
activity.
Hydroxynitrile lyase biocatalysis with a,b-unsaturated al-
iphatic aldehydes has been well reported in the literature.5
However, HNL biocatalysis with structurally similar g,d-
unsaturated aldehydes has not been studied. The d,e-un-
saturated cyanohydrins can serve as very good chiral in-
SYNLETT 2009, No. 8, pp 1237–1240
x
x.
x
x.
2
0
0
9
Advanced online publication: 17.04.2009
DOI: 10.1055/s-0029-1216732; Art ID: D40508ST
© Georg Thieme Verlag Stuttgart · New York

1238
R. Bhunya et al.
LETTER
R1
R3
R3
MeC(OEt)3
EtCO2H
1. LAH
CO2Et
CHO
R2
OH
R2
2. Swern oxidation
R2
R1
R1
R3
R3
1 R1 = R2 = H
2 R1 = R2 = Me
3 R1 = R2 = Et
4 R1 = R2 = Ph
5 R1 = R2 = H, R3 = Me
O
OH
LAH, AlCl3
NaH
OEt
CO2Et
R
EtO2C
P
R
R
n
n
OEt
n
O
1. MeC(OEt)3, EtCO2H
2. LAH
3. Swern oxidation
R = H, n = 0, 1, 2
R = Me, n = 1
CHO
6 R = H, n = 0
7 R = H, n = 1
8 R = H, n = 2
9 R = Me, n = 1
n
R
Scheme 1 Orthoester Claisen rearrangement for the synthesis of g,d-unsaturated aldehydes
Table 1 Comparision of HNL Activity in Various Plants
Plant material
Material assayed
Seed
HNL activity (U/mL)
80 (R)
ee (%)a
93
Prunus avium (wild cherry)
Prunus domestica (Indian plum)
Prunus persica (Peach)
Seed
90 (R)
88
Seed
95 (R)
72
Prunus armeniaca (Apricot)
Prunus americana (Himalayan plum)
Prunus armeniaca Shakarpara cultivar (Apricot)
Seed
206 (R)
93
Seed
102 (R)
89
Seed
280 (R)
96
a Enantiomeric excess (%) was measured by chiral HPLC (OJ-H column; hexane–i-PrOH; 9:1; flow rate 1 mL/min. Benzaldehyde was taken
as a standard substrate. Retention times for (R)- and (S)-mandelonitrile are 14.4 and 19.1 min, respectively.
We subsequently used HNL from shakarpara (ParHNL) tions, synthesized cyanohydrins are derivatized as their
for the asymmetric synthesis of cyanohydrins. In the gen- benzoate esters and chiral HPLC measurements were per-
eral procedure, a vigorously stirred biphasic reaction me- formed (compared with the HPLC trace of racemic
dium was employed,10 with HCN in diisopropylether benzoate esters prepared from racemic d,e-unsaturated
(DIPE) as the cyanating source (Scheme 2). As HCN is a cyanohydrins).
strong cyanating agent the reaction is complete within 2–
6 hours at 10 °C. We also performed a biocatalytic tran-
scyanation approach with acetonecyanohydrin as the
The chemical yield and optical purity of the cyanohydrins
thus synthesized from g,d-unsaturated aldehydes by HNL
biocatalysis are listed in Table 2. As can be seen from
cyanide source for accessing the d,e-unsaturated cyano-
Table 2 it is evident that all the g,d-unsaturated aldehydes
hydrins,11 but the slow decomposition of acetonecyano-
(1–9) are very good substrates for ParHNL as they yield
the respective cyanohydrins with good chemical yield
hydrin under the reaction conditions made the process
time consuming, and a large excess of acetone cyano-
(70–85%) and excellent optical purity (ca. 96–98% ee).
hydrin is required (6 equiv with respect to aldehydes) to
The absolute configuration of all the newly synthesized
cyanohydrins was assigned as R as ParHNL is R-selective.
The g,d-unsaturated aldehydes 1 and 5 yield the respective
cyanohydrins in comparatively lesser time than the other
obtain appreciable amount of conversion. After comple-
tion of the reaction (as indicated by TLC) the product cy-
anohydrins were isolated by extractive workup and
purified. To determine the enantioselectivity of the reac-
R2
CN
R2
R2
CN
ParHNL, pH = 4.0
HCN, DIPE, 10 °C
PhCO2H
CHO
R1 R1
R1 R1
R1 R1
EDCI⋅HCl
R2
OCOPh
R2
OH
R2
1–9
DMAP
ee = 95–98%
(
R)-cyanohydrin
Scheme 2 Biocatalyzed synthesis of d,e-unsaturated cyanohydrins
Synlett 2009, No. 8, 1237–1240 © Thieme Stuttgart · New York

LETTER
Asymmetric Synthesis of d,e-Unsaturated Cyanohydrins
1239
2001, 12, 843. (f) Cruz Silva, M. M.; Melo, M. L.; Parolin,
M.; Tessaro, D.; Riva, S.; Danieli, B. Tetrahedron:
Asymmetry 2004, 15, 21. (g) Li, N.; Zong, M.-H.; Peng,
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Biotechnol. Lett. 2003, 25, 219. (i) Fröhlich, R. F. G.;
Zabelinskaja-Mackova, A. A.; Fechter, M. H.; Griengl, H.
Tetrahedron: Asymmetry 2003, 14, 355. (j) Hernández, L.;
Luna, H.; Ruíz-Terán, F.; Vázquez, A. J. Mol. Catal. B:
Enzym. 2004, 30, 105. (k) Cyanide in Biology; Vennesland,
B.; Conn, E. E.; Knowels, C. J.; Westley, J.; Wissing, F.,
Eds.; Academic Press: New York, 1981.
compounds, possibly due to the fact that the b-carbon is
unsubstituted, whereas for other aldehydes (2–4 and 6–
9)12 the b-carbon is fully substituted and that might hinder
binding in the HNL active site.
In conclusion we have described an efficient biocatalytic
asymmetric synthesis of d,e-unsaturated cyanohydrins
from the corresponding aldehydes. The synthesized cy-
anohydrins exhibit excellent enantioselection and are ob-
tained in good chemical yield. Further functionalization of
those optically pure d,e-unsaturated cyanohydrins to af-
ford enantiomerically pure small organic molecules are
currently in progress in our laboratory.
(2) Kruse, C. G. Chiral Cyanohydrins – Their Manufacture and
Utility as Chiral Building Blocks, In Chirality in Industry
(The Commercial Manufacture and Applications of
Optically Active Compounds); Collins, A. N.; Sheldrake,
G. N.; Crosby, J., Eds.; John Wiley and Sons: New York,
1992, Chap. 14, 279–299.
Table 2 ParHNL-Catalyzed Asymmetric Synthesis of d,e-Unsatur-
ated Cyanohydrins
Substrate
Reaction time (h) Yield (%)
ee (%)a
98
(3) (a) Garcia-Urdiales, E.; Alfonso, I.; Gotor, V. Chem. Rev.
2005, 105, 313. (b) Gregory, R. J. H. Chem. Rev. 1999, 99,
3649. (c) North, M. Tetrahedron: Asymmetry 2003, 14, 147.
(4) (a) Smitskamp-Wilms, E.; Brussee, J.; Van der Gen, A.; van
Scharrenburg, G. J. M.; Sloothaak, J. B. Recl. Trav. Chim.
Pays-Bas 1991, 110, 209. (b) Gerstner, E.; Kiel, U. Z.
Physiol. Chem. 1975, 356, 1853. (c) Xu, L.-L.; Singh, B. K.;
Conn, E. E. Arch. Biochim. Biophys. 1986, 250, 322.
(d) Yemm, R. S.; Poulton, J. E. Arch. Biochim. Biophys.
1986, 247, 440. (e) Albrecht, J.; Jansen, I.; Kula, M.-R.
Biotechnol. Appl. Biochem. 1993, 17, 191. (f) Wajant, H.;
Förster, S.; Selmar, D.; Effenberger, F.; Pfizenmaier, K.
Plant Physiol. 1995, 109, 1231. (g) Wajant, H.; Mundry,
K.-W. Plant. Sci. 1993, 89, 127. (h) Bove, C.; Conn, E. E.
J. Biol. Chem. 1961, 236, 207. (i) Kuroki, G. W.; Conn, E.
E. Proc. Natl. Acad. Sci. U.S.A. 1989, 86, 6978. (j) Wajant,
H.; Förster, S.; Bottinger, H.; Effenberger, F.; Pfizenmaier,
K. Plant. Sci. 1995, 108, 1. (k) Hughes, J.; Lakey, J. H.;
Hughes, M. A. Arch. Biochim. Biophys. 1994, 311, 496.
(5) (a) Nanda, S.; Kato, Y.; Asano, Y. Tetrahedron: Asymmetry
2006, 17, 735. (b) Forster, S.; Roos, J.; Effenberger, F.;
Wajant, H.; Sprauer, A. Angew. Chem., Int. Ed. Engl. 1996,
35, 437. (c) Trummler, K.; Roos, J.; Schwaneberg, U.;
Effenberger, F.; Forster, S.; Pfizenmaier, K.; Wajant, H.
Plant Sci. (Shannon, Irel.) 1998, 139, 19. (d) Ognyanov,
V. I.; Datcheva, V. K.; Kyler, K. S. J. Am. Chem. Soc. 1991,
113, 6992. (e) Griengl, H.; Klempier, N.; Pochlauer, P.;
Schmidt, M.; Shi, N.; Zabelinskaja-Mackova, A. A.
Tetrahedron 1998, 54, 14477. (f) Klempier, N.; Pichler, U.;
Griengl, H. Tetrahedron: Asymmetry 1995, 6, 845.
(g) Warmerdam, E. G. J. C.; van den Nieuwendijk, A. M.
C. H.; Kruse, C. G.; Brussee, J.; van der Gen, A. Recl. Trav.
Chim. Pays-Bas 1996, 115, 20.
2
80
82
CHO
CHO
4.5
98
96
97
5
5
3
78
70
85
CHO
CHO
Et
Et
Ph
Ph
98
98
CHO
CHO
CHO
5
5
82
76
96
98
CHO
CHO
6
6
80
72
95
a Enantiomeric excess (%) was measured by chiral HPLC measure-
ment of the benzoate derivatives of the cyanohydrins (CHIRALPAK
AS-H; hexane–i-PrOH, 49:1; flow rate 0.8 mL/min).
(6) Marcus, J.; Johannes, B.; Van der G en, A. Eur. J. Org.
Chem. 1998, 2513.
(7) Srikrishna, A.; Nagaraju, S.; Kondaiah, P. Tetrahedron
Acknowledgment
1995, 51, 1809.
Financial support from IFS (Sweden, Grant agreement No: F-4192/
1) is gratefully acknowledged. Three of the authors (RB, NJ & TD)
are greateful to CSIR (New Delhi, India) for research fellowships.
(8) Mancuso, A. J.; Brownfain, D. S.; Swern, D. J. Org. Chem.
1979, 44, 4148.
(9) Nanda, S.; Kato, Y.; Asano, Y. Tetrahedron 2005, 61,
10908.
(10) Avi, M.; Fechter, M. H.; Gruber, K.; Belaj, F.; Pochlauer, P.;
Griengl, H. Tetrahedron 2004, 60, 10411.
(11) Enzyme Extraction from Prunus armeniaca (Shakarpara
Spricot)
References and Notes
(1) (a) Kobler, C.; Bohrer, A.; Effenberger, F. Tetrahedron
2004, 60, 10397. (b) Solís, A.; Luna, H.; Manjarrez, N.;
Pérez, H. I. Tetrahedron 2004, 60, 10427. (c) Avi, M.;
Fechter, M. H.; Belaj, F.; Pöchlauer, P.; Griengl, H.
Tetrahedron 2004, 60, 10411. (d) Kobler, C.; Effenberger,
F. Tetrahedron: Asymmetry 2004, 15, 3731. (e) Han, S.;
Chen, P.; Lin, G.; Huang, H.; Li, Z. Tetrahedron: Asymmetry
Ripened fruits were taken and the fleshy cover was removed
to obtain the seeds. The upper layers of the seeds were
cracked with a hammer to obtain the soft kernels. The
kernels were homogenized at 4 °C, with aq K3PO4 buffer (10
Synlett 2009, No. 8, 1237–1240 © Thieme Stuttgart · New York

1240
R. Bhunya et al.
LETTER
mM, pH = 6.0), to give a milky suspension. The suspension
was filtered through four layers of cheese cloth to remove
the insoluble part. After that it was centrifuged (18800 g, 30
min), and removal of the residue gave a crude preparation of
HNL. The crude preparation was fractionated with
(NH4)2SO4. Proteins precipitating with 30% saturation were
collected by centrifugation (18800 g, 20 min), dissolved in
the minimum volume of phosphate buffer and dialyzed
against the same buffer with three changes. The dialyzed
soln was then centrifuged and the supernatant was stored at
4 °C and assayed for HNL activity.
1 H), 5.1 (dd, J = 10.6, 1.4 Hz, 1 H), 5.00 (dd, J = 17.7, 1.4
Hz, 1 H), 4.48 (t, J = 7.6 Hz, 1 H), 1.88 (m, 2 H), 1.1 (s, 6
H). 13C NMR (100 MHz, CDCl3): d = 121.8, 119.4, 113.4,
59.8, 48.7, 36.5, 25.8, 24.6. [a]D27 +8.8 (c 1.0, CHCl3).
Cyanohydrin from 3
1H NMR (400 MHz, CDCl3): d = 5.7 (dd, J = 17.6, 10.6 Hz,
1 H), 5.22 (dd, J = 10.6, 1.4 Hz, 1 H), 5.00 (dd, J = 17.6, 1.4
Hz, 1 H), 4.49 (t, J = 7.6 Hz, 1 H), 1.99 (m, 2 H), 1.45 (m, 4
H), 0.86 (m, 6 H). 13C NMR (100 MHz, CDCl3): d = 145.1,
120.5, 114.7, 58.6, 41.9, 27.67, 27.0, 7.5. [a]D27 +4.4 (c 1.0,
CHCl3).
ParHNL Assay
Cyanohydrin from 4
In a typical assay reaction 1.0 M of benzaldehyde soln (in
DMSO, 40 mL) was dissolved in 400 mM citrate buffer (760
mL, pH = 4.0), followed by addition of enzyme soln (100 mL)
and 1.0 M NaCN soln (100 mL, total reaction volume 1 mL),
and the reaction mixture was incubated in a rotary shaker.
After 5 min, the 100 mL of the reaction mixture was removed
and extracted with 900 mL hexane–2-PrOH (9:1), the organic
layer was analyzed with chiral HPLC for the formation of
(R)-mandelonitrile. A blank reaction was also performed
without enzyme, and the amount of mandelonitrile obtained
was deducted from the biocatalyzed reaction product. One
unit of the enzyme is defined as the amount of the enzyme
that produces 1 mmol of (R)-mandelonitrile under the above
reaction conditions in 1 min. The protein content in all the
HNL was measured by the Bradford method using a Bio-Rad
protein assay kit with BSA as the standard.
1H NMR (400 MHz, CDCl3,): d = 7.50–7.10 (m, 10 H), 6.6
(dd, J = 17.6, 10.6 Hz, 1 H), 5.32 (dd, J = 10.6, 1.4 Hz, 1 H),
4.98 (dd, J = 17.6, 1.4 Hz, 1 H), 4.42 (t, J = 7.6 Hz, 1 H),
2.80 (m, 2 H). 13C NMR (100 MHz, CDCl3): d = 145.0,
144.7, 143.2, 128.6, 128.5, 128.2, 127.7, 127.6, 119.9,
114.5, 59.3, 52.64, 44.8. [a]D27 +10.5 (c 0.5, CHCl3).
Cyanohydrin from 5
1H NMR (400 MHz, CDCl3): d = 5.16 (t, J = 6.4 Hz, 1 H),
4.46 (t, J = 7.6 Hz, 1 H), 2.2 (m, 2 H), 1.85 (m, 2 H), 1.75 (s,
3 H), 1.7 (s, 3 H). 13C NMR (100 MHz, CDCl3): d = 134.6,
123.2, 119.4, 61.6, 36.7, 27.6, 23.4, 18.8. [a]D27 +2.1 (c 1.0,
CHCl3).
Cyanohydrin from 6
1H NMR (400 MHz, CDCl3): d = 5.75 (dd, J = 17.4, 10.6 Hz,
1 H), 5.20–5.08 (m, 2 H), 4.45 (t, J = 6.8 Hz, 1 H), 2.01 (d,
J = 6.8 Hz, 2 H), 1.80–1.50 (m, 8 H). 13C NMR (100 MHz,
CDCl3): d = 143.7, 120.7, 113.9, 59.3, 47.8, 45.4, 37.0, 36.7,
23.0, 22.9. [a]D27 +6.4 (c 0.8, CHCl3).
General Procedure for the Synthesis of d,e-Unsaturated
Cyanohydrins by ParHNL
To a soln of g,d-unsaturated aldehyde 1–9 in DIPE, a soln of
ParHNL (300 IU/mmol of aldehyde, DIPE/enzyme; 1:1 v/v)
was added, and the resulting mixture was stirred vigorously
until an emulsion was formed (the pH of the enzyme soln
having been previously adjusted to 4.0 with 10% citric acid
soln). Freshly prepared HCN in DIPE (2 equiv) was added to
the mixture, and the temperature was kept at 10 °C. After
completion of the reaction it was extracted thoroughly with
Et2O several times, and the organic layer was dried
(Na2SO4). Evaporation of the solvent yielded the crude
cyanohydrins, which were purified by chromatography.
Preparation of HCN in DIPE
Sodium cyanide (10 g) and citric acid (0.1 g) were dissolved
in H2O (100 mL). The soln was cooled in an ice–water bath
and extracted with DIPE (50 mL), while acidifying with
33% HCl until pH 5.5. The H2O layer, which contained a
suspension of NaCl, was extracted twice with DIPE (25 mL).
The combined DIPE layers were stored in a dark bottle. The
above procedure must be performed in a well-ventilated
fume hood and impermeable gloves must be worn.
Cyanohydrin from 7
1H NMR (400 MHz, CDCl3): d = 5.66 (dd, J = 17.4, 10.6 Hz,
1 H), 5.20 (d, J = 10.6 Hz, 1 H), 5.08 (d, J = 17.4 Hz, 1 H),
4.48 (t, J = 7.2 Hz, 1 H), 1.9 (d, J = 7.2 Hz, 2 H), 1.70–1.46
(m, 10 H). 13C NMR (100 MHz, CDCl3): d = 144.7, 120.8,
27
115.2, 58.5, 46.3, 39.2, 36.0, 35.5, 26.1, 21.9, 21.8. [a]D
+4.8 (c 1.2, CHCl3).
Cyanohydrin from 8
1H NMR (400 MHz, CDCl3): d = 5.75 (dd, J = 17.4, 10.6 Hz,
1 H), 5.2 (dd, J = 10.6, 1.4 Hz, 1 H), 5.05 (dd, J = 17.6, 1.4
Hz, 1 H), 4.48 (m, 1 H), 1.9 (m, 2 H), 1.70–1.40 (m, 12 H).
13C NMR (100 MHz, CDCl3): d = 146.1, 120.7, 113.4, 58.8,
46.9, 42.3, 38.0, 37.2, 30.0, 22.3. [a]D27 +22.2 (c 0.6,
CHCl3).
Cyanohydrin from 9
1H NMR (400 MHz, CDCl3): d = 5.75 (dd, J = 17.4, 10.6 Hz,
1 H), 5.15 (dd, J = 10.6, 1.4 Hz, 1 H), 5.00 (dd, J = 17.6, 1.4
Hz, 1 H), 4.48 (m, 1 H), 2.0 (m, 2 H), 1.60–1.20 (m, 9 H),
0.90 (d, J = 7.6 Hz, 3 H). 13C NMR (100 MHz, CDCl3): d =
147.2, 120.5, 112.9, 58.8, 40.4, 38.1, 34.6, 33.9, 31.9, 29.9,
29.8, 21.9. [a]D27 +11.5 (c 1.2, CHCl3).
(12) Cyanohydrin from 2
1H NMR (400 MHz, CDCl3): d = 5.8 (dd, J = 17.7, 10.6 Hz,
Synlett 2009, No. 8, 1237–1240 © Thieme Stuttgart · New York

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