458
F. Khachik
PAPER
Hydroboration of 5 with a Commercial Solution of BH3·THF at
0 °C
filtration and the solvent was evaporated under reduced pressure to
give 0.70 g of a crude product. Column chromatography of the res-
idue on silica gel (hexane–acetone, 95:5 to 90:10) gave two main
fractions. The first fraction was identified as (3R,3¢R)-zeaxanthin-
3,3¢-diacetate (12) and the second fraction was identified as
(3R,3¢S)-zeaxanthin-3-acetate (11).
To a stirred soln of 5 (1 g, 1.82 mmol) in THF (30 mL) at 0 °C under
argon was added a 1 M soln of BH3·THF (6.0 mL, 6.0 mmol) in 15
min. After 3 h, no detectable amount of 5 was shown by HPLC to
be present. The mixture was cooled to –10 °C and was sequentially
treated with MeOH (3 mL), 3 M NaOH (3 mL), and 30% H2O2 (3
mL), and worked up as described above. HPLC analysis (eluent A)
of the crude product showed the presence of 2 and 3 as coeluting
peaks (77%), 8 (17%), and 9 (6%). Purification of the product by
column chromatography (hexane–acetone, 95:5 to 70:30) gave a
mixture of zeaxanthins 2 and 3; yield: 0.62 g (1.09 mmol, 60%).
(3R,3¢R)-Zeaxanthin-3,3¢-diacetate (12)
Yield: 0.28 g [0.43 mmol, 41% from (2 + 3)].
1H NMR (400 MHz, CDCl3): d = 1.08 (s, 6 H), 1.11 (s, 6 H), 1.59
(t, J = 12 Hz, 2 H), 1.73 (s, 6 H), 1.77 (m, 2 H), 1.98 (d, J = 2 Hz,
12 H), 2.07 (s, 6 H), 2.14 (dd, J = 17, 8 Hz, 2 H), 2.46 (dd, J = 17,
5 Hz, 2 H), 5.07 (m, 2 H), 6.10 (m, 2 H), 6.13 (m, 2 H), 6.16 (d,
J = 12 Hz, 2 H), 6.27 (br m, 2 H), 6.38 (d, J = 15 Hz, 2 H), 6.60–
6.70 (m, 4 H).
13C NMR (100 MHz, CDCl3): d = 12.75, 12.82, 21.47, 21.49, 28.52,
30.00, 36.70, 38.46, 44.02, 48.43, 68.43, 124.89, 125.28, 125.62,
130.09, 131.44, 135.59, 136.47, 136.50, 137.64, 137.85, 138.67,
170.83.
Hydroboration of 5 with BH3·SMe2
To a soln of 5 (1 g, 1.82 mmol) in CH2Cl2 (30 mL) under argon was
added a 2 M soln of BH3·SMe2 (1.9 mL, 3.8 mmol) at r.t. in 5 min.
After 3 h, no detectable amount of 5 was shown by HPLC to be
present. The mixture was cooled to –10 °C and was sequentially
treated with MeOH (3 mL), 3 M NaOH (3 mL), and 30% H2O2 (3
mL), and worked up as described above. HPLC analysis (eluent A)
of the crude product showed the presence of 2 and 3 as coeluting
peaks (75%), 8 (23%), and 9 (2%). Purification of the product by
column chromatography (hexane–acetone, 95:5 to 70:30) gave a
mixture of zeaxanthins 2 and 3; yield: 0.57 g (1.00 mmol, 55%).
HRMS (ESI+): m/z [M]+ calcd for C44H60O4: 652.448612; found:
652.448200.
UV/Vis (hexane): lmax = 452 nm (main max).
(3R,3¢S)-Zeaxanthin-3-acetate (11)
Hydroboration of 5 with (–)-Isopinocampheylborane–
N,N,N¢,N¢-Tetramethylethylenediamine Complex [(R)-Alpine-
Boramine™]
Yield: 0.256 g [0.42 mmol, 40% from (2 + 3)].
1H NMR (400 MHz, CDCl3): d = 1.08 (s, 9 H), 1.11 (s, 3 H), 1.49
(t, J = 12 Hz, 1 H), 1.59 (t, J = 12 Hz, 1 H), 1.73 (s, 3 H), 1.75 (s, 3
H), 1.77 (m, 2 H), 1.98 (d, J = 2 Hz, 12 H), 2.06 (dd, J = 17, 9.8 Hz,
1 H), 2.07 (s, 3 H), 2.12 (dd, J = 17, 9 Hz, 1 H), 2.40 (dd, J = 17, 6
Hz, 1 H), 2.46 (dd, J = 17, 6 Hz, 1 H), 4.01 (m, 1 H), 5.07 (m, 1 H),
6.12 (m, 3 H), 6.16 (m, 3 H), 6.27 (br m, 2 H), 6.38 (d, J = 15 Hz, 2
H), 6.60–6.70 (m, 4 H).
13C NMR (100 MHz, CDCl3): d = 12.75, 12.82, 21.47, 21.49, 21.62,
28.52, 28.73, 30.00, 30.25, 36.70, 38.46, 42.55, 44.02, 48.43, 65.09,
68.43, 124.89, 124.92, 125.28, 125.57, 125.62, 126.16, 130.06,
130.09, 131.31, 131.44, 132.59, 132.64, 135.59, 135.69, 136.47,
136.50, 137.56, 137.64, 137.75, 137.85, 138.50, 138.67, 170.83.
To a soln of (R)-Alpine-Boramine™ (0.33 g, 0.793 mmol) in THF
(5 mL) was added a soln of BF3·OEt2 (0.2 mL, 0.224 g, 1.58 mmol)
at r.t. under argon and the mixture was stirred for 1 h. The mixture
was then cooled to 0 °C and a soln of 5 (0.24 g, 0.44 mmol) in THF
(5 mL) was added. After 3 h, the mixture was sequentially treated
with MeOH (0.5 mL), 3 M NaOH (0.5 mL), and 30% H2O2 (0.5
mL), and worked up with EtOAc as described above. HPLC analy-
sis (eluent A) of the crude product showed the presence of 2 and 3
as coeluting peaks (85%), as well as 8 (9%) and 9 (6%). Purification
of the product by column chromatography (hexane–acetone, 95:5 to
70:30) gave a mixture of zeaxanthins 2 and 3; yield: 0.100 g (0.176
mmol, 40%). Chiral HPLC analysis (eluent B) of the mixture re-
vealed the ratio of 2/3 = 77:23, corresponding to 54% de for 2.
HRMS (ESI+): m/z [M]+ calcd for C42H58O3: 610.438047; found:
610.438200.
Hydroboration of 5 with (+)-Isopinocampheylborane–
N,N,N¢,N¢-Tetramethylethylenediamine Complex [(S)-Alpine-
Boramine™]
UV/Vis (hexane): lmax = 452 nm (main max).
(3R,3¢R)-Zeaxanthin (2)
The hydroboration of 5 (0.24 g, 0.44 mmol) with (S)-Alpine-
Boramine™ was carried out similar to the above experiment with
(R)-Alpine-Boramine™, to yield a mixture of 2 and 3 (80%), as
well as 8 (13%) and 9 (7%). Purification of the product by column
chromatography (hexane–acetone, 95:5 to 70:30) gave a mixture of
2 and 3; yield: 0.100 g (0.176 mmol, 40%). The ratio of 2/3 = 43:57,
corresponding to 14% de for 3, was determined by chiral HPLC
analysis (eluent B) of the mixture.
The first fraction (12) was dissolved in THF (10 mL) and stirred
with KOH in MeOH (10% wt/v, 2 mL) for 1 h at r.t. under argon.
The product was partitioned between H2O (20 mL) and CH2Cl2 (20
mL). The organic layer was removed and washed with H2O (2 × 20
mL), dried over Na2SO4, and concentrated to dryness to give
(3R,3¢R)-zeaxanthin (2); yield: 0.239 g (0.42 mmol, 98% from 12).
The product was shown by chiral HPLC (eluent B) to consist of 2
(96%) and (3R,3¢S; meso)-zeaxanthin (3, 4%), corresponding to
92% de for 2. The 1H NMR spectrum of this fraction was in agree-
ment with that of (3R,3¢R)-zeaxanthin reported in our earlier publi-
cation.33
Separation of 2 and 3 by Enzyme-Mediated Acylation with
Lipase PS (Pseudomonas cepacia)
A mixture of 2 and 3 (0.6 g, 1.06 mmol) in THF (20 mL) was treated
with immobilized lipase PS (0.6 g) and vinyl acetate (3 mL), and the
mixture was stirred at r.t. under argon. The course of the reaction
was monitored by chiral HPLC (eluent B). After 24 h, HPLC
showed complete conversion of 2 and 3 into (3R,3¢R)-zeaxanthin-3-
acetate (10) and (3R,3¢S)-zeaxanthin-3-acetate (11), as well as mi-
nor quantities of (3R,3¢R)-zeaxanthin-3,3¢-diacetate (12). Stirring
was continued for another 24 h and the progress of the reaction was
monitored by chiral HPLC employing eluent C. When 10 was com-
pletely acylated to 12 (total of 48 h), the enzyme was removed by
(3R,3¢S; meso)-Zeaxanthin (3)
The second fraction (11) was dissolved in THF (10 mL) and stirred
with KOH in MeOH (10% wt/v, 2 mL) for 1 h at r.t. under argon.
The product was worked up as described above for 2 to give
(3R,3¢S; meso)-zeaxanthin (3); yield: 0.233 g (0.41 mmol, 98%
from 11). The product was shown by chiral HPLC (eluent B) to con-
sist of 3 (97%) and (3R,3¢R)-zeaxanthin (2, 3%), corresponding to
94% de for 3. The 1H NMR spectrum of this fraction was identical
with that of (3R,3¢R)-zeaxanthin (2).
Synthesis 2012, 44, 453–459
© Thieme Stuttgart · New York