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LETTER
1034, 721, 700 cm–1. [a]D20 +15.2 (c 1, MeOH); lit.5 [a]D20 +35.6 (c
1.1, MeOH).
3.57 (s, 2 H), 3.71 (s, 3 H), 3.87 (s, 2 H), 4.34 (d, J = 5.8 Hz, 2 H),
4.86 (q, J = 6.0 Hz, 1 H), 5.24–5.32 (m, 1 H), 5.40–5.49 (m, 1 H),
5.93 (br t, J = 4.2 Hz, 1 H), 6.76 (dd, J1 = 7.9 Hz, J2 = 1.9 Hz, 1 H),
6.84 (d, J = 1.7 Hz, 1 H), 6.91 (d, J = 7.9 Hz, 1 H). 13C NMR (75
MHz, CDCl3): d = 14.1, 22.6, 25.2, 25.8, 27.3, 29.1, 29.2, 29.3,
29.4, 29.6, 31.7, 32.0, 33.6, 36.7, 41.0, 41.85, 43.4, 55.9, 74.6,
112.2, 120.0, 122.7, 124.2, 127.0, 127.3, 128.5, 128.6, 129.3, 129.4,
132.7, 133.6, 134.4, 137.6, 139.2, 151.2, 169.7, 171.4, 173.1.
Typical Procedure of the Enzymatic Aminolysis for the Prepa-
ration of 12-Phenylacetylrinvanil (4)
Vanillylamine·HCl (190 mg, 1 mmol) was suspended in dry 2-me-
thyl-2-butanol (20 mL) containing 4 Å MS (500 mg) and Et3N (840
mL). The mixture was agitated 30 min at 30 °C and 250 rpm. Then,
methyl 12-phenylacetylricinoleate (2 g, 4.6 mmol) and CaLB (750
mg) was added, and the mixture was incubated at 30 °C. The reac-
tion was monitored by TLC (hexane–EtOAc, 1:1; ninhydrine as vi-
sualizing reagent). Filtration over Celite and vacuum concentration
afforded 434 mg of 4 (78.7% yield based on the vanillylamine·HCl)
and 1.55 g of pure methyl 12-phenylacetylricinoleate after silica gel
chromatography.
Methyl ricinoleate (8)
Castor oil (20 g) was dissolved in MeOH (155 mL) and heated un-
der reflux for 30 min in the presence of solid KOH (58 mg, 0.28%).
At the end of the reaction (TLC, hexane–EtOAc, 85:15) AcOH (80
mL) was added, and the mixture was evaporated to dryness under
reduced pressure. The residue was redissolved in hexane (30 mL)
and washed with H2O (2 × 25 mL) and with sat. NaCl solution
(1 × 25 mL). The organic phase was dried with anhyd Na2SO4 and
concentrated under reduced pressure, hence, 20.3 g of crude product
afforded 16.67 g of 8 (85% yield) after column chromatography
(400 g silica gel, hexane–EtOAc, 9.5:5 to 9:1 gradient). Purity of 8
(99% pure) was established by HPLC in a Waters HPLC system
equipped with a Waters Symmetry C18 4.6 × 250 mm, 5 mm col-
umn (Milford, MA, USA) eluted with 1.5 mL/min of 85:15 MeCN–
H2O and using a refractive index detector at 35 °C; tR = 6.45 min.
[a]D +15.2 (c 1, MeOH); Lit.5 [a]D +35.6 (c 1.1, MeOH). IR
(film): 3362, 3306, 2928, 2856, 1729, 1646, 1517, 1274, 1034, 721,
700 cm–1. 1H NMR (300 MHz, CDCl3): d = 0.86 (t, 3 H, J = 7.2 Hz),
1.19–1.32 (m, 16 H), 1.46–1.54 (m, 2 H), 1.63 (q, 2 H, J = 7.2 Hz),
1.94 (c, 2 H, J = 6.3 Hz), 2.18 (t, J = 7.8 Hz, 2 H), 2.23–2.32 (m, 2
H), 3.57 (s, 2 H), 3.84 (s, 3 H), 4.32 (d, J = 5.4 Hz, 2 H), 4.86 (q,
J = 6.6 Hz, 1 H), 5.22–5.31 (m, 1 H), 5.38–5.47 (m, 1 H), 5.83 (br
t, J = 4.5 Hz, 1 H), 6.73 (dd, J1 = 7.8 Hz, J2 = 2.1 Hz, 1 H), 6.78 (d,
20
20
J = 1.8 Hz, 1 H), 6.86 (d, J = 8.1 Hz, 1 H), 7.20–7.33 (m, 5 H). 13
C
NMR (75 MHz, CDCl3): d = 14.0, 22.4, 25.1, 25.6, 27.2, 29.01,
29.04, 29.13, 29.16, 29.4, 31.6, 31.8, 33.4, 36.7, 41.7, 43.4, 55.8,
74.5, 110.6, 114.3, 120.7, 124.0, 126.9, 127.0, 128.4, 128.5, 129.1,
129.2, 130.2, 132.5, 145.0, 146.6, 171.3, 173.0. MS (EI): m/z (%) =
551 (30) [M+], 415 (41), 277 (13), 152 (64), 137 (100), 91 (22).
[a]D20 +7.4 (c 1, MeOH), +3.33 (c 1.5, CHCl3); Lit.16 [a]D20 +3.4 (c
1.5, CHCl3). IR (film): 3435, 2928, 2856, 1742, 1439, 1173, 859,
725 cm–1. 1H NMR (400 MHz, CDCl3): d = 0.89 (t, J = 6.8 Hz, 3 H),
1.29–1.33 (m, 16 H), 1.45–1.50 (m, 2 H), 1.62 (q, J = 7.2 Hz, 2 H),
2.04 (c, J = 6.4 Hz, 2 H), 2.21 (t, J = 6.4 Hz, 2 H), 2.30 (t, J = 7.6
Hz, 2 H), 3.61 (q, J = 5.6 Hz, 1 H), 3.67 (s, 3 H), 5.37–5.44 (m, 1
H), 5.52–5.59 (m, 1 H). 13C NMR (100 MHz, CDCl3): d = 14.365,
22.873, 25.149, 25.969, 27.609, 29.316, 39.362, 29.605, 29.810,
32.079, 34.295, 35.570, 37.058, 51.675, 71.644, 125.341, 133.379,
174.371.
Rinvanil (6)
To a suspension of vanillylamine·HCl (1.21 g, 6.4 mmol) in 2-me-
thyl-2-butanol (130 mL), Et3N (6 mL, 42.7 mmol, 6.67 mol equiv)
was added. The mixture was incubated for 30 min at 37 °C and 250
rpm, and reaction started by addition of MS (1.2 g), methyl ricino-
leate (2 g, 6.4 mmol), and CaLB (1.2 g). The reaction was moni-
tored by TLC (hexane–EtOAc, 85:15). Thereafter, enzyme and MS
were filtered over Celite, a mixture of hexane and EtOAc (1:1, 15
mL) added, and the solid formed was filtered over Celite. The fil-
trate was concentrated under vacuum yielding 3.1 g of raw product,
which after column chromatography (45 g silica gel; 70–230 mesh;
hexane–EtOAc, 7:3) afforded 1.94 g of pure 6 (70.2% yield).
[a]D20 +2.9 (c 1, MeOH). 1H NMR (300 MHz, CDCl3): d = 0.88 (t,
J = 6.9 Hz, 3 H), 1.25–1.35 (m, 16 H), 1.44–1.49 (m, 2 H), 1.63 (q,
J = 6.0 Hz, 2 H), 1.99 (c, J = 6.6 Hz, 2 H), 2.16–2.22 (m, 4 H), 3.56
(q, J = 5.4 Hz, 1 H), 3.85 (s, 3 H), 4.32 (d, J = 5.7 Hz, 2 H), 5.34–
5.43 (m, 1 H), 5.49–5.58 (m, 1 H), 5.91 (br t, J = 5.1 Hz, 1 H), 6.72
(dd, J1 = 7.8 Hz, J2 = 1.8 Hz, 1 H), 6.79 (d, J = 2.1 Hz, 1 H), 6.83
(d, J = 8.1 Hz, 1 H). 13C NMR (75 MHz, CDCl3): d = 14.0, 22.5,
25.6, 27.2, 28.9, 29.01, 29.8, 29.1, 29.2, 29.4, 31.7, 35.2, 36.6, 36.7,
43.4, 55.8, 71.4, 110.7, 114.4, 120.6, 125.2, 130.2, 133.1, 145.0,
146.7, 173.0.
Methyl 12-Phenylacetylricinoleate (9)
In a three-necked round-bottom flask 8 (13.5 g, 43 mmol) and phe-
nylacetic acid (11.66 g, 85.7 mmol) were suspended in CH2Cl2 (150
mL). The reaction mixture was cooled to 0 °C in an ice bath and
DCC (17.6 g, 85.6 mmol) was added. Stirring was continued for 10
min, DMAP (6.3 g, 30 mmol) was added and stirred for an addition-
al 15 min at 0 °C. Thereafter, stirring was continued for 1 h at r.t.
The reaction mixture was then refluxed until the reaction was com-
plete (TLC, hexane–EtOAc, 85:15), filtered over Celite and concen-
trated in a rotatory evaporator. The residue was suspended in
hexane–EtOAc (9:1, 50 mL), vacuum filtered over Celite, and
washed with hexane–EtOAc (9:1, 100 mL); it was then dried over
anhyd Na2SO4 and concentrated in rotatory evaporator (24.68 g of
a crude product). After column chromatography 16.37 g of 9 were
obtained (88.5% yield).
[a]D20 +29.6 (c 1, MeOH). IR (film): 2929, 2856, 1737, 1459, 1437,
1253, 1164, 1023, 722, 700 cm–1. 1H NMR (300 MHz, CDCl3): d =
0.86 (t, J = 6.0 Hz, 3 H), 1.21–1.29 (m, 16 H), 1.50–1.54 (m, 2 H),
1.61 (q, J = 7.2 Hz, 2 H), 1.95 (c, J = 6.6 Hz, 2 H), 2.21–2.32 (m, 4
H), 3.58 (s, 2 H), 3.65 (s, 3 H), 4.87 (q, J = 6.6 Hz, 1 H), 5.22–5.32
(m, 1 H), 5.39–5.48 (m, 1 H), 7.21–7.33 (m, 5 H). 13C NMR (75
MHz, CDCl3): d = 14.0, 22.4, 25.1, 27.2, 29.0, 29.1, 29.4, 31.6,
31.8, 33.5, 34.0, 41.7, 51.3, 74.4, 124.1, 126.8, 128.4, 129.1, 132.5,
134.3, 171.2, 174.2. HRMS–FAB+: m/z calcd for C27H43O4 [M +
H]+: 431.3161; found: 431.3151.
12,4′-Diphenylacetylrinvanil (7)
In a three-necked flask rinvanil (6, 330 mg, 0.76 mmol) and pheny-
lacetic acid (227 mg, 1.67 mmol, 2.2 mol equiv) were disolved in
CH2Cl2 (5 mL). The solution was cooled to 0 °C and then added
DCC (312 mg, 1.52 mmol, 2 mol equiv) and DMAP (92 mg, 0.76
mmol). After stirring for 20 min at 0 °C and 2 h at r.t. (TLC; hex-
ane–EtOAc, 1:1), the reaction mixture was filtered over Celite and
washed with CH2Cl2. The amount of 550 mg of concentrated raw
product yielded 390 mg of 7 (76.5% yield, yellow oil) after column
chromatography (hexane–EtOAc, 7:3).
Acknowledgment
1H NMR (300 MHz, CDCl3): d = 0.86 (t, J = 7.1 Hz, 3 H), 1.21–
1.28 (m, 16 H), 1.50–1.52 (m, 2 H), 1.63 (q, J = 6.2 Hz, 2 H), 1.96
(c, J = 7.4 Hz, 2 H), 2.16 (t, J = 7.7 Hz, 2 H), 2.21–2.35 (m, 2 H),
The authors acknowledge DGAPA-UNAM for Ignacio Regla sab-
batical fellowship at IBT-UNAM and for grant PAPIIT-IN226706-
3. Authors are also grateful to Ma de los Angeles Peña, Javier Pérez-
Synlett 2008, No. 18, 2869–2873 © Thieme Stuttgart · New York