6732 J . Org. Chem., Vol. 61, No. 19, 1996
Notes
(()-th r eo-Eth yl 3-(4-Meth oxyp h en yl)-2,3-d ia cetoxyp r o-
p ion a te (4). To a stirred solution of diol 3 (1.92 g, 8 mmol) in
pyridine (20 mL) was added acetic anhydride (15 mL), and the
reaction mixture was kept in dark for 48 h at rt. On usual
aqueous workup, ether extraction followed by concentration and
column purification gave pure diacetate 4: 2.38 g (92% yield):
indicated 96% ee [as seen by signal ratio (0.02 :0.98) for benzylic
protons at δ 6.67 and 6.77, respectively].
Eth yl (2S,3R)-2,3-Dih yd r oxy-3-(4-m eth oxyp h en yl)p r o-
p ion a te (7). To an ice-cold solution of hydroxyacetate 5 (100
mg) in dry ethanol (2mL) was added anhyd K2CO3 (5 mg), and
the reaction mixture was stirred at rt for 3 h after which it was
filtered through Celite and washed with ethanol. The combined
ethanol solution on concentration in vacuo gave a thick oil which
was dissolved in ethyl acetate (15 mL), washed successively with
water and brine, and dried over Na2SO4. Removal of ethyl
acetate in vacuo followed by silica gel column chromatographic
purification gave (2S,3R) diol 7, 73 mg (86% yield): mp 87-89
1
mp 56-58 °C, H NMR (CDCl3, 200 MHz) δ 1.25 (t, J ) 7.3 Hz,
3H), 2.10 (s, 3H), 2.14 (s, 3H), 3.80 (s, 3H), 4.15 (q, J ) 4.8 Hz,
2H), 5.30 (d, J ) 4.8 Hz, 1H), 6.23 (d, J ) 4.8 Hz, 1H), 6.88 (d,
J ) 9.8 Hz, 2H), 7.42 (d, J ) 9.8 Hz, 2H); 13C NMR δ (CDCl3, 50
MHz) 13.7, 20.0, 20.4, 54.9, 61.4, 73.3, 74.1, 113.6, 127.4, 128.2,
159.7, 166.8, 169.0, 169.5; MS (m/e) 324, 264, 222, 206, 193, 179,
161, 150, 137, 121, 109, 91, 77; IR (Nujol) νmax 1740, 1730, 1720,
°C; [R]25 ) -4.8° (c 2.0, CHCl3) (1H NMR and IR identical to
D
1610 cm-1
. Anal. Calcd for C16H20O7: C, 59.25; H, 6.22.
that of 3).
Found: C, 59.10; H, 6.46.
Eth yl (2R,3S)-2,3-Dih yd r oxy-3-(4-m eth oxyp h en yl)p r o-
p ion a te (8). The reaction of diacetate 6 (100 mg) with anhyd
K2CO3 (5 mg) in dry ethanol (2mL) for 16 h similarly furnished
(2R,3S) diol 8, 62 mg (84% yield): mp 88-90 °C, (lit.8a 68-70
Lip a se-Ca ta lyzed Hyd r olysis of (()-th r eo-Eth yl 3-(4-
Meth oxyp h en yl)-2,3-d ia cetoxyp r op ion a te (4). A solution of
(()-diacetate 4 (324 mg, 1 mmol) in isooctane:benzene (2:1)
mixture (20 mL) was added to a suspension of Amano PS lipase
(275 mg) in 5 mM aqueous sodium phosphate (10 mL) at pH
7.0. The reaction mixture was stirred at 25 °C for 180 h after
which it was filtered through Celite and extracted with ethyl
acetate (25 mL × 3). The combined organic layer after usual
workup and concentration in vacuo gave an oily residue which
was subjected to column chromatography. Elution with 12%
ethyl acetate:petroleum ether gave ethyl (2R,3S)-3-(4-methoxy-
°C); [R]25 ) +4.3° (c 2.0, CHCl3) [lit.8a +5.0° (c 1.08, CHCl3)]
D
(1H NMR and IR identical to that of 3 and 7).
Bis-MTP A-E st er s of (()-Diol 3, (2S,3R)-Diol 7, a n d
(2R,3S)-Diol 8. To a solution of diol (12 mg, 0.05 mmol) in
pyridine (0.1 mL) was added 0.5 M solution of (S)-(+)-MTPA-
Cl14 in EDC (0.3 mL) at 0 °C, and the reaction mixture was
further stirred for 8 h at 0 °C. Usual workup furnished
corresponding bis-MTPA-derivatives as thick oil, for analysis by
1H NMR.
Bis-MTP A-ester s of (()-d iol 3: 1H NMR (CDCl3, 200 MHz)
δ 1.16-1.30 (m, 6H), 3.40 (bs, 6H), 3.62 (bs, 6H), 3.82 (s, 3H),
3.87 (s, 3H), 4.12-4.25 (m, 4H), 5.41 (d, J ) 2.9 Hz, 1H), 5.47
(d, J ) 3.5 Hz, 1H), 6.48 (d, J ) 2.9 Hz, 1H), 6.52 (d, J ) 3.5 Hz,
1H), 6.62 (d, J ) 9.7 Hz, 2H), 6.84 (d, J ) 9.7 Hz, 2H), 7.11 (d,
J ) 9.7 Hz, 2H), 7.21 (d, J ) 9.7 Hz, 2H), 7.30-7.52 (m, 20H).
Bis-MTP A-ester of (2S,3R)-d iol 7: 1H NMR (CDCl3, 200
MHz) δ 3(S)-H, 6.47 (d, J ) 2.9 Hz), 3(R)-H, 6.52 (d, J ) 3.5
Hz), the integral ratios of these protons indicated 98% ee of
(2S,3R)-diol 7.
phenyl)-2,3-diacetoxypropionate (6), 165 mg (51% yield): [R]25
D
) +26.4° (c 2.0, CHCl3) (1H NMR and IR spectral data identical
with compound 4) and with 18% ethyl acetate:petroleum ether
gave ethyl (2S,3R)-3-(4-methoxyphenyl)-2-hydroxy-3-acetoxypro-
pionate (5) 118 mg (42% yield): mp 48-50 °C, [ R]25 ) -37.1°
D
(c 2.0, CHCl3); 1H NMR (CDCl3, 200 MHz) δ 1.30 (t, J ) 8.1 Hz,
3H), 2.12 (s, 3H), 3.02 (bs, 1H), 3.85 (s, 3H), 4.25 (q, J ) 8.1 Hz,
2H), 4.37 (bs, 1H), 6.05 (d, J ) 2.7 Hz, 1H), 6.90 (d, J ) 10.8
Hz, 2H), 7.35 (d, J ) 10.8 Hz, 2H); 13C NMR (CDCl3, 50 MHz)
δ 14.2, 21.0, 55.4, 62.3, 73.8, 75.5, 114.0, 128.5-129.0 (2-
carbons), 159.9, 169.9, 172.1. MS (m/e) 282, 223, 206, 179, 161,
149, 137, 121, 109, 104, 94, 77, 65. IR (Nujol) νmax 3420, 1730,
1720, 1610 cm-1. Anal. Calcd for C14H18O6: C, 59.57; H, 5.00.
Found: C, 59.76; H, 5.16.
Bis-MTP A-ester of (2R,3S)-d iol 8: 1H NMR (CDCl3, 200
MHz), δ 2(R)-H 5.40 (d, J ) 2.9 Hz), 2(S)-H 5.48 (d, J ) 3.5 Hz),
the integral ratios correspond to 86% ee of (2R,3S)-diol 8.
Hydrolyses reactions with other enzymes were similarly
carried out on (()-diacetate 4 (1 mmol) in organic solvent (20
mL) and buffer solution (10 mL) using PPL (500 mg), PLAP (500
mg), Amano PS (275 mg), Novozym-435 (300 mg), BLAP (500
mg), and Bioprotease-alk (275 mg). For details see Table 1.
MTP A-Ester of (2S,3R)-Hyd r oxya ceta te 5. To a solution
of hydroxyacetate 5 (14 mg, 0.05 mmol) in pyridine (0.1 mL) was
added 0.5 M solution of (S)-(+)-MTPA-Cl14 in EDC (0.2 mL) at
0 °C, and the reaction mixture was stirred at rt for 12 h. On
usual aqueous workup, ether extraction and concentration in
vacuo furnished MTPA-derivative of 5 as thick oil: 1H NMR
(CDCl3, 200 MHz) δ 1.22 (t, J ) 7.3 Hz, 3H), 2.10 (s, 3H), 3.48
(s, 3H), 3.83 (s, 3H), 4.20 (q, J ) 7.3 Hz, 2H), 5.35 (d, J ) 4.6
Hz), 5.43 (d, J ) 4.2 Hz), 6.23 (d, J ) 4.6 Hz), 6.33 (d, J ) 4.2
Hz), 6.88 (d, J ) 9.8 Hz, 2H), 7.28 (d, J ) 9.8 Hz, 2H), 7.35-
7.45 (m, 5H). On expansion, the signals at δ 6.23 and 6.33 were
in a ratio of 0.02:0.98, indicating 96% ee. The 1H NMR spectrum
of (2S,3R)-hydroxyacetate 5 (10 mg) in CDCl3 (0.5 mL) with
chiralshiftreagent,tris[3-[(heptafluoropropyl)hydroxymethylene]-
(+)-camphorato]europium(III) (10 mg) in CDCl3 (0.2 mL)
Ack n ow led gm en t. We thank Professor D. Basava-
iah, University of Hyderabad for a generous gift of
PLAP, BLAP enzymes, and Amano Pharmaceutical Co.,
J apan, for providing Amano PS. S.B.D. thanks CSIR,
New Delhi, for the award of a research fellowship.
K.N.G. acknowledges J awaharlal Nehru Centre for
Advanced Scientific Research, Bangalore, of which he
is a Honorary Senior fellow.
Su p p or tin g In for m a tion Ava ila ble: 1H NMR spectra of
4, 5, MTPA derivative of 5, and bis-MTPA derivatives of 3 and
7 (10 pages). This material is contained in libraries on
microfiche, immediately follows this article in the microfilm
version of the journal, and can be ordered from the ACS; see
any current masthead page for ordering information.
J O960835L