4
OYAMA ET AL.
2.5 hours at room temperature, additional (S)-MTPACl
(11 μL, 59 μmol) was added to the reaction mixture. After
stirring for 19.5 hours at room temperature, the reaction
mixture was quenched with distilled water (2 mL) and
concentrated under reduced pressure. The resultant
crude product was purified by preparative HPLC
(Develosil RPAQUEOUS-AR-5, 8.0 mm ϕ × 250 mm,
Nomura Chemicals) with (5% ! 62%) MeCN aqueous
solution to give (R)-MTPA ester 11 (4.7 mg, 30%) as a
55.5, 55.4, 55.1, 25.5; HRMS (ESI) calcd for C29H30F3O8
[M + H]+ 563.1887, found 563.1900.
3.7 | Synthesis of 5,7,30,40-tetramethyl-O-
epicatechin (13)
To a solution of (−)-epicatechin (6) (102 mg, 0.351 mmol)
in DMF (5 mL) was added K2CO3 (290 mg, 2.10 mmol) at
room temperature. After stirring for 5 minutes at room
temperature, MeI (0.15 mL, 2.41 mmol) was added. This
solution was stirred for 6 hours at room temperature, and
then additional MeI (75 μL, 1.21 mmol) and K2CO3
(219 mg, 1.58 mmol) were added. After stirring for
16.5 hours at room temperature, the reaction mixture
was quenched with distilled water (10 mL). The crude
products were extracted with hexane/AcOEt = 4/1. The
combined extracts were dried over anhydrous Na2SO4, fil-
tered, and concentrated under reduced pressure. The
resultant crude product was purified by flash column
chromatography (hexane/AcOEt = 1/2) to give 13
21
white solid. [α]D +15.8ꢀ (c 0.21, CHCl3), mp 128-130ꢀC;
IR (KBr) 2945, 1743, 1593, 1522, 1458, 1267, 1169,1022,
814 cm−1
;
1H NMR (500 MHz, CDCl3) δ 7.32 (t,
J = 7.5 Hz, 1H), 7.22 (t, J = 7.5, 2H), 7.16 (d, J = 7.5 Hz,
2H), 6.88 (dd, J = 8.0, 1.5 Hz, 1H), 6.80 (d, J = 1.5 Hz,
1H), 6.76 (d, J = 8.0 Hz, 1H), 6.12 (s, 2H), 5.60 (dt,
J = 8.5, 6.0 Hz, 1H), 4.88 (d, J = 8.5 Hz, 1H), 3.88 (s, 3H),
3.80 (s, 3H), 3.78 (s, 3H), 3.75 (s, 3H), 3.39 (s, 3H), 3.19
(dd, J = 16.0, 6.0 Hz 1H), 2.80 (dd, J = 16.0, 8.5 Hz 1H);
13C NMR (125 MHz, CDCl3) δ 165.4, 160.0, 158.5, 155.1,
149.3, 148.9, 131.7, 129.2, 129.1, 128.1, 126.9, 120.0, 111.0,
110.2, 100.3, 93.1, 92.1, 78.7, 71.6, 55.9, 55.7, 55.5, 55.4,
25.5; HRMS (ESI) calcd for C29H30F3O8 [M + H]+
563.1887, found 563.1893.
19
(99 mg, 81%) as a white solid. [α]D –54.7ꢀ (c 0.41,
CHCl3); mp 140-142ꢀC; IR (KBr) 3508, 2902, 1624, 1591,
1
1518, 1462, 1329, 1259, 1159, 822, 781 cm−1; H NMR
(500 MHz, CDCl3) δ 7.09 (d, J = 2.0 Hz, 1H), 7.05 (dd,
J = 8.0, 2.0 Hz, 1H), 6.92 (d, J = 8.0, Hz, 1H), 6.20 (d,
J = 2.0, Hz, 1H), 6.12 (d, J = 2.0, Hz, 1H), 4.97 (s, 1H),
4.29 (brs, 1H), 3.92 (s, 3H), 3.90 (s, 3H), 3.80 (s, 3H), 3.78
(s, 3H), 2.95 (dd, J = 17.0, 2.0 Hz, 1H), 2.89 (dd, J = 17.0,
4.0 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 159.7, 159.3,
155.2, 149.1, 148.9, 130.8, 118.6, 111.2, 109.6, 100.3, 93.3,
92.2, 78.4, 66.5, 56.0, 55.5, 55.4, 28.1; HRMS (ESI) calcd
for C19H23O6 [M + H]+ 347.1489, found 347.1486.
3.6 | Synthesis of (S)-MTPA ester 12 of
5,7,30,40-tetramethyl-O-catechin (12)
To a solution of 5,7,30,40-tetramethyl-O-catechin (10)
(15.3 mg, 44.2 μmol), Et3N (24 μL, 173 μmol), and DMAP
(6 mg, 49 μmol) in 1,2-dichloroethane (0.5 mL) was
added (R)-MTPACl (33 μL, 176 μmol) at room tempera-
ture. After stirring for 19 hours at room temperature, the
reaction mixture was quenched with distilled water
(2 mL) and concentrated under reduced pressure. The
resultant crude product was purified by preparative
HPLC (Develosil RPAQUEOUS-AR-5, 8.0 mm
ϕ × 250 mm, 8.0 mm ϕ × 250 mm, Nomura Chemicals)
3.8 | Synthesis of (R)-MTPA ester 14 of
5,7,30,40-tetramethyl-O-epicatechin (14)
To a solution of 5,7,30,40-tetramethyl-O-epicatechin (13)
(10.8 mg, 31 μmol), Et3N (16 μL, 115 μmol), and DMAP
(5.1 mg, 42 μmol) in 1,2-dichloroethane (0.5 mL) was
added (S)-MTPACl (11 μL, 59 μmol) at room tempera-
ture. After stirring for 21 hours at room temperature, the
reaction mixture was quenched with distilled water
(2 mL) and concentrated under reduced pressure. The
resultant crude product was purified by preparative
HPLC (Develosil RPAQUEOUS-AR-5, 8.0 mm
ϕ × 250 mm, Nomura Chemicals) with (5% ! 62%)
MeCN aqueous solution to give (R)-MTPA ester 14
with (5% ! 62%) MeCN aqueous solution to give (S)-
21
MTPA ester 12 (11 mg, 44%) as a white solid. [α]D
–
29.7ꢀ (c 0.3, CHCl3); mp 121-122ꢀC; IR (KBr) 2947, 1747,
1616, 1502, 1454, 1263, 1142, 1030, 825 cm−1; H NMR
1
(500 MHz, CDCl3) δ 7.33 (t, J = 7.5 Hz, 1H), 7.21 (t,
J = 7.5 Hz, 2H), 7.06 (d, J = 7.5 Hz, 2H), 7.00 (dd, J = 8.0,
2.0 Hz, 1H), 6.94 (d, J = 2.0 Hz, 1H), 6.87 (d, J = 8.0 Hz,
1H), 6.35 (d, J = 2.0 Hz, 1H), 6.11 (d, J = 2.0 Hz, 1H),
5.51 (dt, J = 9.0, 6.0 Hz, 1H), 4.94 (d, J = 9.0 Hz, 1H),
3.91 (s, 3H), 3.82 (s, 3H), 3.80 (s, 3H), 3.75 (s, 3H) 3.30 (s,
3H), 3.26 (dd, J = 16.0, 6.0 Hz, 1H), 2.66 (dd, J = 16.0,
9.0 Hz, 1H); 13C NMR (125 MHz, CDCl3) δ 165.7, 160.0,
158.6, 155.1, 149.5, 149.2, 131.9, 129.6, 129.5, 128.2, 127.1,
120.3, 111.2, 110.4, 100.5, 93.1, 92.2, 78.6, 72.4, 56.0, 55.8,
21
(9.3 mg, 52%) as a colorless oil. [α]D –8.0ꢀ (c 0.38,
CHCl3); IR (neat) 2943, 1745, 1621, 1515, 1270, 1146,
1
1026, 755 cm−1; H NMR (500 MHz, CDCl3) δ 7.29 (t,
J = 8.0 Hz, 1H), 7.17 (t, J = 8.0 Hz, 2H), 7.10 (d,