PAPER
Synthesis of (+)-Erysotramidine
3291
Minor Diastereoisomer a-Alcohol
7), 6.30 (ddd, J = 10.0, 5.6, 2.0 Hz, 1 H, H-2), 6.70 (s, 1 H, ArH),
6.83 (dd, J = 10.0, 3.2 Hz, 1 H, H-1), 7.00 (s, 1 H, ArH).
2
5
Oil; [a]D –89.7 (c = 1.7, CHCl3).
1
13
H NMR (400 MHz, CDCl ): d = 1.52–1.73 (m, 4 H, 2 CH ), 1.9–
C NMR (100.6 MHz, CDCl ): d = 24.6 (CH ), 27.2 (CH ), 35.0
2 2 3 3
3
2
3
2
2
2
.0 (m, 2 H, CH ), 2.45 (dd, J = 17.2, 9.4 Hz, 1 H, CHH), 2.63 (d,
(CH ), 37.0 (CH ), 55.9 (OCH ), 56.0 (OCH ), 64.6 (C), 108.7
2
J = 17.2, 10.1 Hz, 1 H, CHH), 2.74 (m, 1 H, CH), 2.82 (m, 1 H,
ArCHH), 2.92 (m, 1 H, ArCHH), 3.21 (m, 1 H, NCHH), 3.86 (s, 3
H, OCH ), 3.87 (s, 3 H, OCH ), 4.06 (m, 1 H, NCHH), 4.52 (m, 1
(CH), 112.1 (CH), 118.9 (CH), 124.1 (CH), 126.4 (C), 128.7 (C),
136.0 (CH), 146.8 (C), 148.3 (C), 157.9 (C), 171.3 (C=O).
3
3
+
ESIMS: m/z (%) = 297.9 (M , 46.3).
H, CH), 6.62 (s, 1 H, ArH), 6.77 (s, 1 H, ArH).
+
HRMS: m/z calcd for C H NO : 297.1365; found: 297.1354.
1
3
18 19
3
C NMR (100.6 MHz, CDCl ): d = 18.7 (CH ), 27.7 (CH ), 28.2
2 2 2 2 3
3
2
2
(
CH ), 31.4 (CH ), 35.1 (CH ), 35.1 (CH ), 44.9 (CH), 55.9 (OCH ),
3
-O-Desmethylerysotramidine 15
5
6.3 (OCH ), 64.1 (C), 68.8 (CH), 108.6 (CH), 112.0 (CH), 125.6
3
To a solution of lactam 14 (46 mg, 0.15 mmol) in dioxane (8 mL) at
(
C), 134.4 (C), 147.6 (C), 148.0 (C), 172.2 (C=O).
r.t. was added SeO (163 mg, 1.5 mmol) and formic acid (69 mg, 1.5
2
+
ESIMS: m/z (%) = 318.1 (MH , 100).
mmol). The resulting mixture was refluxed for 4 d, then cooled to
r.t. and aq 10% KOH was added. The product was extracted into
CH Cl and the combined organic layers were dried (Na SO ), fil-
+
HRMS: m/z calcd for C H NO : 317.1627; found: 317.1627.
1
8
23
4
2
2
2
4
tered and concentrated under reduced pressure. Purification by sili-
ca gel chromatography (MeOH–CH Cl , 3:100) gave firstly
1
,2-Didehydro-15,16-Dimethoxy-8-oxoerythrinan (13)
A solution of alcohol 12 (535 mg, 1.69 mmol) and Burgess reagent
603 mg, 2.5 mmol) in anhyd, degassed benzene (15 mL), was re-
2
2
recovered 14 (34 mg), followed by the desired product a-alcohol 15
(
2
5
(
10 mg, 21%, or 79% based on recovered 14); [a] +147 (c = 0.2,
D
3a 23
fluxed under an inert atmosphere for 6 h. The mixture was cooled to
r.t., evaporated in vacuo and purified by flash column chromatogra-
phy using silica gel (eluent: PE–EtOAc, 1:2) to give alkene 13 as a
CHCl ) {Lit. [a]D +182 (c = 0.25, CHCl )}.
3
3
–
1
IR (CHCl ): 3604, 2936, 1672, 1363, 1109, 1051, 862 cm .
3
2
5
yellow oil (413 mg, 80%); [a]D +401 (c = 0.4, CHCl3).
1
H NMR (400 MHz, CDCl ): d = 1.68 (dd, J = 11.6, 10.4 Hz, 1 H,
3
–
1
IR (CHCl ): 2936, 2834, 1681, 1362, 1122, 997, 866 cm .
H-4), 2.80 (dd, J = 11.6, 5.2 Hz, 1 H, H-4), 2.95–3.11 (m, 2 H, H-
11), 3.58 (ddd, J = 12.8, 7.6, 5.6 Hz, 1 H, H-10), 3.75 (s, 3 H,
OCH ), 3.85 (s, 3 H, OCH ), 3.93–4.00 (dt, J = 12.8, 7.6, 1 H, H-
3
1
H NMR (400 MHz, CDCl ): d = 1.75 (ddd, J = 16.8, 11.6, 6.8 Hz,
3
3
3
1
2
H, H-4), 1.99–2.07 (m, 2 H, H-7), 2.18–2.23 (m, 1 H, H-3), 2.29–
.35 (m, 1 H, H-4), 2.72 (dd, J = 16.4, 9.2 Hz, 1 H, H-6), 2.78–3.00
1
0), 4.30 (m, 1 H, H-3), 6.01 (s, 1 H, H-7), 6.31 (d, J = 10.0 Hz, 1
H, H-1), 6.71 (s, 1 H, ArH), 6.79 (s, 1 H, ArH), 6.87 (dd, J = 10.0,
(
m, 3 H, H-11 and H-3), 3.30–3.38 (m, 1 H, H-10), 3.80 (s, 3 H,
2
.4 Hz, 1 H, H-2).
OCH ), 3.86 (s, 3 H, OCH ), 4.11 (ddd, J = 13.2, 7.2, 4.0 Hz, 1 H,
H-10), 5.99 (br s, 2 H, CH=CH), 6.62 (s, 1 H, ArH), 6.74 (s, 1 H,
ArH).
3
3
1
3
C NMR (100.6 MHz, CDCl ): d = 27.1 (CH ), 37.4 (CH ), 45.1
3
2
2
(CH ), 55.9 (OCH ), 56.1 (OCH ), 66.4 (CH), 66.7 (C), 108.1 (CH),
2
3
3
1
3
112.2 (CH), 120.2 (CH), 123.5 (CH), 126.4 (C), 128.5 (C), 139.3
CH), 147.1 (C), 148.6 (C), 157.2 (C), 171.1 (C=O).
C NMR (100.6 MHz, CDCl ): d = 22.5 (CH ), 29.3 (CH ), 31.7
2 2 2 3
3
2
2
(
(
(
CH ), 34.9 (CH ), 38.4 (CH ), 39.6 (CH), 55.9 (OCH ), 56.0
OCH ), 61.2 (C), 107.9 (CH), 111.6 (CH), 125.2 (C), 127.7 (CH),
+
+
ESIMS: m/z (%) = 313.9 (M , 100.0), 648.8 (2 M + Na, 83.0).
3
1
29.1 (CH), 133.3 (C), 147.6 (C), 147.9 (C), 172.2 (C=O).
+
HRMS: m/z calcd for C H NO : 313.1314; found: 313.1304.
1
8
19
4
+
ESIMS: m/z (%) = 299.9 (M , 72).
+
(+)-Erysotramidine (2)
A mixture of alcohol 15 (7 mg, 0.022 mmol), 85% KOH (30 mg),
HRMS: m/z calcd for C H NO : 299.1521; found: 299.1533.
1
8
21
3
Et NBr (30 mg), and MeI (0.5 mL) in THF (4 mL) was stirred at r.t.
4
1
5,16-Dimethoxy-1,2,6,7-tetradehydro-8-oxoerythrinan (14)
for 36 h, then poured into ice water (5 mL) and extracted with
CHCl (20 mL). The extract was dried (Na SO ), concentrated and
A solution of LDA (3.86 mL, 2.76 mmol, 0.8 M in THF) at –78 °C
was added dropwise to a solution of starting lactam 13 (345 mg,
1
3
2
4
purified by silica gel chromatography (PE–EtOAc, 1:1) to give the
.15 mmol) in THF (5 mL). The resulting solution was stirred at this
desired target molecule (+)-erysotrimidine 2 as a colourless oil (6.8
temperature for 30 min, then (PhSe) (780 mg, 2.5 mmol) in THF
2
25
5
21
mg, 95%); [a] +65 (c = 0.25, CHCl ) {Lit. [a] +121 (c = 1.0,
D
3
D
(10 mL) was added dropwise. The mixture was stirred for another 1
CHCl )}.
3
h at –78 °C before quenching with 1 N HCl and extracted with
CH Cl . The combined organic extracts were dried (Na SO ), fil-
–
1
IR (CHCl ): 2927, 2854, 1672, 1463, 1364, 1100, 994, 892 cm .
2
2
2
4
3
tered, and concentrated under reduced pressure to give a crude prod-
uct. This was dissolved in 3:1 MeOH–H O (16 mL) and NaIO
1
H NMR (400 MHz, CDCl ): d = 1.72 (dd, J = 11.6, 10.0 Hz, 1 H,
3
2
4
H-4), 2.82 (dd, J = 11.6, 4.4 Hz, 1 H, H-4), 2.97–3.14 (m, 2 H, H-
1
1
(
2.14 g, 10 mmol) was added. The resulting mixture was stirred at
1), 3.36 (s, 3 H, OCH ), 3.63 (ddd, J = 12.8, 7.2, 5.6 Hz, 1 H, H-
3
r.t. for 4 h, then filtered and concentrated under reduced pressure.
Purification of the residue by column chromatography (eluent: PE–
EtOAc, 1:1) provided 150 mg (43% two steps) of the doubly unsat-
0), 3.78 (s, 3 H, OCH ), 3.86 (s, 3 H, OCH ), 3.85–3.90 (m, 1 H,
3
3
H-3), 4.01 (ddd, J = 12.8, 8.4, 7.2 Hz, 1 H, H-10), 6.04 (s, 1 H, H-
), 6.35 (d, J = 10 Hz, 1 H, H-2), 6.73 (s, 1 H, ArH), 6.81 (s, 1 H,
7
2
5
urated lactam 14 as an orange oil; [a]D +43.7 (c = 0.44, CHCl3).
ArH), 6.92 (dd, J = 10.0, 2.4 Hz, 1 H, H-1).
The ee was determined as 93.2% by HPLC (Chiracel OD Column,
13
C NMR (100.6 MHz, CDCl ): d = 27.1 (CH ), 37.4 (CH ), 41.4
2 3 3 3
3
2
2
4
0% IPA in hexane, 0.4 mL/min), the retention times were 19.9 min
(
CH ), 55.9 (OCH ), 56.1 (OCH ), 56.5 (OCH ), 66.4 (CH), 74.8
(minor) and 22.4 min (major).
(
C), 108.1 (CH), 112.2 (CH), 120.3 (CH), 124.2 (CH), 126.5 (C),
–
1
IR (CHCl ): 2936, 2837, 1681, 1361, 1285, 1068, 908, 867 cm .
128.6 (C), 136.3 (CH), 147.0 (C), 148.5 (C), 157.0 (C), 171.0
(C=O).
3
1
H NMR (400 MHz, CDCl ): d = 1.84 (dt, J = 12.0, 5.6 Hz, 1 H, H-
3
+
+
4
2
3
3
), 2.17–2.27 (m, 1 H, H-3), 2.33 (dd, J = 12.0, 4.8 Hz, 1 H, H-4),
.42 (dt, J = 19.6, 5.6 Hz, 1 H, H-3), 2.98 (t, J = 6.8 Hz, 2 H, H-11),
ESIMS: m/z (%) = 328.1 (M + 1, 100.0), 655.3 (2 M + 1, 34.5),
677.2 (2 M + 23, 90.2).
+
.57 (dt, J = 12.8, 6.8 Hz, 1 H, H-10), 3.78 (s, 3 H, OCH ), 3.84 (s,
+
3
HRMS: m/z calcd for C H NO : 327.1471; found: 327.1472.
1
9
21
4
H, OCH ), 4.04 (dt, J = 12.8, 6.8 Hz, 1 H, H-10), 5.89 (s, 1 H, H-
3
Synthesis 2005, No. 19, 3287–3292 © Thieme Stuttgart · New York