6-Benzyloxymethyl-1,5,6,10b-tetrahydrobenzo[g]indolizin-
3(2H)-one 32
m, 2-Hα), 2.45–2.38 (1 H, m, 2-Hβ) and 1.91–1.81 (1 H, m, 1-
Hβ); δC(100 MHz, APT, CDCl3) 173.5 (C), 138.3 (C), 134.2 (C),
127.3 (CH), 127.0 (CH), 126.9 (CH), 124.9 (CH), 63.6 (CH2),
56.7 (CH), 39.8 (CH2), 39.5 (CH), 31.5 (CH2) and 27.4 (CH2).
A solution of the ethoxylactam 31 (94 mg, 0.27 mmol) in formic
acid (6 cm3) was stirred at room temperature for 22 h and then
evaporated under reduced pressure. The residue was dissolved
in dichloromethane and washed with dilute aqueous sodium
hydrogen carbonate. The organic layers were dried (Na2SO4)
and evaporated under reduced pressure. The residue was puri-
fied by flash column chromatography, eluting with ethyl
acetate–light petroleum (bp 40–60 ЊC) (3:1), to give the tricyclic
lactam 32 (58 mg, 71%) as an oil (Found: MHϩ, 308.1669.
C20H21NO2 requires MH, 308.1650), which NMR spectroscopy
showed to be a mixture of diastereoisomers (8.4:1); νmax/cmϪ1
1,2,3,5,6,10b-Hexahydrobenzo[g]indolizine-6-methanol 34
A solution of the (6R*,10bS*)-alcohol 33 (210 mg, 0.97 mmol)
in dry THF (18 cm3) was added to a stirred suspension of lith-
ium aluminium hydride (75 mg, 1.94 mmol) in dry THF (2 cm3)
under argon at 0 ЊC. The mixture was heated at reflux for 1 h,
then cooled and poured into a mixture of diethyl ether and ice.
The organic layer was separated and the aqueous layer was
extracted with diethyl ether (3 × 50 cm3). The combined organic
layers were dried (MgSO4) and evaporated under reduced pres-
sure. The residue was purified by flash column chromatography,
eluting with dichloromethane–methanol (17:3) to yield the
amine 34 (183 mg, 93%) as an oil (Found: MHϩ, 204.1388.
C13H17NO requires MH, 204.1388); νmax/cmϪ1 3354 (O᎐H);
δH (400 MHz, CDCl3) 7.26–7.08 (4 H, m, ArH), 4.09 (1 H, dd, J
2.7 and 9.9, CHHOH), 3.38 (1 H, dt, J 2.0 and 3.2 and 9.9,
CHHOH), 3.35 (1 H, d, J 11.1, 5-Hβ), 3.22–3.17 (2 H, m), 2.99
(1 H, br s, 6-H), 2.83 (1 H, d, J 11.1, 5-Hα), 2.43–2.34 (2 H, m),
1.96–1.87 (2 H, m) and 1.77–1.69 (1 H, m); δC(100 MHz, APT,
CDCl3) 138.5 (C), 135.2 (C), 128.0 (CH), 126.9 (CH), 126.5
(CH), 124.9 (CH), 70.4 (CH2), 64.8 (CH), 54.1 (CH2), 53.0
(CH2), 40.0 (CH), 29.0 (CH2) and 21.5 (CH2); m/z (CI) 204
(MHϩ).
1716 and 1682 (C᎐O); m/z (FAB ϩ ve) 308 (MHϩ). The two
᎐
isomers were separated by PLC, eluting with dichloromethane–
acetone (9:1), for NMR analysis.
For the major (6R*,10bS*)-isomer: δH (400 MHz, CDCl3)
7.37–7.09 (9 H, m, ArH), 4.76 (1 H, t, J 8.2, 10b-H), 4.58 and
4.47 (each 1 H, d, J 11.7, PhCHH), 4.57 (1 H, d, J 13.1, 5-Hβ),
3.49 (1 H, ddd, J 9.4, 4.3 and 4.0, 6-H), 3.35 (1 H, t, J 9.4,
CHHOBn), 3.11 (1 H, t, J 9.4 and 4.3, CHHOBn), 3.05 (1 H,
dd, J 13.1 and 4.0, 5-Hα), 2.70–2.54 (2 H, m, 1-Hα and 2-Hβ),
2.46 (1 H, m, 2-Hα) and 1.75 (1 H, m, 1-Hβ); δC(100 MHz, APT,
CDCl3) 173.6 (C), 138.2 (C), 137.9 (C), 133.7 (C), 130.1 (CH),
128.3 (CH), 127.8 (CH), 127.5 (CH), 127.3 (CH), 126.8 (CH),
124.8 (CH), 73.5 (CH2), 73.3 (CH2), 56.8 (CH), 39.4 (CH), 38.1
(CH2), 31.8 (CH2) and 27.9 (CH2).
For the minor (6S*,10bS*)-isomer: δH (400 MHz, CDCl3)
7.35–7.11 (9 H, m, ArH), 4.76 (1 H, t, J 8.0, 10b-H), 4.56 and
4.52 (each 1 H, d, J 12.5, PhCHH), 4.43 (1 H, dd, J 13.1 and
6.2, 5-Hβ), 3.81 (1 H, dd, J 9.5 and 4.8, CHHOBn), 3.68 (1 H,
dd, J 9.5 and 6.7, CHHOBn), 3.25 (1 H, m, 6-H), 3.06 (1 H, dd,
J 13.1 and 9.7, 5-Hα), 2.70–2.51 (2 H, m, 1-Hα and 2-Hβ), 2.44 (1
H, m, 2-Hα) and 1.92–1.82 (1 H, m, 1-Hβ); δC(100 MHz, APT,
CDCl3) 173.2 (C), 138.1 (C), 138.0 (C), 134.7 (C), 128.4 (CH),
127.7 (2 × CH), 127.2 (CH), 127.1 (CH), 127.0 (CH), 124.8
(CH), 73.2 (CH2), 71.3 (CH2), 56.7 (CH), 40.2 (CH2), 37.6
(CH), 31.6 (CH2) and 27.5 (CH2).
(1,2,3,5,6,10b-Hexahydrobenzo[g]indolizin-4-ium-6-yl)methyl
4-[(E)-2-(isopropoxycarbonyl)ethenyl]phenylphosphonate 35
To a stirred suspension of the phosphonic acid 14 (55 mg, 0.20
mmol) in dry DMF (1 cm3) at Ϫ15 ЊC under argon was added
thionyl chloride (20 mm3, 0.24 mmol). The resultant mixture
was stirred at 0 ЊC for 1 h and then a solution of the alcohol 34
(82 mg, 0.40 mmol) in dry DMF (1 cm3) was added and the
mixture was stirred at room temperature for a further 24 h.
Water was added (1 cm3) and the mixture was extracted with
diethyl ether (6 × 10 cm3). The combined organic layers were
dried (MgSO4) and evaporated under reduced pressure. The
residue was purified by PLC, eluting with propan-1-ol–water–
ammonia (18:1:1), to yield the phosphonate ester 35 (32
mg, 35%) as an amorphous solid (Found: MHϩ, 456.1933.
C25H30NO5P requires MH, 456.1939); νmax/cmϪ1 3139–3030
6-Hydroxymethyl-1,5,6,10b-tetrahydrobenzo[g]indolizin-3(2H)-
one 33
The mixture of diastereoisomeric benzyl ethers 32 (85 mg, 0.28
mmol) and 10% palladium-on-carbon (85 mg) were stirred in
absolute ethanol (2 cm3) under an atmosphere of hydrogen for 8
h. The mixture was then filtered through Celite, washing with
more absolute ethanol. The filtrate and washings were evapor-
ated under reduced pressure and the residue was purified by
flash column chromatography, eluting with dichloromethane–
tetrahydrofuran (4:1), to give a mixture of the diastereoiso-
meric alcohols 33 (35 mg, 58%) as a solid. Recrystallisation from
ethanol gave the (6R*,10bS*)-isomer as prisms, mp 157–158 ЊC
(Found: C, 71.7; H, 7.0; N, 6.35%; MHϩ, 218.1181. C13H15NO2
requires C, 71.9; H, 6.95; N, 6.45%; MH, 218.1181); νmax/cmϪ1
(N᎐H) and 1703 (C᎐O); δ (500 MHz, CD OD) 7.71 (2 H, dd, J
᎐
H
3
11.9 and 8.0, ArH), 7.66 (1 H, d, J 16.0, CH᎐C), 7.59 (2 H, dd, J
᎐
8.0 and 2.8, ArH), 7.30–7.21 (4 H, m, ArH), 6.54 (1 H, d, J 16.0,
C᎐CH), 5.09 (1 H, septet, J 6.3, CHMe ), 4.49 (1 H, dd, J 7.3
᎐
2
and 8.4), 4.25 (1 H, m), 4.03 (1 H, m), 3.60–3.43 (5 H, m), 2.71
(1 H, m), 2.22 (2 H, m), 2.05 (1 H, quintet, J 11.1) and 1.31 (6 H,
d, J 6.3, CHMe2); δC(100 MHz, APT, CD3OD) 168.0 (C), 145.1
(CH), 138.9 (C, J 176), 137.7 (C), 133.7 (C), 133.1 (CH, J 9),
132.7 (C), 129.0 (CH, J 14), 128.8 (CH), 128.7 (CH), 127.9
(CH), 127.6 (CH), 120.8 (CH), 69.5 (CH), 66.4 (CH2), 65.0
(CH), 55.9 (CH2), 50.9 (CH2), 36.4 (CH), 30.8 (CH2), 22.1
(CH2) and 22.1 (Me); m/z (FAB ϩ ve) 456 (MHϩ).
3324 (O᎐H) and 1672 (C᎐O); δ (400 MHz, CDCl ) 7.28–7.10 (4
᎐
H
3
H, m, ArH), 4.86 (1 H, t, J 7.8, 10b-H), 4.50 (1 H, d, J 13.3, 5-
Hβ), 3.67–3.60 and 3.37–3.31 (each 1 H, m, CH2OH), 3.13–3.00
(3 H, m, 5-Hα, 6-H and OH), 2.76–2.60 (2 H, m, 2-Hβ and 1-
Hα), 2.52–2.45 (1 H, m, 2-Hα) and 1.91–1.81 (1 H, m, 1-Hβ);
δC(100 MHz, APT, CDCl3) 174.8 (C), 137.8 (C), 133.9 (C),
129.8 (CH), 127.5 (CH), 126.9 (CH), 125.2 (CH), 64.9 (CH),
57.1 (CH2), 41.2 (CH), 37.6 (CH2), 31.4 (CH2) and 27.8 (CH2);
m/z (CI) 435 (2M ϩ Hϩ), 235 (M ϩ NH4ϩ) and 218 (MHϩ).
For NMR analysis the minor (6S*,10bS*)-isomer was
obtained pure from the mother liquors by PLC eluting with
dichloromethane–methanol (19:1); δH (400 MHz, CDCl3) 7.36
and 7.12 (each 1 H, dd, J 8.8 and 3.6, 7- and 10-H), 7.23 (2 H,
m, 8- and 9-H), 4.77 (1 H, t, J 8.0, 10b-H), 4.29 (1 H, dd, J 11.3
and 10.5, 5-Hα), 3.98 (1 H, dd, J 11.2 and 3.7, CHHOH), 3.90 (1
H, dd, J 11.3 and 5.8, CHHOH), 3.12 (2 H, m, 6-H and 5-Hβ),
2.88 (1 H, br s, OH), 2.70–2.62 (1 H, m, 1-Hα), 2.59–2.50 (1 H,
(1,2,3,5,6,10b-Hexahydrobenzo[g]indolizin-4-ium-6-yl)methyl
4-[(E)-2-carboxyethenyl]phenylphosphonate 25
A solution of the ester 32 (21 mg, 46.2 µmol) in methanolic
potassium hydroxide (2.7 mol dmϪ3; 1 cm3) was stirred under
argon at room temperature for 24 h and then evaporated under
reduced pressure. The residue was dissolved in water (10 cm3)
and Dowex-50WX8-400 (NH4ϩ) ion exchange resin was added
until the pH dropped to between 9 and 10. The resin was filtered
off and the filtrate was lyophilised to yield the acid 25 (18 mg,
95%) as an amorphous solid (Found: MHϩ, 414.1481.
C22H24NO5P requires MH, 414.1470); νmax/cmϪ1 3422–3144
(O᎐H) and 1700 (C᎐O); δ (500 MHz, CD OD) 7.70 (2 H, dd, J
᎐
H
3
11.8 and 8.1, ArH), 7.55 (2 H, dd, J 2.9 and 8.1, ArH), 7.51 (1
H, d, J 16.0, CH᎐C), 7.32–7.21 (4 H, m, ArH), 6.55 (1 H, d, J
᎐
J. Chem. Soc., Perkin Trans. 1, 1997
1023