mixture was filtered and the filtrate concentrated to give crude
dihydrofuranoquinoline (؊)-3R which on purification by PLC
(EtOAc–hexane, 1:1, Rf 0.5) yielded the title compound (0.027
g, 57%); mp 136–138 ЊC (Et2O–MeOH) [lit.,27 137–138 ЊC];
[α]D Ϫ47.0 (c 0.76, MeOH) (lit.,27 [α]D ϩ44, MeOH); 1H NMR
(500 MHz, CDCl3) δ 1.28 (3 H, s, Me), 1.45 (3 H, s, Me), 1.66
(1 H, br, OH), 3.58 (1 H, dd, J3a,3b 15.5, J3a,2 8.8, H-3a), 3.65
(1 H, dd, J3b,3a 15.5, J3b,2 7.9, H-3b), 4.21 (3 H, s, OMe), 4.64
(1 H, dd, J2,3a 8.8, J2,3b 7.9, H-2), 7.29 (1 H, dd, J6,5 8.2, J6,7 7.0,
H-6), 7.55 (1 H, dd, J7,6 7.0, J7,8 8.3, H-7), 7.73 (1 H, d, J8,7 8.3,
H-8), 8.01 (1 H, d, J5,6 8.2, H-5); 13C NMR (125 MHz, CDCl3)
δ 24.3, 26.2, 29.0, 58.2, 71.5, 86.4, 101.6, 120.0, 122.1, 123.4,
126.7, 129.8, 147.3, 159.0, 168.7; m/z 259 (53%), 200 (100).
(؉)-(3R,4S)- and (؊)-(3S,4R)-trans-3-Bromo-4-(2-methoxy-
2-phenyl-2-trifluoromethylacetoxy)-3,4-dihydro-5-methoxy-
2,2-dimethyl-2H-pyrano[2,3-b]quinolines (20RSR* and
20SRR*)
Racemic bromohydrin 19 (0.585 g, 1.05 mmol) was converted
into the corresponding MTPA esters [(ϩ)-MTPA-chloride, 0.49
g, 1.94 mmol]. Separation of the esters by multiple elution PLC
(hexane–EtOAc–MeOH; 8:1:1) gave the high Rf diastereo-
isomer 20RSR* (0.038 g, 40%), mp 156–158 ЊC (from i-Pr2O–
MeOH), [α]D ϩ13.9 (c 0.6, CHCl3) (Found: C, 54.1; H, 4.2; N,
2.5. C25H23BrF3NO5 requires C, 54.1; H, 4.2; N, 2.5%); 1H
NMR (500 MHz, CDCl3) δ 1.26 (3 H, s, C(Me)2), 1.59 (3 H, s,
C(Me)2), 3.59 (3 H, s, OMe), 4.09 (3 H, s, OMe), 4.18 (1 H, d,
J3,4 3.8, H-3), 6.78 (1 H, d, J4,3 3.8, H-4), 7.38–7.47 (4 H, m, Ar-
H), 7.60–7.72 (3 H, m, Ar-H), 7.93 (2 H, dd, J 8.5, 16.2, Ar-H);
m/z 555 (81Br, 19%), 553 (79Br, 20) and 226 (100). The low Rf
diastereoisomer 20SRR* was obtained as a colourless gum
(0.0346 g, 36%); [α]D Ϫ55.8 (c 1.3, CHCl3) (Found: C, 53.5; H,
4.8; N, 2.6. C25H23BrF3NO5 requires C, 54.1; H, 4.2; N, 2.5%);
1H NMR (500 MHz, CDCl3) δ 1.57 (3 H, s, C(Me)2), 1.66 (3 H,
s, C(Me)2), 3.49 (3 H, s, OMe), 4.03 (3 H, s, OMe), 4.33 (1 H, d,
J3,4 4.3, H-3), 6.81 (1 H, d, J4,3 4.3, H-4), 7.39–7.44 (4 H, m,
Ar-H), 7.62–7.70 (3 H, m, Ar-H), 7.87–7.92 (2 H, m, Ar-H);
m/z 555 (81Br, 18), 553 (79Br, 18) and 226 (100).
(؉)-(S)-Platydesmine (3S)
Treatment of bromoacetate 15R (0.1 g, 0.26 mmol, [α]D ϩ34)
with KOt-Bu, as described for bromoacetate 15S, gave platy-
desmine 3S (0.045 g, 67%), [α]D ϩ47 (c 0.71, MeOH) (lit.,27
[α]D ϩ44, MeOH).
(؊)-(2R)-Platydesmine methiodide (4RI)
A solution of (Ϫ)-platydesmine 3R, (0.02 g, 0.08 mmol, [α]D
Ϫ47) in EtOH (3 cm3), containing a few drops of MeI, was
refluxed (1.5 h). The reaction mixture was cooled and the solid
iodide salt (؊)-4RI (0.018 g, 56%) was collected by filtration,
[α]D Ϫ31 (c 0.64, MeOH) [lit.,9 [α]D ϩ30, MeOH]. The sample
was spectrally indistinguishable from the sample of iodide salt
obtained from S. japonica.
(؊)-(3S,4S)-3,4-Dihydro-3,4-epoxy-5-methoxy-2,2-dimethyl-
2H-pyrano[2,3-b]quinoline (21SS)
A solution of (ϩ)-bromo-MTPA ester 20RSR* (0.69 g, 1.24
mmol) in dry THF (20 cm3) was treated with KOt-Bu (0.42 g,
3.74 mmol) at room temperature (24 h). The reaction mixture
was filtered, the filtrate concentrated, and the product purified
by PLC (CHCl3–EtOAc; 4:1, Rf 0.64) to yield the epoxide 21SS
as a viscous oil (0.262 g, 81%), [α]D Ϫ142 (c 0.95, CHCl3)
(Found: Mϩ, 257.1050. C15H15NO3 requires Mϩ, 257.1052); 1H
NMR (500 MHz, CDCl3) δ 1.42 (3 H, s, C(Me)2), 1.69 (3 H, s,
C(Me)2), 3.60 (1 H, d, J3,4 4.4, H-3), 4.16 (3 H, s, OMe), 4.49
(1 H, d, J4,3 4.3, H-4), 7.40–7.45 (1 H, m, H-8), 7.62–7.67 (1 H,
m, H-7), 7.85 (1 H, d, J5,6 8.3, H-6), 7.99 (1 H, d, J9,8 8.1, H-9);
m/z 257 (100).
(؉)-(2S)-Platydesminium methiodide (4SI)
(ϩ)-Platydesmine 3S (0.02 g, 0.08 mmol) ([α]D ϩ47) was con-
verted to the (Ϫ)-iodide 4RI (0.02 g, 63%), [α]D ϩ31 (c 0.74,
MeOH) by the procedure given for the (Ϫ)-enantiomer 3R.
(؉)-(3R)-3-Hydroxy-4,4-dimethyl-4-butyrolactone (31)
Methyl 4-methylpent-3-enoate (1.0 g, 7.8 mmol) on reaction
with AD-mix-β (11.0 g) yielded crude lactone 31 (0.6 g, 59%)
under identical conditions to those used earlier. PLC purifi-
cation (Et2O, Rf 0.25) gave butyrolactone 31 as a colourless oil,
spectrally identical with literature values;24 [α]D ϩ11.5 (c 2.2,
CHCl3) [lit.8 [α]D ϩ7.1, CHCl3]. The 3,5-dinitrobenzoate
derivative 33 of (ϩ)-lactone 31 was obtained as colourless
crystals, mp 151 ЊC (from hexane–CHCl3) [lit.,24 151–152 ЊC];
(؉)-(3R,4R)-3,4-Dihydro-3,4-epoxy-5-methoxy-2,2-dimethyl-
2H-pyrano[2,3-b]quinoline (21RR)
1
(Ϫ)-Bromo-MTPA ester 20SRR* (0.735 g, 1.33 mmol) was
treated as described for the (ϩ)-bromo-MTPA ester 20RSR* to
yield epoxide 21RR as an oil (0.279 g, 82%). [α]D ϩ144.0 (c 1.47,
CHCl3).
[α]D ϩ5 (c 1.0, CHCl3) (lit.,24 [α]D ϩ5) H NMR (500 MHz,
CDCl3) δ 1.55 (3 H, s, C(Me)2), 1.60 (3 H, s, C(Me)2), 2.80 (1 H,
dd, J2a,3 2.0, J2a,2b 18.7, H-2a), 3.26 (1 H, dd, J2b,3 6.7, J2b,2a 18.7,
H-2b), 5.55 (1 H, dd, J3,2a 2.0, J3,2b 6.7, H-3), 9.15 (2 H, t, J 2.1,
Ar), 9.28 (1 H, t, J 2.1, Ar-H).
(؉)-(S)-Geibalansine (7S)
( )-trans-3-Bromo-4-hydroxy-3,4-dihydro-5-methoxy-2,2-
dimethyl-2H-pyrano[2,3-b]quinoline (19RS/SR)
(Ϫ)-Epoxide 21SS (0.047 g, 0.18 mmol) was hydrogenated in
MeOH solution (10 cm3) using Pd-C (10%) catalyst at ambient
temperature. The crude hydrogenated product was purified by
PLC (CHCl3–EtOAc; 4:1) to give (ϩ)-(S)-geibalansine 7S as a
colourless oil which solidified on standing (0.037 g, 78%); mp
181–182 ЊC (from i-Pr2O–MeOH) (lit.,17 mp 179 ЊC); [α]D ϩ12.0
To a stirring solution (~5 ЊC) of 5-methoxy-2,2-dimethyl-2H-
pyrano[2,3-b]quinoline 18 (0.762 g, 3.16 mmol) in aqueous
tetrahydrofuran (THF, 100 cm3–H2O, 10 cm3) was added, in
small portions, N-bromosuccinimide (0.62 g, 3.48 mmol). After
stirring (24 h) at ambient temperature, the solution was concen-
trated, diluted with water and the product extracted into
chloroform (3 × 30 cm3). The organic extracts were dried
(MgSO4) and the solvent evaporated under reduced pressure to
give the crude product. PLC purification (CHCl3) yielded
racemic bromohydrin 19 (1.655 g, 78%) (Rf 0.57, CHCl3–
EtOAc, 4:1); mp 164–165 ЊC (from i-Pr2O–MeOH) (Found: C,
53.1; H, 4.6; N, 4.9; Br, 23.8. C15H16NO3Br requires C, 53.3; H,
4.8; N, 4.2; Br, 23.6%); 1H NMR (500 MHz, CDCl3) δ 1.56 (3 H,
s, C(Me)2), 1.74 (3 H, s, C(Me)2), 4.16 (3 H, s, OMe), 4.31 (1 H,
d, J3,4 7.1, H-3), 5.41 (1 H, d, J4,3 7.1, H-4), 7.38–7.43 (1 H, m,
H-8), 7.62–7.67 (1 H, m, H-7), 7.87 (1 H, d, J6,7 8.5, H-6), 7.94
(1 H, d, J9,8 8.3, H-9); m/z 339 (81Br, 100%) and 337 (79Br, 100).
1
(c 0.86, MeOH); H NMR (500 MHz, CDCl3) δ 1.46 (3 H, s,
C(Me)2), 1.49 (3 H, s, C(Me)2), 3.00 (1 H, dd, J4a,3 6.2, J4a,4b
17.2, H-4a), 3.20 (1 H, dd, J4b,3 5.1, J4b,4a 17.3, H-4b), 3.95–3.99
(1 H, m, H-3), 3.99 (3 H, s, OMe), 7.32–7.38 (1 H, m, H-8),
7.56–7.61 (1 H, m, H-7), 7.82 (1 H, d, J6,7 8.4, H-6), 7.89 (1 H, d,
J9,8 8.3, H-9); m/z 259 (100%).
(؊)-(R)-Geibalansine (7R)
(ϩ)-Epoxide 21RR (0.071 g, 0.27 mmol) was treated as
described for (Ϫ)-(3S,4S)-epoxide 21SS and yielded (Ϫ)-(R)-
geibalansine 7R (0.062 g, 87%); mp 180–181 ЊC (from i-Pr2O–
MeOH); [α]D Ϫ12.0 (c 1, MeOH).
J. Chem. Soc., Perkin Trans. 1, 2000, 3397–3405
3403