Study of alkaloids of the Siberian and Altai flora 9. Synthesis of amino derivatives of elatidine

Article abstract of DOI:10.1023/A:1022103922923

New secondary-tertiary diamines were prepared from elatidal imines with primary amino alcohols, derivatives of natural amino acids of the S-series. N-Methylation of the diamines yielded bi-tertiary diamines unable to undergo quaternization with MeI due to

Full text of DOI:10.1023/A:1022103922923

2290
Russian Chemical Bulletin, International Edition, Vol. 51, No. 12, pp. 2290—2294, December, 2002
Chemistry of Natural Compounds,
Bioorganic, and Biomolecular Chemistry
Study of alkaloids of the Siberian and Altai flora
9
.* Synthesis of amino derivatives of elatidine
J. Ganbaatar, S. A. Osadchii, E. E. Shults, and G. A. Tolstikovb
a
b
bꢀ
аInstitute of Chemistry and Chemical Technology of Mongolian Academy of Sciences,
5
4ꢀ56 ul. Jukova, 211051 UlanꢀBator, Mongolia.
Fax: (109 7611) 32 1993. Eꢀmail: inst_chemistry@arvis.ac.mn
b
N. N. Vorozhtsov Novosibirsk Institute of Organic Chemistry,
Siberian Branch of the Russian Academy of Sciences,
prosp. Akad. Lavrent´eva, 630090 Novosibirsk, Russian Federation.
Fax: +7 (383 2) 34 4752. Eꢀmail: schultz@nioh.nsc.ru
9
New secondaryꢀtertiary diamines were prepared from elatidal imines with primary amino
alcohols, derivatives of natural amino acids of the Sꢀseries. NꢀMethylation of the diamines
yielded biꢀtertiary diamines unable to undergo quaternization with MeI due to steric hinꢀ
drance.
Key words: diterpene alkaloids, elatidine, elatidal, aldimines, diamines.
This study continues a series of works dealing with the
a single geometric isomer, presumably, with the Еꢀconꢀ
figured imino group, because the steric restrictions assoꢀ
ciated with the imine bond formation are less proꢀ
synthesis of 18ꢀaminoꢀ18ꢀdeoxy elatidine derivatives on
2
the basis of elatidal (1). The initial compounds used were
1
elatidal imines with the Sꢀalanine, Sꢀvaline, and Sꢀtyꢀ
rosine methyl esters and with Sꢀvalinol, Sꢀtyrosinol, and
Sꢀmethioninol (2—7), which are formed in high yields in
the condensation of elatidal 1 with the appropriate amines
nounced. An attempt to reduce the C=N bond in imine
2 by NaBH resulted in a complex mixture of products.
4
Obviously, this is due to the side processes involving the
ester group. A satisfactory yield of diamine 8 (71%) was
(
Scheme 1).
According to H NMR spectroscopy, each imine 2—4
formed upon complete conversion of the initial elatidal 1 is
attained in the catalytic hydrogenation (H , Pd/C) of
imine 2. The reduction of imines 5—7 on treatment with
2
1
NaBH gave rise to the corresponding diamines 9—11,
4
containing both secondary and tertiary amino groups in
*
For Part 8, see Ref. 1.
one molecule. NꢀMethylation of the secondaryꢀtertiary
Published in Russian in Izvestiya Akademii Nauk. Seriya Khimicheskaya, No. 12, pp. 2127—2131, December, 2002.
066ꢀ5285/02/5112ꢀ2290 $27.00 © 2002 Plenum Publishing Corporation
1

Synthesis of elatidine aminoderivatives
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 12, December, 2002 2291
Scheme 1
Reagents, conditions, and product yields: i. RNH (–H O): (a) Sꢀalanine methyl ester, CHCl , 2 (95%); (b) Sꢀvaline methyl ester,
2
2
3
CHCl , 3 (92%); (с) Sꢀtyrosine methyl ester, CHCl , 4 (87%); (d) Sꢀvalinol, MeOH, 5 (90%); (e) Sꢀtyrosinol, MeOH, 6 (92%);
3
3
(
f) Sꢀmethioninol, MeOH, 7 (94%); ii. (g) H , Pd/C, EtOH, 8, (71%); iii. NaBH , MeOH: (h) 9 (80%); (i) 10 (82%); (j) 11 (81%);
2
4
iv. MeI then NH OH (–HI): (k) 12 (90%); (l) 13 (91%); (m) 15 (85%).
4
diamines 9 and 10 yielded biꢀtertiary diamines 12 and 13,
tometer. The molecular weights and the elemental compositions
of new compounds were determined using a Finnigan MAT
highꢀresolution mass spectrometer (version MS 8200, EI, 70 eV).
Melting points were measured on a Koefler stage.
which are not quaternized on treatment with methyl ioꢀ
3
dide. It is known that elatidine, containing a tertiary N
atom in the ring, cannot be converted into iodomethylate.
Apparently, this is due to steric hindrance to the formaꢀ
tion of the tetracoordinated N atom. We showed that
Nꢀmethylation of 18ꢀmethylaminoꢀ7,8ꢀmethylenediꢀ
oxyꢀ1α,6β,14α,16βꢀtetramethoxyꢀ20ꢀethylaconitane (14)
yields 18ꢀdimethylamino derivative (15). Despite the fact
that the exocyclic N atom in compound 15 bears substituꢀ
ents (methyl groups) that are less bulky than those in the
similar fragment of compounds 12 and 13, diamine 15
still does not undergo quaternization with methyl iodide.
Apparently, the lack of coordination reactivity in the exoꢀ
cyclic tertiary N atom of compounds 12, 13, and 15 is
also due to the above reasons.
The optical rotation was measured on a Polamat A polarimꢀ
eter (Carl Zeiss, λ = 578 nm). Specific rotation was expressed in
–1
(
deg mL) (g dm) , and the concentrations of solutions were
–1
1
13
expressed in g (100 mL) . The H and C NMR spectra of
tyrosinol oxalate and compounds 9, 10, and 12 were reꢀ
1
corded on a Bruker ACꢀ400 instrument ( H, 400.13 MHz;
1
3
C, 100.61 MHz) and the spectra of other compounds were
1
measured on a Bruker ACꢀ200 spectrometer ( H, 200.13 MHz;
13
C, 50.32 MHz) for 10% solutions of compounds (in CDCl3,
unless indicated otherwise) at 25 °C using the deuterium signal
of the solvent for resonance stabilization. The chemical shifts
(
δ) were referred to the signals of internal CHCl : δ 7.24 and
3 H
13
δC 76.90. The signal multiplicity in the C NMR spectra
were determined by standard procedures in the Jꢀmodulation
4
Thus, we synthesized elatidal imines with Sꢀalanine,
Sꢀvaline, and Sꢀtyrosine methyl esters and with Sꢀvalinol,
Sꢀtyrosinol, and Sꢀmethioninol. Catalytic hydrogenation
of elatidal imine with the Sꢀalanine methyl ester and the
NaBH4 reduction of elatidal imines with Sꢀvalinol,
Sꢀtyrosinol, and Sꢀmethioninol furnished the correspondꢀ
ing amino derivatives of elatidine containing both secꢀ
ondary and tertiary amino groups in one molecule.
NꢀMethylation of these diamines yielded biꢀtertiary diꢀ
amines, which are not quaternized on treatment with meꢀ
thyl iodide due to steric hindrance.
mode (JMOD) and with offꢀresonance proton irradiation. The
13
C NMR chemical shifts for newly synthesized compounds are
1
13
presented in Table 1. The H and C NMR signals were asꢀ
5
signed using data for model compounds: elatidine and the iniꢀ
tial Sꢀvalinol, Sꢀtyrosinol, and Sꢀmethioninol, and Sꢀalanine,
Sꢀvaline, and Sꢀtyrosine methyl esters. Since the assignment of
1
all H NMR signals is a complicated task, only the data of
characteristic signals are presented for the newly synthesized
compounds.
Freshly distilled solvents and pure grade reagents were used
in the work, together with the following initial compounds.
2
0
Elatidal (m.p. 146.5—148.0 °C (Et O), [α ]
–17.2
2
578
6
(
c 5, CHCl )) was prepared by a previously described procedure.
3
7
SꢀAlanine methyl ester synthesized by a known procedure
Experimental
from Sꢀalanine produced at the pilot plant of the Institute of
Bioorganic Chemistry of the Ukrainian Republic had b.p. 38 °C
IR spectra were recorded on a Vector 22 spectrometer and
UV spectra were measured on a Specord UVꢀVIS spectrophoꢀ
1
(
14 Torr) (cf. Ref. 8: b.p. 38 °C (14 Torr)). H NMR, δ: 0.91 (d,
3
H, 3´ꢀMe, J = 7 Hz); 3.12 (q, 1 H, C(2)H, J = 7 Hz); 3.31 (s,

2292
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 12, December, 2002
Ganbaatar et al.
Table 1. Chemical shifts (δ) of signals in the 13C NMR spectra of compounds 2—4, 8—13, and 15
Atom
δ
2
3
4*
8
9
10
11
12
13
15
C(1)
C(2)
C(3)
C(4)
C(5)
C(6)
C(7)
C(8)
83.1
25.8
32.5
42.4
53.1
89.6
91.8
83.3
39.7
48.0
49.3
27.7
38.3
81.4
34.6
81.1
64.1
170.6
52.3
50.2
13.6
93.2
55.0
57.4
59.1
55.8
172.2
67.7
19.0
—
83.2
25.6
32.6
42.7
53.3
89.4
91.6
83.4
39.8
48.1
49.3
27.6
38.4
81.5
34.7
81.2
64.1
171.1
52.2
50.1
13.7
93.3
55.1
57.5
59.1
55.9
171.9
80.4
31.0
16.3
19.2
—
84.5
26.7
33.0
43.6
53.2
90.3
93.3
84.7
41.1
49.2
50.6
28.9
39.6
83.1
36.3
82.5
65.1
174.1
53.3
51.3
14.2
94.4
55.6
57.7
59.5
56.3
173.4
76.1
39.3
—
83.0
26.1
31.6
36.6
52.5
89.0
91.7
82.9
39.4
48.0
49.5
27.4
38.2
81.2
34.4
81.2
63.9
54.2
54.2
50.0
13.5
93.0
54.7
57.0
58.1
55.7
175.8
57.3
18.7
—
83.2
26.4
32.2
37.0
53.8
89.6
91.8
83.2
39.6
48.4
49.4
27.6
38.3
81.4
34.1
83.3
64.5
54.9
54.6
50.3
13.7
93.0
54.9
57.6
59.0
56.0
65.2
28.8
18.3
19.3
60.2
—
83.2
26.3
32.0
36.9
53.5
89.4
91.9
83.2
39.6
48.2
49.5
27.6
38.2
81.4
34.2
81.4
64.3
54.7
54.1
50.3
13.7
93.0
54.9
57.5
58.7
55.9
60.9
37.2
62.2
—
83.1
26.2
32.0
36.8
54.8**
89.6
91.7
83.0
39.4
48.2
49.4
27.5
38.2
81.2
34.1
81.2
64.2
54.7
53.7
50.1
13.6
92.9
55.8
58.5
58.8
57.4
53.5**
30.9
30.7
62.6
—
83.4
26.4
32.5
39.0
48.4
91.8
91.8
83.2
38.3
39.5
49.6
27.7
36.3
81.4
34.1
81.3
64.3
60.6
54.9
50.3
13.7
92.9
54.9**
57.6
59.2
55.9
72.6
28.1
19.7
22.0
66.3
—
83.1
26.4
32.6
38.5
48.2
89.9
91.7
83.3
38.2
39.5
49.4
27.6
36.6
81.3
34.0
81.3
64.3
61.1
54.9
50.3
13.7
92.9
54.3
57.5
59.2
55.9
68.8
31.0
63.6
—
82.5
25.6
31.7
39.3
54.2
89.1
90.9
82.8
39.0
47.6
48.8
27.1
37.5
80.7
33.4
79.0
62.8
72.4
54.4
49.6
13.0
92.6
54.5
57.1
59.2
55.5
—
—
—
—
—
—
—
—
—
—
—
—
—
56.4
—
C(9)
C(10)
C(11)
C(12)
C(13)
C(14)
C(15)
C(16)
C(17)
C(18)
C(19)
N—CH CH3
N—CH CH3
OCH O
2
2
2
1
6
1
1
ꢀOMe
ꢀOMe
4ꢀOMe
6ꢀOMe
C(1´)
C(2´)
C(3´)
C(4´)
C(5´)
C(1″)
C(2″)
C(3″)
C(4″)
C(5″)
C(6″)
—
—
—
—
—
—
—
51.7
—
—
—
—
—
—
—
—
—
51.2
—
—
—
128.9
131.8
116.1
157.2
116.1
131.8
52.5
—
129.3
115.4
129.9
155.0
129.9
115.4
—
—
—
—
—
—
—
—
—
—
—
—
129.8
115.4
129.6
154.7
129.6
115.4
—
54.3
—
—
—
—
—
—
—
51.5
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
—
54.6**
—
—
CO CH3
2
NMe
NMe2
SMe
—
—
—
—
—
—
—
15.2
—
*
*
Solution in CD OD.
3
* The chemical shifts of the signals may have to be interchanged.
3
5
H, OMe). 13C NMR, δ: 175.5 (C(1)); 48.5 (C(2)); 19.1 (C(3));
0.2 (OMe). SꢀAlanine methyl ester hydrochloride synthesized
31.3 (C(3)); 18.2 and 16.3 (2 Me). SꢀValine methyl ester hydroꢀ
7
20
chloride synthesized by the same procedure had [α]
+14
5
78
7
20
23
by the same procedure had [α]
+7 (c 2, MeOH) (cf. Ref. 9:
(c 3.9, H O) (cf. Ref. 7: [α]
+16 (c 4.12, H O)).
5
78
2
D
2
2
0
7
[
α]D +9.0 (c 2, MeOH)).
SꢀTyrosine methyl ester synthesized from Sꢀtyrosine (Kiev
plant of Medical Preparations) had m.p. 135—136 °C (EtOAc),
7
SꢀValine methyl ester synthesized from Sꢀvaline had b.p.
0 °C (40 Torr), [α]5782 +42.1 (c 8.6, anhydrous MeOH)
0
[α]578 +30.5 (c 3.1, MeOH) (cf. Ref. 10: m.p. 135—136 °C
20
8
1
20
1
(
(
cf. Ref. 7: b.p. 80 °C (40 Torr)). H NMR, δ: 0.72 and 0.78
both d, each 3 H, C(3)Me , J = 7 Hz); 1.84 (septet d, 1 H,
(EtOAc), [α]D +25.75 (c 3.1, MeOH)). H NMR, δ: 2.84 (dd,
1 H, J = 12.5 and J = 7 Hz) and 2.93 (dd, 1 H, J = 12.5 and
2
C(3)H, J = 7 and J = 5 Hz); 3.12 (d, 1 H, C(2)H, J = 5 Hz);
.54 (s, 3 H, OMe). 13C NMR, δ: 175.0 (C(1)); 59.0 (C(2));
J = 6.5 Hz) (C(3)H ); 3.63 (m, 1 H, C(2)H); 6.74 (dm, 2 H,
J = 8 Hz) and 7.01 (dm, 2 H, J = 8 Hz) (АА´BB´ system, H(3´),
2
3

Synthesis of elatidine aminoderivatives
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 12, December, 2002 2293
H(5´) and H(2´), H(6´)). 13C NMR, δ: 176.4 (C(1)); 56.8 (C(2));
18ꢀ(Е)ꢀ[1SꢀMethoxycarbonyl)ethylimino]ꢀ7,8ꢀmethyleneꢀ
dioxyꢀ1α,6β,14α,16βꢀtetramethoxyꢀ20ꢀethylaconitane (2). Thick
oil, [α]57820 –55.5 (c 3.1, MeOH). Found, m/z: 562.3256 [M] .
4
1
0.8 (C(3)); 52.3 (OMe); 128.8 (C(1´)); 116.4 (C(2´), C(6´));
31.3 (C(2´), C(5´)); 157.4 (C(4´)).
+
SꢀMethionine methyl ester,11 b.p. 124—125 °C (11 Torr)
C H N O . Calculated: M 562.3254. H NMR, δ: 0.98 (t,
1
3
0
46
2
8
(
cf. Ref:11 b.p. 124—125 °C (11 Torr)). H NMR, δ: 1.48 (br.s,
1
3 H, NCH CH ); 1.31 (d, 3 H, C(3´)H , J = 7 Hz); 3.13, 3.18,
2 3 3
2
2
H, NH ); 1.70—2.00 (m, 2 H, C(3)H ); 2.08 (s, 3 H, SMe);
3.25 and 3.33 (all s, each 3 H, 1ꢀ, 6ꢀ, 14ꢀ and 16ꢀOMe); 3.61 (s,
3 H, CO Me); 4.93 and 4.96 (both s, each 1 H, OCH O); 7.40
(s, 1 H, C(18)H). IR (KBr), ν/cm : 731, 940, 962, 1007, 1051,
1090, 1123, 1379, 1450, 1662 (C=N), 1743 (C=O), 2822, 2878,
2933 and 2973.
2
2
.60 (t, 2 H, C(4´)H , J = 7.3 Hz); 3.56 (dd, 1 H, C(2´)H, J = 8
2
2
2
1
3
–1
and J = 5 Hz); 3.71 (s, 3 H, OMe). C NMR, δ: 175.24
C(1)); 52.30 (C(2)); 29.45 (C(3)); 33.05 (C(4)); 51.0 (OMe)
(
and 14.29 (SMe). The hydrochloride with the composition
C H NO S•HCl, prepared by a previously described proceꢀ
dure, had [α]578 +27 (c 5, H O) (cf. Ref. 11: [α]
18ꢀ(Е)ꢀ(2ꢀMethylꢀ1Sꢀmethoxycarbonylpropylimino)ꢀ7,8ꢀ
methylenedioxyꢀ1α ,6β,14α,16βꢀtetramethoxyꢀ20ꢀethylaconitane
(3). Amorphous powder, [α]57820 –60.5 (c 3.7, MeOH). Highꢀ
6
13
2
1
1
20
19
+26.8
2
D
(
c 5, H O)).
2
SꢀValinol prepared by a known procedure12 from Sꢀvaline
Reanal) had m.p. 31—32 °C, b.p. 75 °C (6 Torr), [α]57833 +17
c 11, EtOH) (cf. Ref. 13: m.p. 31—32 °C, b.p. 75 °C (6 Torr),
resolution MS, m/z: 590.3568 [M] . C H N O . Calculated:
+
3
2
50
2
8
1
(
(
M 590.3567. H NMR, δ: 0.77 and 0.82 (both d, each 3 H,
C(2´)Me J = 7 Hz); 1.00 (t, 3 H, NCH CH ); 3.10, 3.20, 3.27
2
2
3
Ref.: [α]578 +17.0 (c 11, EtOH)). 1H NMR, δ: 0.416 and
7
33
and 3.35 (all s, each 3 H, 1ꢀ, 6ꢀ, 14ꢀ, and 16ꢀOMe); 3.63 (s, 3 H,
CO Me); 4.94 and 4.97 (both s, each 1 H, OCH O); 7.35 (s,
0
.424 (both d, each 3 H, C(3)Me , J = 6.8 Hz); 1.12 (m, 1 H,
2
2
2
–
1
C(3´)H); 2.05 (m, 1 H, C(2)H); 2.79 (dd, 1 H, J = 10.5 and J =
1 H, C(18)H). IR (KBr), ν/cm : 960, 982, 1015, 1037, 1081,
1122, 1140, 1207, 1309, 1463, 1672 (C=N), 1743 (C=O), 2822,
2882, 2918 and 2974.
8
.3 Hz), 3.11 (dd, 1 H, J = 10.5 and J = 3.7 Hz) (CH OH).
2
1
3
C NMR, δ: 63.7 (C(1)); 57.6 (C(2)); 30.0 (C(3)); 17.3 and
8.4 (2 Me).
SꢀTyrosinol was prepared by reduction of the Sꢀtyrosine
1
18ꢀ(Е)ꢀ[2ꢀ(4ꢀHydroxyphenyl)ꢀ1Sꢀmethoxycarbonylethylꢀ
imino]ꢀ7,8ꢀmethylenedioxyꢀ1α ,6β,14α ,16βꢀtetramethoxyꢀ20ꢀ
ethylaconitane (4). Amorphous powder, [α]57820 –72.5 (c 3.8,
MeOH). Found (%): C, 65.27, 65.43; H, 8.07, 8.23; N, 4.18,
4.08. C H N O . Calculated (%): C, 66.02; H, 7.71; N, 4.28.
methyl ester with LiAlH4 in ether by a previously described
procedure14 (cf. Ref. 15), which we modified in the following
way. Excess CO was passed through a methanolic solution of
crude tyrosinol to precipitate Li CO and Al (CO ) . The preꢀ
2
36 50
2
9
1
H NMR (CD OD), δ: 1.09 (t, 3 H, NCH CH , J = 7 Hz);
2
3
2
3 3
3
2
3
cipitated carbonates were separated by centrifugation, the suꢀ
3.13, 3.26, 3.30 and 3.36 (all s, each 3 H, 1ꢀ, 6ꢀ, 14ꢀ and
pernatant was concentrated in vacuo, and the residue was dried
at 50 °C (3 Torr) to give pure Sꢀtyrosinol as a thick oil. H NMR
16ꢀOMe); 3.73 (s, 3 H, CO Me); 4.98 and 5.00 (both s, each 1 H,
2
1
OCH O); 6.71 (dm, 2 H, J = 8 Hz) and 6.94 (dm, 2 H, J =
2
(
(
3
4
CD OD), δ: 2.48 (dd, 1 H, C(3)H , J = 14 and J = 8 Hz); 2.72
8 Hz) (АA´ВB´ system, H(3″), H(5″) and H(2″), H(6″), respecꢀ
tively); 7.06 (s, 1 H, C(18)H). IR (KBr), ν/cm– : 935, 961, 980,
1038, 1089, 1129, 1171, 1201, 1270, 1333, 1380, 1446, 1517,
1615, 1660 (C=N), 1742 (C=O), 2821, 2878, 2931, 2973.
UV (EtOH), λmax/nm (logε): 226 (3.83) and 279 (3.08).
3
a
1
dd, 1 H, C(3)H , J = 14 and J = 6 Hz); 3.00 (m, 1 H, C(2)H);
b
.38 (m, 1 H, C(1)H ); 3.57 (dd, 1 H, C(1)H , J = 11 and J =
a
b
Hz); 6.77 (m, 2 H, C(2´)H and C(6´)H) and 7.03 (m, 2 H,
13
C(3´)H and C(5´)H). C NMR, δ: 66.6 (C(1)); 55.5 (C(2)); 39.8
C(3)); 130.1 (C(1´)), 131.2 (C(2´), C(6´)); 116.7 (C(3´), C(5´));
57.5 (C(4´)). SꢀTyrosinol oxalate (C H NO ) •H C O , preꢀ
(
1
18ꢀ[(1SꢀMethoxycarbonyl)ethylamino]ꢀ7,8ꢀmethylenedioxyꢀ
1α ,6β,14α,16βꢀtetramethoxyꢀ20ꢀethylaconitane (8). A solution
of compound 2 (0.75 g, 1.34 mmol) in 7 mL of EtOH was
hydrogenated over Pd supported on activated carbon (0.90 g of
9
13
2 2
2
2
4
1
4
20
pared by a known method, had [α]5
(
the oxalate (D O), δ: 3.10 (dd, 1 H, J = 14.0 and J = 7.5 Hz)
and 3.14 (dd, 1 H, J = 14.0 and J = 7.0 Hz) (C(3)H ); 3.80 (m,
1
(
–20 (c 1, H O)
2
78
1
17
cf. Ref. 14: [α]D –20 (c 1, H O)). The H NMR spectrum of
2
1
8
the IKTꢀ3ꢀ25 catalyst, Pd content 0.25%) at 20 °C (760 Torr)
until a theoretical amount of hydrogen has been absorbed. The
catalyst was filtered off and washed with EtOH (2×7 mL). The
solvent was removed from the filtrate in vacuo (bath temperature
50 °C) and the residue was dissolved in 2 mL of CHCl3 and
2
2
H, C(2)H); 3.85 (dd, 1 H, J = 12.0 and J = 6.7 Hz) and 4.03
dd, 1 H, J = 12.0 and J = 3.4 Hz) (C(1)H ); 7.13, 7.42 (both dm,
2
each 2 H, АА´BB´ system, H(3´), H(5´) and H(2´), H(6´), J =
13
8
1
1
Hz). C NMR, δ: 61.45 (C(1)); 55.30 (C(2)); 34.61 (C(3));
28.18(C(1´)); 131.60 (C(2´), C(6´)); 116.76 (C(3´), C(5´));
subjected to preparative TLC on Al O3 (5/40 µm Chemapol,
2
Czechia) containing 1% luminophore Кꢀ35 and 3% Na CO
in the Bu OMe—CHCl3 solvent system (9 : 1, v/v). The
2
3
–
t
55.66 (C(4´)) and 174.05 (2 CO ).
2
SꢀMethioninol synthezised1 from Sꢀmethionine methyl esꢀ
6
UVꢀabsorbing band of the sorbent with R 0.87 was collected.
f
ter had b.p. 120 °C (3 Torr), [α]5782 –10 (c 1.5, EtOH) (cf.
Ref. 16: b.p. 104—108 °C (0.05 Torr), Ref. 17: b.p. 110—132 °C
(
C(3)H ); 1.87 (s, 3 H, SMe); 2.34 (m, 2 H, C(4)H ); 2.71 (m,
1
(
(
0
The target product was eluted with the same solvent system.
Removal of the solvent from the eluate and drying of the residue
at 50 °C (3 Torr) gave 0.54 g (71%) of compound 8 as an
5 Torr), [α]D2 –9.7 (c 1.5, EtOH)). H NMR, δ: 1.40 (m, 2 H,
1
1
2
0
amorphous powder, [α]
+4.5 (c 4.4, CHCl ). Found,
2
2
578
3
+
H, C(2)H); 3.08 (dd, 1 H, C(1)H , J = 10 and J = 7 Hz); 3.42
m/z: 564.3417 [M] . C H N O . Calculated: M 564.3410.
30 48 2 8
H NMR, δ: 0.90 (t, 3 H, NCH CH , J = 7 Hz); 1.12 (d, 3 H,
a
13
1
dd, 1 H, C(1)H , J = 10 and J = 4 Hz). C NMR, δ: 66.0
b
2 3
C(1)); 51.8 (C(2)); 33.0 (C(3)); 30.8 (C(4)) and 15.2 (SMe).
C(2´)H , J = 7 Hz); 3.10, 3.13, 3.21 and 3.27 (all s, each 3 H,
3
1
8ꢀMethylaminoꢀ7,8ꢀmethylenedioxyꢀ1α,6β,14α,16βꢀtetraꢀ
1ꢀ, 6ꢀ, 14ꢀ, and 16ꢀOMe); 4.91 (s, 2 H, OCH O). IR (KBr),
2
–
1
methoxyꢀ20ꢀethylaconitane (14) was prepared by a known
method.2
Imines 2—7 were synthesized by a general procedure. The
spectral or analytical characteristics of imines 5—7 were not
ν/cm : 728, 753, 964, 1010, 1089, 1126, 1171, 1200, 1298,
1385, 1446, 1738 (C=O), 2752, 2822, 2930 and 3337 (NH).
Diamines 9—11 were prepared by reducing imines 5—7
with NaBH4 according to the general procedure of imine reꢀ
2
2
determined.
duction.

2294
Russ.Chem.Bull., Int.Ed., Vol. 51, No. 12, December, 2002
Ganbaatar et al.
1
8ꢀ(1SꢀHydroxymethylꢀ2ꢀmethylpropylamino)ꢀ7,8ꢀ
18ꢀDimethylaminoꢀ7,8ꢀmethylenedioxyꢀ1α ,6β,14α ,16βꢀ
tetramethoxyꢀ20ꢀethylaconitane (15). Thick oil. Found,
methylenedioxyꢀ1α,6β,14α,16βꢀtetramethoxyꢀ20ꢀethylaconitane
2
0
+
(
[
9). Thick oil, [α]5
+10 (c 2.0, CHCl ). Found, m/z: 564.3788
m/z: 506.3345 [M] . C H N O . Calculated: M 506.3366.
78
3
28 46
2
6
+
1
1
M] . C H N O . Calculated: M 564.3774. H NMR, δ: 0.83
H NMR, δ: 0.86 (t, 3 H, NCH Me, J = 7.1 Hz); 3.05, 3.14,
2
31
52
2
7
and 0.90 (both d, each 3 H, C(2´)Me , J = 6.8 Hz); 0.98 (t, 3 H,
3.22, 3.28 (all s, each 3 H, 1ꢀ, 6ꢀ, 14ꢀ, and 16ꢀOMe); 3.43 (s,
6 H, NMe ); 4.83 and 4.88 (both s, each 1 H, OCH O).
IR (KBr), ν/cm : 731, 753, 920, 950, 964, 1007, 1088, 1117,
1161, 1199, 1227, 1386, 1450, 1469, 2821, 1881, 2933, 2971.
UV (EtOH), λmax/nm (logε): 219 (3.95).
2
NCH CH , J = 7.1 Hz); 3.19, 3.28, 3.31 and 3.37 (all s, each 3 H,
2
3
2
2
–
1
1
ꢀ, 6ꢀ, 14ꢀ, and 16ꢀOMe); 4.98 and 5.01 (both s, each 1 H,
–
1
OCH O). IR (KBr), ν/cm : 963, 1090, 1123, 1159, 1197, 1386,
2
1
453, 1467, 2818, 2875, 2932, 2959.
8ꢀ[1SꢀHydroxymethylꢀ2ꢀ(4ꢀhydroxyphenyl)ethylamino]ꢀ
,8ꢀmethylenedioxyꢀ1α ,6β,14α ,16βꢀtetramethoxyꢀ20ꢀethylꢀ
1
7
This work was financially supported by the Russian
Foundation for Basic Research (Project No. 01ꢀ03ꢀ
32431).
+
aconitane (10). Amorphous powder. Found, m/z: 627.3646 [M] .
C H N O . Calculated: M 627.3645. H NMR, δ: 0.98 (t,
1
3
5
51
2
8
3
H, NCH CH , J = 7.1 Hz); 3.20 (6 H), 3.29 (3 H) and 3.37
2 3
(
3 H) (all s, 1ꢀ, 6ꢀ, 14ꢀ, and 16ꢀOMe); 4.99 and 5.00 (both s,
References
each 1 H, OCH O); 6.72 (dm, 2 H, J = 8.2 Hz) and 6.94 (dm,
2
2
H, J = 8.2 Hz) (АA´ВB´ system, H(3″), H(5″) and H(2″),
–
1
H(6″), respectively). IR (KBr), ν/cm : 1089, 1120, 1199,
227, 1265, 1449, 1516, 2819, 2881, 2930, 2965. UV (EtOH),
λmax/nm (logε): 225 (3.92) and 280 (3.20).
8ꢀ[1SꢀHydroxymethylꢀ3ꢀ(methylthio)propylamino]ꢀ7,8ꢀ
methylenedioxyꢀ1α,6β,14α,16βꢀtetramethoxyꢀ20ꢀethylaconitane
1. N. V. Anferova, I. Yu. Bagryanskaya, Yu. V. Gatilov,
J. Ganbaatar, S. A. Osadchii, E. E. Shults, and G. A.
Tolstikov, Izv. Akad. Nauk, Ser. Khim., 2002, 1812 [Russ.
Chem. Bull., Int. Ed., 2002, 51, 1965].
1
1
2. J. Ganbaatar, D. Batsuren, S. A. Osadchii, E. E. Shults, and
G. A. Tolstikov, Izv. Akad. Nauk, Ser. Khim., 2002, 497
[Russ. Chem. Bull., Int. Ed., 2002, 51, 535].
+
(
11). Thick oil. Found, m/z: 596.4 [M] . C H N O S. Calcuꢀ
31 52 2 7
lated: M = 596.4. For a fragment ion, found, m/z: 565.3312.
C31H52N O S – OCH = C30H49N O S. Calculated: M =
3. M. S. Rabinovich, Zh. Obshch. Khim., 1954, 24, 2242 [J. Gen.
Chem. USSR, 1954, 24 (Engl. Transl.)].
2
1
7
3
2
6
5
65.3311. H NMR, δ: 0.95 (t, 3 H, NCH CH , J = 7 Hz); 2.01
2 3
(
s, 3 H, SMe); 3.15, 3.24, 3.27, 3.32 (all s, each 3 H, 1ꢀ, 6ꢀ, 14ꢀ,
4. H. O. Kalinowski, S. Berger, and S. Braun,
1
3
and 16ꢀOMe); 4.94 and 4.96 (both s, each 1 H, OCH O).
IR (KBr), ν/cm : 732, 911, 963, 1046, 1090, 1120, 1160, 1197,
CꢀNMRꢀSpektroskopie,
Georg
Thieme
Verlag,
2
–
1
Stuttgart—New York, 1984, S. 47; 63.
1
2
446, 1464, 2820, 2881, 2921. UV (EtOH), λmax/nm (logε):
19 (3.95).
NꢀMethylation of compounds 9, 10 and 14. A solution of the
5. S. A. Osadchii, N. A. Pankrushina, M. M. Shakirov, E. E.
Shults, and G. A. Tolstikov, Izv. Akad. Nauk, Ser. Khim.,
2000, 552 [Russ. Chem. Bull., Int. Ed., 2000, 49, 557].
6. S. A. Osadchii, E. E. Shults, and G. A. Tolstikov, Izv. Akad.
Nauk, Ser. Khim., 2001, 868 [Russ. Chem. Bull., Int. Ed.,
2001, 50, 907].
substrate (1 mmol) in 1.2 mL of MeI was sealed and kept at
0 °C for 72 h. Excess MeI was removed, and the residue was
2
dissolved in 2.5 mL of CHCl and washed with 0.15 mL of 25%
3
NH OH. The organic layer was separated, the solvent was reꢀ
moved, and the residue was dried in vacuo at 50 °C (3 Torr).
7. R. Schwyzer, B. Iselin, H. Kapeller, B. Riniker, W. Bittel,
and U. Zuber, Helv. Chim. Acta, 1958, 41, 1273.
4
1
8ꢀ[Nꢀ(1SꢀHydroxymethylꢀ2ꢀmethylpropyl)ꢀNꢀmethylꢀ
8. K. Weil and W. Kuhn, Helv. Chim. Acta, 1944, 27, 1648;
Chem. Abstrs., 1946, 40, 2170 .
9. Fluka Catalogue, 1995—1996, p. 61.
5
amino]ꢀ7,8ꢀmethylenedioxyꢀ1α ,6β,14α ,16βꢀtetramethoxyꢀ20ꢀ
ethylaconitane (12). Thick oil, [α]5782 –34 (c 1.5, CHCl ). For
0
3
the fragment ion, found m/z: 547.3743. C H N O – OCH =
10. E. Fischer, Justus Liebigs Ann. Chem., 1907, 354, 34; Ber.
Deutsch. Chem. Ges., 1908, 41, 855, Anm. 2.
11. M. Brenner and R. W. Pfister, Helv. Chim. Acta, 1951,
34, 2085.
3
1
2
54
2
7
3
C H N O . Calculated: M 547.3747. H NMR, δ: 0.77 and
31
51
2
6
0
.95 (both d, each 3 H, C(2´)Me , J = 6.5 Hz); 0.98 (t, 3 H,
2
NCH Me, J = 7.0 Hz); 2.27 (s, 3 H, NMe); 3.19, 3.28, 3.32,
2
3
.37 (all s, each 3 H, 1ꢀ, 6ꢀ, 14ꢀ, and 16ꢀOMe); 4.99 and 5.03
12. A. I. Meyers, D. A. Dickman, and T. R. Bailey, J. Am. Chem.
Soc., 1985, 107, 7974.
–
1
(
both s, each 1 H, OCH O). IR (KBr), ν/cm : 731, 962, 1010,
2
1
121, 1161, 1198, 1386, 1449, 1469, 2817, 2883 and 2933.
8ꢀ{Nꢀ[1SꢀHydroxymethylꢀ2ꢀ(4ꢀhydroxyphenyl)ethyl]ꢀNꢀ
13. M. J. McKennon, A. I. Mayers, K. Drauz, and M. Schwarm,
J. Org. Chem., 1993, 58, 3568.
1
methylamino}ꢀ7,8ꢀmethylenedioxyꢀ1α ,6β,14α ,16βꢀtetramethꢀ
oxyꢀ20ꢀethylaconitane (13). Amorphous powder, [α]57820 –33
14. P. Karrer, P. Portmann, and M. Suter, Helv. Chim. Acta,
1949, 32, 1156.
(
c 4.2, CHCl ). For the fragment ion, found m/z: 611.3662.
15. A. Dornow, G. Messwarb, and H. H. Frey, Chem. Ber.,
1950, 83, 445.
3
C H N O – CH O = C H N O . Calculated: M 611.3696.
1
3
6
53
2
8
2
35 51
2
8
H NMR, δ: 0.98 (t, 3 H, NCH Me, J = 7.1 Hz); 2.31 (s, 3 H,
16. R. R. Gebhard and P.Karrer, Helv. Chim. Acta, 1955, 38, 915.
17. H. Seki, K. Koga, H. Matsuo, S. Ohki, I. Matsuo, and
S. Yamada, Chem. Pharm. Bull., 1965, 13, 995.
18. V. A. Semikolenov, I. L. Simakova, and G. V. Sadovnichii,
Khim. promꢀt´ [Chem. Ind.], 1996, No. 3, 184 (in Russian).
2
NMe); 3.22, 3.29, 3.30 and 3.38 (all s, each 3 H, 1ꢀ, 6ꢀ, 14ꢀ, and
1
2
6ꢀOMe); 4.99 and 5.03 (both s, each 1 H, OCH O); 6.69 (dm,
2
H, J = 8.2 Hz) and 6.89 (dm, 2 H, J = 8.2 Hz) (АA´ВB´ system,
–
1
H(3″), H(5″) and H(2″), H(6″), respectively). IR (KBr), ν/cm
:
7
2
2
32, 962, 1033, 1090, 1116, 1162, 1199, 1450, 1516, 2819,
883 and 2932. UV (EtOH), λmax/nm (logε): 224 (3.80) and
80 (3.04).
Received June 14, 2002