A stereostructural study of 17-hydroxylupanine and its perchlorate

Article abstract of DOI:10.1007/s007060070040

The bisquinolizidine carbinolamine 17-hydroxylupanine was synthesized de novo from lupanine using 2,3-dichloro-5,6-dicyano-1,4-benzoquinone; its structure was established by NMR techniques. The equatorial position of the hydroxy group as well as the prevailing boat form of ring C were determined. As expected, the carbinolamine converted into the C17=N16 anhydronium perchlorate upon treatment with HClO₄. NMR analysis of the salt revealed a conformational equilibrium within rings A and D, whereas rings B and C remain rigid.

Full text of DOI:10.1007/s007060070040

Monatshefte fuÈr Chemie 131, 1073±1081 (2000)
A Stereostructural Study of
17-Hydroxylupanine and its Perchlorate
Ã
ꢀ
Jacek Thiel, Wøadysøaw Boczon , and Waleria Wysocka
ꢀ
Faculty of Chemistry, Adam Mickiewicz University, PL-60780 Poznan, Poland
Summary. The bisquinolizidine carbinolamine 17-hydroxylupanine was synthesized de novo from
lupanine using 2,3-dichloro-5,6-dicyano-1,4-benzoquinone; its structure was established by NMR
techniques. The equatorial position of the hydroxy group as well as the prevailing boat form of ring
C were determined. As expected, the carbinolamine converted into the C17ˆN16 anhydronium
perchlorate upon treatment with HClO4. NMR analysis of the salt revealed a conformational
equilibrium within rings A and D, whereas rings B and C remain rigid.
Keywords. Bisquinolizidine alkaloids; Con®guration; Conformation; NMR spectroscopy; DDQ
oxidation.
Introduction
In continuation of our research on the stereochemistry of conformationally labile
lupine alkaloids [1, 2] we took interest in the analogous features of their
carbinolamine derivatives. To the best of our knowledge, due to their low stability
the spatial structures of these compounds have not yet been investigated. In the so
far described compounds 17-hydroxysparteine [3], (‡)-2-hydroxy-17-oxo-ꢀ-
isosparteine (lupanoline) [4], and 17-hydroxylupanine [5] only the locations of
the OH groups have been determined, whereas their con®gurations, not to mention
their conformational equilibria, remain unknown. 17-Hydroxylupanine is a
particular case, since even its isolation have not been reported yet. Edwards and
coworkers have described the formation of this compound during action of silver
Â
oxide on lupanine [5]. Similarly, Wiewiorowski and Legocki [6] have postulated the
generation of 17-hydroxylupanine during oxygenation of the parent alkaloid by
means of a mercuric acetate/EDTA complex. These authors as well as Edwards and
his collaborators settled for isolation of 17-hydroxylupanine as its perchlorate,
which in fact is the 17-dehydrolupaninium salt [5, 6].
Since isolation of 17-hydroxylupanine was not feasible by the above methods,
it was necessary to ®nd another access to this carbinolamine. For this purpose,
DDQ (2,3-dichloro-5,6-dicyano-1,4-benzoquinone) seemed promising because of
its oxygenating properties [7, 8]. According to Refs. [9, 10] it could be expected
Ã
Corresponding author

1074
J. Thiel et al.
that DDQ would dehydrogenate lupanine at carbon atoms C-17 and/or C-11, where
then a hydroxyl group might be introduced.
Results and Discussion
Action of DDQ on lupanine (in dioxane and under argon) causes precipitation of a
crude product which upon treatment by hydrochloric acid, aqueous NaOH, and
ethyl ether gave the expected alkaloid as the free base. 1H and 13C NMR as well as
IR spectra of the perchlorate of the product were identical with those of 17-
dehydrolupaninium perchlorate synthesized according to Marion and Leonard via
oxidation of lupanine by NBS [9]. Due to severe signal overlapping, most of the ꢁH
values had to be taken from DQF-COSY, HMQC, HETCOR and (in the case of the
perchlorate) NOESY spectra. The NMR data of compounds 3 and 4 are presented
in Tables 1 and 2.
The above-mentioned overlap of the proton signals also obscured the DQF-
COSY spectra, making it dif®cult to detect all linkages between protonated carbon
atoms. Carbon-carbon bonds ®rmly established by 2D NMR spectroscopy are
Table 1. NMR data of 17-hydroxylupanine (3); for numbering, see Scheme 1; ꢁ in ppm J in Hz
Carbon
atom
13C-1H correlations
(HMQC, HETCOR)
1H-1H correlations
(DQF-COSY)
ꢁC (DEPT)
ꢁH, multiplicity, J
2
3
170.69
32.98 (CH2)
2.44, m
1.64, 1.86, 2.28
1.64, 1.86, 2.44
2.28, 2.44, 1.86
2.28, 2.44, 1.88(?), 1.64
1.86 (?)
2.28, m
4
5
19.86 (CH2)
26.97 (CH2)
1.64, m
1.86, m
1.88, m
1.88, m
6
7
8
59.52 (CH)
43.46 (CH)
25.02 (CH2)
3.34, dd ?
1.84, 1.88
1.84, ddddd ?
2.35, m (eq)
1.28, dt, 12.3, 2.4, 2.4 (ax)
1.65, m
3.76, 3.34, 2.35, 1.28, 1.65
1.84, 4.50, 1.28, 1.65
2.35, 1.84, 1.65
4.50, 2.51, 2.35, 1.28, 1.84, 1.92
2.51, 1.65, 2.35
4.50, 1.65
9
34.84 (CH)
47.22 (CH2)
10
4.50, dt, 13.1, 2.4, 2.4 (eq)
2.51, dd, 13.2, 2.4 (ax)
1.92, m
11
12
60.41 (CH)
33.74 (CH2)
1.65, 1.52
1.52, m
1.92
1.52, m
13
14
15
17
25.25 (CH2)
25.76 (CH2)
51.62 (CH2)
85.75 (CH)
1.76, dm, ꢀ12.0
1.35, dt ?, 12.0, 3.9, 3.9
1.57, m
1.35
1.76
3.35
1.57, m
3.35, m (eq)
2.00, td, 12.0, 12.0, 3.0 (ax)
3.76, bs
2.00, 1.57
3.35, 1.57
1.84

Structure of 17-Hydroxylupanine
1075
Table 2. NMR data of 17-dehydrolupaninium perchlorate (4); for numbering, see Scheme 1; ꢁ in ppm,
J in Hz
Carbon
atom
13C-1H correlations
1H-1H correlations
NOESY
ꢁC (DEPT)
ꢁH, multiplicity, J
DQF-COSY
2
3
169.33
32.30 (CH2)
ꢀ2.16, m
ꢀ2.16, m
1.55, m
1.55, 1.66
1.55, 1.66
ꢀ2.16, 2.11
ꢀ2.16, 2.11
1.63, 1.55
1.63
4
5
6
7
8
19.49 (CH2)
27.13 (CH2)
59.17 (CH)
37.63 (CH)
21.58 (CH2)
2.11, 1.66
2.11, 1.55
1.66, m
2.11, m
1.63, 3.68, 1.55, 1.66 1.55
1.63, m
2.11, 3.68
8.94, ꢀ2.16
3.68, ddd, 10.2,
5.1, 2.4
3.25, 2.11, 1.63
3.25, 2.71, 2.11, 1.77
1.63
3.25, ddddd ?
ÆJ ˆ 17.1
1.99, ddt, 13.2,
3.2, 3.2, 2.6
1.77, m
8.94, 3.68, 2.10
1.99, 1.77
8.94, 3.68, 2.11
1.99, 1.77, 1.63
3.25, 2.10, 1.77, 4.62 3.25, 1.77
3.25, 2.10, 1.99, 8.94 3.68, 3.25, 2.71, 1.99
9
31.97 (CH)
46.55 (CH2)
2.10, m
4.62, 2.71, 1.99
1.77, 3.25
4.62, 3.76, 3.25
2.71, 1.77
10
4.62, dt, 13.4,
2.3, 2.3 (eq)
2.71, dd, 13.5,
2.7 (ax)
2.71, 2.10, 1.99
3.76, 2.71, 2.10
4.62, 2.10
1.92, 1.73
4.62, 3.68, 2.10, 1.77
11
12
13
14
15
66.42 (CH)
32.50 (CH2)
22.21 (CH2)
26.04 (CH2)
60.58 (CH2)
3.76, É-dd,
ꢀ10.6, ꢀ4.9
1.92, m
3.89, 2.10, 1.92
1.76, 4.62
3.76
3.76
1.76, 1.73, 3.76
3.76, 1.92
1.73, m
1.76
1.92
1.76
1.88, m
4.16, 3.89
4.16, 3.89
1.75, m
4.16, 3.89
4.16, 3.89
4.16, É-dd,
ꢀ12.4, ꢀ2.8 (eq)
3.89, É-td,
ꢀ12.1, ꢀ3.3 (ax)
8.94, dddd ?, 4.7
3.89, 1.88, 1.75
8.94, 3.89, 1.88, 1.75
4.16, 1.88, 1.75, 8.94 4.16, 3.76, 1.88, 1.75
3.25, 3.76, 3.89, 1.77 4.16, 3.25, 1.63
17
177.62 (CH)
shown in Scheme 1 as solid lines; completion of the lacking links, marked as dotted
lines in Scheme 1, was performed on the basis of the criteria discussed below.
The discussed alkaloids feature 13C NMR signals which are very close to those
of C3, C4, C5, and C10 of rings A and B of the starting lupanine 1 (ꢁC ˆ 33.0,
19.6, 26.7, and 46.6 ppm, respectively) [11]. In particular, the resonances at 32.98
(Table 1) and 32.30 (Table 2) ppm belong to ꢂ carbon atoms relative to carbonyl
groups of ꢁ-lactams, those at 47.22 (Table 1) and 46.55 (Table 2) ppm are
characteristic of carbons in position ꢂ in relation to a ꢁ-lactam nitrogen atom [11].

1076
J. Thiel et al.
Scheme 1. Transformation of lupanine (1) into its perchlorate (4); solid lines in structures 2 and 4
denote C±C bonds established by 2D NMR techniques; dotted lines show C±C and C±N bonds
deduced from the data as discussed in the text
The occurrence of a bicyclic ꢁ-lactam is further supported by the ꢃCˆO bands at
1636 and 1633 cm in the IR spectra of the alkaloid and its perchlorate [12, 13].
1
Consequently, the above results point to the presence of unchanged rings A and B
of the parent lupanine.
Apart from the C7 and C9 methine and the C8 methylene groups common with
ring B, ring C of the free alkaloid comprises a methine carbon characterized by
ꢁC ˆ 85.75 ppm. This chemical shift cannot originate from the ꢂ-effect of only one
electron withdrawing substituent, since methine groups bonded to nitrogen appear
within a range of 57 < ꢁC < 68 ppm, whereas those linked with hydroxylic oxygen
resonate between 64 and 70 ppm as observed in model bisquinolizidine alkaloids
[11]. Therefore, besides the action of the nitrogen atom, the signal considered is
also affected by the in¯uence of the hydroxylic group, whose presence (though
‡ꢁ
attempts towards acetylation failed) is con®rmed by the MS data: m=z ˆ 264 M
and 247 (M±OH). The proton from the methine group under consideration is
coupled with a proton from a CH group appearing at ꢁC ˆ 43.46 ppm. The latter
resonance is due to the deshielding effect of the OH group onto the ꢀ-carbon atom,
i.e. on C7 [14] (Áꢁ ˆ ‡11.1 ppm with respect to unsubstituted lupanine [11, 15]).
Such a position of the hydroxyl group simultaneously localizes the second nitrogen
atom which links the carbon atoms at 85.75 (C17) and 60.41 ppm (C11), thus
closing ring C (see Scheme 1 and Table 1).
Ring D, apart from methylene groups at 33.74 (coupled with C11) and 51.62
(C15); ꢂ to N16 and coupled with C14, must contain the CH2 group at 25.25 ppm,
though its connections with the remaining fragments of the molecule remain
undetected.

Structure of 17-Hydroxylupanine
1077
Similarly to other sparteine alkaloids, the ꢁC values of C-12 and C-14 in the
latter ring depend on the conformational equilibrium between chair and boat form
of ring C [16]. In the case of the chair conformer, the above values are shifted
up®eld due to the ꢄ-gauche effect between C8 and C12 and between C17 and C14.
Instead, such a shift should not be expected for the boat form for which no syn-
clinal effect occurs.
The boat form population was estimated using the method of Eliel [17] adapted
to the case of bisquinolizidine alkaloids by Wysocka and Brukwicki [16]. Taking
into account the chemical shift of C-14 and C-12 (Table 1), the values of 97.2% and
91.7% were found, respectively.
The dominating variety with the boat C ring demands the H-17 hydrogen atom
to be situated either pseudo-axially or pseudo-equatorially. In the latter case, due to
an almost zero value (model inspection) of the H-C7-C17-H dihedral angle, one
should expect a rather large 3JHH coupling constant. On the other hand, in the case
of the pseudo-axial orientation, this angle amounts to ꢀ 100ꢂ. Hence, small
values of the coupling constant can be expected. Based on Altona's dependency
3
[18], JHH amounts to 0.88 and 1.06 Hz when the torsinal angle H-C7-C17-H is
90ꢂ or 100ꢂ, respectively. Therefore, the broadened singlet of H-17 indicates its
pseudo-axial position (see 3 in Scheme 1).
The conversion of 17-hydroxylupanine into its perchloate (3 ! 4, Scheme 1)
not only con®rms the location of the OH group at C17 but also offers an
opportunity to reinvestigate this salt by means of NMR spectroscopy which,
similarly to the parent compound, gives also an insight into subtle structural details
which have not been studied so far.
The C7 methine group of ring B (Scheme 1) in the perchlorate is connected to a
CH group showing the greatest ꢁC value (Table 2). Since the 13C NMR spectrum of
the salt does not reveal any other sp2 methine group, the signal at 177.62 ppm must
‡
belong to the HCˆN < moiety which comprises the second (N16) of the two
nitrogen atoms. The sp2 hybridization of N16 increases the 13C chemical shift of its
ꢂ-carbons. In particular, this concerns C11 and C15; their ÁꢁC values relative to
the substrate amount to 8.96 and 6.01 ppm. Therefore, the appearance of a methine
group at 66.42 ppm as well as an NOE effect between H11 and H9 protons allow a
closure of ring C, although the DQF-COSY spectrum exhibits no connection
between the corresponding methine groups. It should be added that, in spite of the
above, NOEs were found between other vicinal protons which were detected in the
DQF-COSY spectrum (Table 2).
Apart from C11 and C15 and the corresponding C12 and C14 methylene
groups bound to them, the methylene group resonating at 22.21 ppm should be
included into ring D; again, DQF-COSY connectivities with the remaining
methylenes in ꢀ-position relative to N16 remain obscure (see Scheme 1).
The closure of the bisquinolisidine rings A, B, C, and D of 4 which ensues from
the analysis of the data from Table 2 is consistent with X-ray results [19].
Moreover, treatment of 4 with aqueous KOH affords the alkaloid 3.
The above NMR analysis of 4 should be supplemented with a discussion
concerning the steric structure of the salt. Its NOESY spectrum shows 1,3-diaxial
interactions between protons at C6, C10, and C8 (see Table 3). This testi®es to a
chair form of ring B. Instead, an NOE appearing between the axial protons H5 and

1078
J. Thiel et al.
H3 is not indicative of a chair form of ring A, the more so that the lactam fragment
3
is a factor ¯attening this ring. However, taking into account the value of JHH for
the C6-H (10.2 Hz, denoting 1,2-diaxial interaction with C5-H) and also inspecting
the model, one may conclude that the C5, C6, N1, C2, and C3 atoms occupy
approximately a planar position, whereas C4 rises above this plane towards the C7-
C8-C9 bridge. Such an envelope conformer [20] seems to be the dominant form of
ring A similar to the analogous fragment of angustifoline [21] for which the
corresponding coupling constant amounts to 10.7 Hz. The latter alkaloid, however,
features a small contribution of another conformer in which the C4 methylene
3
group is oriented in the opposite direction to that of the C7-C8-C9 bridge. J for
the perchlorate under discussion also deviates from the analogous value for
3
sparteine with a rigid chair ring A featuring JHH ˆ 13.2 Hz [22]. A contribution
from another conformer of ring A, similar to that of angustifoline, seems quite
probable.
Formation of the double bond between C17 and N16 also induces ¯attening
into ring C, comprising, in particular, C7, C17, N16, and C11 [19]. C9 may also
participate in this ¯attening, since no vicinal coupling of H9 and H11 is observed,
whereas an NOE occurs between them (see Table 2). This coupling disappears
when the H-C9-C11-H dihedral angle adopts a value of ꢀ90ꢂ, and this corresponds
to the molecular model. Besides the NOE mentioned, H11 shows the usual 1,3-
diaxial Overhauser enhancement with H15ax. Unfortunately, due to severe overlap-
ping of the NOESY signals, it was not possible to locate the 1,3-diaxial interactions
of H13 proton with H15ax and H11. In other words, the chair form of ring D could
not be con®rmed by 1,3-diaxial NOEs.
The existence of a chair fragment would have been indicated by signal of H15ax
1
provided that this resonance had appeared as a dtd in the H NMR spectrum.
Instead, one observes averaged multiplicities of not only H15ax but also of H15eq
and H11. The protons appearing in such a form belong to the planar H-
C17ˆN16 < C15,C11 fragment which also participates in ring C together with the
chair ring B (vide supra), generating a rather rigid 3,7-diazabicyclo [3.3.1]nonane
(bispidine) system within the molecule of 4. Its rigidity is evidenced by
multiplicities of H6, H8eq, H10eq and H10ax and, in particular, by W couplings
between H10eq and H8eq as well as between H7 and H9 (see Table 2).
Geometrical stabilization of rings B and C, as deduced from the above data, is
additionally con®rmed by NOEs of H17 with H5ax and H15eq as well as by
Overhauser interactions between the pairs H15ax H11 and H10eq H11 (see Table
2). As a consequence, the sp2 nitrogen N16 from ring C introduces a strain onto the
C11-N16-C15 bond angle which amounts to 113.9ꢂ in the solid state [19]. Hence,
relative to 3, the geometry of ring D is destablized in 4. The protons bound to C11
1
and C15 appear, as mentioned above, in the H NMR spectrum in pseudo-dd or
pseudo-dt forms. Such shapes of the resonances should not result from couplings of
the allylic type between the H17 and H11, H15ax as detected by means of the DQF-
COSY spectrum, since H15eq, which does not show this kind of coupling, also
appears in a diffuse form. Moreover, a decoupling experiment (irradiating H17
8.94 ppm with different decoupler powers) did not cause any change in the shapes
of the resonances of H11, H15ax, and H15eq. Therefore, since the geometrical
stability of the hydrogens at C17, C11, and C15 cannot be the reason for the signal

Structure of 17-Hydroxylupanine
1079
deformation discussed, the explanation of this phenomenon should be searched in
the interaction with the protons of the methylene chain C12-C13-C14. Hence, the
observed spectral picture is due to changes in dihedral angles H-C11-C12-H and H-
C15-C14-H which would result from a conformational equilibrium within ring D
changing from its chair variety to a twisted chair. To this end it should be
mentioned that a conformational disorder of the terminal piperidinium rings is also
a feature of the dehydrosparteinium perchlorate crystals [19]. Since their crystal
packing forces do not hamper the disorder, then all the more their absence in
DMSO-d6 solution should favor the conformational freedom of the piperidinium
ring D.
Experimental
The NMR spectra of 17-hydroxylupanine (3) and 17-dehydrolupaninium perchlorate (4) were
obtained on a Varian Unity spectrometer at observation frequencies of 299.949 (1H) and 75.429
1
(13C) MHz using solutions of ꢀ0.16 M 3 in CDCl3 and ꢀ0.2 M 4 in DMSO-d6 (internal TMS). H
NMR: spectral width 4000 Hz, acquisition time 3.744 s, 64 transients, 90ꢂ pulse widths 20.0 and
21.3 ms for 3 and 4. 13C NMR: spectral width 16501.7 Hz, acquisition time 1.815 s, 90ꢂ pulse width
8.7 ms, 4096 and 1024 transients for 3 and 4. Phase sensitive DQF-COSY spectra [23]: 1924.5 Â
1924.5 and 3146.1 Â 3146.1 Hz, acquisition times of 0.532 s and 0.325 ms, 90ꢂ pulse widths of 21.4
and 21.3 ms for 3 and 4, 1.5 s relaxation delay; 2 Â 320 FIDs with 32 transients each and 2 Â 524
FIDs with 32 transients each were accumulated for 3 and 4 respectively. The NOESY spectrum of 4
was run in the phase-sensitive mode [24] for a spectral width of 3146.1 Â 3146.1 Hz, 2 Â 262 FIDs
with 32 transients each, 90ꢂ pulse width 21.3 ms 2.0 s relaxation delay, 0.400 s mixing time, 0.325 s
acquisition time. The HMQC spectrum [25] of 3 was acquired with a spectral width of 2706.2 Â
8481.8 Hz, 2.0 s relaxation delay, 0.189 s acquisition time, 11 ms 90ꢂ pulse width, 128 Â 2 FIDs with
1
128 transients each, optimized for JCH ˆ 132 Hz. The HETCOR spectrum [26, 27] of 4 was
recorded with a spectral width of 16501.7 Â 1234.9 Hz collecting 256 FIDs with 128 transients each,
1
1.5 s relaxation delay, 0.062 s acquisition time, 11.0 ms 90ꢂ pulse width, JCH ˆ 135 Hz. The IR
spectra were obtained on a FT-IR Bruker IFS 113v spectrometer using KBr discs. The mass spectra
were measured on an AMD 402 instrument (AMD-INTECTRA Germany) using EI ionization with a
sample evaporation temperature of 150ꢂC, an ionization potential of 75 eV, and 8 kV accelerating
voltage.
17-Hydroxylupanine (3; C15H24N2O2)
A three-necked ¯ask (100 cm3) equipped with a re¯ux condenser and magnetic stirrer was ¯ushed
for 10 min with Ar passing through a washer with anhydrous benzene as protection against air
oxidation prior to addition of 150 mg (0.6 mmol) of lupanine in 12 cm3 of dioxane freshly distilled
from LiAlH4. A slow stream of Ar was passed through the system for 20 min. A solution of 138 mg
(0.6 mmol) of DDQ in 6 cm3 of dry dioxane was introduced into the reaction mixture which
immediately darkened, soon became opaque, and produced a precipitate. Purging with Ar was
continued for 4 h, and the mixture was left stirring over-night. The ¯ow of Ar was then resumed,
139 mg of DDQ in 6 cm3 of dry dioxane were added, and the reaction mixture was re¯uxed for 4 h.
The mixture was allowed to cool and the precipitate was ®ltered off. The air-dried precipitate was
well crushed and treated by 5 cm3 of ꢀ3 N HCl on a sinter funnel. The acidic ®ltrate was diluted with
5 cm3 of water and 0.3 cm3 of 40% aqueous NaHSO3, transferred into a separatory funnel, cooled to
ꢀ12ꢂC, and made strongly alkaline by addition of small portions of ꢀ50% aqueous NaOH under
cooling. The second ethereal extract showed a negative Dragendorff test [28]. The combined ethereal

1080
J. Thiel et al.
extracts were dried for 2 h over KOH pellets. Removal of the solvent in vacuo gave 89 mg of the
alkaloid in a form of a transparent resin. This product was treated with a few droplets of CH2Cl2,
upon which it crystallized within several minutes. The mother liquor was removed, and the crystals
were washed with a small amount of CH2Cl2 yielding 70 mg (44%) 3. The compound can be stored
for a week at 15ꢂC. The alkaloid dissolved in CDCl3 is stable for ꢀ24 h. After four days, the
1
solution shows considerable changes in its H NMR spectrum.
MS: m=z ˆ 264 (M‡ꢁ), 247 (M-OH); IR (KBr): ꢃ ˆ 3143, 2933, 2862, ꢀ 2795, ꢀ 2765, 1636,
1447, 1422, 1257, 1131, 1091, 1067, 727, 695 cm 1; NMR: see Table 1; the 13C NMR spectrum
shows the presence of a small amount of another compound featuring, among others, signals at 91.8
and 15.8 ppm.
The precipitate remaining after the above treatment of the crude product by 3 N HCl was again
washed with ꢀ1 N HCl (3 Â 5 cm3), 0.3 cm3 of 40% aqueous NaHSO3, and 15 cm3 of H2O. The
alkaloids were isolated from the obtained acidic liquid as described above. The yield was 20 mg.
TLC (SiO2; CH2Cl2: CH3OH:CH3OH saturated with NH3 ˆ9.5:0.9:0.1 (v/v)) of this product
showed, apart from 3 (Rf ꢃ 0.11), some unreacted lupanine (Rf ꢃ 0.44) and a compound of low
polarity (Rf ꢃ 0.73).
17-Dehydrolupaninium perchlorate (4; C15H23ClN2O5)
30 mg (0.11 mmol) of 3 were dissolved in several cm3 of methanol and then treated with a
methanolic solution of perchloric acid up to pH ꢃ 6. The solvent was removed in vacuo, and the
obtained resin treated by a very small amount of methanol gave 19 mg (48%) of crystalline 4.
IR (KBr): ꢃ ˆ 3050, 3030, 2950, 2876, 1682, 1633, 1457, 1450, 1412, 1370, 1358, 1347, 1332,
1312, 1265, 1173, 919, 623 cm 1; NMR: see Table 2
Hydrolysis of 4
63 mg (0.17 mmol) 4 were treated with 10 cm3 of ꢀ20% aqueous KOH and exhaustively extracted
with chloroform (Dragendroff's test [28]). Prior to the extraction, the solvent was shaken six times
with water to remove the stabilizing ethanol. The combined chloroform extracts (35 cm3) were
®ltered through a very small amount of basic alumina (Woelm), and the solvent was removed in
vacuo to give ꢀ50 mg of slightly contaminated 3.
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Â
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Received March 13, 2000. Accepted March 21, 2000