Synthesis of (+)-(S)-streptenol A and biomimetic synthesis of (2R,4S)- and (2S,4S)-2-(pent-3-enyl)piperidin-4-ol

Article abstract of DOI:10.1002/(SICI)1522-2675(19990707)82:7<1111::AID-HLCA1111>3.0.CO;2-L

(+)-(S)-Streptenol A is synthesized by coupling a 1,3-dithiane with an optically pure epoxide. The absolute configuration of (+)-(S)-streptenol A is thereby correlated with that of (S)-malic acid. Stereoselective reduction of an oxime that could easily be

Full text of DOI:10.1002/(SICI)1522-2675(19990707)82:7<1111::AID-HLCA1111>3.0.CO;2-L

Helvetica Chimica Acta ± Vol. 82 (1999)
1111
Synthesis of (+)-(S)-Streptenol A and Biomimetic Synthesis of
(2R,4S)- and (2S,4S)-2-(Pent-3-enyl)piperidin-4-ol
by Heribert Dollta), Peter Hammannb), and Siegfried Blechertc)*
a) F. Hoffmann-La Roche AG, PRPC-S, Grenzacherstr. 125, CH-4070 Basel
b) Core Research Function, DI & A, HMR Deutschland GmbH, D-65926 Frankfurt am Main
c) Institut für Organische Chemie der TU Berlin, Strasse des 17. Juni 124, D-10623 Berlin
(‡)-(S)-Streptenol A is synthesized by coupling a 1,3-dithiane with an optically pure epoxide. The absolute
configuration of (‡)-(S)-streptenol A is thereby correlated with that of (S)-malic acid. Stereoselective
reduction of an oxime that could easily be prepared from streptenol A gave the (3S,5R)- and (3S,5S)-
aminostreptenols, and after cyclization, configurationally pure 2,4-functionalized piperidine alkaloids.
Introduction. ± Product screening of metabolites found in nature is not only an
essential feature in the area of pharmacological research, but it is also a valuable tool to
enlarge the kit of building blocks for organic syntheses. Nature is thereby very often an
exciting guide in synthesis. After a biosynthetic pathway is clarified, it is one of the most
challenging fields of interest to find analogous procedures in the laboratory and to
transfer them to new synthetic problems in an ensuing step. The secondary metabolite
streptenol A (Scheme 1) is one of the four known streptenols with antitumor activity
and the ability to inhibit the cholesterol biosynthesis and to act as an immunostimulator
Scheme 1. Streptenols and Piperidine Alkaloids Obtained During a Fermentation

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Helvetica Chimica Acta ± Vol. 82 (1999)
[1]. The streptenols are produced by Streptomyces luteogriseus during a fermentation
reaction [1b][2]. In the culture broth, these streptenols are accompanied by piperidine
alkaloids and streptazoline. Feed experiments [3] have thereby shown that the
streptenols are metabolized during the fermentation and are thus the biosynthetic
precursors of the above-mentioned alkaloids. We describe here the asymmetric
synthesis of (‡)-(S)-streptenol A using a coupling reaction of the Seebach aldehyde
dithioacetal 1 with the optically pure epoxide 2. After an N-atom was introduced, the
streptenol A skeleton was cyclized, and the piperidine alkaloids were obtained like it is
demonstrated by nature.
Results and Discussion. ± (S)-Streptenol A. The transetherification product from
ethyl vinyl ether and but-3-en-2-ol was rearranged to the aldehyde 3 needed for the
ꢀUmpolungꢁ [4] (Scheme 2). (E)-Selectivity was thereby granted by the six-membered
Scheme 2. a) CH2Cl2, molecular sieves 4 Š, 08, 1.5 h. b) 1, BuLi, THF, 158, 3 h; then ‡ 8, 08, 7 days. c) MeOH,
r.t., 24 h. d) THF, r.t., 5 min.

Helvetica Chimica Acta ± Vol. 82 (1999)
1113
transition state that is passed during the 3,3-sigmatropic rearrangement and that prefers
a chair configuration, in which the Me group takes the energetically favorable
equatorial position. Treatment of 3 with propane-1,3-dithiol in the presence of boron
trifluoride etherate led finally to the 1,3-dithiane 1 as a mixture of diastereoisomers.
The absolute configuration of the epoxide 2, needed as the coupling partner for the 1,3-
dithiane 1, was taken from the chiral pool. Total reduction of (S)-malic acid (4) resulted
in butan-1,2,4-triol 5 [5] which could be transformed into a suitable epoxide for the
streptenol synthesis according to a procedure by Di Fabio [6]. In a regioselective
tritylation ( ! 6a) followed by a tosylation, a mixture of the products 6b was obtained.
This regioisomer mixture was treated with potassium carbonate, yielding the desired
epoxide 8 from one regioisomer besides the unreacted tosylated regioisomers 7 which
were finally separated from 8 chromatographically. Thus, purification of 6a,b during
the reaction sequence was not necessary.
Known procedures were first used ( 208, 12 h) [7] for the ring-opening reaction of
8 with deprotonated 1. However, it turned out that the epoxide 8 was inert under these
conditions which is certainly due to the steric hindrance caused by the bulky trityl
group. To force the reaction a little bit more, the temperature was increased, but only
up to 08 because of the known fact that solutions of deprotonated 1,3-dithianes are
stable only for a very short time at a higher temperature [8]. The optimal conditions
were found when deprotonated 1 was stirred with 8 at 08 for one week yielding 56% of
the coupling product 9, while 38% of the epoxide 8 and 26% of the dithiane 1 could be
isolated unchanged. Subsequent acid-catalyzed (TosOH) detritylation of 9 gave the
thioketale 10 of streptenol A, and desulfuration was achieved by means of HgClO4 ´
3 H2O, to profit from the described advantages [9][10] of this system, rather than by
means of the classical reagent HgO/HgCl. Thus, after 5 min stirring of 10 with a
solution of HgClO4 ´ 3 H2O in THF/CHCl3 at room temperature, the thioketal cleavage
was complete. The target streptenol A had to be removed from the mercury slurry very
quickly and completely since the presence of mercury traces caused the destruction of
the product after a few days, even at low temperature. The isolated streptenol A
showed identical spectroscopic data and optical rotation as the natural product from
streptomycetes (see [11]). Thus the absolute configuration of streptenol A was
correlated with (S)-malic acid.
Stereoselective Amination of (S)-Streptenol A. The classical one-pot procedure [12]
of imine formation and reduction failed when applied to (S)-streptenol A, giving only
poor yields of aminostreptenol and streptenol B as the main product instead.
Therefore, we used the (E)- and (Z)-O-benzyloximes 11a,b of (S)-streptenol A, which
were obtained in high yield on treatment with O-benzylhydroxylamine hydrochloride
in pyridine and could be separated chromatographically (Scheme 3). Because the (E)-
and (Z)-oximes may lead to a different stereochemistry on oxime reduction, it was
important to establish their double-bond configuration. This was successfully done by
C,H-COSY NMR experiments. It is known that C(a) (Z) to the O-atom appears at
higher field than the C(a) (E) to the O-atom does [13]. The less polar oxime showed at
36.9 ppm a CH2 group that possesses a C,H correlation to the dd of the CH2(a) protons,
and the more polar one a correlation between the CH2(a) proton and a CH2 group at
41.3 ppm; thus, the less polar material is the (Z)-oxime 11b.

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Helvetica Chimica Acta ± Vol. 82 (1999)
Scheme 3. Stereoselective Reduction of the Oximes of (S)-Streptenol A
With different reduction methods, it was found in general that the (E)-oxime 11a
was reduced under milder conditions faster and smoother than the (Z)-oxime 11b (see
Table 1). LiAlH4 gave the aminostreptenols in a one-step procedure; however, d.e.
values were not satisfying, and an elevated temperature was necessary, especially for
the (Z)-oxime. To increase the selectivity, the oxime was activated in acidified solutions
while the reaction temperature was kept low. Efficient reducing agents under acid
conditions were NaCNBH3 and TABH (tetramethylammonium triacetoxyboronhy-
dride). High d.e. values, fast reaction times, and high yields are reported [14] for the
resulting (R)- or (S)-configured secondary hydroxylamines. However, again the
oximes 11 of streptenol A reacted much slower than the examples reported in the
literature (see Table 1). Finally, the obtained hydroxylamines 12a,b were reduced
further with LiAlH4, and chromatographic workup gave the pure aminostreptenols
13a,b.

Helvetica Chimica Acta ± Vol. 82 (1999)
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Table 1. Conditions for the Reduction of the Oximes 11
Reagent
Solvent
Temp [8C]
Time [h]
Ratio 12a/12b
Yield [%]
11a (E)
11b (Z)
11a (E)
11b (Z)
11a (E)
11b (Z)
LiAlH4
LiAlH4
THF
THF
MeCN/HOAc
MeCN/HOAc
MeCN/HOAc
MeCN/HOAc
60 to ‡ 20
12
72
5
5
60
108
39 : 61
50 : 50
66 : 34
30 : 70
81 : 19
50 : 50
67
31
50
50
98
92
‡ 50
TABHa)
TABHa)
NaCNBH3
NaCNBH3
15
15
20
20
a) TABH ˆ Tetramethylammonium triacetoxyboronhydride.
Absolute Configuration of the Aminostreptenols 13a,b. The less polar amino-
streptenol 13a was transformed into the cyclic carbamate 14 on reaction with 1,1'-
1
carbonylbis[1H-imidazole]. The H-NMR data of the latter established its (4R,6R)-
configuration, which was also supported by PM3 calculations (see Fig.).
Figure. PM3-Optimized conformations of the (4R,6R)- and (4S,6R)-carbamates 14 and 14', respectively, of
aminostreptenol A
The CH2 protons of the ring moiety of 14 showed very different shifts in the 1H-NMR spectrum (1.37 and
2.10 ppm) so that the coupling constants could be measured. Both protons exhibited a ddd coupling pattern,
typical for the protons at C(5). Because of the anisotropy in cyclic carbamates, the axial proton at C(5) of 14 is
the one at higher field. This Hax C(5) showed three large coupling constants (13.2, 10.8, 10.8 Hz), which is in
agreement with a (4R,6R)-configuration for 14. Indeed, according to the PM3 calculations (see Fig.), the most
comfortable conformation of the carbamate 14 is a slightly flat-bottomed boat with eq/eq substituents at C(4)
and C(6). The dihedral angle between both protons at the substituted centers and Hax C(5) is 178.58 and
161.38. Because of the additional geminal coupling, Hax C(5) of 14 should show three large coupling
constants which is in accord with the 1H-NMR experiment. For the (4S,6R)-carbamate 14', the calculations
suggest a twist-boat conformation with eq/ax substituents in which only the protons at C(6) and C(5) exhibit a
great dihedral angle (162.78); therefore, Hax C(5) of 14' would show only two large coupling constants in the
1H-NMR.
Piperidine Alkaloids. A leaving group at the primary OH group of the amino-
streptenols 13 should allow an intramolecular cyclization involving the nucleophilic N-
atom; thereby, the relative configuration of the aminostreptenols should be preserved
in the resulting piperidine. For this purpose, the aminostreptenols 13 were mesylated.
This could be achieved stepwise in the sequence NH2, primary OH ( ! 15), and
secondary OH group ( ! 16; Scheme 4). However, better yields and smoother
reactions were obtained on total mesylation of 13. Treatment of the resulting trimesyl
derivatives 16 with 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) gave the cyclization
products 17. Using the same conditions for the dimesyl derivatives 15, the piperidinols

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Helvetica Chimica Acta ± Vol. 82 (1999)
Scheme 4. Biomimetic Synthesis of Piperidine Alkaloids. The formulae of the b series are shown.
18 were formed directly. Finally, the natural products 19 were obtained after reduction
with SMAH (sodium methoxy(ethoxy)aluminum hydride) which could be performed
stepwise starting with 17: At 508, only the O-mesyl group was reduced ( ! 18), and at
1408 also the N-mesyl group was removed.
The coupling constants in the 1H-NMR spectra could be used to determine different
conformations of the piperidines 17 ± 19, which were a consequence of their different
sterically demanding substituents. The results are listed in Table 2.
Table 2. Coupling Constants and Conformations of the Piperidines 17 ± 19
J(H,H) [Hz]
Positiona)
Conformation
chair
17a (2R,4S)
18a (2R,4S)
19a (2R,4S)
17b (2S,4S)
18b (2S,4S)
19b (2S,4S)
H
H
H
H
H
H
H
H
H
H
H
H
C(2): 5.0, 5.5, < 6.0
ax R C(2)
eq MesO
eq R C(2)
ax OH
eq R C(2)
ax OH
ax R C(2)
ax MesO
ax R C(2)
eq OH
ax R C(2)
eq OH
C(4): 4.5, 4.5, 11.5, 11.5
C(2): 4.5, 4.5, 11.3, 11.3
C(4): 6.2, 6.2, 6.2, 6.2
C(2): 2.8, 6.4, 6.4, 10.0
C(4): 3.1, 3.1, 3.1, 3.1
C(2): 6.9, 6.9, 6.9, 6.9
C(4): 3.0, 3.0, 3.0, 3.0
C(2): 5.5, 5.5, 5.5, <5.5
C(4): 4.5, 4.5, < 6.0, 12.0
C(2): 2.4, 7.2, 7.2, 12.0
C(4): 4.5, 4.5, 11.0, 11.0
chair
chair
chair
twist-boat
chair
a) R ˆ MeCHˆCHCH2CH2.

Helvetica Chimica Acta ± Vol. 82 (1999)
1117
Experimental Part
General. For molecular calculations, the program package SPARTAN Vers. 2.0. from Wavefunction Inc.,
Irvine, USA, was used. All solvents were freshly distilled and dried by using standard methods. Column
chromatography (CC): silica gel (0.03 ± 0.06 mm) from Baker. TLC: foils (silica gel 60F 254, 0.2 mm) from
Merck. Optical rotations: Perkin-Elmer-141 polarimeter. IR Spectra: Perkin-Elmer-881: rel. intensities are
given. NMR Spectra: Bruker AC200 and AM400 at 200 and 400 MHz, resp. for 1H; Bruker AM270 and AM400
for 13C and DEPT; d in ppm rel. to the internal standard SiMe4, coupling constants J in Hz; the J of higher spin
systems were verified by simulation techniques; isomer ratios of diastereoisomer mixtures were derived from
suitable NMR integrals. GC/MS analysis: HP 5890II with MSD 5971A and a CP-Sil 5CB column (12.5 m,
0.2 mm, 0.33 mm film); carrier gas He; the starting temp. 458 for 4 min, then temp. increase with a rate of 88/min,
end temp. 1258; peak intensities are given. Mass spectra: Variant MAT 711, ionization potential 70 eV.
Microanalyses: elemental analyzer 1106 Carlo Erba.
2-[(E)-Pent-3-enyl]-1,3-dithiane (1). At 08, propane-1,3-dithiol (714 mg, 6.6 mmol) was added to 3 (500 mg,
5.1 mmol) and 4-Š molecular sieves (250 mg) in anh. CH2Cl2 (20 ml) under Ar. The slow addition of BF3 ´ OEt2
(1.283 ml, 10.2 mmol) followed, and the mixture was stirred for 1.5 h. It was quenched with sat. NaHCO3 soln.
(12 ml) and extracted with CH2Cl2. The extract was washed with sat. NaHCO3 and sat. NaCl soln., dried
(MgSO4), and evaporated. Bulb-to-bulb distillation of the residue at 858/1.5 mbar yielded 549mg (57%) of 1.
Colorless liquid. Rf (petroleum ether/tBuOMe 10 : 1) 0.55. IR (CHCl3): 3020 (45.3), 2964 (45.7), 2905 (52.8),
1425 (57.3), 1262 (17.0), 1205 (54.6), 1098 (16.8), 1028 (17.9), 968 (54.4), 720 (0.0). 1H-NMR (400 MHz,
CDCl3): 1.33 (dddd, J ˆ 6, 1.5, 1.5, 1.5, 6 H, Me(5')); 1.80 (dt, J ˆ 7, 7, 4 H, CH2(1')); 1.87 (dm, J ˆ 14, 2 H,
1
1 H C(5)); 2.12 (dm, J ˆ 14, 2 H, 1 H C(5)); 2.19 (dddqt, J ˆ 7, 7, 7, 1.5, 1, 2 H, CH2(2') ); 2.26 (dddm, J ˆ 7,
1
7, 7, 2 H, CH2(2')); 2.79 ± 2.91 (m, 8 H, CH2(4), CH2(6)); 4.02 (t, J ˆ 7, 1 H C(2)) ); 4.04 (t, J ˆ 7, 1 H C(2));
5.39 (dtq, J ˆ 15, 7, 1.5, 2 H, H C(3')); 5.49 (dqt, J ˆ 15, 6, 1, 2 H, H C(4')). 13C-NMR (50 MHz, CDCl3): 12.6,
1
1
1
1
17.8 ) (q, C(5')); 23.7, 25.8 ) (t, C(2')); 25.8 (t, 2 C(5)); 30.08 ), 30.12 (t, 2 C(4), 2 C(6)); 34.96, 34.99 )
1
1
1
(t, C(1')); 46.5 ), 46.7 (d, C(2)); 125.1, 125.9 ) (d, C(4')); 128.6, 129.4 ) (d, C(3')). GC/MS: tR 14.448 min; 188
(56, M ), 133 (26, [M C4H7] ), 119 (100, [133 CH2] ), 106 (24, [119 CH] , C3H6S2 ), 55 (16, C4H7 ). HR-
MS: 188.0694 (C9H16S2 ; calc. 188.0693).
‡
‡
‡
‡
‡
‡
‡
(‡)-(2S)-1-{2-[(E)-Pent-3-enyl]-1,3-dithian-2-yl}-4-(trityloxy)butan-2-ol (9). At 408, 1.6m BuLi (1 ml)
was added very slowly to a soln. of 1 (276 mg, 1.47 mmol) in anh. THF (10 ml). Then it was stirred for 3 h at
158. After cooling to 208, a soln. of 8 (486 mg, 1.47 mmol) in anh. THF (2 ml) was added dropwise. The
mixture was warmed to 08 and stirred for a week. Addition of sat. NH4Cl soln. (30 ml), extraction with CH2Cl2,
drying (MgSO4) of the org. layer, and evaporation gave a residue which was purified by CC (silica gel,
petroleum ether/tBuOMe 20 : 1, then 10 : 1, and finally 2 : 1): recycled 1 (26%) and 8 (38%), and 9 (430 mg
56%). Slightly yellow solid. Rf (petroleum ether/tBuOMe 2 : 1) 0.28. [a]D ˆ‡ 7.6 (c ˆ 1.16, CH2Cl2). IR
(CHCl3): 3483 (76.4), 3017 (33.1), 2934 (30.8), 1450 (28.6), 1228 (16.7), 1076 (0.0), 1034 (21.4), 708 (3.4), 674
(53.1), 633 (50.3). 1H-NMR (400 MHz, CDCl3): 1.64 (d, J ˆ 5, Me(5'')); 1.68 ± 1.78 (m, 1 H C(5')); 1.80 ± 2.12
(m, 1 H C(1), CH2(1''), CH2(2''), CH2(3), 1 H C(5')); 2.28 (dd, J ˆ 15, 9, 1 H C(1)); 2.74 ± 2.82 (ddd, J ˆ
14.5, 6.5, 3, Heq C(4'), Heq C(6')); 2.88, 2.95 (each ddd, J ˆ 14.5, 9.5, 3, Hax C(4'), Hax C(6')); 3.18 ± 3.32
(m, 2 H C(4)); 4.14 ± 4.22 (m, H C(2)); 5.34 ± 5.51 (m, H C(3''), H C(4'')); 7.20 ± 7.33 (m, 9 arom. H); 7.44
(dd, J ˆ 8, 1, 6 arom. H). 13C-NMR (100 MHz, CDCl3): 17.9 (q, C(5'')); 25.0 (t, C(5')); 26.0, 26.3 (t, C(4'),
C(6')); 27.2 (t, C(2'')); 38.0 (t, C(1'')); 39.5 (t, C(3)); 44.7 (t, C(1)); 52.0 (s, C(2')); 61.0 (t, C(4)); 66.7 (d, C(2));
86.8 (s, Ph3C); 125.6 (d, C(4'')); 126.9 (d, 3Cp); 127.8 (d, 6Co); 128.8 (d, 6Cm); 130.1 (d, C(3'')); 144.1 (s, 3Cipso).
‡
‡
‡
‡
‡
MS (1708): 518 (1, M ), 463 (6, [M C4H7] , 275 (38, [M Tr] ), 243 (100, Tr ), 187 (18, [275 C4H8O2] ), 55
‡
‡
(4, C4H7 ). HR-MS: 518.2313 (C32H38O2S2 ; calc. 518.2313). Anal. calc. for C32H38O2S2: C 74.09, H 7.38; found:
C 73.77, H 6.72.
(‡)-(2S)-4-{2-[(E)-Pent-3-enyl]-1,3-dithian-2-yl}butane-1,3-diol (10). A soln. of 9 (420 mg, 0.8 mmol) in
MeOH (42 ml) and TsOH (84 mg, 0.5 mmol) were stirred at r.t. for 24 h. Evaporation, CC (petroleum ether/
tBuOME 1:2) of the residue yielded 10 (89 mg, 40%). Colorless oil. [a]D ˆ‡ 15.4 (c ˆ 1.78, CH2Cl2). Rf
(petroleum ether/tBuOME 1 : 2) 0.35. IR (CHCl3): 3624 (72.6), 3449 (45.5), 3017 (0.0), 3011 (10.7), 2944 (7.8),
1441 (25.2), 1427 (18.9), 1418 (25.9), 1206 (0.3), 1071 (0.0), 968 (33.9), 718 (56.0). 1H-NMR (400 MHz,
CDCl3): 1.60 ± 1.70 (m, 1 H C(5')); 1.66 (dd, J ˆ 6.5, 1.5, Me(5'')); 1.73 ± 1.83 (m, 1 H C(5')); 1.86 ± 1.98
(m, CH2(1''), 1 H C(2)); 1.98 ± 2.16 (m, CH2(2''), 1 H C(2)); 2.16 ± 2.34 (m, 1 H C(4)); 2.41 (dd, J ˆ 15.5,
9.5, 1 H C(4)); 2.75 ± 2.88 (m, H C(4'), H C(6'), OH); 2.96, 3.01 (each ddd, J ˆ 14.5, 9.5, 3.5, Hax C(4'),
1
)
Data of the more abundant diastereoisomer, else sum of the overlapped signals.

1118
Helvetica Chimica Acta ± Vol. 82 (1999)
Hax C(6')); 3.80 ± 3.86 (m, 2 H C(1)); 3.90 (d, J ˆ 1, OH); 4.21 ± 4.32 (m, H C(3)); 5.35 ± 5.54 (m, H C(3''),
C(4'')). 13C-NMR (50MHz, CDCl3): 17.9 (q, C(5'')); 24.8 (t, C(5')); 26.0, 26.3 (t, C(4'), C(6')); 27.2
(t, C(2'')); 39.1 (t, C(1'')); 39.6 (t, C(2)); 44.8 (t, C(4)); 51.8 (s, C(2')); 61.2 (t, C(1)); 68.7 (d, C(3)); 125.8
H
‡
‡
‡
(d, C(4'')); 130.0 (d, C(3'')). MS (2408): 276 (21, M ), 221 (30, [M C4H7] ), 201 (29, [M C3H7O2] ), 187
‡
‡
‡
‡
(36, [201 CH2] ), 169 (18, [M C3H7S2] ), 151 (57, [169 H2O] ), 107 (54, C3H7S2 ), 95 (65, [M C3H6S2
‡
‡
‡
‡
‡
C3H7O2] ), 75 (39, C3H7O2 ), 69 (22, C5H9 ), 55 (100, C4H7 ). HR-MS: 276.1218 (C13H24O2S2 ; calc. 276.1218).
(S)-Streptenol A (ˆ (3S,8E)-1,3-Dihydroxydec-8-en-5-one). To a soln. of 10 (104 mg, 0.37 mmol) in THF/
CHCl3 2 : 5 (7 ml), Hg(ClO4)2 ´ 3 H2O (367 mg, 0.8 mmol) in THF (6 ml) was added slowly and then stirred for
5 min at r.t. The mixture was neutralized with sat. Na2CO3 soln. and extracted with CHCl3, the org. layer washed
t
with brine, dried (MgSO4), evaporated, and the residue purified by CC (silica gel, BuOMe/petroleum ether
3 : 1); 39 mg (57%) of (S)-streptenol A. Rf (AcOEt/hexane 4 : 1) 0.56. [a]D ˆ‡ 23.0 (c ˆ 1.05, CHCl3) ([11]:
1
[a]D ˆ‡ 23.0 (c ˆ 1.05, CHCl3)). H-NMR (400 MHz, CDCl3): 1.64 (dd, J ˆ 1.0, 5.5, Me(10)); 1.76 (dddm, J ˆ
6.5, 6.5, 6.5, 2 H C(2)); 2.26 (dddm, J ˆ 7.0, 7.0, 7.0, 2 H C(7)); 2.50 (t, 7.0, 2 H C(6)); 2.60 (m, 2 H C(4));
4.10 ± 4.30 (m, 2
H C(1), H C(3)); 5.52 ± 5.34 (m, H C(8), H
C(9)). 13C-NMR (50 MHz, CDCl3):
17.7 (q, C(10)); 26.4 (t, C(7)); 37.8 (t, C(2)); 43.2 (t, C(6)); 49.2 (t, C(4)); 60.5 (t, C(1)); 67.1 (d, C(3));
126.0 (d, C(9)); 129.1 (d, C(8)); 211.2 (s, C(5)). Anal. calc. for C10H18O3: C 64.49, H 9.74; found: C 64.76,
H 9.19.
(‡)-(3R,5E,8E)- and (‡)-(3R,5Z,8E)-1,3-Dihydroxydec-8-en-5-one O-Benzyloxime (11a and 11b, resp.).
To a mixture of O-benzylhydroxylamin hydrochloride (840 mg, 5.3 mmol) and pyridine (1.8 ml) in anh. THF
(3 ml), a soln. of (S)-streptenol A (600 mg, 3.2 mmol) in anh. THF (0.2 ml) was added dropwise. The mixture
was stirred for 20 h at r.t. H2O was added, the mixture extracted with AcOEt, the extract dried (MgSO4) and
evaporated, and the residue purified by CC (petroleum ether/tBuOMe 2 :1): 891 mg (95%) of slightly yellow oil.
Separation of the (Z)- and (E)-isomer was easily achieved by CC.
Data of 11a: Rf (AcOEt/hexane/MeOH 1:1:0.2) 0.76. [a]D ˆ‡ 11.4 (c ˆ 1, MeOH). 1H-NMR (400 MHz,
CDCl3): 1.64 (dd, J ˆ 1.0, 6.0, 3 H C(10)); 1.60 ± 1.98 (m, 2 H C(2)); 2.12 ± 2.21 (m, 2 H C(7)); 2.28 (d, J ˆ
3.0, 1 H C(4)); 2.32 (d, J ˆ 9.0, 1 H C(4)); 2.37 (t, J ˆ 8.0, 2 H C(6)); 3.78 ± 3.84 (m, 2 H C(1)); 4.38
(dddd, J ˆ 3.0, 3.0, 9.0, 9.0, 1 H C(3)); 5.06, 5.07 (s, PhCH2); 5.32 ± 5.48 (m, H C(8), H C(9)); 7.26 ± 7.38
(m, 2 Ho, 2 Hm, Hp). 13C-NMR (100 MHz, CDCl3): 17.8 (q, C(10)); 28.4 (t, C(6)); 29.4 (t, C(7)); 37.8 (t, C(2));
41.3 (t, C(4)); 61.1 (t, C(1)); 68.4 (d, C(3)); 75.6 (t, PhCH2); 125.9 (d, C(9)); 127.7 (d, Cp); 127.9 (d, 2 Co); 128.3
(d, 2 Cm); 129.6 (d, C(8)); 137.9 (s, Cipso); 160.0 (s, C(5)). Anal. calc. for C17H25NO3: C 69.29, H 8.36; found:
C 69.27, H 8.34.
Data of 11b: Rf (AcOEt/hexane/MeOH 1 :1:0.2) 0.85. [a]D ˆ‡ 21 (c ˆ 1, MeOH). 1H-NMR (400 MHz,
CDCl3): 1.64 (d, J ˆ 6.0, 3 H C(10)); 1.66 ± 1.74 (m, 2 H C(2)); 2.16 ± 2.26 (m, 2 H C(7)); 2.26 ± 2.32
(m, 2 H C(6)); 2.40 (dd, J ˆ 4.0, 13.0, 1 H C(4)); 2.68 (dd, J ˆ 8.0, 13.0, 1 H C(4)); 3.74 ± 3.87
(m, 2 H C(1)); 4.14 (ddm, J ˆ 4.0, 8.0, 1 H C(3)); 5.08 (s, PhCH2); 5.34 ± 5.51 (m, H C(8), H C(9));
7.26 ± 7.40 (m, 2 Ho, 2 Hm, Hp). 13C-NMR (50 MHz, CDCl3): 17.8 (q, C(10)); 29.2 (t, C(7)); 35.2 (t, C(6)); 36.9
(t, C(4)); 38.8 (t, C(2)); 60.9 (t, C(1)); 69.3 (d, C(3)); 75.5 (t, PhCH2); 125.7 (d, C(9)); 127.7 (d, Cp); 128.0
(d, 2 Co); 128.3 (d, 2 Cm); 129.7 (d, C(8)); 137.6 (s, Cipso); 158.8 (s, C(5)). Anal. calc. for C17H25NO3: C 69.29,
H 8.36; found: C 69.21, H 8.37.
(3R,5R,8E)- and (3R,5S,8E)-5-[(Benzyloxy)amino]dec-8-ene-1,3-diol (12a and 12b, resp.). The prepara-
tion of 12 gave best diastereoselectivities following the procedures below. Starting with 11b (Z) a ratio 12b/12a
of 70 :30 was obtained if 11b was added dropwise at 158 to a suspension of 10 equiv. of TABH in AcOH/
MeCN 1 : 1. The mixture was stirred for 5 h, sat. Na2CO3 soln. added, and the mixture extracted with AcOEt.
Purification by CC (petroleum ether/tBuOMe 1 : 2) yielded 50% of a colorless oil.
Starting with 11a (E) a ratio 12a/12b of 81:19 was obtained if 11a was treated with 10 equiv. of NaCNBH3
for 60 h at 208 in AcOH/MeCN 1 : 1. Yield 98%. Rf (tBuOMe) 0.29. IR (CHCl3): 3624 (85.0), 3015 (11.5), 2939
(0.0), 2857 (21.1), 1455 (12.7), 1439 (18.2), 1365 (37.4), 1205 (45.7), 1074 (15.5) 969 (8.0), 909 (25.9), 700
(6.4). 1H-NMR (400 MHz, CDCl3): 1.65 (d, J ˆ 5, 6 H C(10)); 1.34 ± 1.86 (m, 4 H C(2), 4 H C(4),
1
4 H C(6)); 1.94 ± 2.08 (m, 4 H C(7)); 3.00 (dddd, J ˆ 6.5, 6.5, 6.5, 6.5, H C(5)); 3.18 ) (dddd, J ˆ 7, 7, 7, 3,
1
H
C(5)); 3.76 ± 3.90 (m, 4 H C(1)); 3.96 (dddd, J ˆ 6, 6, 6, 6, H C(3)); 4.10 ) (dddd, J ˆ 9, 9, 3, 3, H C(3));
4.64 ± 4.76 (m, PhCH2); 5.32 ± 5.48 (dqm, overlapped, J ˆ 15, 5, 2 H C(8), 2 H C(9)); 7.24 ± 7.41 (m, 4 Ho,
1
1
1
4 Hm, 2 Hp). 13C-NMR (50 MHz, CDCl3): 17.9 (2q, C(10)); 28.6, 29.2 ) (t, C(7)); 30.8 ), 32.8 (t, C(6)); 37.4 ),
1
1
1
1
38.4 (t, C(4)); 38.5 ), 38.8 (t, C(2)); 57.8 ), 61.2 (d, C(5)); 61.5, 61.8 ) (t, C(1)); 69.3 ), 78.1 (d, C(3)); 76.3,
76.4 ) (t, PhCH2); 125.6, 125.8 ) (d, C(9)); 128.0, 128.1 ) (d, C(4')); 128.45, 128.5 ) (2d, 2 Co, 2 Cm); 130.2 ),
130.4 (d, C(8)); 137.2 (2s, Cipso). MS (1208): 294 (0.25, [M ‡ H] ), 224 (17, [M C5H9] ), 91 (100, Bn ), 77 (18,
1
1
1
1
1
‡
‡
‡

Helvetica Chimica Acta ± Vol. 82 (1999)
1119
‡
‡
‡
‡
‡
‡
C6H5 ), 69 (26, C5H9 ), 65 (10, C5H5 ), 55 (46, C4H7 ), 51 (10, C4H3 ). HR-MS: 224.1287 (C12H18O3N ; calc.
224.1287). Anal. calc. for C17H27NO3: C 69.59, H 9.28; found: C 69.36, H 9.35.
(
)-(3R,5R,8E)- and ( )-(3R,5S,8E)-5-Aminodec-8-ene-1,3-diol (13a and 13b, resp.). Method 1: A (Z/E)-
oxime mixture 11 (1.947 g, 6.7 mmol) in anh. THF (17 ml) was added slowly at r.t. to a suspension of LiAlH4
(1.58 g, 42 mmol) in anh. THF (22 ml). The mixture was stirred for 16 h, a Na2SO4 soln. added carefully, and the
precipitate that formed filtered. The filtrate was extracted with AcOEt and the org. layer dried (MgSO4) and
evaporated: 985 mg of 13a/13b (78%), suitable for further transformations without purification. The
diastereoisomers could be separated by CC (CH2Cl2/MeOH/NH3 6 :1:0.1).
Method 2: A soln. of 12a (93 mg, 0.32 mmol) in anh. THF (1 ml) was added at 788 to a suspension of
LiAlH4 (50 mg, 1.3 mmol) in anh. THF (1 ml) under Ar. The mixture was slowly warmed to r.t. and then
refluxed for 10 h. Workup and CC as described in Method 1 yielded 46 mg (77%) of 13a (3R,5R). Rf (CH2Cl2/
MeOH/NH3 90 : 15 : 1.5) 0.25. [a]D
ˆ
15 (c ˆ 1, MeOH). 1H-NMR (400 MHz, CDCl3): 1.24 ± 1.42
(m, 2 H C(6)); 1.46 ± 1.62 (m, 1 H C(2), 2 H C(4)); 1.64 ± 1.72 (m, 1 H C(2)); 1.66 (dd, J ˆ 1.0, 6.0,
3 H C(10)); 1.96 ± 2.10 (m, 2 H C(7)); 2.88 (dddd, J ˆ 2.5, 5.0, 7.5, 10.0, H C(5)); 3.04 ± 3.28 (br., 4 H));
3.78 ± 3.86 (m, 2 H C(1)); 4.09 (dddd, J ˆ 2.0, 4.0, 8.0, 10.0, H C(3)); 5.34 ± 5.50 (m, H C(8), H C(9)).
13C-NMR (100 MHz, CDCl3): 17.7 (q, C(10)); 28.5 (t, C(7)); 39.2 (t, C(6)); 39.9 (t, C(2)); 42.1 (t, C(4)); 52.0
(d, C(5)); 60.5 (t, C(1)); 72.3 (d, C(3)); 125.3 (d, C(9)); 130.3 (d, C(8)). Anal. calc. for C10H21NO2: C 64.13,
H 11.38; found: C 64.09, H 11.41.
The procedure described for 13a was applied to 12b for the preparation of 13b (3R,5S). Rf (CH2Cl2/MeOH/
1
NH3 90 :15 :1.5) 0.19. [a]D
ˆ
19.6 (c ˆ 1, MeOH). H-NMR (400 MHz, CDCl3): 1.44 ± 1.64 (5 H), 1.74 ± 1.84
(1 H) (m, 2 H C(2), 2 H C(4), 2 H C(6)); 1.65 (dd, J ˆ 1.0, 6.0, 3 H C(10)); 1.96 ± 2.10 (m, 2 H C(7));
2.86 ± 3.18 (br., 4 H); 3.18 (dddd, J ˆ 3.0, 7.0, 7.0, 7.0, H C(5)); 3.85 (t, J ˆ 6.0, 2 H C(1)); 4.18 (dddd, J ˆ 3.0,
3.0, 6.0, 9.0, H C(3)); 5.34 ± 5.52 (m, H C(8), H C(9)). 13C-NMR (50 MHz, CDCl3): 17.8 (q, C(10)); 29.1
(t, C(7)); 37.3 (t, C(6)); 38.8 (t, C(2)); 41.3 (t, C(4)); 48.2 (d, C(5)); 60.8 (t, C(1)); 68.7 (d, C(3)); 125.5
(d, C(9)); 130.3 (d, C(8)). Anal. calc. for C10H21NO2: C 64.13, H 11.38; found: C 64.08, H 11.35.
(
)-(4R,6R)-6-(2-Hydroxyethyl)-4-[(E)-pent-3-enyl]-1,3-oxazinan-2-one (14). A soln. of 13a (99 mg,
0.53 mmol) and 1,1'-carbonylbis[1H-imidazole] (91 mg, 0.56 mmol) in THF (20 ml) was stirred for 12 h. The
volatile components were evaporated. Then, H2O (130 ml) was added, the mixture extracted with AcOEt (4 Â
40 ml), the org. layer dried (MgSO4) and evaporated, and the residue submitted to CC (CH2Cl2/MeOH 20 : 1);
97 mg (85%) of 14 (4R,6R). Rf (CH2Cl2/MeOH 20 : 1) 0.24. [a]D
ˆ
46.6 (c ˆ 6.5 mg/ml, MeOH). 1H-NMR
(400 MHz, CDCl3): 1.37 (ddd, J ˆ 10.8, 10.8, 13.2, 1 Hax C(5)); 1.60 (m, 2 H C(1'')); 1.63 (m, 3 H C(5''));
1.85 (m, 2 H C(1')); 2.05 (m, 2 H C(2'')); 2.10 (m, two J > 9.0, 1 Heq C(5)); 3.50 (m, H C(4)); 3.70
(m, 2 H C(2')); 4.45 (m, H C(6)); 5.45 (m, H C(3''), H C(4'')). C,H-COSY (CDCl3): 18.0 (q, C(5'')); 29.0
(t, C(2'')); 34.2 (t, C(5)); 36.8 (t, C(1'')); 39.1 (t, C(1')); 51.5 (d, C(4)); 58.5 (t, C(2')); 75.9 (d, C(6)); 126.8
(d, C(4'')); 131.2 (d, C(3'')); 157.3 (s, C(2)). Anal. calc. for C11H19NO3: C61.94, H 8.98: found: C 62.92, H 9.23.
(
)-(3R,5R,8E)- and (‡)-(3R,5S,8E)-Methanesulfonic Acid 3-Hydroxy-5-[(methylsulfonyl)amino]dec-8-
enyl Ester (15a and 15b, resp.). To 13a (150 mg, 0.8 mmol) in anh. CH2Cl2 (5 ml), Et3N (235 ml, 1.7 mmol) and
finally MesCl (126 ml, 1.6 mmol) were added dropwise at 08. After 2 h stirring, the mixture was washed with
NaHCO3 soln. and extracted with AcOEt. Drying (MgSO4) and evaporation gave a residue which was purified
by CC (CH2Cl2/MeOH/NH3 140 :5 :1). 206 mg (75%) of 15a. Rf (CH2Cl2/MeOH/NH3 90 :5 :1) 0.38. [a]D
ˆ
1.9
(c ˆ 8 mg/ml, MeOH). 1H-NMR (400 MHz, CDCl3): 1.52 ± 1.70 (m, 2 H C(4), 2 H C(6)); 1.66 (dd, J ˆ 1.0,
6.0, 3 H C(10)); 1.78 (dddd, J ˆ 5.0, 5.0, 10.0, 15.0, 1 H C(2)); 1.97 (dddd, J ˆ 3.0, 6.0, 9.0, 15.0, 1 H C(2));
2.04 ± 2.12 (m, 2 H C(7)); 2.97 (s, 1 MeSO2); 3.04 (s, 1 MeSO2); 3.54 (m, 1 H C(5)); 3.97 (ddm, J ˆ 3.0, 5.0,
1 H C(3)); 4.34 (ddd, J ˆ 5.0, 9.0, 9.5, 1 H C(1)); 4.46 (ddd, J ˆ 6.0, 9.5, 10.0, 1 H C(1)); 4.94 (m, NH);
5.35 ± 5.53 (m, H C(8), H C(9)). 13C-NMR (100 MHz, CDCl3): 17.9 (q, C(10)); 28.5 (t, C(7)); 35.9 (t, C(6));
36.9 (t, C(2)); 37.3 (q, MeSO3); 41.7 (q, MeSO2N); 42.7 (t, C(4)); 52.7 (d, C(5)); 66.1 (d, C(3)); 67.0 (t, C(1));
126.2 (d, C(9)); 129.7 (d, C(8)).
As described for 15a, 15b was obtained from 13b. Rf (CH2Cl2/MeOH/NH3 90 :5 :1) 0.52. [a]D ˆ‡ 7.0 (c ˆ
5 mg/ml, MeOH). 1H-NMR (400 MHz, CDCl3): 0.9 ± 2.1 (m, 2 H C(2), 2 H C(4), 2 H C(6), 2 H C(7),
3 H C(10)); 3.01 (s, MeSO3); 3.10 (s, MeSO2N); 3.60 (m, 1 H C(5)); 3.85 (m, 1 H C(3)); 4.25 (d, J ˆ 9.0,
NH); 4.40 (m, 1 H C(1)); 4.52 (m, 1 H C(1)); 5.95 (m, H C(8), H C(9)). 13C-NMR (50 MHz, CDCl3):
17.9 (q, C(10)); 29.1 (t, C(7)); 30.5 (t, C(6)); 36.1 (t, C(2)); 37.4 (q, MeSO3); 40.1 (t, C(4)); 41.7 (q, MeSO2N);
51.4 (d, C(5)); 69.1 (d, C(3)); 67.5 (t, C(1)); 126.2 (d, C(9)); 129.8 (d, C(8)).
(
)-(3R,5R,8E)- and (‡)-(3R,5S,8E)-Methanesulfonic Acid 5-[(Methylsulfonyl)amino]-3-[(methylsulfo-
nyl)oxy]dec-8-enyl Ester (16a and 16b, resp.). To a soln. of 13a (240 mg, 1.28 mmol) in anh. CH2Cl2 (8 ml), Et3N
(720 ml, 5.2 mmol) and MesCl (403 ml, 5.1 mmol) were added at 08. The mixture was stirred for 2 h, quenched

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Helvetica Chimica Acta ± Vol. 82 (1999)
with sat. Na2CO3 soln. and extracted with AcOEt. Drying (MgSO4) and evaporation under high vacuum yielded
505 mg (94%) of 16a, which could be used without further purification. Rf (tBuOMe/petroleum ether 2 :1) 0.06.
[a]D
ˆ
3.54 (c ˆ 1, CH2Cl2). 1H-NMR (400 MHz, CDCl3): 1.50 ± 1.85 (m, 2 H C(4), 2 H C(6)); 1.60 (d, J ˆ
6.1, 3 H C(10)); 2.00 ± 2.10 (m, 2 H C(7)); 1.97 ± 2.28 (m, 2 H C(2)); 3.00 (s, MeSO2); 3.02 (s, MeSO2); 3.10
(s, MeSO2); 3.55 (m, 1 H C(5)); 4.28 ± 4.37 (m, 2 H C(1)); 4.63 (d, J ˆ 8.6, NH); 5.03 (m, 1 H C(3)); 5.30 ±
5.50 (m, H C(8), H C(9)). 13C-NMR (50 MHz, CDCl3): 17.8 (q, C(10)); 28.6 (t, C(7)); 33.6 (t, C(6)); 35.3
(t, C(2)); 37.3 (q, MeSO3); 38.4 (q, MeSO3); 41.2 (t, C(4)); 41.9 (q, MeSO2N); 50.6 (d, C(5)); 65.4 (t, C(1)); 76.2
(d, C(3)); 126.3 (d, C(9)); 129.3 (d, C(8)). Anal. calc. for C13H27NO8S3: C 37.04, H 6.46; found: C 36.33, H 6.06.
As described for 16a, 16b was obtained from 13b. Rf (tBuOMe/petroleum ether 2 :1) 0.14. [a]D ˆ‡ 8.76 (c ˆ
1, CH2Cl2). 1H-NMR (400 MHz, CDCl3): 1.45 ± 1.80 (m, 2 H C(4), 2 H C(6)); 1.65 ± 1.93 (m, 2 H C(2));
1.70 (d, J ˆ 5.5, 3 H C(10)); 2.09 ± 2.16 (m, 2 H C(7)); 3.04 (s, MeSO2); 3.08 (s, MeSO2); 3.12 (s, MeSO2); 3.70
(m, 1 H C(5)); 4.12 ± 4.22 (m, 2 H C(1)); 4.41 (d, J ˆ 8.0, NH); 4.91 (m, 1 H C(3)); 5.68 ± 5.79 (m, H C(8),
H
C(9)). 13C-NMR (50 MHz, CDCl3): 17.8 (q, C(10)); 28.5 (t, C(7)); 34.8 (t, C(6)); 35.4 (t, C(2)); 37.3
(q, MeSO3); 38.5 (q, MeSO3); 40.1 (t, C(4)); 42.3 (q, MeSO2N); 50.7 (d, C(5)); 65.6 (t, C(1)); 76.1 (d, C(3));
126.4 (d, C(9)); 129.4 (d, C(8)).
(‡)-(2R,4S,3E)- and ( )-(2S,4S,3E)-Methanesulfonic Acid 1-(Methylsulfonyl)-2-(pent-3-enyl)piperidin-4-
yl Ester (17a and 17b, resp.). A soln. of 16a (505 mg, 1.22 mmol) and DBU (4 ml) in anh. THF (42 ml) was
stirred for 12 h at r.t. H2O was added and the mixture extracted with AcOEt. The org. layer was dried (MgSO4)
and evaporated and the residue chromatographed (AcOEt/petroleum ether/i-PrOH 1 :5 :0.25): 390 mg (98%)
of 17a. Rf (AcOEt/petroleum ether/i-PrOH 1:4 :0.25) 0.16. [a]D
ˆ
8.5 (c ˆ 1, MeOH). IR (CHCl3): 3031
(27.8), 3026 (28.4), 2939 (35.6), 1457 (48.6), 1336 (0.4), 1205 (17.3), 1176 (0.9), 1148 (4.1), 941 (0.0), 851
(25.0), 812 (44.5). 1H-NMR (400 MHz, CDCl3): 1.65 (dd, J ˆ 6.0, 1.0, 3 H C(5')); 1.68 ± 1.76 (m, 2 H C(1'));
1.80 (ddm, J ˆ 11.5, 5, 1 Heq C(3)); 1.88 (ddd, J ˆ 12, 11.5, 5.5, 1 Hax C(3)); 2.05 (td, J ˆ 7, 6.5, 2 H C(2'));
2.11 ± 2.20 (ddmp, J ˆ 15, 2.5, 2 H C(5)); 2.90 (s, MeSO2); 3.03 (s, MeSO2); 3.10 (ddd, J ˆ 15, 15, 2.5,
1 Hax C(6)); 3.87 (dm, J ˆ 15, 1 Heq C(6)); 4.15 (ddm, J ˆ 5.5, 5, 1 Heq C(2)); 4.92 (dddd, J ˆ 11.5, 11.5,
4.5, 4.5, 1 Hax C(4)); 5.39 (dqt, J ˆ 15.5, 6.5, 1 H C(3')); 5.48 (dq, J ˆ 15.5, 6, 1 H C(4')). 13C-NMR (50 MHz,
CDCl3): 17.8 (q, C(5')); 29.2 (t, C(2')); 30.7 (t, C(1')); 32.3 (t, C(5)); 35.2 (t, C(3)); 38.7 (t, C(6)); 38.9
(q, MeSO3); 40.9 (q, MeSO2N); 52.8 (d, C(2)); 74.8 (d, C(4)); 126.4 (d, C(4')); 129.2 (d, C(3')). MS (858): 325
‡
‡
‡
‡
‡
(1.3, M ), 310 (0.6, [M Me] ), 256 (13, [M C5H9] ), 230 (11, [M OMes] ), 189 (2, [230 C3H5] ), 161
‡
‡
‡
‡
(42, [189 C2H4] ), 160 (100, [161 H] ), 82 (78, [161 Mes] ), 55 (65, C4H7 ). HR-MS: 325.1018
(C12H23NO5S2 ; calc. 325.1018). Anal. calc. for C12H23NO5S2: C 44.29, H 7.12; found: C 44.25, H 7.20.
‡
As described for 17a, 17b was obtained from 16b. Rf (AcOEt/petroleum ether/i-PrOH 1:4 :0.25) 0.10.
[a]D ˆ‡ 10.7 (c ˆ 1, MeOH). 1H-NMR (400 MHz, CDCl3): 1.65 (d, J ˆ 4.6, 3 H C(5')); 1.72 ± 2.16
(m, 2 H C(1'), 2 H C(2'), 2 H C(3), 2 H C(5)); 2.91 (s, MeSO2); 3.04 (s, MeSO2); 3.35 (ddd, J ˆ 4.0,
11.5, 15.4, 1 Hax C(6)); 3.68 (dm, J ˆ 15.4, 1 Heq C(6)); 4.02 (dddd, J ˆ 6.9, 6.9, 6.9, 6.9, 1 Heq C(2)); 5.10
(dddd, J ˆ 3.0, 3.0, 3.0, 3.0, 1 Heq C(4)); 5.34 ± 5.54 (m, H C(3'), H C(4')). 13C-NMR (100 MHz, CDCl3):
18.0 (q, C(5')); 29.8 (t, C(2')); 30.6 (t, C(1')); 32.3 (t, C(5)); 32.7 (t, C(3)); 35.2 (t, C(6)); 38.6 (q, MeSO3); 40.8
(q, MeSO2N); 51.1 (d, C(2)); 75.4 (d, C(4)); 126.2 (d, C(4')); 129.7 (d, C(3')). Anal. calc. for C12H23NO5S2:
C 44.29, H 7.12; found: C 44.31, H 7.57.
(‡)-(2R,4S,3E)- and ( )-(2S,4S,8E)-1-(Methylsulfonyl)-2-(pent-3-enyl)piperidin-4-ol (18a and 18b, resp.).
Method 1: Using compound 15a, structure 18a could be obtained as described for 17a. Method 2: A 70%
suspension of SMAH in toluene (400 mg) was dried under high vacuum. Under Ar, the residue was dissolved in
anh. diglyme (1.5 ml). To this soln., 17a (50 mg, 0.15 mmol) was added, and the mixture was stirred for 2 h at 608.
Then Na2SO4 soln. was added and the precipitate filtered off, washed with sat. NaCl soln., and extracted with
AcOEt. Drying (MgSO4) and evaporation gave a residue which was purified by CC (silica gel, AcOEt/MeOH/
NH3 6 :1:0.1): 27 mg (72%) of 18a. Rf 0.57 (CH2Cl2/MeOH 20 :1). [a]D
ˆ
34.29 (c ˆ 16.5 mg/ml, MeOH).
1H-NMR (400 MHz, CDCl3): 1.62 ± 1.68 (m, 2 H C(1'), 2 H C(5)); 1.65 (dm, J ˆ 4.7, 3 H C(5')); 1.92 ± 2.08
(m, 2 H C(2'), 2 H C(3)); 2.90 (s, MeSO2); 3.08 (ddd, J ˆ 2.0, 13.3, 15.4, 1 Hax C(6)); 3.83 (ddd, J ˆ 2.0, 4.1,
15.4, 1 Heq C(6)); 3.95 (dddd, J ˆ 4.5, 4.5, 11.3, 11.3, 1 Hax C(2)); 4.10 (dddd, J ˆ 6.2, 6.2, 6.2, 6.2,
1 Heq C(4)); 5.36 ± 5.55 (m, H C(3'),
H
C(4')). 13C-NMR (50 MHz, CDCl3): 17.8 (q, C(5')); 29.4
(t, C(2')); 30.9 (t, C(1')); 34.7 (t, C(5)); 37.6 (t, C(3)); 39.1 (t, C(6)); 40.8 (q, MeSO2N); 53.1 (d, C(2)); 64.5
‡
‡
(d, C(4)); 126.1 (d, C(4')); 129.9 (d, C(3')). MS (1208): 247 (0.6, M ), 178 (100.0, [M C5H9] ), 160 (10,
‡
‡
‡
‡
[178 H2O] , 134 (50, [M Mes H2O Me] ), 55 (44, C4H7 ). HR-MS: 247.1242 (C11H21NO3S , calc.
247.1242). Anal. calc. for C11H21NO3S: C 53.41, H 8.56; found: C 53.19, H 8.47.
As described for 18a, 18b was obtained from 17b. Rf (AcOEt/hexane 1:1) 0.45. [a]D ˆ‡ 17.76 (c ˆ 13 mg/
ml, MeOH). 1H-NMR (400 MHz, CDCl3): 1.54 ± 1.67 (dm, J ˆ 14.0, 1 Hax C(5)); 1.64 (d, J ˆ 6.0, 3 H C(5'));

Helvetica Chimica Acta ± Vol. 82 (1999)
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1.67 ± 1.80 (m, 2 H C(1')); 1.86 (ddd, J ˆ 5.5, 12.0, 12.0, 1 Hax C(3)); 2.02 (ddd, J ˆ 7.0, 7.0, 7.0, 2 H C(2'));
2.10 ± 2.20 (dm, J ˆ 12.0, 1 Heq C(3)); 2.10 ± 2.20 (dm, J ˆ 2.5, 1 Heq C(5)); 2.89 (s, MeSO2); 3.02 (OH); 3.10
(ddd, J ˆ 2.5, 14.0, 14.0, 1 Hax C(6)); 3.88 (dm, J ˆ 14.0, 1 Heq C(6)); 4.15 (dddd, J ˆ 5.5, 5.5, 5.5, <5.5,
1 Heq C(2)); 4.90 (dddm, J ˆ 4.5, 4.5, 12.0, 1 Hax C(4)); 5.35 ± 5.52 (m, H C(3'), H C(4')). 13C-NMR
(50 MHz, CDCl3): 17.8 (q, C(5')); 29.2 (t, C(2')); 30.7 (t, C(1')); 32.3 (t, C(5)); 35.2 (t, C(3)); 38.7 (t, C(6)); 40.8
(q, MeSO2); 52.8 (d, C(2)); 74.7 (d, C(4)); 126.4 (d, C(4')); 129.2 (d, C(3')). Anal. calc. for C11H21NO3S:
C 53.41, H 8.56; found: C 53.26, H 8.53.
(‡)-(2R,4S,3E)- and ( )-(2S,4S,3E)-2-(Pent-3-enyl)piperidin-4-ol (19a and 19b, resp.). The procedure for
the preparation of 19a was similar to the preparation of 18a: 17a (737 mg, 2.3 mmol) was treated with SMAH
(5.9 g) in anh. diglyme (15 ml) as described. However, the temp. was first kept at 608 for 1 h, then increased to
1408 and kept for 12 h. Workup as described for 18 and CC (AcOEt/MeOH/NH3 5 :1:0.1) yielded 289 mg (75%)
of 19a. Rf (AcOEt/MeOH/NH3 5 :1:0.1) 0.08. [a]D
ˆ
2.24 (c ˆ 25 mg/ml, MeOH). 1H-NMR (400 MHz,
CDCl3): 1.48 ± 1.65 (m, 1 H C(1'), 1 H C(3), 1 H C(5)); 1.65 (d, J ˆ 4.9, 3 H C(5')); 1.68 ± 1.77
(m, 1 H C(1'), 1 H C(3), 1 H C(5)); 1.95 ± 2.20 (m, 2 H C(2')); 2.30 ± 2.60 (br., 2 H); 2.86 (ddd, J ˆ 3.0,
4.6, 12.2, 1 Heq C(6)); 2.94 (dddd, J ˆ 2.8, 6.4, 6.4, 10.0, 1 Hax C(2)); 3.04 (ddd, J ˆ 3.1, 12.2, 12.2,
1 Hax C(6)); 4.14 (dddd, J ˆ 3.1, 3.1, 3.1, 3.1, 1 Heq C(4)); 5.37 ± 5.49 (m, H C(3'), H C(4')). 13C-NMR
(50 MHz, CDCl3): 17.9 (q, C(5')); 29.0 (t, C(2')); 33.3 (t, C(1')); 36.4 (t, C(5)); 39.5 (t, C(6)); 40.7 (t, C(3)); 50.1
‡
‡
(d, C(2)); 64.8 (d, C(4)); 125.2 (d, C(4')); 130.8 (d, C(3')). MS (1008): 169 (7, M ), 167 (10, [M H2] ), 152 (7,
‡
‡
‡
‡
‡
[M OH] ), 149 (34, [167 H2O] ), 140 (23, [167 HCN] ), 126 (10, [140 CH2] ), 113 (20, [M C4H7] ),
‡
‡
‡
‡
100 (100, [M C5H9] ), 97 (8, C6H11N , [M H2O and retro-Diels-Alder] ), 82 (20, [100 H2O ), 69 (15,
C5H9) , 56 (41, [97 C3H5] ), 55 (32, C4H7 ). HR-MS: 169.1467 (C10H19NO ; calc. 169.1467). Anal. calc. for
C10H19NO: C 70.96, H 11.31; found: C 70.43, H 11.11.
‡
‡
‡
‡
As described for 19a, 19b was obtained from 17b. Rf (AcOEt/MeOH/NH3 5 :1:0.1) 0.24. [a]D ˆ‡ 7.3 (c ˆ
25 mg/ml, MeOH). 1H-NMR (400 MHz, CDCl3): 1.30 ± 1.50 (m, 1 H C(1'), 1 H C(5)); 1.65 (dd, J ˆ 1.0, 5.5,
3 H C(5')); 1.60 ± 1.80 (m, 1 H C(1'), 1 H C(5)); 1.90 ± 2.00 (m, 2 H C(3)); 2.00 ± 2.10 (m, 2 H C(2'));
2.51 (dddd, J ˆ 2.4, 7.2, 7.2, 12.0, 1 Hax C(2)); 2.62 (ddd, J ˆ 2.5, 12.5, 12.5, 1 Hax C(6)); 3.12 (ddd, J ˆ 2.7, 4.6,
12.5, 1 Heq C(6)); 3.64 (dddd, J ˆ 4.5, 4.5, 11.0, 11.0, 1 Hax C(4)); 5.40 ± 5.46 (m, H C(3'), H C(4')).
13C-NMR (100 MHz, CDCl3): 17.9 (q, C(5')); 29.0 (t, C(2')); 36.2 (t, C(1')); 36.7 (t, C(5)); 42.5 (t, C(6)); 44.7
(t, C(3)); 54.8 (d, C(2)); 69.3 (d, C(4)); 125.2 (d, C(4')); 130.8 (d, C(3')). Anal. calc. for C10H19NO: C 70.96,
H 11.31; found: C 70.81, H 11.24.
REFERENCES
[1] a) D. Niederer, U. Sequin, Helv. Chim. Acta 1990, 73, 2129; b) S. Grabley, P. Hammann, H. Kluge, J. Wink,
J. Antibiot. 1991, 44, 797.
[2] Y. Romeyke, M. Keller, H. Kluge, S. Grabley, P. Hammann, Tetrahedron 1991, 47, 3335; W. Keller-
Schierlein, D. Wuthier, Helv. Chim. Acta 1983, 66, 1253; T. Takeuchi, M. Ishizuka, H. Otai, M. Hamada,
Jpn. Kokai Tokkyo Koho 1989; A. Arnone, R. Cardillo, G. Nasini, O. Vajna de Pava, S. Quaroni,
Phytochemistry 1988, 27, 3611.
[3] M. Mayer, R. Thiericke, J. Org. Chem. 1993, 58, 3486.
[4] W. Oppolzer, S. Siles, R. Snowden, B. Bakker, M. Petrzilka, Tetrahedron 1985, 41, 3497.
[5] H. Hayashi, K. Nakanishi, C. Brandon, J. Marmur, J. Am. Chem. Soc. 1973, 95, 8749; L. Borjesson, C.
Welch, Tetrahedron 1992, 48, 6325.
[6] R. Di Fabio, Gazz. Chim. Ital. 1988, 118, 209.
[7] S. Torii, K. Uneyama, M. Isihara, J. Org. Chem. 1974, 39, 3645; B. Jones, R. Grayshan, J. Chem. Soc., Chem.
Commun. 1970, 741.
[8] D. Seebach, E. Corey, J. Org. Chem. 1975, 40, 231.
[9] E. Corey, B. Erickson, J. Org. Chem. 1971, 36, 3553.
[10] E. Fujita, Y. Nagao, K. Kaneko, Chem. Pharm. Bull. 1978, 26, 3743.
[11] W. Keller-Schierlein, D. Wuthier, Helv. Chim. Acta 1983, 66, 1253.
[12] D. Ryckman, R. Stevens, J. Org. Chem. 1987, 52, 4274; R. Williams, P. Ehrlich, W. Zhai, J. Hendrix, ibid.
1987, 52, 2616; R. Danheiser, J. Morin, E. Salaski, J. Am. Chem. Soc. 1985, 107, 8066.
[13] G. Hawkes, K. Herwig, J. Roberts, J. Org. Chem. 1974, 39, 1017; H. Kalinowski, S. Berger, S. Braun,
ꢀ13C-NMR Spektroskopieꢁ, Thieme Verlag, Stuttgart-New York, 1984.
[14] D. Williams, M. Osterhout, J. Am. Chem. Soc. 1992, 114, 8750.
Received April 10, 1999