Synthesis of two piperidine alkaloids, (-)-deoxoprosopinine and (-)-deoxoprosophylline, from 6-hydroxylated dihydrosphingosine derivatives

Article abstract of DOI:10.1016/j.tetasy.2007.08.028

(-)-Deoxoprosopinine 1 [(2S,3R,6S)-6-dodecyl-2-hydroxymethylpiperidin-3-ol] and (-)-deoxoprosophylline 3 [(2S,3R,6R)-6-dodecyl-2-hydroxymethylpiperidin-3-ol] were synthesized from (6R)- and (6S)-6-mesyloxydihydrosphingosine derivatives 7 and 7′, respectiv

Full text of DOI:10.1016/j.tetasy.2007.08.028

Tetrahedron: Asymmetry 18 (2007) 2104–2107
Synthesis of two piperidine alkaloids, (ꢀ)-deoxoprosopinine and
(ꢀ)-deoxoprosophylline, from 6-hydroxylated
dihydrosphingosine derivativesI
Ken-ichi Fuhshuku and Kenji Mori*
Glycosphingolipid Synthesis Group, Laboratory for Immune Regulation, RIKEN Research Center for Allergy and Immunology,
Hirosawa 2-1, Wako-shi, Saitama 351-0198, Japan
Received 24 July 2007; accepted 23 August 2007
Abstract—(ꢀ)-Deoxoprosopinine 1 [(2S,3R,6S)-6-dodecyl-2-hydroxymethylpiperidin-3-ol] and (ꢀ)-deoxoprosophylline 3 [(2S,3R,6R)-
6-dodecyl-2-hydroxymethylpiperidin-3-ol] were synthesized from (6R)- and (6S)-6-mesyloxydihydrosphingosine derivatives 7 and 70,
respectively, by intramolecular cyclization to generate a piperidine ring.
ꢀ 2007 Published by Elsevier Ltd.
1. Introduction
skin.20 The same C18 carbon skeleton of 1, 3 and 8
would make the present approach especially favourable.
The intermediates 8 and 80 were previously prepared from
(S)-Garner’s aldehyde 921 while the enantiomers 10 and 100
were secured by a lipase-catalyzed asymmetric process.20
An African plant Prosopis africana produces several
2,6-disubstituted piperidin-3-ols as Prosopis alkaloids.2
Their unique structures together with antibiotic and anaes-
thetic properties rendered the alkaloids 1–4 (Scheme 1)
popular synthetic targets. Indeed, there have been at least
17 different syntheses reported of the enantiomers of deoxo-
prosopinine 1 and deoxoprosophylline 3.3–19 These synthe-
ses start from the chiral building blocks of natural (amino
acids,3,7,8,12,16 malic acid,6 vitamin C10 and carbo-
hydrates5,15,18,19) or synthetic origins.4,9,11,13,14,17
2. Results and discussion
Scheme 2 summarizes our synthesis of (ꢀ)-deoxoproso-
pinine 1 and (ꢀ)-deoxoprosophylline 3. Coupling of
(S)-Garner’s aldehyde 9 with (R)-3-tert-butyldimethylsi-
lyl(TBS)oxy-1-pentadecyne 10 was executed as reported
previously to give (4S,10R,40R)-8.20 After removal of
the TBS protecting group of 8, the resulting alkynediol
11 was hydrogenated over a palladium catalyst to give 6-
hydroxylated dihydrosphingosine derivative (4S,10R,40R)-
12. Treatment of 12 with aqueous acetic acid afforded triol
(2S,3R,6R)-13. Protection of the 1,3-diol system of 13 as
benzylidene acetal yielded (2S,4R,5S,30R)-14, which was
mesylated to furnish 7, the precursor for cyclization.
In continuation of our recent work on (+)-carpamic acid 5,
we became interested in synthesizing 1 and 3 by cyclization
of the derivatives of sphingosine 6. Our retrosynthetic anal-
ysis of (ꢀ)-1 and (ꢀ)-3 is shown in Scheme 1. The piperi-
dine alkaloid 1 or 3 could be obtained by cyclization of 7
or 70 to generate a new C–N bond. The 6-mesyloxylated
and protected dihydrosphingosine 7 or 70 would be pre-
pared from the known compound 8 or 80, which served
as the key intermediates for the synthesis of ceramides B,
4, 7 and 8, the 6-hydroxylated new ceramides in human
Treatment of mesylate 7 with sodium hydride in THF
smoothly effected cyclization to give crystalline
(1S,2S,4R,6S)-15 in 89% yield based on 14. Finally, re-
moval of the benzylidene protective group with methanolic
hydrogen chloride was followed by treatment with sodium
q Synthesis of sphingosine relatives, Part 29. For Part 28, see: Ref. 1.
Corresponding author. Fax: +81 48 467 9381; e-mail: kjk-mori@
arion.ocn.ne.jp
*
hydroxide to give (ꢀ)-deoxoprosopinine 1, mp 87–88 ꢁC,
Present address: Department of Biotechnology, Toyama Prefectural
University, Toyama 939-0398, Japan.
24
½aꢁD ¼ ꢀ14:3 (c 0.54, CHCl3). The overall yield of (ꢀ)-1
0957-4166/$ - see front matter ꢀ 2007 Published by Elsevier Ltd.
doi:10.1016/j.tetasy.2007.08.028

K. Fuhshuku, K. Mori / Tetrahedron: Asymmetry 18 (2007) 2104–2107
2105
HO
HO
HO
OH
1'
Ref. 20
b
4
1
O
HO
( )8
( )8
N
H
N
H
4'
( )10
OTBS
( )10
NBoc
X
X
OR
(-)-deoxoprosopinine
(2S,3R,6S)-1 X = H2
(-)-prosopinine
(-)-deoxoprosophylline
(2S,3R,6R)-3 X = H2
(-)-prosophylline
(R)-10
(4S,1'R,4'R)-8 R = TBS
(4S,1'R,4'R)-11 R = H
a
(2S,3R,6S)-2 X = O
(2S,3R,6R)-4 X = O
OH
OH
HO
HO
c
d
( )11
( )10
( )10
HO
O
CO2H
HO
NBoc
OH
NHBoc
OH
( )7
N
H
NH2
(4S,1'R,4'R)-12
(2S,3R,6R)-13
(+)-carpamic acid
5
C18-sphingosine 6
Ph
Ph
2
1
4
Ph
O
O
O
6
( )11
O
O
HO
HO
f
g
O
( )10
N
Boc
*
3
( )10
*
( )11
NHBoc
OR
N
H
NHBoc
OMs
(2S,4R,5S,3'R)-14 R = H
(2S,4R,5S,3'R)-7 R = Ms
(1S,2S,4R,6S)-15
e
1 or 3
7 or 7'
HO
HO
OH
CHO
NBoc
+
( )11
N
H
O
O
*
*
( )10
( )10
OTBS
10 or 10'
NBoc
8 or 8'
OTBS
(2S,3R,6S)-1
Similarly
(S)-Garner's
aldehyde
9
HO
HO
Boc = t-BuOCO- ; Ms = MeSO2- ; TBS = t-Bu(Me)2Si-
( )10
OTBS
(S)-10'
( )11
N
H
Scheme 1. Retrosynthetic analysis of (ꢀ)-deoxoprosopinine 1 and (ꢀ)-
deoxoprosophylline 3.
(2S,3R,6R)-3
was 46% based on 8 (7 steps). In the same manner, (S)-100
Scheme 2. Synthesis of (ꢀ)-deoxoprosopinine 1 and (ꢀ)-deoxoprosoph-
ylline 3. Reagents and conditions: (a) TBAF, THF, 99%; (b) H2, Pd(OH)2/
C, EtOAc, 86%; (c) AcOH–H2O (8:2), 94%; (d) PhCH(OMe)2, PPTS,
CH2Cl2, 89%; (e) MsCl, C5H5N, 0 ꢁC; (f) NaH, THF, reflux, 89% (2
steps); (g) (i) HCl in MeOH; (ii) NaOH, H2O, 72%.
was converted to (ꢀ)-deoxoprosophylline 3, mp 88–89 ꢁC,
24
½aꢁD ¼ ꢀ14:2 (c 0.58, CHCl3). The overall yield of (ꢀ)-3
was 34% based on 80 (7 steps). The IR, 1H and 13C
NMR spectra of our synthetic (ꢀ)-1 and (ꢀ)-3 were identi-
cal to those reported previously.5,9,18
1
spectrometer. H and 13C NMR spectra were recorded on
Jeol AL-270 (270 MHz) and AL-400 (400 MHz) (CHCl3
at dH = 7.26 and dC = 77.00 as an internal standard). Mass
spectra were recorded on JMS-SX102A. Column chromato-
graphy was carried out with Silica Gel 60 (spherical; 100–
210 lm, 37558-79) purchased from Kanto Chemical Co.,
and thin-layer chromatography was carried out with
Merck Silica Gel 60 F254 thin-layer plates (1.05715).
3. Conclusion
A new and efficient synthesis of (ꢀ)-deoxoprosopinine 1
and (ꢀ)-deoxoprosophylline
3 was accomplished by
employing the cyclization of 6-mesyloxydihydrosphingo-
sine derivatives 7 and 70 as the key step. Sphingosine deriv-
atives have proven to be versatile starting materials for the
synthesis of piperidine alkaloids.
4.2. tert-Butyl 4-(10,40-dihydroxyhexadecyl)-2,2-dimethyl-
3-oxazolidinecarboxylate 12 and 120
4. Experimental
4.1. General
4.2.1. (4S,10R,40R)-Isomer 12. To an ice-cooled solution
of (4S,10R,40R)-8 (3.98 g, 7.01 mmol) in dry THF
(56.0 mL), a solution of TBAF (1.0 M in THF, 14.0 mL,
14.0 mmol) was added. The reaction mixture was stirred
for 2 h at room temperature, and diluted with water. The
mixture was extracted with EtOAc. The organic extract
was washed with brine, dried over anhydrous MgSO4 and
concentrated in vacuo. The residue was purified by silica
All melting points (mp) are uncorrected. Refractive indices
(nD) were measured on an Atago 1T refractometer. Optical
rotation values were measured on a Jasco DIP-1010 instru-
ment. IR spectra were recorded on Jasco FT/IR-460 plus

2106
K. Fuhshuku, K. Mori / Tetrahedron: Asymmetry 18 (2007) 2104–2107
gel column chromatography (100 g). Elution with hexane–
EtOAc (10:1 to 2:1) afforded (4S,10R,40R)-11 (3.16 g, 99%).
This compound was immediately employed for the next
step without further purification. To a suspension of
Pd(OH)2 (0.275 g, 20% on carbon) in EtOAc (20.0 mL),
11 (2.72 g, 6.00 mmol) was added. The reaction mixture
was vigorously stirred for 7 days at room temperature
under a H2 atmosphere, and filtered through a Celite
pad. The filter cake was washed with EtOAc and concen-
trated in vacuo. The residue was purified by silica gel
column chromatography (150 g). Elution with hexane–
EtOAc (10:1 to 2:1) afforded 12 (2.37 g, 86%), mp 62.0–
4.4. 5-tert-Butoxycarbamido-4-(30-hydroxypentadecyl)-
2-phenyl-1,3-dioxacyclohexane 14 and 140
4.4.1. (2S,4R,5S,30R)-Isomer 14. A mixture of (2S,3R,
6R)-13 (512 mg, 1.23 mmol), PhCH(OMe)2 (368 lL,
2.45 mmol), PPTS (340 mg, 1.35 mmol) and CH2Cl2
(12.0 mL) was stirred for 24 h at room temperature and
neutralized with a saturated aqueous NaHCO3 solution.
The mixture was extracted with Et2O. The organic extract
was successively washed with
a saturated aqueous
NaHCO3 solution, water and brine, dried over anhydrous
MgSO4 and concentrated in vacuo. The residue was puri-
fied by silica gel column chromatography (25 g). Elution
with hexane–EtOAc (10:1 to 3:1) afforded 14 (552 mg,
63.0 ꢁC (colourless powder from hexane–EtOAc);
26
½aꢁD ¼ ꢀ16:8 (c 1.02, CHCl3); IR (KBr) mmax 3400, 1697,
1676; dH (270 MHz, CDCl3): 0.88 (3H, t, J 6.6), 1.25–
1.75 (41H, m), 2.80–2.97 (2H, m), 3.52–4.42 (5H, m); Anal.
Calcd for C26H51NO5: C, 68.23; H, 11.23; N, 3.06. Found:
C, 68.05; H, 11.41; N, 3.05.
89%), mp 120.5–121.0 ꢁC (colourless powder from
26
hexane–EtOAc); ½aꢁD ¼ þ25:0 (c 0.54, CHCl3); IR (KBr)
mmax 3346, 1683, 1531; dH (270 MHz, CDCl3): 0.88 (3H, t,
J 6.6), 1.25 (22H, m), 1.46 (9H, s), 1.55–2.00 (5H, m),
3.46–3.73 (4H, m), 4.30 (2H, m), 5.45 (1H, s), 7.30–7.40
(3H, m), 7.46–7.49 (2H, m); dC (67.5 MHz, CDCl3): 14.2,
22.8, 25.8, 28.0, 28.4, 28.5, 29.4, 29.71, 29.74, 32.0, 32.9,
37.5, 47.4, 69.9, 71.8, 80.0, 81.3, 101.0, 126.0, 128.2,
128.8, 137.6, 155.0; Anal. Calcd for C30H51NO5: C,
71.25; H, 10.16; N, 2.77. Found: C, 71.02; H, 10.16; N,
2.72.
4.2.2. (4S,10R,40S)-Isomer 120. In the same manner,
(4S,10R,40S)-80 (3.12 g, 5.49 mmol) yielded 1.93 g (78%)
of 120, mp 106.5–107.5 ꢁC (colourless powder from hex-
26
ane–EtOAc); ½aꢁD ¼ ꢀ15:1 (c 1.03, CHCl3); IR (KBr) mmax
3302, 1694; dH (270 MHz, CDCl3): 0.88 (3H, t, J 6.6), 1.25–
1.72 (41H, m), 3.24 (2H, m), 3.57 (2H, m) 3.73–4.43 (3H,
m); Anal. Calcd for C26H51NO5: C, 68.23; H, 11.23; N,
3.06. Found: C, 68.00; H, 11.39; N, 3.00.
4.4.2. (2S,4R,5S,30S)-Isomer 140. In the same manner,
(2S,3R,6S)-130 (612 mg, 1.47 mmol) yielded 646 mg (87%)
of 140, mp 92.0–93.0 ꢁC (colourless powder from hexane–
4.3. 2-tert-Butoxycarbamidoctadecane-1,3,6-triol 13 and 130
26
EtOAc); ½aꢁD ¼ þ19:7 (c 0.54, CHCl3); IR (KBr) mmax
3355, 1685, 1525; dH (270 MHz, CDCl3): 0.88 (3H, t, J
6.6), 1.25 (22H, m), 1.45 (9H, s), 1.59–1.91 (5H, m),
3.47–3.76 (4H, m), 4.30 (2H, m), 5.45 (1H, s), 7.29–7.40
(3H, m), 7.45–7.49 (2H, m); dC (67.5 MHz, CDCl3): 14.2,
22.8, 25.8, 27.8, 28.4, 28.5, 29.4, 29.72, 29.74, 29.8, 32.0,
32.6, 37.8, 46.9, 69.9, 71.5, 80.1, 80.9, 101.1, 126.0, 128.2,
128.9, 137.6, 155.1; Anal. Calcd for C30H51NO5: C,
71.25; H, 10.16; N, 2.77. Found: C, 71.23; H, 10.21; N,
2.67.
4.3.1. (2S,3R,6R)-Isomer 13. A mixture of (4S,10R,40R)-
12 (602 mg, 1.32 mmol) and AcOH (80% in water,
26.0 mL) was stirred for 24 h at room temperature and
neutralized with a saturated aqueous NaHCO3 solution.
The mixture was extracted with CHCl3. The organic
extract was washed with a saturated aqueous NaHCO3
solution, dried over anhydrous Na2SO4 and concentrated
in vacuo. The residue was purified by silica gel column
chromatography (30 g). Elution with CHCl3–MeOH (60:1
to 20:1) afforded 13 (514 mg, 94%), mp 105.0–106.0 ꢁC
4.5. tert-Butyl 6-dodecyl-2-phenylhexahydro[1,3]dioxino-
[5,4-b]pyridine-5-carboxylate 15 and 150
26
(colourless powder from CHCl3); ½aꢁD ¼ þ3:3 (c 0.53,
CHCl3); IR (KBr) mmax 3353, 1669, 1529; dH (270 MHz,
CDCl3): 0.88 (3H, t, J 6.6), 1.26 (20H, m), 1.45 (9H, s),
1.39–1.74 (6H, m), 3.10 (3H, br s), 3.53 (1H, br s), 3.69–
3.80 (3H, m), 3.99 (1H, m), 5.37 (1H, br s); dC
(67.5 MHz, CDCl3): 14.2, 22.8, 25.9, 28.5, 29.4, 29.7,
30.1, 32.0, 33.2, 37.2, 55.0, 62.7, 71.9, 73.9, 79.8, 155.9;
Anal. Calcd for C23H47NO5: C, 66.15; H, 11.34; N, 3.35.
Found: C, 65.91; H, 11.52; N, 3.33.
4.5.1. (1S,2S,4R,6S)-Isomer 15. To an ice-cooled solution
of (2S,4R,5S,30R)-14 (552 mg, 1.09 mmol) in dry pyridine
(9.0 mL), MsCl (340 lL, 4.39 mmol) was added in one por-
tion. The reaction mixture was stirred for 48 h at 4 ꢁC and
diluted with water. The mixture was extracted with Et2O.
The organic extract was washed with a saturated aqueous
CuSO4 solution, water, a saturated aqueous NaHCO3 solu-
tion and brine, dried over anhydrous MgSO4 concentrated
in vacuo. The residual 7 was dissolved in dry THF
(10.0 mL), cooled to 0 ꢁC, and NaH added (60% in mineral
oil, 135 mg, 3.38 mmol). The reaction mixture was stirred
4.3.2. (2S,3R,6R)-Isomer 130. In the same manner,
(4S,10R,40S)-120 (298 mg, 0.651 mmol) yielded 252 mg
(93%) of 130, mp 98.0–99.0 ꢁC (colourless powder from
26
CHCl3); ½aꢁ ¼ þ5:8 (c 0.53, CHCl3); IR (KBr) mmax
3364, 1694, D1567; dH (270 MHz, CDCl3): 0.87 (3H, t, J
6.6), 1.25 (20H, m), 1.44 (9H, s), 1.38–1.75 (6H, m), 3.50
(1H, br s), 3.59–3.80 (6H, m), 3.96 (1H, m), 5.45 (1H, br
s); dC (67.5 MHz, CDCl3): 14.2, 22.8, 25.8, 28.5, 29.4,
29.7, 29.8, 31.6, 32.0, 34.4, 37.9, 55.3, 62.5, 72.6, 74.3,
79.7, 156.0; Anal. Calcd for C23H47NO5: C, 66.15; H,
11.34; N, 3.35. Found: C, 66.04; H, 11.54; N, 3.31.
at reflux for 48 h and diluted with water. The mixture
was extracted with Et2O. The organic extract was washed
with brine, dried over anhydrous MgSO4 and concentrated
in vacuo. The residue was purified by silica gel column
chromatography (30 g). Elution with hexane–EtOAc (30:1
to 10:1) afforded 15 (474 mg, 89%, 2 steps), mp 81.0–
82.0 ꢁC (colourless needles from hexane–EtOAc);
26
½aꢁD ¼ ꢀ24:3 (c 0.54, CHCl3); IR (KBr) mmax 1699; dH

K. Fuhshuku, K. Mori / Tetrahedron: Asymmetry 18 (2007) 2104–2107
2107
(270 MHz, CDCl3): 0.89 (3H, t, J 6.6), 1.27 (22H, m), 1.46
(9H, s), 1.41–1.98 (4H, m), 3.33 (1H, ddd, J 4.6, 9.9, 9.9),
3.67 (1H, ddd, J 4.9, 9.6, 9.6), 4.32 (1H, br s), 4.45 (1H,
dd, J 10.9, 10.9), 4.83 (1H, dd, J 4.0, 11.2), 5.57 (1H, s),
7.29–7.40 (3H, m), 7.47–7.52 (2H, m); dC (67.5 MHz,
CDCl3): 14.2, 22.8, 26.0, 26.4, 26.5, 28.5, 29.4, 29.6, 29.7,
32.0, 52.3, 52.7, 70.7, 78.3, 80.1, 101.1, 126.0, 128.2,
128.8, 137.9, 154.6; HRMS (FAB): [M+H]+ calcd for
C30H49NO4þ, 487.3662; found, 487.3660.
2.52–2.59 (2H, m, 2, 6-H), 3.46 (1H, ddd, J 4.6, 9.1, 10.6,
3-H), 3.70 (1H, dd, J 5.3, 10.9, 2-CHH–OH), 3.83 (1H,
dd, J 4.8, 10.6, 2-CHH–OH); dC (100 MHz, CDCl3):
14.2, 22.8, 26.3, 29.4, 29.69, 29.74, 29.9, 31.3, 32.0, 34.0,
36.7, 56.0, 63.2, 64.8, 70.8; HRMS (FAB): [M+H]+ calcd
for C18H37NO2þ, 299.2824; found, 299.2824.
Acknowledgement
4.5.2. (1S,2S,4R,6R)-Isomer 150. In the same manner,
(2S,4R,5S,30S)-14 (304 mg, 0.601 mmol) yielded 201 mg
Our thanks are due to Dr. Y. Masuda for his kind supply
of the starting materials, (R)-10 and (S)-100.
(69%, 2 steps) of 150 as a colourless oil, n2D6 ¼ 1:4960;
26
½aꢁD ¼ ꢀ24:3 (c 0.54, CHCl3); IR (KBr) mmax 1696; dH
(270 MHz, CDCl3): 0.89 (3H, t, J 6.6), 1.27 (20H, m),
1.48 (9H, s), 1.44–1.79 (4H, m), 2.01–2.15 (2H, m), 3.51–
3.65 (2H, m), 4.01 (1H, m), 4.16 (1H, ddd, J 5.6, 10.2,
10.2), 4.92 (1H, m), 5.57 (1H, s), 7.30–7.41 (3H, m),
7.48–7.52 (2H, m); dC (67.5 MHz, CDCl3): 14.7, 23.2,
24.3, 24.6, 27.7, 29.0, 29.9, 30.13, 30.17, 30.21, 32.4, 39.0,
52.3, 54.3, 72.2, 76.5, 80.6, 102.4, 126.6, 128.7, 129.3,
138.2, 156.3; HRMS (FAB): [M+H]+ calcd for
C30H49NO4þ, 487.3662; found, 487.3665.
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4.6.1. (2S,3R,6S)-Isomer, (ꢀ)-deoxoprosopinine 1. A mix-
ture of (1S,2S,4R,6S)-15 (77.4 mg, 0.159 mmol) and dry
HCl (10% in MeOH, 3.2 mL) was stirred for 48 h at room
temperature and concentrated in vacuo. The residue was
mixed with a solution of NaOH (15% in water, 3.2 mL)
and stirred for 3 h at room temperature. The mixture was
extracted with CH2Cl2, dried over MgSO4 and concen-
trated in vacuo. The residue was purified by silica gel col-
umn chromatography (2 g). Elution with toluene–EtOH
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72%), mp 87.0–88.0 ꢁC (colourless needles from CHCl3)
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[synthesis of (+)-30].
24
(Ref. 5: mp 89.0–89.5 ꢁC); ½aꢁD ¼ ꢀ14:3 (c 0.54, CHCl3)
21:5
11. Yang, C.; Liao, L.; Xu, Y.; Zhang, H.; Xia, P.; Zhou, W.-S.
Tetrahedron: Asymmetry 1999, 10, 2311–2318, [synthesis of
(+)-30].
{Ref. 5: ½aꢁD ¼ ꢀ15:9 (c 0.28, CHCl3)}; IR (KBr) mmax
3372, 3114, 2920, 2849, 1451, 1055; dH (400 MHz, CDCl3):
0.88 (3H, t, J 6.5, Me), 1.26 (22H, m, 10, 20, 30, 40, 50, 60, 70,
80, 90, 100, 110-H2), 1.45–1.79 (4H, m, 4, 5-H2), 2.08 (3H, br
s, OH · 2, NH), 2.77 (1H, m, 6-H), 2.88 (1H, m, 2-H), 3.54
(1H, m, 3-H), 3.61 (1H, dd, J 5.6, 10.6, 2-CHH–OH), 3.66
(1H, dd, J 8.0, 10.4, 2-CHH–OH); dC (100 MHz, CDCl3):
14.2, 22.8, 26.5, 27.4, 28.7, 29.4, 29.7, 29.8, 32.0, 34.0,
49.8, 58.0, 62.3, 68.1; HRMS (FAB): [M+H]+ calcd for
C18H37NO2þ, 299.2824; found, 299.2826.
12. Datta, A.; Kumar, J. S. R.; Roy, S. Tetrahedron 2001, 57,
1169–1173, [synthesis of (ꢀ)-3].
13. Comins, D. L.; Sandelier, M. J.; Grillo, T. A. J. Org. Chem.
2001, 66, 6829–6832, [synthesis of (+)-10].
14. Ma, N.; Ma, D. Tetrahedron: Asymmetry 2003, 14, 1403–
1406, [synthesis of (ꢀ)-3].
15. Dransfield, P. J.; Gore, P. M.; Prokes, I.; Shipman, M.;
Slawin, A. M. Z. Org. Biomol. Chem. 2003, 1, 2723–2733,
[synthesis of (+)-30].
16. Jourdant, A.; Zhu, J. Heterocycles 2004, 64, 249–259,
[synthesis of (ꢀ)-3].
4.6.2. (2S,3R,6R)-Isomer, (ꢀ)-deoxoprosophylline 3. In
the same manner, (1S,2S,4R,6R)-150 (80.4 mg, 0.165
17. Chavan, S. P.; Praveen, C. Tetrahedron Lett. 2004, 45, 421–
423, [synthesis of (ꢀ)-3 and (+)-30].
mmol) yielded 38.6 mg (78%) of 3, mp 88.0–89.0 ꢁC (col-
24
ourless needles from CHCl3) (Ref. 5: mp 90.5 ꢁC); ½aꢁD
¼
18. Wang, Q.; Sasaki, N. A. J. Org. Chem. 2004, 69, 4767–4773,
[synthesis of (+)-10].
19. Tzanetou, E. N.; Kasiotis, K. M.; Magiatis, P.; Haroutou-
nian, S. A. Molecules 2007, 12, 735–744, [synthesis of (+)-30].
20. Masuda, Y.; Mori, K. Eur. J. Org. Chem. 2005, 4789–
4800.
21
ꢀ14:2 (c 0.58, CHCl3) {Ref. 5: ½aꢁD ¼ ꢀ13:9 (c 0.25,
CHCl3)}; IR (KBr) mmax 3267, 2922, 2850, 1468, 1059; dH
(400 MHz, CDCl3): 0.88 (3H, t, J 6.5, Me), 1.12 (1H, dddd,
J 3.4, 13.3, 13.3, 13.3, 5-H), 1.25–1.43 (23H, m, 4-H, 10, 20,
30, 40, 50, 60, 70, 80, 90, 100, 110-H2), 1.74 (1H, m, 5-H), 2.04
(1H, dd, J 3.6, 12.3, 4-H), 2.19 (3H, br s, OH · 2, NH),
21. Garner, P.; Park, J. M. J. Org. Chem. 1987, 52, 2361–2364.