A concise total synthesis of (+)-deoxocassine and (-)-deoxoprosophylline from d-xylose

Article abstract of DOI:10.1016/j.tetlet.2012.06.058

A concise total synthesis of (+)-deoxocassine (1) and (-)- deoxoprosophylline (2) has been achieved for the first time from d-xylose. The key steps involved in these synthesis are alkyl Grignard reaction, S _N2 substitution of mesylate by azide,

Full text of DOI:10.1016/j.tetlet.2012.06.058

Tetrahedron Letters 53 (2012) 4551–4554
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A concise total synthesis of (+)-deoxocassine and (ꢀ)-deoxoprosophylline from
D-xylose
⇑
Ch. Kishore, A. Srinivas Reddy, J. S. Yadav, B. V. Subba Reddy
Natural products Chemistry, Indian Institute of Chemical Technology, Hyderabad 500 007, India
a r t i c l e i n f o
a b s t r a c t
Article history:
A concise total synthesis of (+)-deoxocassine (1) and (ꢀ)-deoxoprosophylline (2) has been achieved for
Received 9 April 2012
Revised 9 June 2012
Accepted 12 June 2012
Available online 19 June 2012
the first time from D-xylose. The key steps involved in these synthesis are alkyl Grignard reaction, SN2
substitution of mesylate by azide, Wittig reaction, and reductive amination.
Ó 2012 Elsevier Ltd. All rights reserved.
Keywords:
Piperidine alkaloids
D-Xylose
Natural products
SN2 substitution
Reductive amination
2,6-Disubstituted piperidin-3-ols are the most abundantly
found alcohols in nature and have attracted much attention due
to their ability to mimic carbohydrate substrates in a variety of
enzymatic processes.1 Due to their ability of selective inhibition
of enzymes which are involved in processing of glycoproteins,
piperidine alkaloids have been perceived as important targets in
the study of biochemical pathways.2 Among them, prosophylline,
deoxoprosophylline, and cassine are medicinally important be-
cause of their potent anesthetic, analgesic, and antibiotic proper-
ties.3 Deoxoprosophylline and cassine alkaloids (Fig. 1) have been
isolated from the plants prospis and cassia, respectively. Since their
discovery in the 1960s, many efforts have been devoted to the syn-
thesis of these alkaloids and their derivatives such as deoxocassine
(1)4 and deoxoprosophylline (2).5
in the literature.6a Oxidative cleavage of 6 gave the hydroxy alde-
hyde 7.6b The chloroketone 4 was prepared by Swern oxidation
of 2-halo-1-terdecanol 3 which was in turn prepared by ring-
opening of epichlorohydrin with undecylmagnesium bromide.
Treatment of chloroketone 4 with one equivalent of triphenylphos-
phine in chloroform under reflux conditions gave the Wittig salt
which was then converted into a stable ylide 5 by treating with
20% NaOH solution (Scheme 2).7
Wittig olefination of 7 with ylide 5 in toluene under reflux con-
ditions gave the
a,b-unsaturated ketone 8 with trans-selectivity
which was confirmed by 1H NMR spectroscopy. Reduction of olefin
8 with 10% Pd/CaCO3/C under hydrogen atmosphere in methanol
gave the saturated ketone 9. Mesylation of hydroxyl group of 9
with methanesulfonyl chloride in the presence of triethylamine
followed by treatment with sodium azide under reflux conditions
gave the corresponding azide 11. Reductive amination of azide
In view of their potential use in medicinal chemistry, we have
devised a novel synthetic route to the total synthesis of deoxocas-
sine (1), a simple analogue of natural alkaloid cassine from the
inexpensive
D-xylose. By applying a similar strategy, we also
achieved the total synthesis of deoxoprosophylline (2).
In our retrosynthetic analysis, we envisaged that the target mol-
ecule (1) could be synthesized from azidoketone 11 which could in
HO
N
H
turn be prepared from
a,b-unsaturated ketone 8. Compound 8
(+)-Deoxocassine(1)
could easily be prepared from 3-hydroxyaldehyde 7 and an ylide
5 as shown in Scheme 1.
The synthesis of (1) began from D-xylose. Accordingly, D-xylose
was converted into compound 6 using known procedures reported
HO
HO
N
H
(-)-Deoxoprosophylline (2)
⇑
Corresponding author. Fax: +91 40 27160512.
E-mail address: basireddy@iict.res.in (B.V. Subba Reddy).
Figure 1. (+)-Deoxocassine (1) and (ꢀ)-deoxoprosophylline (2).
0040-4039/$ - see front matter Ó 2012 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2012.06.058

4552
Ch. Kishore et al. / Tetrahedron Letters 53 (2012) 4551–4554
HO
HO
HO
N
N
H
H
(2)
O
(1)
OH
O
OH
BnO
OBn
OBn
OH
OH
O
O
BnO
Ph3P
+
Ph3P
O
+
O
OBn
OBn
1-Bromoundecane
Scheme 1. Retrosynthetic analysis of (+)-deoxocassine (1).
1-Bromoundecane
D-Xylose
D-Xylose
Scheme 4. Retrosynthetic analysis of (ꢀ)-deoxoprosophylline (2).
and subsequent debenzylation were achieved simultaneously in
the presence of 10% Pd(OH)2/C under hydrogen atmosphere to pro-
duce the enantiopure (+)-deoxocassine (1) in 80% yield (Scheme 3).
Next, we extended this approach to the total synthesis of (ꢀ)-
deoxoprosophylline (2). Retrosynthetic analysis of deoxoprosoph-
ylline is shown in Scheme 4.
O
OH
H5IO6
OH
BnO
BnO
D-Xylose
O
EtOAc/H2O
rt
OH
BnO
OBn
13
12
Accordingly,
D-xylose was converted into 2,4-dibenzyloxy-3-
OH
O
5
Pd/C/CaCO3
H2, MeOH
BnO
hydroxybutanal 13 using known procedures reported in the litera-
( )
10
ture.8,4 The coupling of aldehyde 13 with ylide 5 gave the olefin
Toluene, reflux
OBn
14
75% from 12
OH
OH
O
OMs
O
n-C11H23MgBr
(COCl)2, DMSO
MsCl, Et3N
O
Cl
BnO
BnO
( )
Cl
( )
( )
10
10
DCM
0 °C-rt
Et3N, DCM, -78 °C
80%, 2 steps
10
CuCN, THF
-10 °C
OBn
15
OBn
16
3
O
O
PPh3
CHCl3, reflux
85%
N3
O
Cl
PPh3
HO
( )10
Pd(OH)2/C
NaN3
( )10
BnO
( )10
reflux
DMF,
70%, 2steps
aq.NaOH,
H2, MeOH HO
80%
4
5
( )10
N
OBn
H
17
(2)
Scheme 2. Preparation of a stable ylide 5.
Scheme 5. Synthesis of (ꢀ)-deoxoprosophylline (2).
14.9 Reduction of olefin 14 followed by mesylation of a secondary
hydroxyl group and then substitution of a resulting mesylate with
sodium azide gave the compound 17 in 70% yield over three steps.
Treatment of compound 17 with 10% Pd(OH)2/C under hydrogen
OH
O
OH
H5IO6
D-Xylose
O
EtOAc/H2O
rt
OH
OBn
7
BnO
6
atmosphere gave the enantiopure deoxoprosophylline
2
(Scheme 5). The spectral data for the target molecule 14c,g and
24b are in good agreement with the data reported in literature.10
Our synthetic approach provides higher overall yield (29% for
deoxoprosophylline and 19% for deoxocassine), from a readily
OH
O
OH
O
5
Pd/C/CaCO3
H2, MeOH
( )
( )10
Toluene, reflux
10
OBn
OBn
75% from 6
accessible starting material,
D-xylose. In our approach, most of
8
9
the steps are highly stereoselective affording a single isomer,
which can be used for making both target molecules in gram scale.
In summary, we have demonstrated a short and efficient syn-
thetic route for the total synthesis of deoxocassine and deoxopro-
N3
O
OMs
O
MsCl, Et3N
NaN3
( )
( )
10
10
reflux
DMF,
0°C- rt
DCM,
OBn
OBn
10
sophylline starting from D-xylose as a source of chirality. The key
70%, 2steps
11
steps involved in this synthesis are Grignard reaction, Wittig olef-
ination, and one-pot reductive cyclization with concomitant
debenzylation.
HO
10% Pd(OH)2/C
H2, MeOH
80%
N
Acknowledgements
H
(1)
Scheme 3. Synthesis of (+)-deoxocassine (1).
Ch.K thanks UGC and A.S.R. thanks CSIR, New Delhi, India for the
award of fellowships.

Ch. Kishore et al. / Tetrahedron Letters 53 (2012) 4551–4554
4553
Removal of the solvent followed by purification on silica gel column
Supplementary data
chromatography (n-hexane/EtOAc, 9:1) afforded the pure product, 8; 300 mg.
Yield: 75%. ½a 2D0
ꢂ
+11.5 (c 0.15, CHCl3) 1H NMR (500 MHz, CDCl3): d 0.88 (t,
.
Supplementary data associated with this article can be found, in
the online version, at http://dx.doi.org/10.1016/j.tetlet.2012.06. 058.
J = 6.9 Hz, 3H), 1.13 (d, J = 6.9 Hz, 3H), 1.26 (br s, 18H), 1.61 (t, J = 6.9 Hz, 2H),
2.54 (t, J = 6.9 Hz, 2H), 3.85 (m, 1H), 3.93 (m, 1H), 4.41 (d, J = 11.8 Hz, 1H), 4.62
(d, J = 11.8 Hz, 1H), 6.22 (d, J = 16.8 Hz, 1H), 6.67 (dd, J = 15.8, 6.9 Hz, 1H), 7.27–
7.33 (m, 5H); 13C NMR (75 MHz, CDCl3): d 14.2, 18.1, 22.8, 24.1, 29.4, 29.8, 32.0,
40.4, 69.3, 77.1, 82.5, 127.8, 127.9, 128.0, 128.6, 141.2. 209.6. ESI-MS: m/z:
411(M+Na).
References and notes
(2R,3S)-3-(Benzyloxy)-2-hydroxyoctadecan-6-one (9): To a stirred solution of
compound 8 (270 mg, 0.70 mmol) in ethyl acetate was added 5% Pd/CaCO3
(50 mg). The resulting mixture was stirred under hydrogen atmosphere for 4–
5 h. Upon completion, the mixture was filtered through the bed of Celite and
washed with EtOAc. The solvent was evaporated to get the crude product 9
which was used for the next step without further purification. 240 mg, in
1. (a) Numata, A.; Ibuka, T. In The Alkaloids; Brossi, A., Ed.; Academic Press: New
York, 1987; Vol. 31, (b) Strunz, G. M.; Findlay, J. A. In The Alkaloids; Brossi, A.,
Ed.; Academic Press: New York, 1985; Vol. 26, p 89.
2. (a) Asano, N.; Nash, R. J.; Molyneux, R. J.; Fleet, G. W. J. Tetrahedron: Asymmetry
2000, 11, 1645; (b) El Ashry, E. S. H.; Rashed, N.; Shobier, A. H. S. Pharmazie
2000, 55, 331.
quantitative yield. Colorless liquid. ½a D20
ꢂ
+68 (c 0.1, CHCl3).1H NMR (300 MHz,
3. (a) Sansores-Peraza, P.; Rosado-allado, M.; Brito-Loeza, W.; Mena-Rejon, G. J.;
Quijano, L. Fitoteirapia 2000, 71, 690; (b) Ahmad, A.; Khan, K. A.; Ahmad, V. U.;
Qazi, S. Planta Med. 1986, 4, 285; (c) Astudillo, S. L.; Jurgens, S. K.; Schmeda-
Hirschmann, G.; Riffith, G. A.; Holt, D. H.; Jenkins, P. R. Planta Med. 1999, 65,
161; (d) Aguinaldo, A. M.; Read, R. W. Phytochemistry 1990, 29, 2309.
4. (a) Noël, R.; Vanucci-Bacqué, C.; Fargeau-Bellassoued, M.-C.; Lhommet, G. Eur. J.
Org. Chem. 2007, 476; (b) Andrés, J. M.; Pedrosa, R.; Pérez-Encabo, A. Eur. J. Org.
Chem. 2007, 1803; (c) Cassidy, M. P.; Padwa, A. Org. Lett. 2004, 6, 4029; (d) Rao,
V. K. S.; Kumar, P. Tetrahedron 2006, 62, 9942; (e) Raghavan, S.; Mustafa, S.
Tetrahedron 2008, 64, 10055; (f) Ma, D.; Ma, N. Tetrahedron Lett. 2003, 44, 3963;
(g) Leverett, C. A.; Cassidy, M. P.; Padwa, A. J. Org. Chem. 2006, 71, 8591; (h) Liu,
L.-X.; Ruan, Y.-P.; Guo, Z.-Q.; Huang, P.-Q. J. Org. Chem. 2004, 69, 6001.
5. (a) Abraham, E.; Brock, E. A.; Candela-Lena, J. I.; Davies, S. G.; Georgiou, M.;
Nicholson, R. L.; Perkins, J. H.; Roberts, P. M.; Russell, A. J.; Sánchez-Fernández,
E. M.; Scott, P. M.; Smith, A. D.; Thomson, J. E. Org. Biomol. Chem. 2008, 6, 1665;
(b) Liu, R.-C.; Wei, J.-H.; Wei, B.-G.; Lin, G.-Q. Tetrahedron: Asymmetry 2008, 19,
2731; (c) Ojima, I.; Vidal, E. S. J. Org. Chem. 1998, 63, 7999; (d) Fuhshuku, K.;
Mori, K. Tetrahedron: Asymmetry 2007, 18, 2104; (e) Datta, A.; Kumar, J. S. R.;
Roy, S. Tetrahedron 2001, 57, 1169; (f) Jourdant, A.; Zhu, J. Tetrahedron Lett.
2001, 42, 3431; (g) Chavan, S. P.; Praveen, C. Tetrahedron Lett. 2004, 45, 421; (h)
Arévalo-García, E. B.; Colmenares, J. C. Tetrahedron Lett. 2008, 49, 6972; (i)
Kokatla, H. P.; Lahiri, R.; Kancharla, P. K.; Doddi, V. R.; Vankar, Y. D. J. Org. Chem.
2010, 75, 4608; (j) Saitoh, Y.; Moriyama, Y.; Takahashi, T. Tetrahedron Lett.
1980, 21, 75; (k) Dransfield, P. J.; Gore, P. M.; Prokes, I.; Shipman, M.; Slawin, A.
M. Z. Org. Biomol. Chem. 2003, 1, 2723; (l) Ma, N.; Ma, D. Tetrahedron:
Asymmetry 2003, 14, 1403.
CDCl3): d 0.88 (t, J = 6.9 Hz, 3H), 1.20 (d, J = 6.4 Hz, 3H), 1.26 (br s, 18H), 1.49–
1.56 (m, 2H), 1.81–1.87 (m, 2H), 2.31–2.41 (m, 2H), 2.45–2.58 (m, 2H), 3.29–
3.35 (m, 1H), 3.84–3.94 (m, 1H), 4.46–4.64 (m, 2H), 7.30–7.37 (m, 5H); 13C
NMR (75 MHz, CDCl3): d 14.1, 18.0, 21.9, 22.6, 23.8, 29.2, 29.3, 29.4, 29.6, 31.9,
37.9, 42.8, 67.8, 67.4, 71.8, 81.7, 127.7, 127.8, 128.3, 128.4, 211.7. ESI-MS: m/z:
413 [M+Na]; HRMS calcd for C25H42O3Na 413.30262, found: 413.30217.
(2R,3S)-3-(Benzyloxy)-6-oxooctadecan-2-yl-methanesulfonate (10): To a solution
of alcohol 9 (250 mg, 0.67 mmol) in dry CH2Cl2 was added Et3N (0.186 mL,
1.34 mmol) at 0 °C. To this solution, mesyl chloride (0.05 ml, 0.68 mmol) was
added and the mixture was allowed to stir at room temperature. After 2 h, the
mixture was quenched with water and extracted with ethyl acetate. The
organic layer was dried over anhydrous Na2SO4. Removal of the solvent
followed by purification on silica gel column chromatography (n-hexane/
EtOAc, 9:1) gave the mesylate 10. Liquid ½a D20
ꢂ
ꢀ15 (c 0.3, CHCl3) 1H NMR
(500 MHz, CDCl3): d 0.88 (t, J = 6.9 Hz, 3H), 1.25 (m, 18H), 1.43 (d, J = 7.0 Hz,
3H), 1.47–1.53 (m, 2H), 1.69–1.76 (m, 1H), 1.84–1.91 (m, 1H), 2.25–2.34 (m,
2H), 2.40–2.53 (m, 2H), 3.0 (s, 3H), 3.49–3.52 (m, 1H), 4.45 (d, J = 11.0 Hz, 1H),
4.72 (d, J = 11.5 Hz, 1H), 4.96–5.01 (m, 1H), 7.30–7.37 (m, 5H); 13C NMR
(75 MHz, CDCl3): d 14.0, 16.8, 22.6, 23.3, 23.7, 29.2, 29.3, 29.4, 29.6, 31.8, 37.8,
37.9, 38.7, 42.8, 72.4, 79.6, 79.8, 127.9, 128.1, 128.2, 128.4, 200.0. ESI-MS: m/z:
491 [M+Na]; HRMS calcd for C26H44O5SNa 491.2801, found: 491.2799.
(2S,3S)-2-Azido-3-(benzyloxy)octadecan-6-one (11): To
a stirred solution of
compound 10 (297 mg, 0.63 mmol) was added a solution of sodium azide
(165 mg, 2.5 mmol) in DMF. The mixture was stirred at 90 °C for 8–9 h. The
reaction mixture was diluted with water and extracted with ether and dried
over Na2SO4 and the solvent was evaporated to get the crude product which
was further purified by column chromatography (n-hexane/EtOAc, 19:1) that
6. (a) Spewha, M. Helv. Chim. Acta. 1993, 1832; (b) Sharma, G. V. M.; Krishna, D.
Tetrahedron: Asymmetry 2008, 19, 2092.
7. Corey, E. J.; Su, W.-G. Tetrahedron Lett. 1984, 25, 5119.
8. Kurihara, K.; Sugimoto, T.; Saitoh, Y.; Igarashi, Y.; Hirota, H.; Moriyama, Y.;
Tsuyuki, T.; Takahashi, T. Bull. Chem. Soc. Jpn. 1985, 58, 3337.
gave azidoketone 11. 70% yield from 10, 180 mg, colorless liquid. ½a D20
ꢀ9.0 (c
ꢂ
0.25, CHCl3); 1H NMR (300 MHz, CDCl3): d 0.88 (t, J = 6.9 Hz, 3H), 1.26 (m, 22H),
1.47–1.56 (m, 2H), 1.68–1.79 (m, 1H), 1.84–1.96 (m, 1H), 2.29–2.35 (m, 2H),
2.45 (t, J = 6.9 Hz, 2H), 3.34–3.40 (m, 1H), 3.49–3.57 (m, 1H), 4.52 (d,
J = 11.5 Hz, 1H), 4.64 (d, J = 11.5 Hz, 1H), 7.35 (m, 5H); 13C NMR (75 MHz,
CDCl3): d 14.0, 15.3, 22.6, 23.8, 24.4, 29.2, 29.4, 29.6, 31.9, 37.8, 42.8, 59.6, 72.8,
80.8, 127.7, 127.9, 128.4, 139.0, 210.7. ESI-MS: m/z: 438 [M+Na]; HRMS calcd
for C25H41N3O2Na 438.3091, found: 438.3083.
9. Morita, M.; Motoki, K.; Akimoto, K.; Natori, T.; Sakai, T.; Sawa, E.; Yamaji, K.;
Koezuka, Y.; Kobayashi, E.; Fukushima, H. J. Med. Chem. 1995, 38, 2176.
10. Experimental procedures: 1-Chlorotetradecane-2-ol (3): 1-Bromoundecane
(500 mg, 2.12 mmol) was added to the suspension of Mg metal (50 mg,
2.13 mmol) in dry THF and the resulting mixture was allowed to stir under
heating until all magnesium metal disappears. To this solution was added a
mixture of CuCN and epichlorohydrin (300 mg, 3.19 mmol) in THF at ꢀ10 °C.
The resulting solution was allowed to stir for 30 min and then quenched with a
saturated solution of ammonium chloride. The organic layer was separated and
the aqueous layer was extracted with ethyl acetate (2 ꢁ 15 mL) and the
combined organic layers were dried over Na2SO4. Removal of the solvent
followed by purification on silica gel column chromatography (EtOAc/n-
hexane, 1:19) afforded the compound 3, colorless liquid. 1H NMR (300 MHz,
CDCl3): d 0.88 (t, J = 6.9 Hz, 3H), 1.26 (br s, 22H), 3.48 (m, 1H), 3.64 (m, 2H),
3.81 (m, 1H. 13C NMR (75 MHz, CDCl3): d 14.1, 22.7, 25.5, 29.3, 29.5, 29.6, 31.5,
34.2, 50.6, 71.5.
(+)-Deoxocassine (1): To a solution of azidoketone 11 (150 mg, 0.36 mmol) in
EtOH (5 mL) and conc. HCl (0.25 mL) was added Pd(OH)2/C (100 mg) and the
resulting mixture was stirred under hydrogen atmosphere for 18 h. After
completion, the catalyst was removed by filtration over Celite and washed with
EtOAc. The organic layer was concentrated in vacuo. The resulting residue was
dissolved in water (5 mL) and extracted with diethyl ether (5 mL). The aqueous
layer was neutralized with 1 N NaOH and extracted thoroughly with CHCl3
(3 ꢁ 5 mL). The combined organic layers were dried over Na2SO4 and
concentrated in vacuo. Purification of the crude product by column
chromatography (n-hexane/EtOAc, 3:7) gave (+)-deoxocassine (1) as a white
solid. 70 mg in 80% yield. Overall yield 16.5% from
D
-xylose. mp 45–48 °C (lit.4b
½ ꢂ
+12.8 (c 0.1, CHCl3) (lit.4b a D20 +11.8 (c 1, CHCl3)); 1H NMR
,
mp 48–50 °C), ½a 2D0
ꢂ
1-Chlorotetradecane-2-one (4): To a stirred solution of oxalyl chloride (0.3 ml,
3.62 mmol) in DCM at ꢀ78 °C was added DMSO (0.4 ml, 7.24 mmol) dropwise.
(500 MHz, CDCl3): d 0.87 (t, J = 6.9 Hz, 3H), 1.15 (d, J = 6.7 Hz, 3H), 1.19–1.45
(m, 22H), 1.45–1.55 (m, 2H), 1.88–1.97 (m, 2H), 2.55–2.62 (m, 2H), 2.77–2.85
(m, 1H), 3.56–3.58 (m, 1H); 13C NMR (75 MHz, CDCl3): d 14.0, 18.0, 22.6, 25.2,
25.7, 29.3, 29.4, 29.5, 29.6, 31.8, 31.9, 36.2, 55.9, 57.3, 67.7. ESI-MS: m/z: 284
[M+H]. HRMS calcd for C18H38NO [M+H] 284.2948, found: 284.2947.
After 30 min,
a
solution of compound
3
(450 mg, 1.81 mmol) in
dichloromethane was added dropwise to the above mixture at the same
temperature. After 1 h, Et3N (1.8 ml, 12.67 mmol) was added dropwise at
ꢀ78 °C. Upon completion, the reaction was quenched with water and then
extracted with dichloromethane (15 mL). The organic layer was dried over
Na2SO4 and evaporated to get a crude product which was further purified by
column chromatography. (3% EtOAc/n-hexane), yellow solid. 1H NMR
(300 MHz, CDCl3): d 0.86 (t, J = 6.9 Hz, 3H), 1.26 (m, 22H), 1.62 (m, 2H), 2.58
(t, J = 6.8 Hz, 2H), 4.08 (s, 2H). 13C NMR (75 MHz): d 14.1, 22.6, 23.6, 29.1, 29.3,
29.4, 29.5, 29.6, 31.9, 33.8, 39.7, 48.2, 202.8.
TPP (410 mg, 1.54 mmol) was added to a solution of chloroketone 4 (380 mg,
1.54 mmol) in chloroform and the reaction mass was refluxed for 4–6 h. The
reaction mass was washed with 20% NaOH solution two times. Organic layer
was dried over Na2SO4 and solvent was evaporated in vacuo to get the crude
(E,2R,3R)-1,3-Bis(benzyloxy)-2-hydroxyoctadec-4-en-6-one (14): To
a stirred
solution of aldehyde (13) in toluene was added a solution of Wittig ylide 5
in toluene. The resulting mixture was stirred under reflux for 4–5 h. Upon
completion; the mixture was washed with brine and dried over anhydrous
Na2SO4. Removal of the solvent followed by purification on silica gel column
chromatography (n-hexane:EtOAc, 9:1) gave the pure product 14 in 70% yield.
Liquid. ½a 2D0
ꢂ
ꢀ20 (c 0.1, CHCl3). 1H NMR (300 MHz, CDCl3): d 0.88 (t, J = 6.9 Hz,
3H), 1.25 (m, 22H), 1.46–1.59 (m, 1H), 2.28 (t, J = 7.3 Hz, 2H), 2.39–2.49 (m,
2H), 3.43–3.55 (m, 2H), 3.69–3.79 (m, 1H), 4.06–4.14 (m, 1H), 4.36–4.62 (m,
2H), 6.24 (d, J = 16.8 Hz, 1H), 6.66 (dd, J = 6.4, 16.2 Hz, 1H), 7.27 (m, 10H); 13C
NMR (75 MHz, CDCl3): d 14.1, 22.6, 24.0, 29.2, 29.3, 29.4, 29.5, 29.6, 31.9, 40.3,
70.8, 71.8, 72.5, 73.5, 78.9, 127.8, 127.9, 128.0, 128.2, 128.3, 128.4, 128.5, 132.0,
141.8, 200.3. ESI-MS: m/z: 517 [M+Na]; HRMS calcd for C32H46O4Na 517.3288,
found: 517.3284.
ylide
5 (600 mg), which was used for the next reaction without further
purification.
(E,2R,3S)-3-(Benzyloxy)-2-hydroxyoctadec-4-en-6-one (8): Colorless liquid. To a
stirred solution of aldehyde (7) (200 mg, 1.03 mmol) in toluene, ylide
5
(ꢀ)-Deoxoprosophylline (2): The above procedure of (+)-deoxocassine was
adopted for the synthesis of (ꢀ)-deoxoprosophylline. The white solid was
obtained by column chromatography using methanol in dichloromethane as
(590 mg, 1.23 mmol) was added in toluene and the mixture was stirred under
reflux for 4–5 h. The reaction mixture was quenched with water and extracted
with ethyl acetate. The organic layer was dried over anhydrous Na2SO4.

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Ch. Kishore et al. / Tetrahedron Letters 53 (2012) 4551–4554
eluent. White solid, mp 88–91 °C (lit.4b mp 89–91 °C). Overall yield 22.5% from
1.40–1.05 (m, 22H), 0.93 (t, J = 6.8 Hz, 3H); 13C NMR (75 MHz, CDCl3): d 14.1,
22.6, 23.5, 26.2, 29.3, 29.6, 29.7, 29.8, 31.9, 33.9, 36.5, 56.2, 63.2, 70.7. ESI-MS:
m/z: 300 [M+H]; HRMS calcd for C18H38NO2 [M+H] 300.2897, found: 300.2893.
D
-xylose, ½a 2D0
ꢂ
ꢀ11.1 (c 0.1, CHCl3), (lit.4b
½
a 2D0
ꢂ
ꢀ10.3 (c 0.1, CHCl3)); 1H NMR
(300 MHz, CDCl3): d 3.82 (dd, J = 10.7, 4.4 Hz, 1H), 3.70 (m, 1H), 3.45 (m, 1H),
2.62–2.40 (m, 2H), 2.41–2.30 (m, 1H), 2.10–1.80 (m, 2H), 1.81–1.63 (m, 2H),