A common strategy for the stereoselective synthesis of anhydrophytosphingosine pachastrissamine (jaspine B) and N,O,O,O-tetra-acetyl d-lyxo-phytosphingosine

Article abstract of DOI:10.1016/j.tetlet.2011.08.170

The highly stereoselective Grignard addition on chiralimine 8 and opening of chiral epoxide 9 with Grignard reagent have been used as key steps in the stereoselective synthesis of cytotoxic anhydrophytosphingosine pachastrissamine (jaspine B) and N,O,O,O-

Full text of DOI:10.1016/j.tetlet.2011.08.170

Tetrahedron Letters 52 (2011) 6076–6079
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
A common strategy for the stereoselective synthesis of
anhydrophytosphingosine pachastrissamine (jaspine B)
and N,O,O,O-tetra-acetyl D-lyxo-phytosphingosine
⇑
G. Srinivas Rao, B. Venkateswara Rao
Organic Division III, Indian Institute of Chemical Technology, Hyderabad 500607, India
a r t i c l e i n f o
a b s t r a c t
Article history:
The highly stereoselective Grignard addition on chiralimine 8 and opening of chiral epoxide 9 with Grig-
nard reagent have been used as key steps in the stereoselective synthesis of cytotoxic anhydrophytosp-
hingosine pachastrissamine (jaspine B) and N,O,O,O-tetra-acetyl D-lyxo-phytosphingosine.
Received 1 August 2011
Revised 29 August 2011
Accepted 30 August 2011
Available online 2 September 2011
Ó 2011 Elsevier Ltd. All rights reserved.
Tetrahydrofuran backbone is a ubiquitous heterocyclic unit
found in a number of biologically active natural products.1 Pachas-
trissamine (1, Fig. 1) is an anhydrophytosphingosine derivative,
which was initially isolated from a marine sponge Pachastrissa
sp. in 2002 by Higa and co-workers.2 Soon after, the same com-
pound was isolated from a different marine sponge Jaspis sp. and
named jaspine B 1 by Debitus and co-workers.3 This marine natural
product exhibits a high cytotoxic activity against various tumor
cell lines in vitro.2,3
sphingosines.7b,11 In this Letter, we describe an efficient method
for the preparation of D
-lyxo-phytosphingosine 3.12
In continuation of our efforts for the synthesis of polyhydroxy-
lated pyrrolidines13 and carbasugars,14 utilizing Grignard reaction
on chiralimine, recently we published stereo-selective synthesis of
D
-ribo-phytosphingosine 2 and 2-epi-jaspine B 1a from D
-ribose.15
Herein we wish to report a common strategy for stereoselective
synthesis of anhydro-phytosphingosine pachastrissamine 1 and
N,O,O,O-tetra-acetyl
D-lyxo-phytosphingosine 6 from readily avail-
Pachastrissamine 1 possesses three contiguous stereogenic cen-
ters in the tetrahydrofuran core. The novel structural features and
able -ascorbicacid. Lyxo-phytosphingosine 3 can be considered as
L
an acyclic analog of jaspine B 1. Therefore, biological studies on 3
and its analogs will be helpful in understanding the cytotoxicity of
jaspine B 1, which inturn will be useful in designing new analogs
with better therapeutic activity. The retro synthetic analysis of
interesting biological activity of pachastrissamine
1
have
prompted chemists to develop several synthetic approaches to it
and its isomers.4 We published the first total synthesis of jaspine
B 1 and its C2 epimer 1a.5 We also published the synthesis of the
C2 and C3 epimer 1b and an enantiomer of jaspine B 1c and their
biological activity in comparison to jaspine B 15b and synthesis of
3-epi-jaspine 1d.5c
Sphingoid bases are long-chain aliphatic compounds typically
possessing a 2-amino-1,3-diol functionality. They are the principal
structural backbone of sphingolipids which play critical roles in
many physiological processes.6 Among the naturally occurring
sphingoid bases, phytosphingosines are one of the most important
and common species.7 More than 60 other sphingoid base
structures have been found in natural sphingolipids. Among them
C18-phytosphingosines 2–5 and their C16–C22 homologues have
been isolated from plants, fungi, human tissues,8 and marine
natural sources (Fig. 2).9 It has alsobeen established thatvarious dia-
stereomers of sphingosines exhibit different activities and metabo-
lism.10 This subtle variation in biological activities over a range of
diastereomers has led to the synthesis of all the diastereomers of
jaspine B 1 and N,O,O,O-tetra-acetyl D-lyxo-phytosphingosine 6 is
depicted in Scheme 1, compound 7 is a key intermediate for the
synthesis of 1 and 6 and it can be obtained from chiralimine 8.
The amino group can be introduced by nucleophilic addition
on chiralimine 8, and which was further envisaged from
compound 9.
The starting material chiral epoxide 9, required for our synthe-
sis was prepared from the L-ascorbicacid using reported procedure
(Scheme 2).16 The regioselective opening of the epoxide 9 with n-
tridecanylmagnesium bromide in the presence of cuprous cyanide
in dry THF provided compound 10, which on acetonide hydrolysis
with 80% aq AcOH afforded diol 11. Selective protection of the
primary hydroxyl group of 11 with tert-butyldimethylsilylchloride
gave silylether 12 and then the secondary hydroxyl groups were
protected with 2, 2-dimethoxy propane in the presence of p-
toluenesulfonic acid to afford 13. Deprotection of silylether in
13 with TBAF gave alcohol 14. The alcohol 14 on Swern oxidation
followed by condensation of aldehyde with benzylamine in the
presence of 4 Å molecular sieves in DCM gave chiralimine 8 and
this was used as such without any purification. Treatment of
⇑
Corresponding author. Tel./fax: +91 40 27193003.
E-mail addresses: venky@iict.res.in, drb.venky@gmail.com (B. Venkateswara
crude chiralimine
8 with vinylmagnesium bromide at 0 °C
Rao).
0040-4039/$ - see front matter Ó 2011 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tetlet.2011.08.170

G. Srinivas Rao, B. Venkateswara Rao / Tetrahedron Letters 52 (2011) 6076–6079
H2N
6077
H2N
OH
H2N
OH
C14H29
H2N
OH
C14H29
OH
C14H29
H2N
OH
C14H29
C14H29
O
O
O
O
O
1c
1d
1a
1b
1
Figure 1. Structures of pachastrissamine and its isomers.
NH2 OH
C14H29
NH2 OH
C14H29
NH2 OH
C14H29
NH2 OH
C14H29
HO
HO
HO
HO
OH
OH
OH
OH
3
4
2
5
D-lyxo-PHS
D-xylo-PHS
D-arabino-PHS
D-ribo-PHS
Figure 2. Structures of C18-phytosphingosines.
H2N
OH
O
C14H29
O
1
BnHN
BnN
O
O
C13H27
C13H27
O
O
AcHN
OAc
O
O
AcO
7
9
8
C14H29
OAc
6
Scheme 1. Retro-synthetic analysis of jaspine B 1 and N,O,O,O-tetra-acetyl
D-lyxo-phytosphingosine 6.
HO
OH
O
OH
HO
O
O
C13H27
ref.16
C13H27
c
f
b
a
HO
O
O
O
O
OH
11
HO
OH
L-ascorbicacid
9
10
O
O
OH
C13H27
e
d
C13H27
C13H27
TBSO
HO
TBSO
BnHN
O
13
12
O
OH
O
14
CbzBnN
BocHN
CbzBnN
HO
O
O
g
h
i
C13H27
C13H27
C13H27
O
7
O
15
O
16
BocHN
HO
TFA·H2N
OH
O
OH
C14H29
AcHN
OAc
j
k
l
C13H27
C14H29
pachastrisamine1 as TFA salt
O
C14H29
O
18
O
19
O
17
Scheme 2. Synthesis of jaspine B 1. Reagents and conditions: (a) C13H27Br, Mg, CuCN, THF, 0 °C, 2 h, 92%; (b) 80% aq AcOH, 4 h, 86%; (c) TBDMSCl, imidazole, CH2Cl2, 2 h, 90%;
(d) 2,2-DMP, pTSA, CH2Cl2, 2 h, 94%; (e) TBAF, THF, 1 h, 90%; (f) (i) (COCl)2, DMSO, CH2Cl2, ꢀ78 °C, Et3N; (ii) BnNH2, CH2Cl2, 4 Å MS; (iii) vinylbromide, Mg, THF, 0 °C (80% over
three steps); (g) CbzCl, NaHCO3, MeOH, 0 °C, 1 h, 92%; (h) (i) O3, CH2Cl2, ꢀ78 °C, 30 min and DMS, 1 h; (ii) NaBH4, MeOH, 1 h (85% for two steps); (i) (i) H2, Pd/C, MeOH, 6 h, (ii)
(Boc)2O, Et3N, CH2Cl2, 2 h, (83% for two steps); (j) (i) MsCl, Et3N, CH2Cl2, DMAP, 0 °C, 30 min, (ii) pTSA, MeOH, 0 °C, 2 h then NaHCO3 (82% for two steps); (k) TFA, CH2Cl2, 2 h,
90%; (l) (Ac)2O, Et3N, CH2Cl2, 6 h (85%).
furnished amino olefin
7
exclusively, as
a
single isomer
bond in 15 with O3/DCM gave an aldehyde, which on treatment
as such with NaBH4 in MeOH gave alcohol 16. Hydrogenation of
16 using Pd/C in MeOH, followed by treatment with (Boc)2O in
the presence of Et3N afforded the common intermediate 17. The
primary hydroxyl group in 17 was converted to mesylate using
MsCl in the presence of Et3N in DCM, as such which on treatment
with p-toluenesulfonic acid in MeOH followed by treatment with
excess NaHCO3 gave the cyclized product 18. Compound 18 on
treatment with TFA/DCM gave the desired product anhy-
drophytosphinosine pachastrissamine (jaspine B) 1 as TFA salt,18a
(Scheme 2). The absolute configuration of the newly generated
stereo center was not confirmed at this stage but as per our earlier
observation it should give the erythro-isomer,15 which presumably
proceeded via b-chelation model
A
or Felkin-Anh model
B
(Fig. 3).17 Since the
a
-alkoxy oxygen of acetonide will not partic-
ipate in chelation as per earlier observation by us15 and others.17
Having the amino compound 7 in hand, we proceeded to the
next stage. The amino functionality in 7 was protected as carba-
mate with CbzCl to give 15. Oxidative degradation of the double

6078
G. Srinivas Rao, B. Venkateswara Rao / Tetrahedron Letters 52 (2011) 6076–6079
Russell, A. J.; Sanchez-Fernandez, E. M.; Smith, A. D.; Thomson, J. E. Tetrahedron:
M
N
M
OR
RO
H
Asymmetry 2007, 18, 2510; (k) Yakura, T.; Sato, S.; Yoshimoto, Y. Chem. Pharm.
Bull. 2007, 55, 1284; (l) Passiniemi, M.; Koskinen, A. M. P. Tetrahedron Lett.
2008, 49, 980; (m) 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.;
Sanchez-Fernandez, E. M.; Scott, P. M.; Smith, A. D.; Thomson, J. E. Org. Biomol.
Chem. 2008, 6, 1665; (n) Venkatesan, K.; Srinivasan, K. V. Tetrahedron:
Asymmetry 2008, 19, 209; (o) Enders, D.; Terteryan, V.; Palecek, J. Synthesis
2008, 2278; (p) Ichikawa, Y.; Matsunaga, K.; Masuda, T.; Kotsuki, H.; Nakano, K.
Tetrahedron 2008, 64, 11313; (q) Reddipalli, G. S.; Venkataiah, M.; Mishra, M.
K.; Fadnavis, N. W. Tetrahedron: Asymmetry 1802, 2009, 20; (r) Inuki, S.;
Yoshimitsu, Y.; Oishi, S.; Fujii, N.; Ohno, H. Org. Lett. 2009, 11, 4478; (s) Inuki, S.;
Yoshimitsu, Y.; Oishi, S.; Fujii, N.; Ohno, H. J. Org. Chem. 2010, 75, 3831; (t)
Yoshimitsu, Y.; Inuki, S.; Oishi, S.; Fujii, N.; Ohno, H. J. Org. Chem. 2010, 75,
3843; (u) Urano, H.; Enomoto, M.; Kuwahara, S. Biosci., Biotechnol., Biochem.
2010, 74, 152; (v) Salma, Y.; Ballereau, S.; Maaliki, C.; Ladeira, S.; Andrieu-
Abadie, N.; Genison, Y. Org. Biomol. Chem. 2010, 8, 3227; (w) Passiniemi, M.;
Koskinen, A. M. P. Org. Biomol. Chem. 2011, 9, 1774; (x) Llaveria, J.; Diaz, Y.;
Matheu, M. I.; Castillon, S. Eur. J. Org. Chem. 2011, 1514; (y) Eleuterio, A. S.;
Quintero, L.; Piscil, F. S. J. Org. Chem. 2011, 76, 5466; For a review, see: (z)
Abraham, E.; Davies, S. G.; Roberts, P. M.; Russell, A. J.; Thomson, J. E.
Tetrahedron: Asymmetry 2008, 19, 1027.
Bn
Bn
OR
Bn
N
O
N
C14H29
C14H29
C13H27
OR
Nu
Nu
O
H
H
H
A
B
Figure 3. b-chelation model (A) and Felkin-Anh model (B).
AcHN
AcO
BocHN
HO
O
OAc
C14H29
a
C13H27
OAc
6
O
17
Scheme 3. Synthesis of N,O,O,O-tetra-acetyl D-lyxo-phtosphingosine. Reagents and
conditions: (a) (i) TFA, CH2Cl2, 2 h, (ii) (Ac)2O, Py, DMAP, CH2Cl2, 4 h (88% over two
steps).
5. (a) Sudhakar, N.; Kumar, A. R.; Prabhakar, A.; Jagadeesh, B.; Rao, B. V.
Tetrahedron Lett. 2005, 46, 325; (b) Chitra, C. J.; Sudhakar, N.; Kumar, A. R.;
Rao, B. V.; Roy, S.; Benerjee, R. Synthesis 2010, 115; (c) Rao, G. S.; Sudhakar, N.;
Rao, B. V.; Basha, S. J. Tetrahedron: Asymmetry 1963, 2010, 21.
6. Merrill, A. H.; Sandhoff, K. Sphingolipids Metabolism and Cell Signaling. In
Biochemistry of Lipids, Lipoprotein and Membranes; Vance, D. E., Vance, J. E., Eds.;
Elsevier: New York, 2002. pp. 373-407.
7. For recent reviews, see: (a) Liao, J.; Tao, J.; Lin, G.; Liu, D. Tetrahedron 2005, 61,
4715; (b) Howell, A. R.; Ndakala, A. J. Curr. Org. Chem. 2002, 6, 365; (c) Curfman,
C.; Liotta, D. Methods Enzymol. 1999, 311, 391; (d) Koskinen, P. M.; Koskinen, A.
M. P. Synthesis 1998, 1075.
which was converted to acetyl derivative 1918b by treating with
acetic anhydride in the presence of Et3N. The spectral data of 12
and 194b were in good agreement with the reported data.
For the synthesis of D-lyxo-phytosphingosine 3 from 17, follow-
ing reactions were carried out (Scheme 3). Global deprotection of
carbamate and hydrolysis of the acetanide in 17 with TFA/DCM
gave 3. For the sake of characterization, it was converted as such
8. Murakami, T.; Taguchi, K. Tetrahedron 1999, 55, 989. and references cited
therein..
9. Higuchi, R.; Kagoshima, M.; Komori, T. Liebigs Ann. Chem. 1988, 19.
10. (a) Inokuchi, J. I.; Usuki, S.; Jimbo, M. J. Biochem. (Tokyo) 1995, 117, 766; (b)
Motoki, K.; Kobayashi, E.; Uchida, T.; Fukushima, H.; Koezuka, Y. Bioorg. Med.
Chem. Lett. 1995, 5, 705; (c) Pushkareva, M.; Chao, R.; Beilawska, A.; Merrill, H.;
Crane, H. M.; Lagu, B.; Liotta, D.; Hannun, Y. A. Biochemistry 1995, 34, 1885.
11. Selected publications for syntheses of phytosphingosines, see Refs. 4j, 4m, 7b
and: (a) Ndakala, A. J.; Hashemzadeh, M.; So, R. C.; Howell, A. R. Org. Lett. 2002,
4, 1719; (b) Raghavan, S.; Rajender, A. J. Org. Chem. 2003, 68, 7094; (c) So, R. C.;
Ndonye, R.; Izmirian, D. P.; Richardson, S. K.; Guerrera, R. L.; Howell, A. R. J. Org.
Chem. 2004, 69, 3233; (d) Singh, O. V.; Kampf, D. J.; Han, H. Tetrahedron Lett.
2004, 45, 7239; (e) Lu, X.; Bittman, R. Tetrahedron Lett. 2005, 46, 3165; (f)
Lombardo, M.; Capdevila, M. G.; Pasi, F.; Trombini, C. Org. Lett. 2006, 8, 3303;
to N,O,O,O-tetra-acetyl
D
-lyxo-phytosphingosine 6,19 by treating
with acetic anhydride in the presence of pyridine, whose spectral
data were in good agreement with the reported data.20
In conclusion we have successfully demonstrated a general
strategy for the synthesis of anhydrophytosphingosine pachastriss-
amine 1 and N,O,O,O-tetra-acetyl
D-lyxo-phytosphingosine 6 by
using Grignard addition on epoxide 9 and chiralimine 8. The salient
feature of this approach is nucleophilic addition on chiralimine for
the introduction of chiral amino group. This strategy is also useful
to make some other analogs and isomers of phytosphingosine and
jaspine B with high stereoselectivity and better activity.
ˆ
(g) Enders, D.; Palecek, J.; Grondal, C. Chem. Commun. 2006, 655; (h) Cai, Y.;
Ling, C. C.; Bundle, D. R. Org. Biomol. Chem. 2006, 4, 1140; (i) Yoon, H. J.; Kim, Y.
W.; Lee, B. K.; Lee, W. K.; Kim, Y.; Ha, H. J. Chem. Commun. 2007, 79; (j) Jeon, J.;
Shin, M.; Yoo, J. W.; Oh, J. S.; Bae, J. G.; Jung, S. H.; Kim, Y. G. Tetrahedron Lett.
2007, 48, 1105; (k) Chang, C. W.; Chen, Y. N.; Adak, A. K.; Lin, K. H.; Tzou, D. L.
M.; Lin, C. C. Tetrahedron 2007, 63, 4310; (l) Jiang, H.; Elsner, P.; Jensen, K. L.;
Falcicchio, A.; Marcos, V.; Jorgensen, K. A. Angew. Chem. Int. Ed. 2009, 48, 6844;
(m) Dubey, A.; Kumar, P. Tetrahedron Lett. 2009, 50, 3425; (n) Pandey, G.;
Tiwari, D. K. Tetrahedron Lett. 2009, 50, 3296; (o) Llaveria, J.; Dıaz, Y.; Matheu,
M. I.; Castillon, S. Org. Lett. 2009, 11, 205; (p) Liu, Z.; Byun, H. S.; Bittman, R. J.
Org. Chem. 2010, 75, 4356; (q) Kumar, P.; Dubey, A.; Puranik, V. G. Org. Biomol.
Chem. 2010, 8, 5074.
Acknowledgements
G.S.R. thanks CSIR, New Delhi for research fellowship. The
authors also thank Dr. J. S. Yadav for his constant support and
encouragement. We also thank DST (SR/S1/OC-14/2007), New
Delhi, for financial assistance.
12. For other methods to synthesize lyxo-PHS: (a) Lu, X.; Byun, H. S.; Bittman, R. J.
Org. Chem. 2004, 69, 5433; (b) Righi, G.; Ciambrone, S.; D’Achille, C.; Leonelli,
A.; Bonini, C. Tetrahedron 2006, 62, 11821; (c) Tsujimoto, T.; Itoa, Y. Tetrahedron
Lett. 2007, 48, 5513; (d) Kumar, I.; Rode, C. V. Tetrahedron: Asymmetry 1975,
2007, 18; (e) Kim, S.; Lee, N.; Lee, S.; Lee, T.; Lee, Y. M. J. Org. Chem. 2008, 73,
1379; (f) Park, J.; Lee, J. H.; Li, Q.; Diaz, K.; Chang, Y. T.; Chung, S. K. Bioorg.
Chem. 2008, 36, 220.
13. (a) Jagadeesh, Y.; Chandrasekhar, B.; Rao, B. V. Tetrahedron: Asymmetry 2010,
21, 2314; (b) Chandrasekhar, B.; Rao, B. V. Tetrahedron: Asymmetry 2009, 20,
1217; (c) Chandrasekhar, B.; Madhan, A.; Rao, B. V. Tetrahedron 2007, 63, 8746;
(d) Madhan, A.; Rao, B. V. Tetrahedron Lett. 2003, 44, 5641.
Supplementary data
Supplementary data associated with this article can be found, in
the online version, at doi:10.1016/j.tetlet.2011.08.170.
References and notes
14. Rao, J. P.; Rao, B. V.; Swarnalatha, J. L. Tetrahedron Lett. 2010, 51, 3083.
15. Rao, G. S.; Rao, B. V. Tetrahedron Lett. 2011, 52, 4861.
1. Faul, M. M.; Huff, B. E. Chem. Rev. 2000, 100, 2407.
2. Kuroda, I.; Musman, M.; Ohtani, I. I.; Ichiba, T.; Tanaka, J.; Gravalos, D. G.; Higa,
T. J. Nat. Prod. 2002, 65, 1505.
16. Elie, A.; Purushotham, V.; Robert, W. L.; Haribansh, K. S.; Amarendra, B. M.;
David, C. J.; Racha, S.; Raymond, P. P. J. Org. Chem. 1988, 53, 2598.
17. Badorrey, R.; Cativiela, C.; Díaz-de-Villegas, M. D.; Díez, R.; Gálvez, J. A. Eur. J.
Org. Chem. 2003, 2268.
3. Ledroit, V.; Debitus, C.; Lavaud, C.; Massiot, G. Tetrahedron Lett. 2003, 44, 225.
4. For previous syntheses, see: (a) Bhaket, P.; Morris, K.; Stauffer, C. S.; Datta, A.
Org. Lett. 2005, 7, 875; (b) Van Den Berg, R. J. B. H. N.; Boltje, T. J.; Verhagen, C.
P.; Litjens, R. E. J. N.; Vander Marel, G. A.; Overkleeft, H. S. J. Org. Chem. 2006, 71,
836; (c) Liu, Y.; Du, J.; Linhardt, R. J. J. Org. Chem. 2006, 71, 1251; (d) Liu, J.; Du,
Y.; Dong, X.; Meng, S.; Xiao, J.; Cheng, L. Carbohydr. Res. 2006, 341, 2653; (e)
Ribes, C.; Falomir, E.; Carda, M.; Marco, J. A. Tetrahedron 2006, 62, 5421; (f) Lee,
T.; Lee, S.; Kwak, Y. S.; Kim, D.; Kim, S. Org. Lett. 2007, 9, 429; (g) Reddy, L. V. R.;
Reddy, P. V.; Shaw, A. K. Tetrahedron: Asymmetry 2007, 18, 542; (h) Ramana, C.
V.; Giri, A. G.; Suryawanshi, S. B.; Gonnade, R. G. Tetrahedron Lett. 2007, 48, 265;
(i) Prasad, K. R.; Kumar, A. S. J. Org. Chem. 2007, 72, 6312; (j) Abraham, E.;
Candela-Lena, J. I.; Davies, S. G.; Georgiou, M.; Nicholson, R. L.; Roberts, P. M.;
18. (a) Spectral data of 1 as TFA salt: white solid; mp 120–125 °C; ½a D26
ꢁ
+16.1 (c 0.8,
EtOH), {lit.2
[a] +18 (c 0.1 EtOH)}; I.R mmax: 2929, 2857, 1461, 1373, 1248,
D
1067, 916, 836, 777, 699 cmꢀ1 1H NMR (CD3OD, 500 MHz): d 4.24 (dd, 1H,
;
J = 3.8 and 5.1 Hz), 3.82–3.93 (m, 2H), 3.79 (dd, 1H, J = 5.1 and 8.9 Hz), 3.68–
3.73 (m, 1H), 1.63 (m, 2H), 1.23–1.48 (m, 24H), 0.89 (t, 3H, J = 6.4 Hz); 13C NMR
(CD3OD, 75 MHz): d 84.4, 70.9, 69.0, 54.4, 33.1, 30.9, 30.8, 30.5, 29.7, 27.2, 23.7,
14.4; ESIMS m/z: 300 (M++1–CF3COOH); HRMS (ESI): Calcd for C18H38NO2
[M+H]+ 300.2902, found 300.2902; (b) spectral data of compound 19: white
solid; mp 98–100 °C; ½a D26
ꢁ
ꢀ24.0 (c 0.6, CHCl3), {lit.4b a 2D2
½ ꢁ ꢀ22.6 (c 1.0 CHCl3)};
I.R mmax: 2916, 2850, 2363, 2330, 1739, 1656, 1550, 1464, 1373, 1230, 1071,

G. Srinivas Rao, B. Venkateswara Rao / Tetrahedron Letters 52 (2011) 6076–6079
6079
725 cmꢀ1
;
1H NMR (CDCl3, 500 MHz): d 5.59 (d, 1H, J = 8.3 Hz), 5.35 (dd, 1H,
1H NMR (CDCl3, 500 MHz): d 5.80 (d, 1H, J = 9.6 Hz), 5.10 (m, 2H), 4.54 (m, 1H),
4.24 (dd, 1H, J = 4.5 and 11.7 Hz), 3.96 (dd, 1H, J = 3.2 and 11.7 Hz), 2.13 (s, 3H),
2.10 (s, 3H), 2.07 (s, 3H), 1.98 (s, 3H), 1.49 (m, 2H), 1.18–1.37 (m, 24H), 0.88 (t,
3H, J = 6.8 Hz); 13C NMR (CDCl3, 75 MHz): d 170.7, 170.5, 170.3, 169.6, 71.7,
71.1, 63.1, 47.3, 31.9, 30.8, 29.6, 29.6, 29.5, 29.4, 29.3, 29.3, 25.1, 23.2, 22.6,
21.0, 20.7, 20.6, 20.5, 14.1; ESIMS m/z: 508 (M+Na)+; HRMS (ESI): Calcd for
J = 3.4 and 5.2 Hz), 4.78 (ddd, 1H, J = 5.6, 7.7 and 7.9 Hz), 4.75 (m, 1H), 4.04 (t,
1H, J = 8.2 Hz), 3.87 (m, 1H), 3.53 (t, 1H, J = 8.2 Hz), 2.15 (s, 3H), 1.97 (s, 3H),
1.40–1.46 (m, 2H), 1.21–1.33 (m, 24H), 0.88 (t, 3H, J = 6.8 Hz); 13C NMR (CDCl3,
75 MHz): d 169.8, 169.7, 81.2, 73.6, 70.0, 51.4, 31.9, 29.7, 29.6, 29.5, 29.4, 29.3,
29.2, 26.0, 23.1, 22.6, 20.6, 14.0; ESIMS m/z: 384 [M+H]+; HRMS (ESI): Calcd for
C
22H41NO4Na [M+Na]+ 406.2933, found 406.2933.
C
26H47NO7Na [M+H]+ 508.3250, found 508.3232.
20. Shirota, O.; Nakanishi, K.; Berova, N. Tetrahedron 1999, 55, 13643.
19. Spectral data of compound 6: ½a D26
ꢁ
ꢀ4.2 (c 1.0, CHCl3), {lit.20 a 2D2
½ ꢁ ꢀ3.1 (c 1.1
CHCl3)}; I.R m ;
max: 2924, 2854, 1742, 1656, 1546, 1461, 1370, 1222, 1027 cmꢀ1