Stereoselective synthesis of pachastrissamine (jaspine B)

Article abstract of DOI:10.1016/j.tet.2006.03.073

A stereoselective synthesis in enantiopure form of the natural anhydrophytosphingosine pachastrissamine (jaspine B), a metabolite isolated from sponges, is described. The chiral epoxide (R)-glycidol was the starting material. Key steps of this synthesis a

Full text of DOI:10.1016/j.tet.2006.03.073

Tetrahedron 62 (2006) 5421–5425
Stereoselective synthesis of pachastrissamine (jaspine B)
a
b,
Celia Ribes,a Eva Falomir,a, Miguel Carda and J. A. Marco
*
*
a
´
´
´
´
Depart. de Q. Inorganica y Organica, Univ. Jaume I, Castellon, E-12080 Castellon, Spain
b
´
Depart. de Q. Organica, Univ. de Valencia, E-46100 Burjassot, Valencia, Spain
Received 17 January 2006; revised 17 March 2006; accepted 22 March 2006
Available online 12 April 2006
Dedicated to Professor J. Barluenga, from the University of Oviedo, on the occasion of his 65th birthday
Abstract—A stereoselective synthesis in enantiopure form of the natural anhydrophytosphingosine pachastrissamine (jaspine B), a metabo-
lite isolated from sponges, is described. The chiral epoxide (R)-glycidol was the starting material. Key steps of this synthesis are a Sharpless
asymmetric epoxidation, an intramolecular stereospecific epoxide opening mediated by a trichloroacetimidate group, and the formation of
a tetrahydrofuran ring via intramolecular nucleophilic displacement.
Ó 2006 Elsevier Ltd. All rights reserved.
OH
1. Introduction
HN
H
O
Sponges of the genus Jaspis (family Coppatiidae) have
received in recent times a considerable attention from scien-
tists because of the interesting pharmacological properties of
its chemical components. Among these, modified peptides1
and nucleosides,2 sterols and other triterpene derivatives,3
unusual bisoxazoles,4 cytotoxic macrolides,5 styryl sulfates,6
unusual terpenes of mixed biogenetic origin,7 a-amino-3-
lactam derivatives (bengamides),8 and brominated tyrosine
derivatives9 are particularly worth mentioning. Very recently,
two cytotoxic anhydrophytosphingosine derivatives, named
jaspine A 1 and B 2, have been isolated from a new species
of the aforementioned genus.10 Compound 2 was found
highly active against the A5409 human lung carcinoma cell
line (IC50¼0.34 mM). Compound 2 had also been isolated
shortly before from another sponge species of the Pachas-
trissa genus (family Calthropellidae) and received the name
pachastrissamine.11,12 It was assayed against the P388,
HT29, MEL28 tumoral cell lines and found cytotoxic at the
submicromolar level. The valuable pharmacological proper-
ties and novel structural features of 213 have prompted us to
undertake its total synthesis in enantiopure form (Fig. 1).
H
O
O
1
H2N
OH
2
Figure 1. Structures of jaspines A and B.
The retrosynthetic strategy for the synthesis of 2 is outlined
in Scheme 1 (P, P0¼protecting groups). Retrocleavage of
one of the C–O bonds in the tetrahydrofuran ring via
PHN
OH
C14H29
H2N
SN
OH
C14H29
O
OH
TsO
2
A
Cl3C
O
OP´
C14H29
OP´
C14H29
N
Very recently, total syntheses of 2 starting from the chiral
pool have been reported.14 As a part of our research program
aimed at developing stereocontrolled syntheses of naturally
occurring bioactive compounds in enantiopure form,15 we
here report our own synthesis of pachastrissamine (jaspine
B) 2 from (R)-glycidol as the chiral starting material.16
HO
HO
O
OH
C
B
O
OP´
HO
C14H29
Keywords: Pachastrissamine (jaspine B); (R)-Glycidol; Sharpless asymmet-
ric epoxidation; Imidate epoxide opening.
D
(R)-glycidol
* Corresponding authors. Tel.: +34 96 3544337; fax: +34 96 3544328;
e-mail: alberto.marco@uv.es
Scheme 1. Retrosynthetic plan for the synthesis of pachastrissamine
(jaspine B) 2.
0040–4020/$ - see front matter Ó 2006 Elsevier Ltd. All rights reserved.
doi:10.1016/j.tet.2006.03.073

5422
C. Ribes et al. / Tetrahedron 62 (2006) 5421–5425
intramolecular nucleophilic displacement gives the open
chain intermediate A. The nitrogen atom is then introduced
(in the retrosynthetic sense) by means of another intra-
molecular nucleophilic displacement in epoxy alcohol C
via oxazoline B. Compound C can be obtained through
Sharpless epoxidation of (E)-allylic alcohol D, to be pre-
pared in turn from (R)-glycidol.
sis of 11 followed by N-Boc protection furnished diol 12.
Removal of the MOM group could be performed with
TMSBr24,25 to provide triol 13, which was then selectively
tosylated at the primary alcohol group. Basic treatment of
monotosylate 14 with K2CO3 in MeOH caused intramolec-
ular tosylate displacement and gave rise to tetrahydrofuran
15. Cleavage of the N-Boc group in 15 with TFA yielded
compound 2, which had spectral properties identical to those
reported in the bibliography for either pachastrissamine11 or
jaspine B.10 Furthermore, acetylation of 2 provided the O,N-
diacetyl derivative 16, with spectral properties also identical
to those reported in the bibliography.10,11
2. Results and discussion
The synthesis of 2 is illustrated in Scheme 2. Commercial
(R)-glycidol was transformed into its known17 TPS ether 3
(for nonstandard acronyms, see Scheme 2). Epoxide opening
in 3 with a n-tridecyl cuprate reagent18 afforded alcohol 4,
which was then protected as its MOM derivative 5.19 Desily-
lation of the latter with TBAF furnished alcohol 6, which
was transformed into the (E)-unsaturated ester 7 as reported
by sequential Swern oxidation and olefination.20 DIBAL
reduction of 7 to (E)-allylic alcohol 8 followed by Sharpless
asymmetric epoxidation with t-BuO2H in the presence of
Ti(iPrO)4 and (ꢀ)-diethyl tartrate21 provided epoxy alcohol
9. Upon reaction with trichloroacetonitrile in the presence of
DBU, 9 furnished the corresponding imino ester derivative
10.22 The nucleophilic intramolecular epoxide opening in
10 was first attempted in the presence of catalytic amounts
of BF3$Et2O but only decomposition was observed. Success
was finally achieved through reaction of imidate 10 in the
presence of Et2AlCl to yield oxazoline 11.23 Acidic hydroly-
3. Conclusions
We have performed a stereoselective synthesis of the natural
anhydrophytosphingosine pachastrissamine (jaspine B) with
(R)-glycidol as the chiral starting material. Since both anti-
podes of glycidol as well of diethyl tartrate (for the Sharpless
asymmetric epoxidation step) are available, our synthetic
concept is flexible enough as to be adaptable to the prepara-
tion of the non-natural antipode of 2 or else diastereomers
thereof. Furthermore, ring-opening of the protected glycidol
with organocopper reagents of various structures would pro-
vide a library of pachastrissamine analogues for structure–
activity studies.
4. Experimental
4.1. General
OMOM
C14H29
6
O
OR
C14H29
d
c
a
HO
TPSO
HO
TPSO
b
1H/13C NMR spectra were measured at 500/125 MHz in
CDCl3 solution at 25 ꢁC. The signals of the deuterated sol-
vent (CDCl3) were taken as the reference (the singlet at
3
4 R = H
5 R = MOM
1
OMOM
OMOM
OMOM
d 7.25 for H NMR and the triplet centered at 77.00 ppm
e
for 13C NMR data). Carbon atom types (C, CH, CH2,
CH3) were determined with the DEPT pulse sequence.
Mass spectra were run by the electron impact (EIMS,
70 eV) or the fast atom bombardment mode (FABMS, m-
nitrobenzyl alcohol matrix) on a VG AutoSpec mass spec-
trometer. IR data are given only for compounds with
relevant functions (OH, C]O) and were recorded as oily
films on NaCl plates (oils) or as KBr pellets (solids). Optical
rotations were measured at 25 ꢁC. Reactions which required
an inert atmosphere were carried out under N2 with flame-
dried glassware. Et2O and THF were freshly distilled from
sodium–benzophenone ketyl and transferred via syringe. Di-
chloromethane was freshly distilled from CaH2. Tertiary
amines were freshly distilled from KOH. Toluene was
freshly distilled from sodium wire. Commercially available
reagents were used as received. Unless detailed otherwise,
‘work-up’ means pouring the reaction mixture into brine,
followed by extraction with the solvent indicated in paren-
thesis. If the reaction medium was acidic (basic), an addi-
tional washing with 5% aq NaHCO3 (aq NH4Cl) was
performed. Drying over anhydrous Na2SO4 and elimination
of the solvent under reduced pressure were followed by
chromatography of the residue on a silica gel column (60–
200 mm) with the indicated eluent. Where solutions were fil-
tered through a Celite pad, the pad was additionally washed
with the same solvent used, and the washings incorporated to
f
EtOOC
C14H29
C14H29
C14H29
O
OH
7
8
9
g
Cl3C
Cl3C
BocNH
OMOM
C14H29
OMOM
C14H29
NH
N
OMOM
C14H29
h
i
O
O
O
HO
OH
OH
12
11
10
j
BocHN
OH
RHN
n
OR
BocHN
OH
C14H29
m
l
C14H29
C14H29
R = H
O
O
RO
k
OH
15
2
13 R = H
14 R = Ts
16 R = Ac
Scheme 2. Synthesis of pachastrissamine (jaspine B) 2. Reaction condi-
tions: (a) CH3(CH2)12MgBr, CuI, THF, ꢀ10/0 ꢁC, 82%; (b) MOMCl,
EtNiPr2, CH2Cl2, 24 h, rt, 94%; (c) TBAF, THF, 3 h, rt, 94%; (d) Ref. 20;
(e) DIBAL, hexane, 0 ꢁC, 2.5 h, 95%; (f) t-BuO2H, (ꢀ)-diethyl tartrate,
Ti(iPrO)4, CH2Cl2, ꢀ20 ꢁC, 24 h, 89%; (g) Cl3CCN, DBU, CH2Cl2,
30 min, 0 ꢁC; (h) Et2AlCl, CH2Cl2, 0 ꢁC/rt, 5 h, 72% overall yield from
9; (i) aq 1 M HCl, THF, 5 h, rt, then NaHCO3, Boc2O, 16 h, rt, 96% overall
yield from 11; (j) TMSBr, CH2Cl2, ꢀ78 ꢁC, 30 min, 75%; (k) TsCl, Et3N,
DMAP, CH2Cl2, 20 min, rt; (l) K2CO3, MeOH, 16 h, rt, 70% overall from
13; (m) TFA, CH2Cl2, 0 ꢁC/rt, 45 min, 75%; (n) Ac2O, Et3N, DMAP,
CH2Cl2, 16 h, rt (Acronyms: CSA¼camphorsulfonic acid; TBAF¼tetra-n-
butyl ammonium fluoride hydrate; TPS¼tert-butyldiphenylsilyl).

C. Ribes et al. / Tetrahedron 62 (2006) 5421–5425
5423
the main organic layer. Nonstandard acronyms are explained
in the caption of Scheme 2.
volatiles in vacuo, the residue was chromatographed on sil-
ica gel (hexane–EtOAc, 4:1) to yield 6 (625 mg, 94%): solid;
mp 39–40 ꢁC, lit.20 mp 36.9–38.1 ꢁC; [a]D +28.7 (c 1.6,
CHCl3), lit.20 [a]D +33.3 (c 2.3, CHCl3); spectral data iden-
tical to those reported.20
4.1.1. (2S)-1-(tert-Butyldiphenylsilyloxy)hexadecan-2-ol
(4). Magnesium turnings (365 mg, ca. 15 mmol) were sus-
pended under N2 in dry THF (10 mL) at room temperature.
A few drops of 1,2-dibromoethane were added to the suspen-
sion via syringe until an effervescence started. A solution of
n-tridecyl bromide (3.6 mL, 14 mmol) in THF (10 mL) was
then added dropwise via syringe. The resulting mixture was
stirred at 50 ꢁC for 30 min.
4.1.4. Ethyl (2E,4S)-4-(methoxymethoxy)octadec-2-
enoate (7). Prepared from 6 as reported.20
4.1.5. (2E,4S)-4-(Methoxymethoxy)octadec-2-en-1-ol (8).
Ester 7 (650 mg, 1.75 mmol) was dissolved in dry hexane
(5 mL) and cooled to 0 ꢁC. Then DIBAL (4 mL, 1 M in hex-
ane) was added and the reaction mixture was stirred at 0 ꢁC
for 2.5 h. Work-up (CH2Cl2) and column chromatography
on silica gel (hexane–EtOAc, 19:1, then 4:1) furnished alco-
hol 8 (546 mg, 95%); solid; mp 44–45 ꢁC; [a]D ꢀ54.8 (c 2,
CHCl3); 1H NMR (500 MHz) d 5.80 (1H, dt, J¼15.5,
5.3 Hz), 5.56 (1H, ddt, J¼15.5, 8, 1.3 Hz), 4.69 (1H, d,
J¼6.8 Hz), 4.52 (1H, d, J¼6.8 Hz), 4.15 (2H, d,
J¼4.5 Hz), 4.00 (1H, dt, J¼8, 6.5 Hz), 3.36 (3H, s), 1.70–
1.35 (6H, m), 1.35–1.20 (21H, s), 0.88 (3H, t, J¼7 Hz); 13C
NMR (125 MHz) d 131.9, 131.7, 76.4 (CH), 93.8, 62.9,
35.6, 31.9, 29.6 (several overlapped peaks), 25.5, 22.7
Powdered CuI (1.33 g, 7 mmol) was gently heated in vacuo
until the solid turned light yellow. The flask was then filled
with Ar and cooled to ꢀ30 ꢁC, followed by addition of dry
THF (30 mL). The previously prepared solution of n-tride-
cylmagnesium bromide was then added dropwise via sy-
ringe. The mixture was then stirred for 15 min at ꢀ30 ꢁC.
The TPS derivative 3 of (R)-glycidol (1.1 g, ca. 3.5 mmol)
was dissolved in dry THF (10 mL) and added dropwise to
the solution of organocopper reagent. The reaction mixture
was then stirred for 15 min at ꢀ10 ꢁC and then for further
4 h at 0 ꢁC. Work-up (Et2O) and column chromatography
on silica gel (hexane–EtOAc, 9:1) afforded pure 4 (1.42 g,
(CH2), 55.4, 14.1 (CH3); IR nmax 3400 (br, OH) cmꢀ1
;
1
82%): oil; [a]D +1.5 (c 1.4, CHCl3); H NMR (500 MHz,
HREIMS m/z (rel int.) 297.2784 (M+ꢀCH2OH, 1), 267 (4),
225 (7), 178 (25), 131 (100), 83 (20). Calcd for C20H40O3–
CH2OH, 297.2793. Anal. Calcd for C20H40O3: C, 73.12; H,
12.27. Found: C, 73.02; H, 12.24.
CDCl3) d 7.70–7.60 (4H, m), 7.45–7.35 (6H, m), 3.72 (1H,
m), 3.68 (1H, dd, J¼10, 3.3 Hz), 3.52 (1H, dd, J¼10,
7.5 Hz), 2.50 (1H, br s, OH), 1.50–1.20 (26H, br m), 1.08
(9H, s), 0.89 (3H, t, J¼7 Hz); 13C NMR (125 MHz,
CDCl3) d 133.3, 133.2, 19.3 (C), 135.6, 135.5, 129.8,
127.8, 71.9 (CH), 68.0, 32.8, 32.0, 29.7 (several overlapped
peaks), 25.5, 22.7 (CH2), 26.9 (ꢂ3), 14.1 (CH3); IR nmax
3460 (br, OH) cmꢀ1; HREIMS m/z (rel int.) 439.3036
(M+ꢀtBu, 9), 199 (100), 139 (36). Calcd for C32H52O2Si–
tBu, 439.3032. Anal. Calcd for C32H52O2Si: C, 77.36; H,
10.55. Found: C, 77.37; H, 10.66.
4.1.6. (2R,3R,4S)-2,3-Epoxy-4-(methoxymethoxy) octa-
decan-1-ol (9). Titanium tetraisopropoxide (0.6 mL, ca.
2 mmol) and D-(ꢀ)-diethyl tartrate (0.38 mL, ca. 2.2 mmol)
were sequentially added at ꢀ20 ꢁC to a stirred suspension
˚
of powdered 4 A molecular sieves (250 mg) in dry CH2Cl2
(5 mL). After stirring for 5 min, a solution of allylic alcohol
8 (526 mg, 1.6 mmol) in dry CH2Cl2 (10 mL) was added, and
the mixture was stirred for 30 min. After this, tert-butyl
hydroperoxide (2.5 mL of a freshly prepared z4 M solution
in toluene, 10 mmol) was added dropwise and the reaction
mixture was further stirred at ꢀ20 ꢁC for 24 h. Work-up
(CH2Cl2) and column chromatography on silica gel (hex-
ane–EtOAc, 7:3) afforded epoxy alcohol 9 (491 mg, 89%):
4.1.2. (2S)-1-(tert-Butyldiphenylsilyloxy)-2-(methoxy-
methoxy)hexadecane (5). Alcohol 4 (1.24 g, 2.5 mmol) was
dissolved in dry CH2Cl2 (25 mL) and treated with MOM
chloride (570 mL, ca. 7.5 mmol), DMAP (12 mg, 0.1 mmol),
and triethyl amine (1.26 mL, ca. 9 mmol). The resulting
solution was stirred at room temperature for 24 h. Work-up
(CH2Cl2) and column chromatography on silica gel (hex-
ane–EtOAc, 19:1) provided compound 5 (1.27 g, 94%): oil;
1
solid; mp 40–41 ꢁC; [a]D ꢀ13.4 (c 1.1, CHCl3); H NMR
(500 MHz) d 4.83 (1H, d, J¼6.8 Hz), 4.63 (1H, d,
J¼6.8 Hz), 3.92 (1H, dq, J¼12.8, 2.2 Hz), 3.63 (1H, dq,
J¼12.8, 4.4 Hz), 3.38 (3H, s), 3.36 (1H, m), 3.02 (1H, dd,
J¼7, 2.2 Hz), 2.99 (1H, dt, J¼4.4, 2.2 Hz), 2.10 (1H, br s,
OH), 1.65–1.50 (2H, m), 1.40–1.20 (24H, br m), 0.87 (3H,
t, J¼7 Hz); 13C NMR (125 MHz) d 77.1, 58.0, 55.6 (CH),
95.5, 61.2, 32.3, 31.9, 29.6 (several overlapped peaks),
25.4, 22.7 (CH2), 55.5, 14.1 (CH3); IR nmax 3450 (br,
OH) cmꢀ1; HRFABMS m/z 345.3009 (M+H)+. Calcd for
C20H41O4, 345.2999. Anal. Calcd for C20H40O4: C, 69.72;
H, 11.70. Found: C, 69.92; H, 11.88.
1
[a]D ꢀ25.4 (c 1.4, CHCl3); H NMR (500 MHz) d 7.70–
7.60 (4H, m), 7.45–7.35 (6H, m), 4.78 (1H, d, J¼6.8 Hz),
4.65 (1H, d, J¼6.8 Hz), 3.70–3.60 (3H, m), 3.36 (3H, s),
1.650–1.20 (26H, br m), 1.07 (9H, s), 0.89 (3H, t, J¼7 Hz);
13C NMR (125 MHz, CDCl3) d 133.6 (ꢂ2), 19.2 (C),
135.7, 135.6, 129.7, 127.7, 78.0 (CH), 96.2, 66.5, 32.0, 31.8,
29.7 (several overlapped peaks), 25.4, 22.7 (CH2), 55.5, 26.9
(ꢂ3), 14.1 (CH3); HREIMS m/z (rel int.) 483.3266 (M+ꢀtBu,
1), 213 (96), 153 (32), 91(50), 71 (100). Calcd for
C34H56O3Si–tBu, 483.3294. Anal. Calcd for C34H56O3Si:
C, 75.50; H, 10.44. Found: C, 75.27; H, 10.32.
4.1.7. (1S,2S)-2-(Methoxymethoxy)-1-[(4S)-(2-trichloro-
methyl-4,5-dihydrooxazol-4-yl)]hexadecan-1-ol (11). A
solution of epoxy alcohol 9 (482 mg, 1.4 mmol) in dry
CH2Cl2 (5 mL) was cooled at 0 ꢁC and treated dropwise
with trichloroacetonitrile (200 mL, 2 mmol) and DBU
(45 mL, 0.3 mmol). The mixture was then stirred for
30 min at 0 ꢁC. Work-up (CH2Cl2) and rapid column chro-
matography on silica gel (hexane–EtOAc, 4:1) gave
4.1.3. (2S)-2-(Methoxymethoxy)hexadecan-1-ol (6). Silyl
ether 5 (1.19 g, 2.2 mmol) was dissolved in dry THF
(20 mL) and treated with a solution of TBAF (680 mg,
2.6 mmol) in dry THF (5 mL). The reaction mixture was
stirred at room temperature until consumption of the starting
material (about 3 h, TLC monitoring!). After removal of all

5424
C. Ribes et al. / Tetrahedron 62 (2006) 5421–5425
trichloroacetimidate 10, which was directly used in the
following reaction.
m/z 418.3547 (M+H)+. Calcd for C23H48NO5, 418.3532.
Anal. Calcd for C23H47NO5: C, 66.15; H, 11.34. Found: C,
66.06; H, 11.40.
A solution of the trichloroacetimidate from above in dry
CH2Cl2 (10 ml) was cooled at 0 ꢁC and treated with diethyl-
aluminum chloride (1 mL of a 1 M solution in hexane,
1 mmol). The reaction mixture was stirred for 5 h at room
temperature and then filtered through a pad of Celite. Solvent
removal in vacuo and column chromatography on silica gel
(hexane–EtOAc, 9:1) yielded 11 (493 mg, 72% overall yield
from 9): oil; [a]D +32.7 (c 1.8, CHCl3); 1H NMR (500 MHz)
d 4.75–4.70 (3H, m), 4.64 (1H, t, J¼9 Hz), 4.42 (1H, dt, J¼9,
5.5 Hz), 3.75–3.65 (2H, m), 3.41 (s, 3H), 2.65 (1H, d,
J¼7 Hz, OH), 1.60 (2H, m), 1.35–1.20 (24H, br m), 0.88
(3H, t, J¼7 Hz); 13C NMR (125 MHz) d 163.6 (C), 79.2,
73.6, 69.1 (CH), 96.7, 73.0, 32.0, 31.1, 29.7 (several overlap-
ped peaks), 25.2, 22.7 (CH2), 56.0, 14.1 (CH3) (the quater-
nary carbon signal from the CCl3 group was not detected);
IR nmax 3440 (br, OH), 1662 (C]N) cmꢀ1; HRFABMS m/z
4.1.10. (2S,3S,4S)-4-(tert-Butyloxycarbonylamino)-2-
(tetradecyl)tetrahydrofuran-3-ol (15). Triol 13 (250 mg,
0.6 mmol) was diluted in dry CH2Cl2 (20 mL), cooled to
0 ꢁC and treated with Et3N (420 mL, 3 mmol), DMAP
(6 mg, 0.05 mmol), and tosyl chloride (343 mg, 1.8 mmol).
The reaction mixture was then stirred at room temperature
until consumption of the starting material (about 20–
30 min). Work-up (CH2Cl2) provided the crude monoto-
sylate 14, which was used directly in the next step.
A solution of crude 14 in MeOH (8 mL) was cooled at 0 ꢁC
and treated with K2CO3 (415 mg, 3 mmol). The reaction
mixture was stirred for 16 h at room temperature and then fil-
tered through a pad of Celite. Solvent removal in vacuo and
column chromatography on silica gel (hexane–EtOAc, 4:1)
afforded 15 (168 mg, 70% overall yield from 13): solid,
mp 110–111 ꢁC; [a]D +6.8 (c 1.0, CHCl3); 1H NMR
(500 MHz) d 5.10 (1H, br d, J¼8 Hz), 4.30 (1H, br s),
4.07 (1H, m), 4.04 (1H, t, J¼8.5 Hz), 3.79 (1H, td, J¼7,
2.8 Hz), 3.58 (1H, t, J¼8.5 Hz), 2.00 (1H, br s, OH), 1.65–
1.55 (2H, m), 1.45 (9H, s), 1.40–1.20 (24H, br m), 0.88
(3H, t, J¼7 Hz); 13C NMR (125 MHz) d 155.7 (C), 82.2
(+Cq), 71.9, 54.3 (CH), 70.3, 31.9, 29.7 (several overlapped
peaks), 26.1, 22.7 (CH2), 28.4, 14.1 (CH3); IR nmax 3365 (br,
OH, NH), 1688 (C]O) cmꢀ1; HRFABMS m/z 400.3463
(M+H)+. Calcd for C23H46NO4, 400.3426. Anal. Calcd for
C23H45NO4: C, 69.13; H, 11.35. Found: C, 69.20; H, 11.42.
488.2111 (M+H)+. Calcd for C22H Cl3NO4, 488.2101.
35
41
Anal. Calcd for C22H40Cl3NO4: C, 54.05; H, 8.25. Found:
C, 54.02; H, 8.11.
4.1.8. (2S,3S,4S)-4-(Methoxymethoxy)-2-(tert-butyloxy-
carbonylamino)octadecan-1,3-diol (12). Oxazoline 11
(489 mg, 1 mmol) was dissolved in THF (6 ml) and treated
with 1 M aq HCl (1.2 mL). The reaction mixture was stirred
at room temperature for 5 h. Solid NaHCO3 (1 g) was then
added, followed by addition of di-tert-butyl dicarbonate
(3 mL of a 1 M solution in THF). The reaction mixture
was then stirred for 16 h at room temperature. Work-up
(EtOAc) and column chromatography on silica gel (hex-
anes–EtOAc, 1:1) furnished 12 (443 mg, 96%): oil; [a]D
4.1.11. Pachastrissamine (jaspine B) (2). A solution of 15
(120 mg, 0.3 mmol) in CH2Cl2 (5 mL) was cooled to 0 ꢁC
and treated with TFA (220 mL, ca. 3 mmol). The reaction
mixture was then stirred for 45 min at room temperature. Af-
ter this time, 2.5 M NaOH in MeOH (2 mL) was added and
the stirring was continued for 5 min. Work-up (CH2Cl2)
and column chromatography on silica gel (CHCl3–MeOH–
aq NH4OH, 95:4:1) furnished 2 (67 mg, 75%): amorphous
solid; [a]D +9 (c 1.5, CHCl3), lit.10 [a]D +7 (c 0.1, CHCl3),
1
+14.4 (c 1.1, CHCl3); H NMR (500 MHz) d 5.40 (1H, br
d, J¼9 Hz), 4.76 (1H, d, J¼6.7 Hz), 4.70 (1H, d,
J¼6.7 Hz), 3.90 (1H, m), 3.75–3.65 (3H, m), 3.55 (1H,
m), 3.41 (s, 3H), 1.65–1.55 (2H, m), 1.44 (9H, s), 1.45–
1.20 (26H, br m), 0.88 (3H, t, J¼7 Hz); 13C NMR
(125 MHz) d 156.0, 79.7 (C), 81.4, 74.6, 52.5 (CH), 97.7,
62.8, 32.0, 31.4, 29.7 (several overlapped peaks), 25.3,
22.7 (CH2), 56.0, 28.4, 14.1 (CH3); IR nmax 3440 (br, OH),
1714 (C]O) cmꢀ1; HREIMS m/z (rel int.) 462.3781
(M+H+, 1), 430 (2), 269 (34), 160 (37), 264 (100), 134
(52), 104 (44), 60 (76), 57 (100). Calcd for C25H52NO6,
462.3794. Anal. Calcd for C25H51NO6: C, 65.04; H, 11.13.
Found: C, 65.02; H, 11.11.
1
lit.11 [a]D +18 (c 0.1, EtOH); H NMR (500 MHz) d 3.92
(1H, dd, J¼8.5, 7.5 Hz), 3.86 (1H, dd, J¼5, 3.5 Hz), 3.73
(1H, ddd, J¼7.5, 7.5, 3.5 Hz), 3.65 (1H, m), 3.51 (1H, dd,
J¼8.5, 7 Hz), 2.00 (1H, br s, OH), 1.70–1.60 (2H, m),
1.45–1.20 (26H, br m), 0.88 (3H, t, J¼7 Hz); 13C NMR
(125 MHz) d 83.3, 71.8, 54.4 (CH), 72.4, 31.9, 29.7 (several
overlapped peaks), 26.4, 22.7 (CH2), 14.1 (CH3); IR nmax
3340 (br, OH, NH) cmꢀ1; HREIMS m/z (rel int.) 299.2774
(M+, 9), 282 (26), 265 (21), 226 (17), 60 (100). Calcd for
C18H37NO2, 299.2824.
4.1.9. (2S,3S,4S)-2-(tert-Butyloxycarbonylamino) octa-
decan-1,3,4-triol (13). A solution of diol 12 (438 mg,
0.95 mmol) in dry CH2Cl2 (10 mL) was cooled at ꢀ78 ꢁC.
Trimethylsilyl bromide (185 mL, 1.4 mmol) was then added
dropwise. The reaction mixture was stirred for 30 min at
ꢀ78 ꢁC. Work-up (EtOAc) and column chromatography
on silica gel (hexane–EtOAc, 1:1) afforded the protected
aminotriol 13 (298 mg, 75%): oil; [a]D ꢀ8.3 (c 1, CHCl3);
1H NMR (500 MHz) d 5.25 (1H, br d, J¼9 Hz), 4.05 (1H,
br d, J¼10.5 Hz), 3.76 (1H, dd, J¼10.5, 4 Hz), 3.63 (1H,
m), 3.53 (1H, m), 3.40 (1H, m), 2.50 (1H, br s, OH), 1.70–
1.60 (2H, m), 1.45 (9H, s), 1.40–1.20 (26H, br m), 0.88
(3H, t, J¼7 Hz); 13C NMR (125 MHz) d 157.2, 80.5 (C),
69.7, 62.1, 53.5 (CH), 73.0, 32.9, 31.9, 29.7 (several overlap-
ped peaks), 26.1, 22.7 (CH2), 28.4, 14.1 (CH3); IR nmax 3400
(br, OH), 3250 (br, NH), 1671 (C]O) cmꢀ1; HRFABMS
4.1.12. N,O-diacetylpachastrissamine (N,O-diacetyl-jas-
pine B) (16). Compound 2 was acetylated under the standard
conditions (Ac2O, Et3N, DMAP, CH2Cl2, room tempera-
ture). Work-up (CH2Cl2) and column chromatography on
silica gel (hexane–EtOAc, 1:1) yielded 1610,11: amorphous
solid; [a]D ꢀ28.4 (c 1, CHCl3); 1H NMR (500 MHz)
d 5.60 (1H, br d, J¼8.2 Hz), 5.40 (1H, dd, J¼5.3, 3.5 Hz),
4.83 (1H, qd, J¼8.2, 5.3 Hz), 4.09 (1H, t, J¼8.2 Hz), 3.90
(1H, ddd, J¼8.2, 5.3, 3.5 Hz), 3.60 (1H, t, J¼8.2 Hz), 2.17
(3H, s), 2.00 (3H, s), 1.55–1.40 (2H, m), 1.35–1.20 (24H,
br m), 0.88 (3H, t, J¼7 Hz); 13C NMR (125 MHz) d 169.9,

C. Ribes et al. / Tetrahedron 62 (2006) 5421–5425
5425
12. The investigated Pachastrissa species contain the same type
´
169.8 (C), 81.2, 73.6, 51.4 (CH), 70.0, 31.9, 29.6 (several
overlapped peaks), 26.0, 22.7 (CH2), 23.2, 20.7, 14.1
of compounds as those of the Jaspis genus: Fernandez, R.;
Dherbomez, M.; Letourneux, Y.; Nabil, M.; Verbist, J. F.;
Biard, J. F. J. Nat. Prod. 1999, 62, 678–680.
(CH3); IR nmax 3215 (NH), 1741, 1642 (C]O) cmꢀ1
;
HREIMS m/z (rel int.) 384 (M+H+, 14), 383.3034 (M+, 4),
340 (14), 323 (27), 264 (100), 157 (30), 114 (44). Calcd
for C22H41NO4, 383.3035.
13. N-Acyl derivatives of a didehydro analogue of 2 (a Z double
bond in the C14 side chain) have recently been isolated from
roots of Incarvillea arguta: Luo, Y.; Yi, J.; Li, B.; Zhang, G.
Lipids 2004, 39, 907–913.
14. From L-serine: (a) Sudhakar, N.; Kumar, A. R.; Prabhakar, A.;
Jagadeesh, B.; Rao, B. V. Tetrahedron Lett. 2005, 46, 325–327;
(b) Bhaket, P.; Morris, K.; Stauffer, C. S.; Datta, A. Org. Lett.
2005, 7, 875–876; From D-ribo-phytosphingosine: (c) van den
Berg, R. J. B. H. N.; Boltje, T. J.; Verhagen, C. P.; Litjens,
R. E. J. N.; van der Marel, G. A.; Overkleeft, H. S. J. Org.
Chem. 2006, 71, 836–839; From D-xylose: (d) Du, Y. G.; Liu,
J.; Linhardt, R. J. J. Org. Chem. 2006, 71, 1251–1253.
Acknowledgements
Financial support has been granted by the Spanish Ministry
of Science and Technology (projects CTQ2005-06688-C02-
01 and CTQ2005-06688-C02-02) and by the BANCAJA-
UJI foundation (project P1-1A2005-15). C.R. thanks the
Spanish Ministry of Education and Science for a pre-doc-
toral fellowship.
´
´
15. (a) Carda, M.; Gonzalez, F.; Sanchez, R.; Marco, J. A. Tetrahe-
dron: Asymmetry 2002, 13, 1005–1010; (b) Carda, M.; Rodrı-
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