Stereochemically reliable syntheses of pachastrissamine and its 2-epi-congener via oxazolidinone precursors from an established starting material N-tert-butoxycarbonyl-protected phytosphingosine

Article abstract of DOI:10.1055/s-0032-1317506

Efficient, stereochemically unambiguous, total syntheses of pachastrissamine and its 2-epi-congener from the readily available common precursor (1R)-1-{(4S,5S)-2-oxo-4-[(trityloxy)methyl]-1,3-oxazolidin-5-yl} pentadecyl methanesulfonate are reported. Syntheses of (3aS,6R,6aR)- and (3aS,6S,6aR)-6-tetradecylhexahydro-2H-cyclopenta[d][1,3]oxazol-2-one by this route have unambiguously resolved a dispute over the structures of these products. Georg Thieme Verlag KG Stuttgart · New York.

Full text of DOI:10.1055/s-0032-1317506

PAPER
▌3609
paper
Stereochemically Reliable Syntheses of Pachastrissamine and Its
2-epi-Congener via Oxazolidinone Precursors from an Established Starting
Material N-tert-Butoxycarbonyl-Protected Phytosphingosine
Stereochemically Reliable Synthesis of Pachastrissamine
Hoon Bae,a Hongjun Jeon,a Dong Jae Baek,a Dongjoo Lee,*b Sanghee Kim*a
a
College of Pharmacy, Seoul National University, San 56-1, Shilim, Kwanak, Seoul 151-742, Republic of Korea
Fax +82(2)8880649; E-mail: pennkim@snu.ac.kr
b
Department of Pharmacology, College of Medicine, Dankook University, San 29, Anseo-dong, Dongnam-gu, Cheonan-si, Chungnam
330-714, Republic of Korea
Fax +82(41)5597899; E-mail: drlee21@dankook.ac.kr
Received: 04.08.2012; Accepted after revision: 06.10.2012
configuration. This claim was based on the observation
Abstract: Efficient, stereochemically unambiguous, total synthe-
that Datta’s spectroscopic results for pachastrissamine (1)
ses of pachastrissamine and its 2-epi-congener from the readily
were inconsistent with those reported by other groups,3
available common precursor (1R)-1-{(4S,5S)-2-oxo-4-[(trityl-
oxy)methyl]-1,3-oxazolidin-5-yl}pentadecyl methanesulfonate are
and that they resembled those of its 2-epi-congener
reported. Syntheses of (3aS,6R,6aR)- and (3aS,6S,6aR)-6-tetradecy- 2.3b,f,l,q,r,w,z,aa,4 To rationalize the unexpected formation of
lhexahydro-2H-cyclopenta[d][1,3]oxazol-2-one by this route have
unambiguously resolved a dispute over the structures of these prod-
ucts.
4 and 2 from lactol 5, Davies and co-workers suggested an
epimerization pathway (Scheme 1) in which aldehyde 6,
generated in situ from lactol 5, readily undergoes C(2)-
epimerization through a β-elimination/1,4-addition se-
Key words: natural products, stereoselective synthesis, heterocy-
cles
quence during the Wittig olefination step, leading, via the
enal 7, to the more sterically favored trans-tetrahydrofu-
ran intermediate 8.2 When Davies and co-workers raised
In 2005, Datta and co-workers reported a total synthesis of
pachastrissamine (also known as jaspine B; 1) (Figure 1)
through construction of the oxazolidinone intermediate 3
from an L-serine-derived chiral bicyclic lactone as an ad-
vanced intermediate.1
the problem of the stereochemical assignment of Datta’s
oxazolidinone structure, spectroscopic data for both 1 and
2 had been published by several research groups, so that
Davies’s claim regarding the structural assignment of
Datta’s pachastrissamine was highly relevant. However,
the lack of available spectroscopic data for 35 and 46 at the
time precluded any firm conclusion with respect to
Davies’s proposal for a revision of the structure of Datta’s
oxazolidinone.
H2N
OH
H2N
OH
C13H27
C13H27
O
O
(+)-pachastrissamine (1)
(+)-2-epi-pachastrissamine (2)
O
CbzHN
H
O
O
base
β-elimination
O
HN
O
OH
HN
O
HN
O
O
– BnOH
O
O
2S
H
H
O
O
C13H27
C13H27
O
O
5
6
oxazolidinone of
pachastrissamine 3
oxazolidinone of
2-epi-pachastrissamine 4
O
O
O
1,4-
addition
Figure 1 Structures of pachastrissamine (1), 2-epi-pachastrissamine
2, and their oxazolidinone derivatives
steps
KOH
HN
O
HN
2
4
O
2R
In 2008, Davies and co-workers2 claimed, in a review, that
the original stereochemical assignment of both Datta’s
synthetic pachastrissamine (1) and its oxazolidinone in-
termediate 3 were incorrect and that the actual structures
should be revised to those of the corresponding 2-epimers
2 and 4, respectively, both of which possess a (2R,3S,4S)
H
H
OH
8
7
Scheme 1 A plausible mechanism for the C(2)-epimerization of
Datta’s lactol 5 during the Wittig reaction, as suggested by Davies and
co-workers (ref. 2)
This situation prompted us to develop an efficient synthe-
sis of both pachastrissamine (1) and its 2-epi-congener 2
via the corresponding oxazolidinone intermediates 3 and
4, respectively, to resolve the dispute regarding the struc-
SYNTHESIS 2012, 44, 3609–3612
Advanced online publication: 05.11.2012
DOI: 10.1055/s-0032-1317506; Art ID: SS-2012-F0644-OP
© Georg Thieme Verlag Stuttgart · New York
0
0
3
9
-
7
8
8
1
1
4
3
7
-
2
1
0
X

3610
H. Bae et al.
PAPER
tures of the oxazolidinones. We developed concise and ef- thetic intermediates, we turned our attention to an investi-
ficient syntheses of both pachastrissamine (1) and its 2- gation of the stereochemical assignment of the disputed
epi-congener 2 from the common precursor 10 through a oxazolidinone structure proposed by Davies and co-
stereoselective intramolecular etherification, with a mini- workers.
mal manipulation of protecting groups.
When we carefully compared the spectroscopic data for
We recently reported a two-step preparation of 10 (90%) the penultimate oxazolidinone reported by Datta and co-
from N-tert-butoxycarbonyl-protected phytosphingosine workers1 with those reported by other groups3k,p and with
9.7 Oxazolidinone 3 was synthesized in two steps from the ours for compound 3,3ad we realized that there was good
common precursor 10 via mesylate 11 (Scheme 2). The agreement in both the 1H- and 13C NMR data, whereas our
secondary hydroxy group of 10 reacted with mesyl chlo- spectroscopic data for oxazolidinone 4 were significantly
ride in pyridine to give the mesylate 11 in 95% yield. For- different from those of Datta and co-workers (Figure 2).
tunately, treatment of the resulting intermediate 11 with The most striking difference between the spectra of oxa-
boron trifluoride etherate at ambient temperature gave the zolidinones 3 and 4 is that 3 has a peak at δ = 3.50 ppm for
oxazolidinone 3 in 90% yield through removal of the trityl two protons at C(5), whereas 4 has a corresponding reso-
group of 11 and concomitant spontaneous internal etheri-
fication.
Having successfully achieved the conversion of 10 into
oxazolidinone 3, we then examined the transformation of
the same precursor 10 into the 2-epimeric oxazolidinone
4. The trityl group on 10 was initially removed with boron
trifluoride etherate to give the diol 12 in 90% yield. The
primary hydroxy group of 12 was then selectively protect-
ed by treatment with tosyl chloride in pyridine. Subse-
quent etherification at high temperature gave the
oxazolidinone 4 in excellent yield. The spectral data for
this product were identical in all respects to those previ-
ously reported by our group,7 confirming that the stereo-
chemistry was completely controlled in the desired
manner during the reaction sequences. Finally, the oxa-
zolidinones 3 and 4 were converted into pachastrissamine
(1) and its 2-epi-congener 2, respectively, by base-
induced cleavage of the cyclic carbamate under standard
hydrolytic conditions (potassium hydroxide in refluxing
ethanol). Pachastrissamine (1) and its 2-epi-congener 2
were generated in good yields, and their spectral data were
in excellent agreement with those reported in the litera-
ture.3b,f,r,z,aa
Having achieved an efficient synthesis of the naturally oc-
curring pachastrissamine (1) and its 2-epi-congener 2, and
Figure 2 Comparisons of 1H NMR spectra of the Datta’s oxazolidi-
armed with a full set of spectroscopic data for all the syn-
none with those of our oxazolidinones 3 and 4
O
O
H2N
OH
a
c
b
HN
O
HN
O
C13H27
C13H27
O
C13H27
O
TrO
OMs
O
BocHN
HO
OH
11
3
(+)-pachastrissamine (1)
ref. 7
HN
O
C13H27
90%
(2 steps)
C13H27
OH
O
O
TrO
OH
H2N
OH
c
d
e
10
9
HN
O
HN
O
C13H27
C13H27
O
C13H27
O
HO
OH
(+)-2-epi-pachastrissamine (2)
12
4
Scheme 2 Reagents and conditions: (a) MsCl, py, r.t., 12 h, 95%; (b) BF3·OEt2, toluene–MeOH, r.t., 12 h, 90%; (c) aq KOH, EtOH, reflux, 12
h, 72%; (d) BF3·OEt2, toluene–MeOH, r.t., 12 h, 90%; (e) TsCl, DMAP, py, reflux, 12 h, 94%.
Synthesis 2012, 44, 3609–3612
© Georg Thieme Verlag Stuttgart · New York

PAPER
Stereochemically Reliable Synthesis of Pachastrissamine
3611
HRMS-FAB: m/z [M + H]+ calcd for C39H54NO6S: 664.3672;
found: 664.3636.
nance at δ = 3.76–3.96 ppm with a splitting pattern. From
this evident difference in the spectral data, we can firmly
conclude that the structure of the penultimate oxazolidi-
none originally reported by Datta and co-workers was cor-
rectly assigned as 3, and that this is the oxazolidinone
form of 1. However, Datta’s reported spectroscopic data
for pachastrissamine are actually those of its 2-epi-conge-
ner 2.
(4S,5S)-4-(Hydroxymethyl)-5-[(1R)-1-hydroxypentadecyl]-1,3-
oxazolidin-2-one (12)
BF3·OEt2 (43 μL, 0.34 mmol) was added to a soln of oxazolidinone
10 (100 mg, 0.17 mmol) in toluene (3 mL) and MeOH (1 mL) at r.t.
and the mixture was stirred for 12 h at r.t. The reaction was
quenched by slow addition of sat. aq NaHCO3, and the aqueous lay-
er was extracted with EtOAc. The organic phases were combined,
washed with brine, dried (Na2SO4), filtered, and concentrated in
vacuo. The residue was purified by flash chromatography [silica
gel, hexanes–EtOAc (1:1)] to give a white solid; yield: 53 mg
(90%); [α]D24 –39.9 (c 0.5, CHCl3).
In conclusion, we have developed efficient and highly re-
gio- and stereocontrolled syntheses of pachastrissamine
(1) and its 2-epi-congener 2 from the readily available
common intermediate oxazolidinone 10. The stereochem-
ical inconsistency between the Datta and co-workers’
penultimate oxazolidinone and their final product cannot
be accounted for by any logical mechanism, because the
stereogenic centers of 3 and 4 remain intact under the hy-
drolytic conditions that are present during the final step.
Biological assays of the synthetic samples will be reported
later.
IR (CHCl3): 3340, 2917, 2850, 1717, 1691, 1054, 941, 705 cm–1.
1H NMR (400 MHz, CDCl3): δ = 0.87 (t, J = 6.2 Hz, 3 H), 1.26–1.48
(m, 24 H), 1.49–1.62 (m, 1 H), 1.65–1.78 (m, 1 H), 3.66 (dd, J = 5.1,
11.4 Hz, 1 H), 3.77 (dd, J = 5.6, 11.4 Hz, 1 H), 3.83–3.92 (m, 2 H),
4.32–4.40 (m, 1 H).
13C NMR [75 MHz, CDCl3–CD3OD (1:3)]: δ = 15.2, 24.3, 26.5,
31.0, 31.29, 31.32, 31.34, 33.6, 35.9, 58.0, 62.0, 69.9, 82.9, 162.1.
HRMS-FAB: m/z [M + H]+ calcd for C19H38NO4: 344.2801; found:
344.2815.
Except as otherwise indicated, all reactions were carried out under
argon in flame- or oven-dried glassware. In aqueous workup, all or-
ganic solns were dried over Na2SO4 or MgSO4 and filtered before
to rotary evaporation at water-aspirator pressure. Reactions were
monitored by TLC on 0.25-mm precoated silica gel plates (Kiesel-
gel 60F254; Merck). Spots were detected by viewing under UV radi-
ation or by colorization through charring after dipping in a soln of
anisaldehyde, HOAc, and H2SO4 in MeOH, in KMnO4 soln contain-
ing H2SO4 and EtOH, or in ceric ammonium molybdate soln con-
taining H2SO4 and EtOH. Flash chromatography was performed on
silica gel (particle size 0.040–0.063 mm; Merck). Yields refer to
chromatographically and spectroscopically pure compounds unless
otherwise noted. Commercial reagents and solvents were used as re-
ceived, except that all solvents were freshly purified and dried by
(3aS,6S,6aS)-6-Tetradecyltetrahydrofuro[3,4-d][1,3]oxazol-
2(3H)-one (3)
BF3·OEt2 (30 μL, 0.24 mmol) was added to a soln of mesylate 11
(80 mg, 0.12 mmol) in toluene (3 mL) and MeOH (1 mL) at r.t., and
the mixture was stirred for 12 h at r.t. The reaction was quenched by
slow addition of sat. aq NaHCO3, and the aqueous layer was extract-
ed with EtOAc. The organic phases were combined, washed with
brine, dried (Na2SO4), and concentrated in vacuo. The residue was
purified by flash column chromatography [silica gel, CH2Cl2–
24
MeOH (15:1)] to give a white solid; yield: 35 mg (90%); [α]D
+57.5 (c 0.5, CHCl3).
IR (CHCl3): 3330, 3240, 2952, 2925, 2847, 1759, 1720, 1463, 1406,
1321 cm–1.
1H NMR (300 MHz, CDCl3): δ = 0.86 (t, J = 6.8 Hz, 3 H), 1.18–1.48
(m, 24 H), 1.67–1.82 (m, 2 H), 3.45–3.54 (m, 2 H), 3.93 (d, J = 10.5
Hz, 1 H), 4.35 (dd, J = 4.1, 7.7 Hz, 1 H), 4.93 (dd, J = 3.8, 7.4 Hz,
1 H), 6.09 (br s, 1 H, NH).
13C NMR (75 MHz, CDCl3): δ = 14.1, 22.7, 26.0, 28.1, 29.3, 29.47,
29.54, 29.61, 29.63, 29.65, 31.9, 57.1, 63.9, 73.3, 77.2, 159.3.
HRMS-FAB: m/z [M + H]+ calcd for C19H36NO3: 326.2695; found:
326.2706.
1
standard techniques immediately before use. H and 13C spectra
were recorded on Bruker AMX-500 (500 MHz), Bruker Avance
400 (400 MHz), or JEOL JNM-LA 300 (300 MHz) spectrometers.
Chemical shifts are reported relative to CHCl3 as an internal stan-
dard (δ = 7.26 for 1H and δ = 77.0 for 13C). IR spectra were recorded
on a PerkinElmer 1600 FT-IR spectrometer, referenced to a poly-
styrene standard. Low- and high-resolution mass spectra were re-
corded at the Seoul National University national center for inter-
university research facilities using JEOL JMS-700 (FAB or Cl).
(3aS,6R,6aS)-6-Tetradecyltetrahydrofuro[3,4-d][1,3]oxazol-
2(3H)-one (4)
(1R)-1-{(4S,5S)-2-Oxo-4-[(trityloxy)methyl]-1,3-oxazolidin-5-
yl}pentadecyl Mesylate (11)
DMAP (5 mg, 0.05 mmol) and TosCl (335 mg, 1.75 mmol) were
added to a soln of diol 12 (200 mg, 0.60 mmol) in pyridine (10 mL)
at r.t. The mixture was refluxed for 12 h then cooled to r.t. The re-
action was quenched by slow addition of H2O, and the aqueous lay-
er was extracted with EtOAc. The organic phases were combined,
washed with brine, dried over Na2SO4, filtered, and concentrated in
vacuo. The residue was purified by flash chromatography [silica
gel, CH2Cl2–MeOH (10:1)] to give a white solid; yield: 36 mg
(94%); [α]D24 +8.2 (c 0.5, CHCl3).
MsCl (27 μL, 0.34 mmol) was added to a soln of oxazolidinone 10
(100 mg, 0.17 mmol) in pyridine (3 mL) at r.t. and the mixture was
stirred for 12 h at r.t. The reaction was quenched by slow addition
of H2O, and the aqueous layer was extracted with EtOAc. The or-
ganic phases were combined, washed with brine, dried (Na2SO4),
filtered, and concentrated in vacuo. The residue was purified by
flash chromatography [silica gel, hexanes–EtOAc (2:1)] to give a
yellowish oil; yield: 106 mg (95%); [α]D24 –13.1 (c 1.0, CHCl3).
IR (CHCl3): 3267, 2925, 2853, 1763, 1598, 1491, 1448, 1358, 1220,
1176 cm–1.
IR (CHCl3): 3249, 2954, 2920, 2850, 1758, 1728, 1703, 1469, 1408,
1250 cm–1.
1H NMR (400 MHz, CDCl3): δ = 0.86 (t, J = 6.8 Hz, 3 H), 1.19–1.55
(m, 26 H), 3.75 (dd, J = 2.5, 10.2 Hz, 1 H), 3.92 (dd, J = 4.9, 10.2
Hz, 1 H), 4.01–4.06 (m, 1 H), 4.30–4.34 (m, 1 H), 4.69 (dd, J = 2.3,
8.1 Hz, 1 H), 5.63 (br s, 1 H, NH).
1H NMR (300 MHz, CDCl3): δ = 0.87 (t, J = 6.3 Hz, 3 H), 1.12–1.47
(m, 24 H), 1.48–1.76 (m, 2 H), 2.76 (s, 3 H), 3.28 (dd, J = 7.8, 9.9
Hz, 1 H), 3.38 (dd, J = 3.9, 9.9 Hz, 1 H), 4.06 (dt, J = 4.1, 7.6 Hz, 1
H), 4.72 (dd, J = 5.0, 8.0 Hz, 1 H), 4.78–4.86 (m, 1 H), 5.72–5.90
(m, 1 H, NH), 7.19–7.33 (m, 9 H), 7.34–7.42 (m, 6 H).
13C NMR (75 MHz, CDCl3): δ = 14.1, 22.7, 25.4, 29.27, 29.35,
29.45, 29.51, 29.61, 29.64, 29.7, 30.6, 31.9, 56.3, 63.0, 72.6, 77.2,
84.0, 84.2, 158.7.
13C NMR (75 MHz, CDCl3): δ = 14.1, 22.6, 24.4, 29.1, 29.27, 29.30,
29.47, 29.53, 29.60, 29.62, 30.6, 31.9, 38.6, 54.6, 62.2, 77.7, 79.0,
87.6, 127.4, 128.0, 128.2, 128.5, 143.0, 157.9.
© Georg Thieme Verlag Stuttgart · New York
Synthesis 2012, 44, 3609–3612

3612
H. Bae et al.
PAPER
Berg, R.; Boltje, T.; Verhagen, C.; Litjens, R.; van der
HRMS-FAB: m/z [M + H]+ calcd for C19H36NO3: 326.2695; found:
326.2674.
Marel, G.; Overkleeft, H. J. Org. Chem. 2006, 71, 836.
(c) Du, Y.; Liu, 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.; Chandrakumar, A. J. Org. Chem. 2007, 72, 6312.
(j) Abraham, E.; Candela-Lena, J. I.; Davies, S. G.;
Georgiou, M.; Nicholson, R. L.; Roberts, P. M.; Russell, A.
J.; Sánchez-Fernández, E. M.; Smith, A. D.; Thomson, J. E.
Tetrahedron: Asymmetry 2007, 18, 2510. (k) Yakura, T.;
Sato, S.; Yoshimoto, Y. Chem. Pharm. Bull. 2007, 55, 1284.
(l) 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. (m) Passiniemi, M.; Koskinen, A. M.
P. Tetrahedron Lett. 2008, 49, 980. (n) Venkatesan, K.;
Srinivasan, K. V. Tetrahedron: Asymmetry 2008, 19, 209.
(o) Enders, D.; Terteryan, V.; Paleček, J. Synthesis 2008,
2278. (p) Ichikawa, Y.; Matsunaga, K.; Masuda, T.;
Kotsuki, H.; Nakano, K. Tetrahedron 2008, 64, 11313.
(q) Canals, D.; Mormeneo, D.; Fabriàs, G.; Llebaria, A.;
Casas, J.; Delgado, A. Bioorg. Med. Chem. 2009, 17, 235.
(r) Reddipalli, G. S.; Venkataiah, M.; Mishra, M. K.;
Fadnavis, N. W. Tetrahedron: Asymmetry 2009, 20, 1802.
(s) Inuki, S.; Yoshimitsu, Y.; Oishi, S.; Fujii, N.; Ohno, H.
Org. Lett. 2009, 11, 4478. (t) Jayachitra, G.; Sudhakar, N.;
Anchoori, R. K.; Rao, B. V.; Roy, S.; Banerjee, R. Synthesis
2010, 115. (u) Vichare, P.; Chattopadhyay, A. Tetrahedron:
Asymmetry 2010, 21, 1983. (v) Inuki, S.; Yoshimitsu, Y.;
Oishi, S.; Fujii, N.; Ohno, H. J. Org. Chem. 2010, 75, 3831.
(w) Yoshimitsu, Y.; Inuki, S.; Oishi, S.; Fujii, N.; Ohno, H.
J. Org. Chem. 2010, 75, 3843. (x) Urano, H.; Enomoto, M.;
Kuwahara, S. Biosci., Biotechnol., Biochem. 2010, 74, 152.
(y) Salma, Y.; Ballereau, S.; Maaliki, C.; Ladeira, S.;
Andrieu-Abadie, N.; Génnison, Y. Org. Biomol. Chem.
2010, 8, 3227. (z) Passiniemi, M.; Koskinen, A. M. P. Org.
Biomol. Chem. 2011, 9, 1774. (aa) Llaveria, J.; Díaz, Y.;
Matheu, M. I.; Castillón, S. Eur. J. Org. Chem. 2011, 1514.
(ab) Sriniavas Rao, G.; Venkateswara Rao, B. Tetrahedron
Lett. 2011, 52, 6076. (ac) Prasad, K. R.; Penchalaiah, K.
Tetrahedron: Asymmetry 2011, 22, 1400. (ad) Lee, H.-J.;
Lim, C.-M.; Hwang, S.-H.; Jeong, B.-S.; Kim, S. Chem.–
Asian J. 2011, 6, 1943. (ae) Cruz-Gregorio, S.; Espinoza-
Rojas, C.; Quintero, L.; Sartillo-Piscil, F. Tetrahedron Lett.
2011, 52, 6370. (af) Zhao, M.-L.; Zhang, E.; Gao, J.; Zhang,
Z.; Zhao, Y.-T.; Qu, W.; Liu, H.-M. Carbohydr. Res. 2012,
351, 126.
(2S,3S,4S)-4-Amino-2-tetradecyltetrahydrofuran-3-ol
[(+)-Pachastrissamine] (1)
1.0 M aq KOH (1 mL) was added to a soln of oxazolone 3 (20 mg,
0.06 mmol) in EtOH (1 mL) at r.t. The mixture was refluxed for 12
h, cooled to r.t., concentrated, and azeotropically dried with MeOH
(3 × 5 mL) and toluene (3 × 5 mL). The residue was purified by flash
column chromatography [silica gel, CH2Cl2–MeOH–NH4OH
(100:10:1)] to give a white solid; yield: 13.3 mg (72%); [α]D24 +23.2
(c 1.0, MeOH).
IR (CHCl3): 3420, 2917, 2851, 1474 cm–1.
1H NMR (300 MHz, CDCl3): δ = 0.87 (t, J = 6.6 Hz, 3 H), 1.24–1.60
(m, 26 H), 2.13 (br s, 3 H), 3.39 (dd, J = 6.9, 8.4 Hz, 1 H), 3.45 (m,
1 H), 3.60 (dd, J = 5.1, 10.8 Hz, 1 H), 3.62 (m, 1 H), 4.11 (dd, J =
6.0, 8.4 Hz, 1 H).
13C NMR (75 MHz, CDCl3): δ = 14.1, 22.7, 26.3, 29.3, 29.4, 29.57,
29.59, 29.7, 29.8, 31.9, 54.3, 71.8, 72.3, 83.2.
HRMS-FAB: m/z [M + H]+ calcd for C18H38NO2: 300.2903; found:
300.2923.
(2R,3S,4S)-4-Amino-2-tetradecyltetrahydrofuran-3-ol
(2-epi-Pachastrissamine) (2)
1.0 M aq KOH (1 mL) was added to a soln of oxazolone 4 (20 mg,
0.06 mmol) in EtOH (1 mL) at r.t. The mixture was refluxed for 12
h, cooled to r.t., concentrated, and azeotropically dried with MeOH
(3 × 5 mL) and toluene (3 × 5 mL). The residue was purified by flash
column chromatography [silica gel, CH2Cl2–MeOH–NH4OH
(100:10:1)] to give a white solid; yield: 13.3 mg (72%); [α]D24 +38.4
(c 1.0, CHCl3).
IR (CHCl3): 3336, 3277, 3096, 2952, 2916, 2849, 1739, 1596,
1469, 1370 cm–1.
1H NMR (400 MHz, CDCl3): δ = 0.86 (t, J = 6.8 Hz, 3 H), 1.15–1.34
(m, 22 H), 1.35–1.47 (m, 2 H), 1.48–1.62 (m, 2 H), 3.35–3.41 (m, 1
H), 3.41–3.50 (m, 1 H), 3.55–3.62 (m, 2 H), 4.11 (dd, J = 6.4, 8.8
Hz, 1 H).
13C NMR (100 MHz, CDCl3): δ = 14.1, 22.7, 25.9, 29.4, 29.56,
29.59, 29.66, 29.67, 31.9, 33.7, 52.6, 73.2, 74.8, 77.2, 85.2.
HRMS-FAB: m/z [M + H]+ calcd for C18H38NO2 300.2903; found:
300.2892.
Acknowledgment
This work was supported by the SRC/ERC program (R-11-2007-
107-02001-0) and the Basic Science Research Program (2011-
0014370) through the National Research Foundation of Korea
(NRF) funded by the Korean government (MEST). We are grateful
to the Research Institute of Pharmaceutical Sciences at Seoul Natio-
nal University for providing some experimental equipment.
Supporting Information for this article is available online at
http://www.thieme-connect.com/ejournals/toc/synthesis.SnuIomprifgtooatrinSugpIoi
(4) Sánchez-Eleuterio, A.; Quintero, L.; Sartillo-Piscil, F.
J. Org. Chem. 2011, 76, 5466.
nnfomartit
(5) Because syntheses of oxazolidinone 3 were reported
independently by Yakura (2007), Ichikawa (2008), and our
group (2011), spectroscopic data for the oxazolidinone
structure 3 of pachastrissamine were not available until
2007; see references 3k, 3p, and 3ad.
References
(1) Bhaket, P.; Morris, K.; Stauffer, C. S.; Datta, A. Org. Lett.
2005, 7, 875.
(6) The first synthesis of oxazolidinone 4 was reported by our
group in 2011. See ref. 7.
(7) Jeon, H.; Bae, H.; Baek, D. J.; Kwak, Y. S.; Kim, D.; Kim,
S. Org. Biomol. Chem. 2011, 9, 7234.
(2) Abraham, E.; Davies, S. G.; Roberts, P. M.; Russell, A. J.;
Thomson, J. E. Tetrahedron: Asymmetry 2008, 19, 1027.
(3) (a) Sudhakar, N.; Kumar, A. R.; Prabhakar, A.; Jagadeesh,
B.; Rao, B. V. Tetrahedron Lett. 2005, 46, 325. (b) van den
Synthesis 2012, 44, 3609–3612
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