Total synthesis of virgineone aglycone and stereochemical assignment of natural virgineone

Article abstract of DOI:10.1016/j.tetlet.2013.03.006

The first total synthesis of virgineone aglycone has been achieved employing the tandem O-acylation-migration reaction and the olefin cross-metathesis as key steps for fragment couplings. The left-hand segment of virgineone was also synthesized. The absolute configuration of the reported virgineone aglycone was determined to be (2S,7RS,26S) based on NMR analyses and the specific rotation values of the synthetic compounds. The absolute configuration of the natural virgineone was presumed to be (2S,7S,26S) based on NMR analyses of the synthetic virgineone aglycone.

Full text of DOI:10.1016/j.tetlet.2013.03.006

Tetrahedron Letters 54 (2013) 2497–2501
Contents lists available at SciVerse ScienceDirect
Tetrahedron Letters
journal homepage: www.elsevier.com/locate/tetlet
Total synthesis of virgineone aglycone and stereochemical assignment
of natural virgineone
⇑
Arata Yajima , Chieko Ida, Kayoko Taniguchi, Shoko Murata, Ryo Katsuta, Tomoo Nukada
Department of Fermentation Science, Faculty of Applied Bioscience, Tokyo University of Agriculture (NODAI), Sakuragaoka 1-1-1, Setagaya-ku, Tokyo 156-8502, Japan
a r t i c l e i n f o
a b s t r a c t
Article history:
The first total synthesis of virgineone aglycone has been achieved employing the tandem O-acylation–
migration reaction and the olefin cross-metathesis as key steps for fragment couplings. The left-hand seg-
ment of virgineone was also synthesized. The absolute configuration of the reported virgineone aglycone
was determined to be (2S,7RS,26S) based on NMR analyses and the specific rotation values of the syn-
thetic compounds. The absolute configuration of the natural virgineone was presumed to be
(2S,7S,26S) based on NMR analyses of the synthetic virgineone aglycone.
Received 4 February 2013
Revised 1 March 2013
Accepted 4 March 2013
Available online 13 March 2013
Keywords:
Virgineone
Ó 2013 Elsevier Ltd. All rights reserved.
Tetramic acid
Absolute configuration
b-Mannoside
Lachnum virgineum
Significant attention has been paid to naturally occurring tetra-
mic acid derivatives due to their unique biological activities, and
there are many reports on the synthetic studies of such tetramic
acids.1 The natural tetramic acid derivatives are known to be bio-
synthesized from an amino acid assembled by a polyketide chain,
so the structural variety exhibited is therefore derived from both
the amino acid moiety and the polyketide chain. Some tetramic
acids possess a cyclized side chain, and others possess a glycosyl-
ated side chain. Although the structure and the stereochemistry
of many tetramic acid natural products have been elucidated, there
exist some tetramic acids whose structures have not previously
been fully elucidated, such as vancoresmycin,2 lydicamycin,3 and
pyrroindomycins.4
albicans, Aspergillus fumigatus, and Trichophyton mentagrophytes.5
It is noteworthy that virgineone was reported to show different
CaFT profiling from radicicol, cyclosporine A, FK506, and rapamycin,
which indicates that the target or mechanism of action (MOA) of vir-
gineone is different from other well-known natural antibiotics. We
were interested in synthesizing virgineone to conduct detailed bio-
logical studies, including the MOA analysis of virgineone. However,
a clarification of the absolute configuration of the natural virgineone
was needed prior to performing the biological studies.
Before starting the synthetic studies we found a slightly curious
difference in the reported 1H NMR spectra of virgineone recorded
in DMSO-d6 and CD3OD.5 A doublet corresponding to the C28
methyl group was observed at 0.80 ppm in DMSO-d6, while two
pairs of doublets were observed at 0.91–0.98 ppm in CD3OD. These
results suggested the following two possibilities: (1) the tautomer-
ism of virgineone caused this difference seen in the different sol-
vent7 or (2) virgineone is a stereoisomeric mixture at C2 and/or
C7 and the corresponding diastereomers were indistinguishable
when DMSO-d6 was used in the NMR analysis. To clarify this, we
focused on virgineone aglycone (2), derived from the natural vir-
gineone because structural analysis of 2 would be easier than that
of 1. Data, including the NMR spectra and specific rotation value of
2 were also reported.5 Thus, we selected 2 as the first synthetic tar-
get to determine the absolute configuration of the natural product.
This Letter describes the first total synthesis of 2 and a left-hand
segment of 1 and the determination of the stereochemistry of
natural virgineone.
A tyrosine-derived tetramic acid, virgineone (1), was isolated
from saprotrophic Lachnum virgineum by Singh and co-workers in
2009.5 Although the structure of 1 was elucidated on the basis of
UV, NMR, and HRESIFTMS analyses as shown in Figure 1, the rela-
tive and absolute configuration of the natural product was not as-
signed, except for the b-D-mannoside portion of the molecule.
From a structural view point, 1 is similar to epicoccamides (3
and 4, Fig. 1) isolated from a jellyfish-derived fungus Epicoccum
purpurascens and the Epicoccum sp. associated with a tree fungus.6
The absolute configuration of epicoccamides has also previously
remained undetermined.
Virgineone was discovered by the Candida albicans fitness test
(CaFT) and shown to exhibit broad-spectrum antifungal activity
against a number of key pathogenic fungal strains such as C.
We assumed that it would be possible to determine the abso-
lute configuration of the C26 stereogenic center by a simple com-
parison of the NMR spectra of the two diastereomers originating
⇑
Corresponding author. Tel./fax: +81 3 5477 2264.
E-mail address: ayaji@nodai.ac.jp (A. Yajima).
0040-4039/$ - see front matter Ó 2013 Elsevier Ltd. All rights reserved.
http://dx.doi.org/10.1016/j.tetlet.2013.03.006

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A. Yajima et al. / Tetrahedron Letters 54 (2013) 2497–2501
Figure 1. Structures of virgineone and related tetramic acids.
from the terminal b-mannoside and the C26 secondary hydroxy
group. We first synthesized the left-hand segment of 1 (Scheme 1).
The racemic glycosyl acceptor 7 was synthesized from the com-
mercially available 5. Alcohol 5 was tosylated, and a dihydroxyla-
tion of the double bond of the obtained tosylate was followed by
a protection of the resulting two hydroxy groups as a benzylidene
acetal to afford 6. Tosylate 6 was converted into the corresponding
iodide, and the resulting iodide was alkylated by allyl cuprate, fol-
lowed by the reductive opening of the benzylidene acetal with DI-
BAL to give ( )-7. Optically active 7 was derived from aldehyde 88
via asymmetric a L-proline as an organ-
-aminoxylation9 employing
ocatalyst. The enantiomeric ratio (er) of (R)-7 was determined to be
99:1 by the HPLC analysis.10 The obtained (R)-7 was glycosylated
with 1011 under Crich’s conditions12 to afford the corresponding
b-mannnoside selectively. The yield of the b-mannnoside was rel-
atively low (ca. 30%) due to the formation of unknown by-products
presumably derived from an unwanted side reaction at the termi-
nal double bond. Fortunately, the side reaction was suppressed by
conducting the glycosylation in the presence of 1-hexene as a scav-
enger to afford the b-mannnoside in 60–70% yield. Although the
minor
the 2-naphthylmethyl (NAP) group by DDQ, the precise
tivity of the glycosylation step could not be determined because of
the difficulty of the separation of the -isomer from other un-
a
-isomer was completely eliminated after the removal of
a/b selec-
a
known compounds. Hydrogenolysis of the two benzyl groups and
a benzylidene acetal concomitant hydrogenation of the terminal
double bond gave (20R)-11. The diastereomeric mixture (20RS)-11
was also synthesized from ( )-7.
Although a significant difference was not observed between the
1H NMR spectra of (20R)- and (20RS)-11, small differences were ob-
13
served in their C NMR spectra. The spectrum of (20RS)-11 was in
good accordance with the left-hand part of virgineone except for
the additional four peaks of 33.4, 68.8, 70.6, and 100.3 ppm (indi-
cated in blue in Scheme 1) assigned to be C30, C20, C1, and C2,
respectively.13 The peaks were also observed in the spectrum of
(20R)-11. Because the additional peaks in the spectrum of (20RS)-
11 (indicated in blue) must be originated from (20R)-11, the abso-
lute configuration of the natural virgineone C26 was determined to
be S.
Next, we planned to synthesize the virgineone aglycone (2)
with a 26S stereochemistry to determine the remaining stereo-
chemistries of C2 and C7. Our retrosynthetic analysis of 2 is shown
in Scheme 2. Considering the synthesis of various virgineone deriv-
atives for future structure–activity relationship studies, we em-
ployed a segment coupling strategy. The appropriate segments A,
B, and C would be assembled employing olefin cross-metathesis14
and the tandem O-acylation–migration.15
Segment A was prepared from 12 derived from 8 in the similar
manner as shown in Scheme 1 via oxidative cleavage of the termi-
nal double bond, addition of vinyl Grignard reagent, and Dess–
Martin oxidation of the resulting hydroxy group to give 13 (= A)
(Scheme 3). Because virgineone aglycone might be a diastereo-
meric mixture as described above, we prepared racemic and opti-
Scheme 1. Synthesis of the left-hand segment of virgineone. The 13C NMR chemical
shifts indicated in red are identical with those of the reported data. Reagents,
conditions and yields: (a) TsCl, py., 0 °C; (b) OsO4, NMO, t-BuOH, H2O, 0 °C to rt, 95%
in two steps; (c) PhCH(OMe)2, CSA, MeCN, 0 °C to rt, 93% for 6, 72% from 9; (d) NaI,
acetone, 70 °C; (e) allylmagnesium bromide, CuI, THF, 0 °C to rt, 62% in two steps;
cally active segments
B and C to compare the synthetic
(f) DIBAL, toluene, ꢀ20 °C, 83% for ( )-7, 96% for (R)-7; (g) PhNO,
L-proline, CH2Cl2,
stereoisomers of 2. Racemic 15 (= B) was synthesized from com-
mercially available 14 by a simple alkylation, and the optically ac-
tive (S)- and (R)-15 were synthesized via an Evans
then NaBH4, EtOH, 0 °C, 57%; (h) CuSO4ꢁ5H2O, MeOH, 54%; (i) 10, BSP, TTBP, Tf2O, 1-
hexene, MS3A, CH2Cl2, ꢀ65 °C, 64%; (j) DDQ, CH2Cl2, H2O, 0 °C to rt, 56%; (k) H2, Pd/
C, t-BuOH, MeOH, 70%.

A. Yajima et al. / Tetrahedron Letters 54 (2013) 2497–2501
2499
Scheme 2. Retrosynthetic analysis of virgineone aglycone.
Scheme 3. Synthesis of virgineone aglycone. Reagents, conditions, and yields: (a) (1) OsO4, NMO, acetone, H2O, 0 °C to rt, (2) NaIO4, ether, H2O, 0 °C to rt, quant.; (b)
vinylmagnesium bromide, THF, ꢀ78 °C, 98%; (c) Dess–Martin periodinane, NaHCO3, CH2Cl2, 0 °C to rt, 97%; (d) LDA, MeI, DMPU, THF, ꢀ15 °C to rt, 60%; (e) PivCl, Et3N, LiCl,
ꢀ20 °C; (f) (S)-16 for (S)-isomer or (R)-16 for (R)-isomer, n-BuLi, THF, ꢀ78 °C; then mixed anhydride, 97% for (S)-isomer and 94% for (R)-isomer; (g) NaHMDS, MeI, THF,
ꢀ78 °C, 76% for (S)-isomer and 96% for (R)-isomer; (h) LiOH, H2O2, THF, H2O, 0 °C, 94% for (S)-isomer and 74% for (R)-isomer; (i) 1 N NaOH aq, MeOH, 0 °C; (j) Meldrum’s acid,
DCC, DMAP, CH2Cl2; (k) AcOEt, reflux, 40% in three steps; (l) DCC, DMAP, CH2Cl2, 76%; (m) 13, Grubbs 2nd catalyst, CH2Cl2, reflux; (n) TFA, CH2Cl2, 37% in two steps; (o) H2,
Pd(OH)2/C, TFA, t-BuOH, 61%.
diastereoselective alkylation16 (dr = 98:2) from 14. The racemic
and optically active 18 (= C) was synthesized from ( )- or (S)-17
via acylation of Meldrum’s acid and the subsequent thermal La-
cey–Dieckmann cyclization.17
With the segments A, B, and C in hand, the couplings of the
segments were investigated (Scheme 3). Our preliminary studies
revealed that the tandem O-acylation–migration reaction was
difficult when employing a carboxylic acid with a long carbon
chain. Thus, we first tried to couple the segments B and C instead
of the segments A and B. Namely, (S)-18 was successfully O-acyl-
ated with (S)-15 in the presence of DCC and a stoichiometric
amount of DMAP, then the DMAP mediated O- to C-migration

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A. Yajima et al. / Tetrahedron Letters 54 (2013) 2497–2501
reaction proceeded smoothly in one pot to give 19.7a Recently,
Yoda and co-workers reported employing a stepwise O-acyla-
tion–acyl rearrangement strategy in their syntheses of naturally
occurring tetramic acids.18 They used CaCl2 or NaI as an additive
to accelerate the rearrangement reaction without an epimeriza-
tion at C20 of the 3-acyltetramic acids. Because the amide nitro-
Acknowledgments
We would like to thank Dr. Takuya Tashiro (RIKEN) for the col-
lection of the MS spectra. We thank Mr. Akihiro Kawajiri for his
assistance with the synthesis. This work was supported by a grant
from the Advanced Research Project of the Tokyo University of
Agriculture.
gen of our substrate 18 was protected by
a Boc group,
epimerization at C5 and/or C20 was suppressed to less than 5%
as determined by the 1H NMR analysis of 19. Next, the olefin
cross-metathesis reaction of 19 with 13 catalyzed by the Grubbs
second-generation catalyst19 gave the coupling product in a mod-
erate yield. After removal of the Boc and the benzylidene acetal
groups by TFA, hydrogenolysis of the benzyl group and concomi-
tant hydrogenation of the double bond furnished the desired vir-
gineone aglycone (2S,7S)-2. The stereoisomeric mixtures of
virgineone aglycones (2S,7RS)-2 and (2RS,7R)-2 were also synthe-
sized in a similar fashion.
Supplementary data
Supplementary data (1H and 13C NMR spectra of 2) associated
with this article can be found, in the online version, at http://
dx.doi.org/10.1016/j.tetlet.2013.03.006.
References and notes
1. (a) Ghisalberti, E. L. In Studies in Natural Products Chemistry; Atta-ur-Rahman,
Ed.; Elsevier: Amsterdam, 2003; Vol. 28, pp 109–163; (b) Royles, B. L. Chem.
Rev. 1995, 95, 1981–2001; (c) Schobert, R.; Schlenk, A. Bioorg. Med. Chem. 2008,
16, 4203–4221.
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2002, 43, 435–438.
3. (a) Hayakawa, Y.; Kanamaru, N.; Morisaki, N.; Furihata, K.; Seto, H. J. Antibiot.
1991, 44, 288–292; (b) Hayakawa, Y.; Kanamaru, N.; Morisaki, N.; Seto, H.;
Furihata, K. Tetrahedron Lett. 1991, 32, 213–216.
4. (a) Ding, W.; Williams, D. R.; Northcote, P.; Seigel, M. M.; Tsao, R.; Ashcroft, J.;
Morton, G. O.; Alluri, M.; Abbanat, D.; Maiese, W. M.; Ellestad, G. A. J. Antibiot.
1994, 47, 1250–1257; (b) Singh, M. P.; Petersen, P. J.; Jacobus, N. V.;
Mroczenski-Widley, M. J.; Maiese, W. M.; Greenstein, M.; Steinberg, D. A. J.
Antibiot. 1994, 47, 1258–1265.
The 1H NMR spectra of (2S,7RS)-2 and (2RS,7R)-2 were in good
accordance with that of the reported virgineone aglycone, while
1H NMR spectrum of (2S,7S)-2 was a partial match.20 Namely,
two pairs of doublets were observed at 0.91–0.98 ppm in the 1H
NMR spectra of (2S,7RS)-2 and (2RS,7R)-2, while only one doublet
was observed at 0.95 ppm in the 1H NMR spectrum of (2S,7S)-2.
These results clearly suggested that the virgineone aglycone is a
diastereomeric mixture. Because the ratio of the diastereomers
is estimated to be approximately 1:1 as judged by the reported
NMR spectra, virgineone aglycone would possess C2 and/or C7
in the completely epimerized form. Next, optical rotation values
of the synthetic isomers were compared to determine the stereo-
chemistry of C2 and C7. As shown in Scheme 3, (2S,7S)-2 and
5. Ondeyka, J.; Harris, G.; Zink, D.; Basilio, A.; Vicente, F.; Bills, G.; Platas, G.;
Collado, J.; González, A.; de la Cruz, M.; Martin, J.; Kahn, J. N.; Galuska, S.;
Giacobbe, R.; Abruzzo, G.; Hickey, E.; Liberator, P.; Jiang, B.; Xu, D.; Roemer, T.;
Singh, S. B. J. Nat. Prod. 2009, 72, 136–141.
6. (a) Wright, A. D.; Osterhage, C.; König, G. M. Org. Biomol. Chem. 2003, 1, 507–
510; (b) Wangun, H. V. K.; Dahse, H.-M.; Hertweck, C. J. Nat. Prod. 2007, 70,
1800–1803.
7. (a) Jeong, Y.-C.; Moloney, M. G. J. Org. Chem. 2011, 76, 1342–1354; (b) Gromak,
V. V.; Avakyan, V. G.; Lakhvich, O. F. J. Appl. Spectrosc. 2000, 67, 205–215; (c)
Broughton, H. B.; Woodward, P. R. J. Comput. -Aided Mol. Des. 1990, 4, 147–153.
8. Bérubé, M.; Poirier, D. Can. J. Chem. 2009, 87, 1180–1199.
9. (a) Zhong, G. Angew. Chem., Int. Ed. 2003, 42, 4247–4250; (b) Brown, S. P.;
Brochu, M. P.; Sinz, C. J.; MacMillan, D. W. C. J. Am. Chem. Soc. 2003, 125, 10808–
10809; (c) Hayashi, Y.; Yamaguchi, J.; Hibino, K.; Shoji, M. Tetrahedron Lett.
2003, 44, 8293–8296.
10. Analytical conditions: column: Chiralcel OB-H, hexane/2-propanol = 100/1,
1 ml/min.
(2S,7RS)-2 exhibited relatively similar [a] values as the reported
D
virgineone aglycone [½a D23
ꢂ
ꢀ60, (c 0.3, MeOH)],5 while (2RS,7R)-2
exhibited an opposite sign and a rather low [
a
]
D
value. This
clearly shows that the methyl group at C7 does not have a signif-
icant effect on the [ values and that the stereochemistry of C2
has a great influence on the [
the NMR analyses and the [
a
]
D
a
]
D values. Considering the results of
values of the synthetic isomers of
a]
D
2, the absolute configuration of the reported virgineone aglycone
is concluded to be 2S,7RS,26S.
Interestingly, careful comparison of the 1H and 13C NMR spec-
tra of the synthetic and the reported virgineone aglycone with
those of the natural virgineone revealed that the natural virgine-
one would not be a diastereomeric mixture. Namely, the addi-
tional peaks observed in the spectra of synthetic (2S,7RS)-2 and
(2RS,7R)-2 and reported aglycone have not been recorded in the
reported 13C NMR spectra of natural virgineone. These results
suggest that C7 of aglycone could have epimerized during the
course of the hydrolysis of the mannoside portion of the natural
virgineone.
11. Compound 10 was prepared from a known compound by protection of its 3-OH
group as benzyl ether. Preparation of the compound: see Boltje, T. J.; Li, C.;
Boons, G.-J. Org. Lett. 2010, 12, 4636–4639.
12. Crich, D.; Smith, M. J. Am. Chem. Soc. 2001, 123, 9015–9020.
13. Physical properties of the synthetic 11: (20R)-11: 1H NMR (400 MHz, CD3OD): d
0.89 (t, J = 7.3 Hz, 3H), 1.26–1.48 (m, 20H), 3.20 (ddd, J = 2.5, 6.0, 9.5 Hz, 1H),
3.44 (dd, J = 3.4, 9.4 Hz, 1H), 3.52–3.59 (m, 2H), 3.68–3.77 (m, 3H), 3.86 (dd,
J = 2.5, 9.6 Hz, 1H), 3.88 (d, J = 3.2 Hz, 1H), 4.53 (s, 1H); 13C NMR (100 MHz,
DMSO-d6): d 14.0, 22.1, 25.1, 28.7, 29.02, 29.04, 29.06, 29.10, 29.2, 31.3, 33.4,
61.4, 67.1, 68.8, 70.6, 73.4, 73.6, 77.5, 100.3; HR-MS-ESI (m/z): [M+Na]+ calcd
for C19H38O7Na, 401.2515; found 401.2505; (20RS)-11: 1H NMR (400 MHz,
CD3OD): d 0.89 (t, J = 7.3 Hz, 3H), 1.26–1.48 (m, 20H), 3.20 (ddd, J = 2.5, 6.0,
9.5 Hz, 1H), 3.41–3.45 (m, 1.5H), 3.52–3.58 (m, 1.5H), 3.67–3.76 (m, 2.5H),
3.85–3.90 (m, 2.5H), 4.53 (s, 1H); 13C NMR (100 MHz, DMSO-d6): d 14.0, 22.1,
25.1, 28.7, 29.02, 29.05, 29.07, 29.10, 29.2, 31.3, 33.4, 33.6, 61.4, 67.1, 68.8,
69.0, 70.5, 70.6, 73.4, 73.6, 77.5, 100.3, 100.6; HR-MS-ESI (m/z): [M+Na]+ calcd
for C19H38O7Na, 401.2515; found 401.2505.
14. Connon, S. J.; Blechert, S. Angew. Chem., Int. Ed. 2003, 42, 1900–1923.
15. Hori, K.; Arai, M.; Nomura, K.; Yoshii, E. Chem. Pharm. Bull. 1987, 35, 4368–
4371.
16. Evans, D. A.; Ennis, M. D.; Mathre, D. J. J. Am. Chem. Soc. 1982, 104, 1737–1739.
17. Jouin, P.; Castro, B.; Nisato, D. J. Chem. Soc., Perkin Trans. 1 1987, 1177–1182.
18. (a) Sengoku, T.; Wierzejska, J.; Takahashi, M.; Yoda, H. Synlett 2010, 2944–
2946; (b) Sengoku, T.; Nagae, Y.; Ujihara, Y.; Takahashi, M.; Yoda, H. J. Org.
Chem. 2012, 77, 4391–4401; (c) Ujihara, Y.; Nakayama, K.; Sengoku, T.;
Takahashi, M.; Yoda, H. Org. Lett. 2012, 14, 5142–5145.
In summary, we achieved the first total synthesis of virgineone
aglycone with an O-acylation–acyl migration and an olefin cross-
metathesis as key steps. We also synthesized the left-hand seg-
ment of virgineone via b-selective mannosylation. The absolute
configuration of the C26 of virgineone was determined to be S
on the basis of a simple comparison of the 13C NMR spectra of
the synthesized left-hand segment to that of the natural product.
The stereochemistry of the C2 and C7 stereogenic centers of re-
ported virgineone aglycon were assigned as 2S,7RS on the basis
of the comparison of the NMR spectra and [a] values of the syn-
D
thesized stereoisomers of virgineone aglycone. Since the 1H NMR
chemical shift of C28-methyl group of the synthetic (2S,7S)-2 is
similar to that of natural virgineone, it is reasonable to assume
that the absolute configuration of C7 of the natural virgineon
would be S. Further studies including the total synthesis of vir-
gineone and the confirmation of C7 stereochemistry of the natural
product are currently underway.
19. Scholl, M.; Ding, S.; Lee, C. W.; Grubbs, R. H. Org. Lett. 1999, 1, 953–956.
20. Physical properties of the synthetic 2: (2S,7S)-2: ½a D25
ꢂ
ꢀ101 (c 0.16, MeOH); 1H
NMR (400 MHz, DMSO-d6): d 0.88 (d, J = 6.4 Hz, 3H), 1.15–1.22 (m, 26H), 1.35–
1.50 (m, 4H), 2.36 (m, 4H), 2.61 (br s, 1H), 2.82 (dd, J = 4.1, 13.7 Hz, 1H), 3.21
(m, 2H), 3.34 (m, 1H), 3.50 (m, 1H), 3.90 (m, 1H), 6.58 (d, J = 8.2 Hz, 2H), 6.92 (d,
J = 8.2 Hz, 2H), 9.08 (s, 1H); 13C NMR (100 MHz, DMSO-d6): d 17.6, 23.4, 25.3,
27.1, 28.8–29.4(ꢃ7), 33.2, 33.6, 36.9, 37.0, 42.0, 61.2, 66.2, 71.3, 100.4, 114.9,
130.6, 155.8, 175.8, 194.6, 210.8; HR-MS-ESI (m/z): [M+Na]+ calcd for

A. Yajima et al. / Tetrahedron Letters 54 (2013) 2497–2501
2501
C34H53O7NNa, 610.3720; found 610.3710; (2S,7RS)-2:
½
a 2D3
ꢂ
ꢀ97 (c = 0.32,
J = 6.4 Hz, 1.5H), 1.15–1.22 (m, 26H), 1.35–1.50 (m, 4H), 2.37 (m, 4H), 2.73 (m,
MeOH); 1H NMR (400 MHz, DMSO-d6): d 0.91 (d, J = 6.4 Hz, 1.5H), 0.96 (d,
J = 6.4 Hz, 1.5H), 1.15–1.22 (m, 26H), 1.35–1.50 (m, 4H), 2.36 (m, 4H), 2.72 (m,
1H), 2.80 (m, 1H), 3.21 (m, 2H), 3.34 (m, 1H), 3.50 (m, 1H), 3.90 (m, 1H), 6.56,
1H), 2.82 (m, 1H), 3.24 (m, 2H), 3.35 (m, 1H), 3.51 (m, 1H), 3.90 (m, 1H), 6.58,
6.59 (2 ꢃ d, J = 8.2 Hz, 2H), 6.90, 6.91 (2 ꢃ d, J = 8.2 Hz, 2H), 9.14 (br s, 1H); 13
C
NMR (100 MHz, DMSO-d6): d; 16.9, 17.2, 23.3, 25.2, 26.6, 26.8, 28.8–29.5(ꢃ7),
32.8, 33.4, 34.3, 36.2, 36.6, 41.8, 65.4, 66.0, 71.2, 100.5, 114.69, 114.74, 126.5,
130.8, 155.8, 175.4, 194.6, 210.7; HR-MS-ESI (m/z): [M+Na]+ calcd for
6.57 (2 ꢃ d, J = 8.2 Hz, 2H), 6.89, 6.91 (2 ꢃ d, J = 8.2 Hz, 2H), 9.11 (br s, 1H); 13
C
NMR (100 MHz, DMSO-d6): d; 17.0, 17.4, 23.4, 25.4, 26.8, 27.0, 28.8–29.5(ꢃ7),
33.0, 33.4, 33.6, 36.3, 36.5, 42.0, 61.7, 66.2, 71.3, 100.6, 114.89, 114.92, 126.6,
130.7, 156.0, 175.5, 194.8, 210.8; HR-MS-ESI (m/z): [M+Na]+ calcd for
C
34H53O7NNa, 610.3720; found 610.3705. Although the NMR spectra of
(2S,7RS)-2 and (2RS,7R)-2 were in good accord with those of the reported
spectra,5 we could not observe a signal (C3, d = 191.7 ppm)5 in the 13C NMR
spectra of our synthetic 2.
C34H53O7NNa, 610.3720; found 610.3717; (2RS,7R)-2:
½ ꢂ +5.3 (c 0.28,
a 2D4
MeOH); 1H NMR (400 MHz, DMSO-d6): d 0.92 (d, J = 6.4 Hz, 1.5H), 0.97 (d,