The total synthesis of trungapeptin A

Article abstract of DOI:10.1055/s-0029-1219205

Trungapeptin A, a novel cyclodepsipeptide isolated from a marine cyanobacterium (Lyngbya majuscula), has been synthesised and its structure unambiguously confirmed. Georg Thieme Verlag Stuttgart New York.

Full text of DOI:10.1055/s-0029-1219205

LETTER
399
The Total Synthesis of Trungapeptin A
The
T
otal Syn
a
thesis of
T
r
b
ungapeptin
A
ien Fécourt, Janos Sapi, Erika Bourguet*
ICMR-UMR-CNRS 6229, Université de Reims-Champagne-Ardenne, Faculté de Pharmacie, IFR53 Biomolécules,
51 Rue de Cognacq-Jay, 51096 Reims Cedex, France
Fax +33(3)26918029; E-mail: erika.bourguet@univ-reims.fr
Received 30 October 2009
Initially, a linear Cbz-protection-based strategy was en-
visaged (Scheme 1). Protection of Cbz-allo-Ile-OH using
trimethylsilylethanol with diisopropylcarbodiimide (DIC)
and 4-dimethylaminopyridine (DMAP) afforded the cor-
responding ester 2 (78% yield). Deprotection of the Cbz
group was performed by catalytic hydrogenolysis in
methanol (95% yield).
Abstract: Trungapeptin A, a novel cyclodepsipeptide isolated from
a marine cyanobacterium (Lyngbya majuscula), has been synthe-
sised and its structure unambiguously confirmed.
Key words: marine cyanobacterium, Lyngbya majuscule, cyclo-
depsipeptide, total synthesis, lactamisation
HBTU-assisted coupling between H-allo-Ile-OTMSE (3)
and Cbz-Pro-OH gave dipeptide intermediate 4 in good
yield (99%). Dipeptide 5, which was obtained by hydro-
genolysis with Pd/C (10%) in methanol, was coupled with
the phenyllactic acid O-acetate in the presence of HBTU,
as activator. Desacetylation of the obtained pseudopeptide
6 (70% yield) with K2CO3 in methanol afforded free hy-
droxy group containing intermediate 7 without epimerisa-
tion.
Marine cyanobacteria have proven to be an exceptional
source of novel potential pharmaceutical agents.1 Some
cyclopeptides isolated from these bacteria are in phase I or
II clinical trials as antitumor agents (didemnin B, crypto-
phycin, arenastatin A, and kahalalide F, amongst others)2
though their mechanism of action has not yet been eluci-
dated.
Trungapeptin A (1) has been isolated from a cyanobacte-
ria (Lyngbya majuscula) collected from the Trung Prov-
ince of Thailand (Figure 1).3 This depsipeptide is built up
from L-Val, L-NMe-Val, L-(3)-phenyllactic acid (Pla), L-
Pro, and L-allo-Ile residues, and an unusual 3-hydroxy-2-
methyl-7-octynoic acid (Hmoya) unit. Preliminary
screening of 1 exhibited no cytotoxicity against KB and
LoVo cells at 10 mg/mL.
To perform the esterification between 7 and Cbz-NMe-
Val-OH, the following coupling systems were tried with-
out success: HATU4 and 2,4,6-collidine,5 DMTMM6 with
NMM, and isobutyl chloroformate with Et3N. In the pres-
ence of DIC and DMAP, depsipeptide 8 was isolated in
moderate yield (33%), which was improved to 70% under
Yamaguchi’s conditions.7
L-Pro
Incorporation of Cbz-Val-OH into 8 was accomplished
following the procedure describe above: thus, debenzyla-
tion of 8 afforded depsipeptide 9 (89%), which reacted
with Cbz-Val-OH in the presence of HBTU or HATU as
coupling agents to give 10 in 35% yield.
L-(3)-phenyllactic acid
N
O
L-allo-Ile
HN
O
O
O
The lower yield was probably due to the steric hindrance
of the N-methylamino acid moiety. During the final de-
benzylation reaction (Pd/C, MeOH) transesterification of
10 occurred with methanol, and the ester bond of 11 was
partially cleaved.
O
L-NMe-Val
O
Me
N
H
N
O
Hmoya
O
L-Val
Introduction of the unusual Hmoya8 structural feature re-
quired previous secondary alcohol protection, which was
accomplished by using tert-butyldimethylsilylchloride
and imidazole in DMF, as described by McNelis et al.9
The protected Hmoya unit 12 was activated with HBTU
and 2,4,6-collidine and then reacted with the depsipeptide
11 to give compound 13 in 18% yield over two steps
(Scheme 2).10 Simultaneous deprotection of the TMSE-
protected terminal acid and alcohol functions of 13 with
TBAF (4 equiv) afforded the corresponding hydroxyacid
(38% yield), which is the direct precursor of cyclisation.
Unfortunately, the final macrolactonisation was unsuc-
cessful; neither Yamaguchi’s method,7 nor organostannyl
1
Figure 1
The scarcity and challenging structure of 1 prompted us to
synthesise this novel cyclodepsipeptide. Herein, we report
several approaches, including a convergent version
employing a Boc-protection strategy, for the first total
synthesis of Trungapeptin A (1), enabling further pharma-
comodulations for complementary biological tests.
SYNLETT 2010, No. 3, pp 0399–0402
Advanced online publication: 15.01.2010
1
2.
0
2.
2
0
1
0
DOI: 10.1055/s-0029-1219205; Art ID: G31709ST
© Georg Thieme Verlag Stuttgart · New York

400
F. Fécourt et al.
LETTER
Pla
NMeVal
Val
Pro
allo-Ile
Peptide
Yield (%)
Cbz
OH
a
2
Cbz
H2N
OTMSE
78
95
99
96
70
b
Cbz
Cbz
OH
OTMSE
OTMSE
3
4
c
b
5
6
AcO
AcO
HO
O
OH
HN
OTMSE
OTMSE
OTMSE
OTMSE
OTMSE
c
d
7
8
9
CbzNMe
OH
90
70
89
e
CbzNMe
b
Cbz OH
O
MeNH
c
10
11
O
O
35
*
Cbz
b
H2N
OTMSE
OTMSE
NMe
NMe
Scheme 1 Reagents and conditions: (a) Me3SiCH2CH2OH, DIC, DMAP, CH2Cl2, 4 h at r.t.; (b) H2, Pd/C (10%), MeOH, 1 h at r.t.; (c) HBTU
or HATU, 2,4,6-collidine, CH2Cl2, 24 h at r.t.; (d) K2CO3, MeOH, 1.5 h, r.t.; (e) 2,4,6-trichlorobenzoylchloride, THF, Et3N, 0 °C, 30 min, then
add 7 in THF and DMAP, 4 h at r.t. [* estimated yield 20–23%].
The DIC and DMAP mediated protection of Cbz-NMe-
Val-OH with trimethylsilylethanol smoothly afforded 14
O
(85% yield). Deprotection of 14 by hydrogenolysis (Pd/C,
N
OTMSE
N
methanol), followed by coupling of the resulting interme-
diate 15 with Boc-Val-OH, in the presence of HATU and
2,4,6-collidine, afforded dipeptide 16 with an improved
yield (76%).
H
a)
OTBS
O
O
O
O
O
Me
HO
Deprotection of 16 with TBAF in THF and subsequent
coupling with pseudopeptide 7 under Yamaguchi’s condi-
tions allowed the isolation of pentadepsipeptide 18 (68%)
as a diastereoisomeric mixture.12 This partial epimerisa-
tion rendered this approach unsuitable, nevertheless, 18
was useful for preliminary esterification tests with the
Hmoya unit.
N
NH2
12
O
11
O
N
HN
O
O
b) c)
As part of these preliminary studies, we attempted a cou-
pling between deprotected 18 and the secondary alcohol
of the Hmoya unit. To this end, the Hmoya unit was trans-
formed into the corresponding trimethylsilylethyl ester 19
(89% yield) by using trimethylsilylethanol with trimethyl-
silylchloride in CH2Cl2. However, TBAF-assisted depro-
tection of 18 and subsequent esterification with 19, did not
give the expected precursor regardless of the conditions
employed (Yamaguchi’s, Mukaiyama’s,13 DIC/DMAP or
n-Bu2SnO). Since the alkyne chain seemed to be more
bulky than expected, we radically changed our strategy.
OTMSE
no
macrolactonisation
O
O
3
Me
N
H
N
1
5
O
4
6
2
7
13
8
O
OTBS
Scheme 2 Reagents and conditions: (a) HBTU, 2,4,6-collidine,
CH2Cl2, 24 h at r.t.; (b) TBAF, THF, 1 h at r.t.; (c) reagents for macro-
lactonisation (see text).
oxide [(n-Bu3Sn)2O and n-Bu2SnO] as catalytic neutral
agents11 gave the expected natural product 1.
We envisaged introducing the Hmoya unit at an earlier
point in the synthesis prior to final macrolactamisation
with the L-Val.
To avoid cleavage during debenzylation, we decided to
change our strategy to one using Boc-protection. In addi-
tion, to improve the efficiency of the coupling reaction
with the N-methyl-containing intermediate, a convergent
synthesis was carried out using pseudopeptide 7 and pro-
tected dipeptide 17, as the main building blocks
(Scheme 3).
The esterification between the Boc-allo-Ile-OH (20) and
19 under Yamaguchi’s conditions led to the formation of
21 in 82% yield (Scheme 4). This compound was depro-
tected with TFA to remove the Boc-group quantitatively.
Tetradepsipeptide 23, obtained in the same manner as de-
scribed in Scheme 1 using the Boc strategy, was easily
Synlett 2010, No. 3, 399–402 © Thieme Stuttgart · New York

LETTER
The Total Synthesis of Trungapeptin A
401
Pro
Pla
allo-Ile
NMeVal
Val
Yield (%)
Peptide
CbzNMe
OH
a
CbzNMe
OTMSE
OTMSE
OTMSE
14
85
96
76
99
b
Boc
Boc
OH
15
MeNH
NMe
c
16
d
17 (+ 7)
OTMSE
OTMSE
NMe
NMe
HO
O
Boc
OH
e
68
18 (diastereoisomeric mixture)
Boc
Scheme 3 Reagents and conditions: (a) Me3SiCH2CH2OH, DIC, DMAP, CH2Cl2, 18 h at r.t.; (b) H2, Pd/C (10%), MeOH, 1 h at r.t.; (c)
HATU, 2,4,6-collidine, CH2Cl2, 24 h at r.t.; (d) TBAF, THF, 1.5 h at r.t.; (e) 2,4,6-trichlorobenzoylchloride, THF, Et3N, 0 °C, 30 min, then add
7 in THF and DMAP, 4 h at r.t.
coupled with 22 in the presence of HBTU/2,4,6-collidine Acknowledgment
as activator (68% yield).14 Deprotection of 24 by TBAF
and then TFA were also carried out quantitatively.
The authors thank the University of Reims Champagne-Ardenne for
financial support. We thank C. Petermann (NMR), P. Sigaut (MS)
and D. Harakat (HRMS) for spectroscopic measurements.
We were pleased to find that the final macrolactamisation
with Carpino’s HATU reagent proceeded in 47% yield.15
The obtained synthetic Trungapeptin A (1) was found to
References and Notes
be identical in all aspects to those of the natural product.16
(1) Tan, L. T.; Sitachitta, N.; Gerwick, W. H. J. Nat. Prod. 2003,
66, 764.
(2) Newman, D. J.; Cragg, G. M. J. Nat. Prod. 2004, 67, 1216.
(3) Bunyajetpong, S.; Yoshida, W. Y.; Sitachitta, N.; Kaya, K.
O
OH
a)
O
TMSEO
J. Nat. Prod. 2006, 69, 1539.
Boc
N
H
O
(4) (a) Carpino, L. A. J. Am. Chem. Soc. 1993, 115, 4397.
(b) Carpino, L. A.; El-Faham, A. J. Org. Chem. 1994, 59,
695. (c) Carpino, L. A.; El-Faham, A.; Albericio, F.
Tetrahedron Lett. 1994, 35, 2279. (d) Carpino, L. A.; El-
Faham, A. J. Org. Chem. 1995, 60, 3561.
(5) Gennari, C.; Mielgo, A.; Potenza, D.; Scolastico, C.;
Piarulli, U.; Manzoni, L. Eur. J. Org. Chem. 1999, 379.
(6) Kunishima, M.; Kawachi, C.; Morita, J.; Terao, K.; Iwasaki,
F.; Tani, S. Tetrahedron 1999, 55, 13159.
b)
19
Boc
OH
O
N
H
O
TMSEO
20
21
O
OH
O
N
c)
H2N
(7) Inanaga, J.; Hirata, K.; Saeki, H.; Katsuki, T.; Yamaguchi,
M. Bull. Chem. Soc. Jpn. 1979, 52, 1989.
+
O
O
O
(8) Fernández, R.; Rodríguez, J.; Quiñoá, E.; Riguera, R.;
Muñoz, L.; Fernández-Suárez, M.; Debitus, C. J. Am. Chem.
Soc. 1996, 118, 11635.
(9) McNelis, B. J.; Sternbach, D. D.; MacPhail, A. T.
Tetrahedron 1994, 50, 6767.
O
O
TMSEO
Me
N
NHBoc
23
22
O
(10) All new compounds gave spectroscopic data in agreement
22
8
6
with the assigned structures. Data for compound 13: [a]D
O
–63.2 (c 0.5, MeOH). Rf = 0.4 (cyclohexane–EtOAc, 5:5).
1H NMR (300 MHz, CDCl3): d = 0.11 (s, 6 H, SiMe2), 0.05
(s, 9 H, SiMe3), 0.79–0.95 (m, 18 H, CH3 Val, CH3 NMeVal,
CH3 alloIle), 0.95 (s, 9 H, SitBu), 0.95–1.39 (m, 7 H, CH2Si,
CH3, CH2 alloIle), 1.40–1.62 (m, 4 H, CH2CH2, H-4, H-5),
1.90–2.22 (m, 9 H, CHb NMeVal, CHb Val, CHb alloIle,
CH2 Pro, ≡CH, CH2, H-6), 2.35–2.40 (m, 1 H, CH2 Pro),
2.47–2.52 (m, 1 H, CH, H-2), 3.03 (s, 3 H, NMe), 3.06–3.08
(m, 2 H, CH2-Ph), 3.28–3.33 (m, 1 H, NCH2), 3.58–3.66 (m,
1 H, NCH2), 3.70–3.75 (m, 1 H, CH, H-3), 4.22 (dd, J = 7.1,
8.6 Hz, 2 H, OCH2), 4.55 (dd, J = 4.1, 8.5 Hz, 1 H, CHa
alloIle), 4.61–4.64 (m, 2 H, CHa Val, CHa Pro), 5.08 (d,
J = 10.3 Hz, 1 H, CHa NMeVal), 5.19–5.20 (m, 1 H, CHa
Pla), 6.93 (d, J = 9.0 Hz, 1 H, NH Val), 7.14 (d, J = 8.4 Hz,
1 H, NH alloIle), 7.23–7.33 (m, 5 H, Ar-H). 13C NMR
(75 MHz, CDCl3): d = –4.5 (SiMe2), –1.5 (SiMe3), 11.7
(CH3 alloIle), 13.7 (CH3), 14.6 (CH3 alloIle), 17.3 (CH2Si),
N
7
HN
5
3
O
O
O
1
O
4
O
d) e) f)
Trungapeptin A (1)
2
O
Me
N
TMSEO
NHBoc
O
24
Scheme 4 Reagents and conditions: (a) 2,4,6-trichlorobenzoyl-
chloride, THF, Et3N, DMAP, 18 h at r.t.; (b) TFA, CH2Cl2, 1 h at r.t.;
(c) HBTU, 2,4,6-collidine, CH2Cl2, 18 h at r.t.; (d) TBAF, THF, 1 h
at r.t.; (e) TFA, CH2Cl2, 1 h at r.t.; (f) HATU, 2,4,6-collidine, CH2Cl2,
3 d at r.t.
Synlett 2010, No. 3, 399–402 © Thieme Stuttgart · New York

402
F. Fécourt et al.
LETTER
68.7 (≡CH), 73.2 (CHa Pla), 74.7 (CH, C-3), 79.4 [Cq,
C(CH3)3], 83.4 (Cq, C-7), 127.0 (CH), 128.5 (CH), 128.5
(CH), 129.0 (CH), 129.0 (CH), 135.6 (Cq), 155.9 (Cq),
168.9 (C=O Pla), 170.4 (C=O NMeVal), 170.5 (C=O Pro),
171.2 (C=O alloIle), 173.4 (C=O Val), 173.5 (C=O, C-1).
HRMS: m/z calcd for C50H80N4O11NaSi: 963.5491; found:
963.5499. MALDI-TOF MS (LD+): m/z (%) = 963.4 (100)
[M + 23]+·, 872.3 (48), 863.4 (23), 575.0(13), 463.6 (18),
447.5 (67).
18.0 (Cq-tBu), 18.3 (CH2, C-6), 18.4 (CH3 Val), 18.8 (CH3
NMeVal), 19.2 (CH3 Val), 19.5 (CH3 NMeVal), 24.8 (CH2,
C-5), 25.2 (CH2 Pro), 25.8 (SitBu), 26.2 (CH2 alloIle), 26.8
(CH2 Pro), 27.3 (CHb NMeVal), 31.4 (CHb Val), 31.4
(NMe), 31.6 (CH2, C-4), 37.2 (CH2-Ph), 37.4 (CHb alloIle),
45.8 (CH, C-2), 47.0 (NCH2 Pro), 53.7 (CHa Val), 55.7 (CHa
alloIle), 59.9 (CHa Pro), 60.9 (CHa NMeVal), 63.5 (OCH2),
68.4 (≡CH), 73.3 (CHa Pla), 74.6 (CH, C-3), 84.0 (Cq, C-7),
128.9 (CH), 129.1 (CH), 129.1 (CH), 129.4 (CH), 129.4
(CH), 135.8 (Cq), 168.9 (C=O Pla), 170.5 (C=O NMeVal),
170.6 (C=O Pro), 172.0 (C=O alloIle), 172.8 (C=O Val),
173.9 (C=O, C-1). HRMS: m/z calcd for C51H87N4O9Si2:
955.6012; found: 955.6008. MALDI-TOF MS (LD+): m/z
(%) = 978.1 (100) [M + 23]+·, 811.9 (57), 689.7 (17), 499.5
(47), 381.6 (28).
(15) Hale, K. J.; Lazarides, L. Org. Lett. 2002, 4, 1903.
(16) Spectroscopic data of synthetic trungapeptin A (1): [a]D
22
–45 (c 0.37, MeOH). 1H NMR (300 MHz, CDCl3): d = 0.85
(m, 6 H, CH3 alloIle), 0.92 (d, J = 6.7 Hz, 3 H, CH3 Val),
0.95 (m, 1 H, CH2 Pro), 0.96 (d, J = 6.7 Hz, 3 H, CH3 Val),
1.06 (d, J = 6.5 Hz, 3 H, CH3 NMeVal), 1.12 (m, 1 H, CH2
alloIle), 1.19 (d, J = 7.1 Hz, 3 H, CH3), 1.31 (m, 1 H, CH2
alloIle), 1.38 (d, J = 6.5 Hz, 3 H, CH3 NMeVal), 1.41 (m,
1 H, CH2, H-5), 1.45 (m, 1 H, CH2 Pro), 1.52 (m, 1 H, CH2,
H-5), 1.70 (m, 1 H, CH2 Pro), 1.85 (m, 1 H, CH2, H-4), 1.88
(m, 1 H, CHb alloIle), 1.99 (t, J = 2.4 Hz, 1 H, ≡CH), 1.99
(m, 1 H, CH2, H-4), 2.05 (m, 1 H, CHb Val), 2.14 (dd,
J = 6.2, 12.5 Hz, 1 H, CH2 Pro), 2.22 (td, J = 2.7, 6.7 Hz,
2 H, CH2, H-6), 2.41 (m, 1 H, CHb NMeVal), 2.49 (dd,
J = 3.3, 7.1 Hz, 1 H, CH, H-2), 2.99 (s, 3 H, NMe), 3.18 (dd,
J = 10.7, 12.7 Hz, 1 H, CH2-Ph), 3.30 (d, J = 7.6 Hz, 1 H,
CHa Pro), 3.34 (m, 1 H, CH2Ph), 3.39 (m, 1 H, NCH2 Pro),
3.50 (m, 1 H, NCH2 Pro), 4.25 (t, J = 8.1 Hz, 1 H, CHa
alloIle), 4.44 (d, J = 9.6 Hz, 1 H, CHa NMeVal), 4.63 (t,
J = 9.5 Hz, 1 H, CHa Val), 4.95 (dt, J = 3.0, 9.9 Hz, 1 H, CH,
H-3), 5.06 (dd, J = 5.5, 10.5 Hz, 1 H, CHa Pla), 5.96 (d,
J = 9.5 Hz, 1 H, NH Val), 7.24–7.36 (m, 5 H, Ar-H), 7.84 (d,
J = 8.3 Hz, 1 H, NH alloIle). 13C NMR (75 MHz, CDCl3):
d = 11.2 (CH3, alloIle), 12.9 (CH3), 15.4 (CH3, alloIle), 17.9
(CH2, C-6), 18.7 (CH3 Val), 19.7 (CH3 Val), 20.1 (CH3
NMeVal), 21.3 (CH3 NMeVal), 21.8 (CH2 Pro), 24.3 (CH2,
C-5), 26.2 (CH2, alloIle), 28.7 (CH2, C-4), 29.5 (CHb
NMeVal), 30.5 (NMe), 30.6 (CH2 Pro), 31.7 (CHb Val), 35.0
(CHb alloIle), 38.2 (CH2-Ph), 43.2 (CH, C-2), 46.5 (NCH2
Pro), 53.7 (CHa Val), 57.3 (CHa alloIle), 61.0 (CHa Pro),
65.5 (CHa NMeVal), 69.3 (≡CH), 74.7 (CH, C-3), 75.0 (CHa
Pla), 83.7 (Cq, C-7), 127.9 (CH), 129.2 (CH), 129.8 (CH),
134.2 (Cq), 169.1 (C=O Pla), 170.3 (C=O, alloIle), 170.4
(C=O Pro), 171.8 (C=O NMeVal), 172.8 (C=O, C-1), 173.6
(C=O Val). MALDI-TOF MS (LD+): m/z (%) = 745.2 (100)
[M + 23]+·, 723.2 (25) [M]+·, 340.5 (33). IR (film): 734, 912,
1149, 1194, 1248, 1374, 1451, 1518, 1649, 1658, 1730,
2848, 2873, 2923, 2957, 3354 cm–1.
(11) Steliou, K.; Szczygielska-Nowosielska, A.; Favre, A.;
Poupart, M. A.; Hannessian, S. J. Am. Chem. Soc. 1980, 102,
7578.
(12) Unfortunately, we were unable to control this reaction;
coupling of Boc-Val-CO-NMe-Val-OH (17) with 7 under
Yamaguchi’s conditions often afforded a mixture of
diastereoisomers.
(13) Saigo, K.; Usui, M.; Kikuchi, K.; Shimada, E.; Mukaiyama,
T. Bull. Chem. Soc. Jpn. 1977, 50, 1863.
(14) Data for compound 24: [a]D25 –81.6 (c 0.5, MeOH).
Rf = 0.28 (cyclohexane–EtOAc, 7:3). 1H NMR (300 MHz,
CDCl3): d = 0.03 (s, 9 H, SiMe3), 0.80–1.02 (m, 20 H, CH3
Val, CH3 NMeVal, CH3 alloIle, CH2Si), 1.19–1.21 (m, 4 H,
CH3, CH2 alloIle), 1.38–1.62 [m, 12 H, C(CH3)3, CH2
alloIle, CH2, H-5], 1.65–1.75 (m, 2 H, CH2, H-4), 1.80–2.05
(m, 6 H, CHb Val, CHb alloIle, CH2-CH2 Pro, ≡CH), 2.10–
2.20 (m, 3 H, CHb NMeVal, CH2, H-6), 2.30–2.40 (m, 1 H,
CH2 Pro), 2.62–2.67 (m, 1 H, CH, H-2), 2.95–3.10 (m, 5 H,
NMe, CH2-Ph), 3.21–3.32 (m, 1 H, NCH2), 3.55–3.62 (m,
1 H, NCH2), 4.15 (dd, J = 7.1, 8.6 Hz, 2 H, OCH2), 4.32–
4.36 (m, 1 H, CHa Val), 4.53–4.62 (m, 2 H, CHa alloIle, CHa
Pro), 4.95 (d, J = 10.3 Hz, 1 H, CHa NMeVal), 5.15–5.21
(m, 3 H, CHa Pla, CH, H-3, NH Val), 7.15–7.30 (m, 6 H, Ar-
H, NH alloIle). 13C NMR (75 MHz, CDCl3): d = –1.5
(SiMe3), 11.7 (CH3 alloIle), 12.5 (CH3), 14.4 (CH3 alloIle),
17.2 (CH2Si), 17.5 (CH3 Val), 18.0 (CH2, C-6), 18.6 (CH3
NMeVal), 19.3 (CH3 Val), 19.6 (CH3 NMeVal), 24.0 (CH2,
C-5), 25.2 (CH2 Pro), 26.3 (CH2 alloIle), 26.6 (CH2 Pro),
27.3 (CHb NMeVal), 28.1 [C(CH3)3], 30.9 (CHb Val), 30.9
(CH2, C-4), 31.6 (NMe), 37.1 (CH2-Ph), 37.1 (CHb alloIle),
43.3 (CH, C-2), 47.0 (NCH2 Pro), 55.2 (CHa Val), 55.7 (CHa
alloIle), 59.8 (CHa Pro), 61.5 (CHa NMeVal), 62.9 (OCH2),
Synlett 2010, No. 3, 399–402 © Thieme Stuttgart · New York

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