A concise stereoselective total synthesis of herbarumin III

Article abstract of DOI:10.1055/s-2008-1067089

A stereoselective total Synthesis of the phytotoxic compound herbarumin III has been achieved by utilizing Crimmins's aldol approach, 1,3-syn asymmetric reduction, and an olefin metathesis reaction as the key steps.

Full text of DOI:10.1055/s-2008-1067089

1
938
PAPER
A Concise Stereoselective Total Synthesis of Herbarumin III
S
J
tereosele
h
ctive Total
S
i
ynthes
l
H
e
l
rbarum
u
in II
I
S. Yadav,* Veerjala Naveen Kumar, Ramisetti Srinivasa Rao, Pabbaraja Srihari
Division of Organic Chemistry I, Indian Institute of Chemical Technology, Hyderabad 500007, India
Fax +91(40)27160387/27160512; E-mail: yadavpub@iict.res.in
Received 27 February 2008; revised 18 March 2008
These compounds were found to inhibit calmodulin-
dependent enzyme camphosphodiesterase on interaction
with bovine brain calmodulin and also showed significant
phytotoxic effects at low concentration in an assay of
monitoring the radical elongation of Amaranthus hypo-
chondriacus seedlings.4a The antifungal activity of her-
barumin III (7) was the same as that of herbarumin I (5),
better than that of herbarumin II (6) (Figure 1), and ten
times better than that of 2,4-dichlorophenoxyacetic acid.4b
All these features make herbarumin III (7) an important
target for total synthesis. Intrigued by the excellent bio-
logical properties and also structural similarity with high-
ly potent lethaloxin (1) and pinolidoxin (2), we became
interested in the total synthesis of herbarumin III (7). In
continuation of our program towards the total synthesis of
natural products containing lactone moieties with variable
Abstract: A stereoselective total synthesis of the phytotoxic com-
pound herbarumin III has been achieved by utilizing Crimmins’s
aldol approach, 1,3-syn asymmetric reduction, and an olefin meta-
thesis reaction as the key steps.
Key words: macrolide, phytotoxic, Crimmins aldol reaction, syn
reduction, olefin metathesis
Macrolides, particularly lactones with medium-sized
rings (8–10-membered), have continued to attract the at-
tention of both biologists and chemists during recent
years, due to the interesting biological properties and
scarce availability of macrolides. A few examples, in par-
ticular of ten-membered-ring-containing macrolides that
1
display potent biological activity are lethaloxin (1), pin-
2
olidoxin (2), and modiolides A and B (3 and 4)
6
3
sizes, the stereoselective total synthesis of herbarumin III
is described here.
(
Figure 1). The phytotoxic nonenolide (7R,9R)-7-hy-
droxy-9-propylnon-5-en-9-olide (herbarumin III, 7) is
one such example, and has been isolated along with the Our synthetic strategy (Scheme 1) relies on the Crimmins
known herbarumin I (5) and herbarumin II (6) (Figure 1) aldol approach starting from butyraldehyde, stereoselec-
during recent investigations on the fermentation broth and tive 1,3-syn reduction and a well-known ring-closing
mycelium of the fungus Phoma herbarum during an in- metathesis. Thus, our retrosynthetic analysis revealed a
4
vestigation into better potent herbicidal acitivity. Her- key fragment 8 (1,3-syn-diol), which could be coupled to
barumin I, II, and III (5–7; Figure 1) have been hex-5-enoic acid and subjected to an intramolecular
structurally elucidated by spectroscopic methods and their Grubbs metathesis reaction to realize the target molecule
5
total syntheses.
(Scheme 1). The key fragment was obtained by a stereo-
HO
HO
HO
R
O
HO
R1
O
O
HO
HO
O
O
O
O
R2
O
O
O
O
O
1
lethaloxin (1)
pinolidoxin (2)
R = OH, modiolide A (3)
R = H, modiolide B (4)
R
= OH, R2 = H; herbarumin I (5)
R1 = R2 = OH; herbarumin II (6)
1
2
R
= R = H; herbarumin III (7)
Figure 1
HO
S
O
OH
O
PMBO
OH
CHO
S
N
O
Ph
herbarumin III (7)
8
9
butyraldehyde
Scheme 1 Retrosynthesis of herbarumin III
SYNTHESIS 2008, No. 12, pp 1938–1942
x
x.
x
x
.
2
0
0
8
Advanced online publication: 16.05.2008
DOI: 10.1055/s-2008-1067089; Art ID: Z05308SS
Georg Thieme Verlag Stuttgart · New York
©

PAPER
Stereoselective Total Synthesis of Herbarumin III
1939
S
O
S
N
S
O
OH
MeNH(OMe)⋅HCl,
1
0
O
OH
Ph
imidazole
MeO
CHO
butyraldehyde
S
N
+
diastereomer
N
TiCl4, DIPEA,
CH2Cl2
78 °C, 30 min
CH2Cl2, r.t.,
12 h, 74%
9a
11
9
–
(9:1 anti/syn)
Ph
72%
(65%:7% anti/syn)
O
OH
OH OH
PMBCl, NaH
MgBr
THF, –78 °C, 3 h
0%
DIBAL-H, THF
+
diastereomer
3a
–78 °C, 2.5 h
81%
DMF, 1.5 h
0 °C to r.t., 89%
1
12
13
7
(
94:6 syn/anti)
(76%:5% syn/anti)
O
O
OPMB OH
OPMB O
HO
,4,6-trichlorobenzoyl chloride
DDQ
14
2
CH2Cl2/H2O (18:1)
97%
8
DMAP, Et3N, 4 h, r.t. to reflux
1%
15
8
O
HO
OH
O
Grubbs II catalyst
CH2Cl2, 18 h, 89%
O
O
16
herbarumin III (7)
Scheme 2
selective syn reduction of the b-hydroxy oxo group, which known literature; the data were found to be identical in all
in turn was obtained by a Crimmins aldol reaction aspects.5
(
Scheme 1).
In conclusion, we have achieved the total synthesis of her-
Accordingly, our synthesis (Scheme 2) started with bu- barumin III in eight steps, in an overall yield of 16%, by
tyraldehyde, which was subjected to a Crimmins aldol utilizing Crimmins’s aldol protocol, asymmetric 1,3-syn
7
reaction with (S)-1-(4-benzyl-2-thioxothiazolidin-3- reduction, and Grubbs olefin metathesis as the key steps.
yl)ethanone (10) in the presence of titanium (IV) chloride; Application of this strategy in the total synthesis of other
this gave the chiral b-hydroxy amide 9, an anti-aldol prod- analogues is currently in progress.
uct, as the major diastereomer. The thiazolidinethione
Column chromatography was performed on 60–120-mesh silica
gel. All the solvents were dried and distilled prior to use. IR spectra
1
3
13
and C NMR spectra were recorded on Varian Gemini 200, Bruker
Avance 300, and Varian Unity 400 MHZ instruments; TMS was
used as an internal standard. Mass spectra were recorded on Micro-
mass VG 7070H (EI), VG Autospec (FABMS), and Micromass
Quatro LC triple quadrupole (ESI) mass spectrometers. Optical ro-
tations were recorded on a JASCO DIP-360 digital polarimeter at
which was coupled with acid 14 by Yamaguchi’s protocol
to yield ester 15 (Scheme 2). Deprotection of ester 15 by
removal of the p-methoxybenzyl group with 2,3-dichloro-
1
1
(
S)-1-(4-Benzyl-2-thioxothiazolidin-3-yl)ethanone (10)
A 2.5 M soln of n-BuLi in hexane (12.6 mL, 31.5 mmol) was added
to a stirred soln of (S)-4-benzylthiazolidin-2-thione (5.50 g, 26.3
mmol) in anhyd THF (55 mL) at 0 °C under N . The resulting mix-
ture was stirred at 0 °C for 30 min. Then AcCl (2.47g, 31.5 mmol)
was added slowly, and the mixture was stirred for 1 h at the same
7
c
5
,6-dicyano-1,4-benzoquinone afforded 16, which on ex-
2
posure to the Grubbs second-generation catalyst yielded
the target herbarumin III (7) in 89% yield (Scheme 2).12
The product thus obtained was characterized by spectro- temperature. The reaction was quenched with sat. aq NH Cl (30
4
scopic analysis and its identity was also confirmed by mL) and the mixture was extracted with EtOAc (2 × 50 mL). The
combined organic extracts were washed with brine (2 × 30 mL),
comparison of these data with those from the earlier
dried (Na SO ), filtered, and concentrated. The residue was purified
2
4
Synthesis 2008, No. 12, 1938–1942 © Thieme Stuttgart · New York

1
940
J. S. Yadav et al.
PAPER
by column chromatography (silica gel, PE–EtOAc, 95:5); this af-
(R)-5-Hydroxyoct-1-en-3-one (12)
forded pure 10.
A 1.0 M soln of vinylmagnesium bromide in THF (8.57 mL, 8.57
mmol) was added to a stirred soln of 11 (0.50 g, 2.85 mmol) in
2
0
Yield: 95%; bright yellow crystals; [a]D +211.0 (c 1.0, CHCl3).
anhyd THF (10 mL) at –78 °C under N . The mixture was stirred at
2
–
1
IR (KBR): 2923, 1702, 1362, 1215, 1018, 701 cm .
–
78 °C for 3 h, then quenched with sat. aq NH Cl (5 mL), and ex-
4
1
tracted with EtOAc (3 × 20 mL). The combined organic extracts
H NMR (200 MHz, CDCl ): d = 2.70 (s, 3 H), 2.85–3.10 (m, 2 H),
3
were washed with brine (1 × 30 mL), dried (Na SO ), filtered, and
3
7
.20–3.30 (m, 1 H), 3.35–3.40 (m, 1 H), 5.25–5.40 (m, 1 H), 7.20–
.40 (m, 5 H).
2
4
concentrated. The residue was purified by column chromatography
silica gel, PE–EtOAc, 85:15); this afforded pure 12.
(
1
3
C NMR (75 MHz, CDCl ): d = 27.2, 32.0, 36.8, 68.4, 127.4, 129.1,
3
Y
i
e
l
d
:
7
0
%
;
y
e
l
l
o
w
o
i
l
;
[
a
]
2
0
–
2
1
.
0
(
c
0
.
5
5
,
C
H
C
l
)
.
1
29.6, 136.7, 170.9, 201.7.
D
3
–
1
+
IR (neat): 3427, 2925, 2855, 1727, 1629, 1261, 1114, 760 cm .
ESI-MS: m/z = 274 [M + Na].
1
H NMR (200 MHz, CDCl ): d = 0.90 (t, J = 7.3 Hz, 3 H), 1.15–1.40
3
(
1
R)-1-[(S)-4-Benzyl-2-thioxothiazolidin-3-yl]-3-hydroxyhexan-
-one (9)
TiCl (0.86 mL, 7.90 mmol) was added dropwise to a stirred soln of
(
m, 4 H), 2.25–2.33 (m, 1 H), 2.68–2.71 (m, 1 H), 2.75–2.85 (br s,
1
H, OH), 3.97–4.17 (m, 1 H), 5.85–5.95 (m, 1 H), 6.17–6.44 (m, 2
4
H).
1
0 (2.0 g, 7.90 mmol) in anhyd CH Cl (34 mL) at –78 °C under N .
2
2
2
13
C NMR (75 MHz, CDCl ): d = 13.9, 18.6, 38.6, 45.8, 67.3, 128.9,
3
The resulting reddish-brown soln was allowed to stir for 5 min, after
which DIPEA (2.75 mL, 15.80 mmol) was added dropwise and stir-
ring was continued for an additional 30 min at –78 °C. Then a soln
of butyraldehyde (2.13 mL, 23.70 mmol) in CH Cl (15 mL) was
1
36.7, 201.3.
+
ESI-MS: m/z = 165 [M + Na].
2
2
transferred by cannula to the reaction mixture. After the mixture had
stirred for 30 min at –78 °C, the reaction was quenched by the addi-
(3R,5R)-Oct-1-ene-3,5-diol (13)
A 20% soln of DIBAL-H in toluene (1.25 mL, 1.76 mmol) was add-
tion of half-saturated NH Cl (10 mL), and the mixture was allowed
ed dropwise to a stirred soln of 12 (0.10 g, 0.70 mmol) in anhyd
4
to warm to r.t. The organic layer was separated and the aqueous lay-
THF (15 mL) at –78 °C under N . The resulting mixture was stirred
2
er was extracted with CH Cl (3 × 50 mL). The combined organic
at –78 °C for 2.5 h. Then the reaction mixture was quenched with
2
2
extracts were washed with brine (2 × 50 mL), dried (Na SO ), fil-
sat. aq NH Cl (5 mL) and extracted with Et O (3 × 10 mL). The
2
4
4
2
tered, and concentrated. The residue was purified by flash column
chromatography (silica gel, PE–EtOAc, 80:20); this afforded pure
aldol compound 9.
combined organic extracts were washed with brine (1 × 20 mL),
dried (Na SO ), filtered, and concentrated. The residue was purified
2
4
by column chromatography (silica gel, PE–EtOAc, 85:15); this af-
2
0
forded pure 13.
Yield: 65%; yellow oil; [a]D +45.9 (c 1.2, CHCl3).
2
0
–
1
Yield: 76%; yellow oil; [a]
D
+1.1 (c 0.5, CHCl ).
3
IR (neat): 3403, 2925, 1691, 1457, 1262, 1163, 1041, 747, 701 cm .
–
1
1
IR (neat): 3417, 2924, 2857, 1457, 1274, 1124, 1074, 760 cm .
H NMR (300 MHz, CDCl ): d = 0.99 (t, J = 6.7 Hz, 3 H), 1.26–1.61
3
1
(
m, 4 H), 2.65–2.73 (br s, 1 H, OH), 2.91 (d, J = 11.3 Hz, 1 H),
H NMR (200 MHz, CDCl ): d = 0.92 (t, J = 7.1 Hz, 3 H), 1.24–1.42
(m, 4 H), 1.56–1.62 (m, 2 H), 3.78–3.95 (m, 1 H), 4.07–4.20 (m, 1
3
2
.97–3.13 (m, 2 H), 3.22–3.35 (m, 1 H), 3.42 (d, J = 11.3, 7.5 Hz, 1
H), 3.58–3.67 (m, 1 H), 4.08–4.15 (m, 1 H), 5.36–5.43 (m, 1 H),
H), 4.26–4.39 (br s, 1 H, OH), 5.05–5.10 (m, 1 H), 5.19–5.27 (m, 1
7
.22–7.43 (m, 5 H).
H), 5.76–5.94 (m, 1 H).
1
3
13
C NMR (75 MHz, CDCl ): d = 14.2, 18.9, 29.9, 32.2, 38.7, 46.1,
C NMR (50 MHz, CDCl ): d = 14.0, 18.5, 40.2, 42.9, 72.2, 73.8,
3
3
6
7.8, 68.5, 127.5, 129.1, 129.6, 136.6, 173.5, 201.5.
114.3, 140.7.
+
ESI-MS: m/z = 346.0 [M + Na].
(
4R,6R)-6-(4-Methoxybenzyloxy)oct-7-en-4-ol (8)
HRMS–FAB: m/z calcd for C H NO S : 324.1096; found:
1
6
22
2
2
A soln of 13 (0.115 g, 0.79 mmol) in anhyd DMF (1 mL) was added
dropwise to a well-stirred soln of freshly activated NaH (0.031 g,
3
24.1091.
0
.79 mmol) in anhyd DMF (2 mL) at 0 °C under N . After 30 min,
2
(
R)-3-Hydroxy-N-methoxy-N-methylhexanamide (11)
a soln of PMBCl (0.124 g, 0.79 mmol) in anhyd DMF (1 mL) was
added dropwise to the mixture at 0 °C, and the mixture was stirred
for 1 h, before being quenched with ice flakes and extracted with
Imidazole (1.03 g, 15.15 mmol) and MeNH(OMe)·HCl (0.648 g,
6
3
stirred at r.t. for 24 h, and then quenched with sat. aq NH Cl (5 mL).
The organic layer was separated and the aqueous layer was extract-
.06 mmol) were added sequentially to a stirred soln of 9 (1.0 g,
.03 mmol) in anhyd CH Cl (15 mL) under N . The mixture was
2
2
2
Et O (3 × 10 mL). The combined organic extracts were washed with
2
4
brine (1 × 20 mL), dried (Na SO ), filtered, and concentrated. The
2
4
residue was purified by column chromatography (silica gel, PE–
ed with CH Cl (3 × 20 mL). The combined organic extracts were
2
2
EtOAc, 95:5); this afforded pure 8.
washed with brine (1 × 30 mL), dried (Na SO ), filtered, and con-
2
4
20
Yield: 89%; colorless oil; [a]D +17.4 (c 0.5, CHCl3).
centrated. The residue was purified by column chromatography (sil-
ica gel, PE–EtOAc, 85:15); this afforded 11.
IR (neat): 3449, 2927, 2856, 1611, 1513, 1461, 1248, 1033, 758
cm .
–
1
2
0
Yield: 74%; yellow oil; [a]D –7.8 (c 1.5, CHCl3).
1H NMR (200 MHz, CDCl
): d = 0.90 (t, J = 7.0 Hz, 3 H), 1.25–1.40
–
1
3
IR (neat): 3448, 2923, 2853, 1728, 1639, 1461, 759 cm .
(
m, 4 H), 1.55–1.77 (m, 2 H), 3.38–3.48 (br s, 1 H, OH), 3.65–3.76
1
H NMR (200 MHz, CDCl ): d = 0.94 (t, J = 7.5 Hz, 3 H), 1.24–1.63
3
(m, 1 H), 3.79 (s, 3 H), 3.88–4.01 (m, 1 H), 4.25 (d, J = 10.9 Hz, 1
H), 4.54 (d, J = 10.9 Hz, 1 H), 5.16–5.25 (m, 2 H), 5.63–5.81 (m, 1
H), 6.81 (d, J = 8.5 Hz, 2 H), 7.18 (d, J = 8.5 Hz, 2 H).
(
m, 4 H), 2.34–2.43 (m, 1 H), 2.56–2.62 (m, 1 H), 3.18 (s, 3 H),
3
.58–3.62 (br s, 1 H, OH), 3.68 (s, 3 H), 3.92–4.04 (m, 1 H).
1
3
C NMR (50 MHz, CDCl ): d = 13.9, 18.7, 31.8, 38.1, 38.6, 61.1,
13
3
C NMR (50 MHz, CDCl ): d = 14.0, 18.5, 39.7, 42.4, 55.1, 69.8,
3
6
7.5, 173.0.
7
1.0, 81.0, 113.8, 117.4, 129.4, 129.9, 138.2, 159.2.
+
ESI-MS: m/z = 198 [M + Na].
+
ESI-MS: m/z = 287 [M + Na].
HRMS–FAB: m/z calcd for C H NO Na: 198.1109; found:
8
17
3
HRMS–FAB: m/z calcd for C H O Na: 287.1615; found:
1
6
24
3
1
98.1106.
2
87.1623.
Synthesis 2008, No. 12, 1938–1942 © Thieme Stuttgart · New York

PAPER
Stereoselective Total Synthesis of Herbarumin III
1941
(
(
4R,6R)-6-(4-Methoxybenzyloxy)oct-7-en-4-yl Hex-5-enoate
15)
H), 4.29–4.42 (m, 1 H), 5.14–5.28 (m, 1 H), 5.38–5.48 (m, 1 H),
5.56 (d, J = 15.6 Hz, 1 H).
Et N (0.014g, 0.14 mmol) and 2,4,6-trichlorobenzoyl chloride
(
acid (14; 0.014 g, 0.13 mmol) in anhyd THF (2 mL) under N at r.t.
The resulting mixture was allowed to stir at r.t. for 2 h before it was
filtered through a pad of silica gel. The filtrate was concentrated to
dryness. The residue was dissolved in toluene (5 mL), and 8 (0.035
g, 0.13 mmol) and DMAP (0.079 g, 0.65 mmol) were added. The
mixture was stirred at r.t. for 3 h and diluted with EtOAc, and the
13
3
C NMR (50 MHz, CDCl ): d = 13.7, 18.3, 25.9, 29.6, 33.6, 34.6,
3
0.031 g, 0.13 mmol) were added to a stirred soln of hex-5-enoic
3
7.3, 40.4, 67.8, 124.7, 134.5, 176.0.
2
+
ESI-MS: m/z = 235 [M + Na].
HRMS–FAB: m/z calcd for C H O Na: 235.1315; found:
1
2
20
3
2
35.1310.
organic layer was separated. The aqueous layer was extracted with References
EtOAc (2 × 5 mL). The combined organic extracts were washed
(
1) (a) Arnone, A.; Nasini, G.; Merlini, L.; Ragg, E.; Assante, G.
J. Chem. Soc., Perkin Trans. 1 1993, 145. (b) Drager, G.;
Kirschning, A.; Thiericke, R.; Zerlin, M. Nat. Prod. Rep.
with sat. aq NaHCO (2 × 5 mL) and brine (1 × 10 mL), dried
3
(
Na SO ), filtered, and concentrated. The residue was purified by
2 4
column chromatography (silica gel, PE–EtOAc, 98:2); this afforded
pure 15.
Yield: 81%; yellow oil; [a]D20 +8.9 (c 0.65, CHCl3).
1996, 13, 365.
(
2) (a) Evidente, A.; Capasso, R.; Abouzeid, M. A.; Lanzetta,
R.; Vurro, M.; Bottalico, A. J. Nat. Prod. 1993, 56, 1937.
(b) Evidente, A.; Lanzetta, R.; Capasso, R.; Vurro, M.;
Bottalico, A. Phytochemistry 1993, 34, 999.
3) Tsuda, M.; Mugishima, T.; Komatsu, K.; Sone, T.; Tanaka,
M.; Mikami, Y.; Kobayashi, J. J. Nat. Prod. 2003, 66, 412.
4) (a) Rivero-Cruz, J. F.; Macias, M.; Cerda-Garcia-Rojas, C.
M.; Mata, R. J. Nat. Prod. 2003, 66, 511. (b) Rivero-Cruz,
J. F.; Garcia-Aguirre, G.; Gerda-Garcia-Rojas, C.; Mata, R.
Tetrahedron 2000, 56, 5337.
–
1
IR (neat): 2928, 2858, 1731, 1513, 1382, 1247, 1035, 758 cm .
1
H NMR (200 MHz, CDCl ): d = 0.87 (t, J = 7.3 Hz, 3 H), 1.20–1.48
3
(
(
(
m, 4 H), 1.54–1.70 (m, 3 H), 1.84–2.08 (m, 3 H), 2.13–2.21 (t,
J = 7.3 Hz, 2 H), 3.65–3.75 (m, 1 H), 3.77 (s, 3 H), 4.18 (d, J = 11.8
Hz, 1 H), 4.47 (d, J = 11.8 Hz, 1 H), 4.87–5.03 (m, 3 H), 5.12–5.25
(m, 2 H), 5.59–5.82 (m, 2 H), 6.79 (d, J = 8.8 Hz, 2 H), 7.17 (d,
J = 8.8 Hz, 2 H).
1
3
C NMR (50 MHz, CDCl ): d = 13.8, 18.3, 24.1, 33.0, 33.8, 36.5,
(5) For earlier syntheses of herbarumin III, see: (a) Gurjar, M.
K.; Karmakar, S.; Mohapatra, D. K. Tetrahedron Lett. 2004,
45, 4525. (b) Nanda, S. Tetrahedron Lett. 2005, 46, 3661.
(c) Salaskar, A.; Sharma, A.; Chattopadhyay, S.
3
4
1
0.0, 55.2, 67.9, 69.5, 72.3, 113.7, 115.2, 116.9, 117.9, 129.0,
29.3, 129.6, 137.7, 138.2, 159.0, 172.9.
+
ESI-MS: m/z = 383 [M + Na].
Tetrahedron: Asymmetry 2006, 17, 325. (d) Gurjar, M. K.;
Nagaprasad, R.; Ramana, C. V.; Karmakar, S.; Mohapatra,
D. K. ARKIVOC 2005, (iii), 237. (e) Boruwa, J.; Gogoi, N.;
Barua, N. C. Org. Biomol. Chem. 2006, 4, 3521. (f) Chen,
X. S.; Da S, J.; Xu, B.-Y.; Xie, Z.-X.; Li, Y. Chem. J. Chin.
Univ. 2007, 28, 2086. (g) Chen, X. S.; Da S, J.; Yang, L. H.;
Xu, B. Y.; Xie, Z. X.; Li, Y. Chin. Chem. Lett. 2007, 18,
HRMS–FAB: m/z calcd for C H O Na: 383.2188; found:
2
2
32
4
3
83.2198.
(
4R,6R)-6-Hydroxyoct-7-en-4-yl Hex-5-enoate (16)
DDQ (0.18 g, 0.083 mmol) was added to a stirred soln of 15 (0.03
g, 0.083 mmol) in CH Cl (2 mL) and H O (0.1 mL) at 0 °C, and the
2
2
2
mixture was stirred at r.t. for 30 min. Then the mixture was
quenched with sat. aq NaHCO (2 mL) and extracted with CH Cl
255. (h) Gupta, P.; Kumar, P. Tetrahedron: Asymmetry
3
2
2
2007, 18, 1688. (i) Lee, J.; Jung, Y. H.; Tae, J. Bull. Korean
Chem. Soc. 2007, 28, 513. (j) Mohapatra, D. K.; Ramesh, D.
K.; Giardello, M. A.; Chorghade, M. S.; Gurjar, M. K.;
Grubbs, R. H. Tetrahedron Lett. 2007, 48, 2621.
(
(
3 × 5 mL). The combined organic extracts were washed with brine
1 × 10 mL), dried (Na SO ), filtered, and concentrated. The residue
2
4
was purified by column chromatography (silica gel, PE–EtOAc,
0:10); this afforded pure 16.
9
(
6) For our few recent contributions on less-than-ten-
membered-ring lactones, see: (a) Sabitha, G.; Yadagiri, K.;
Yadav, J. S. Tetrahedron Lett. 2007, 48, 1651. (b) Srihari,
P.; Kumar, B. P.; Subbarayudu, K.; Yadav, J. S. Tetrahedron
Lett. 2007, 48, 6977. (c) Sabitha, G.; Bhaskar, V.; Yadagiri,
K.; Yadav, J. S. Synth. Commun. 2007, 2491. (d) Yadav, J.
S.; Niranjan Kumar, N.; Reddy, M. S.; Prasad, A. R.
Tetrahedron 2007, 63, 2689. (e) Srihari, P.; Bhasker, E. V.;
Harshavardhan, S. J.; Yadav, J. S. Synthesis 2006, 4041.
For ten- and more-than-ten-membered-ring lactones, see:
2
0
Yield: 97%; colorless liquid; [a]D +8.9 (c 0.65, CHCl3).
–
1
IR (neat): 3446, 2924, 2853, 1733, 1460, 1173, 724 cm .
1
H NMR (200 MHz, CDCl ): d = 0.92 (t, J = 7.1 Hz, 3 H), 1.25–1.39
3
(
m, 4 H), 1.50–1.89 (m, 4 H), 2.03–2.15 (m, 2 H), 2.26 (t, J = 7.1
Hz, 3 H), 4.10–4.19 (m, 1 H), 4.90–5.24 (m, 5 H), 5.60–5.90 (m, 2
H).
1
3
C NMR (50 MHz, CDCl ): d = 13.8, 18.4, 24.0, 29.6, 33.0, 33.8,
3
3
6.8, 41.5, 70.6, 71.5, 114.9, 115.3, 140.5, 172.0.
(
f) Nagaiah, K.; Sreenu, D.; Rao, R. S.; Yadav, J. S.
+
ESI-MS: m/z = 263 [M + Na].
Tetrahedron Lett. 2007, 48, 7173. (g) Yadav, J. S.; Pratap,
T. V.; Rajender, V. J. Org. Chem. 2007, 72, 5882.
(h) Sabitha, G.; Swapna, R.; Babu, R. S.; Yadav, J. S.
Tetrahedron Lett. 2005, 46, 6145. (i) Yadav, J. S.; Reddy, P.
S. R. Synthesis 2007, 1070. (j) Yadav, J. S.; Kumar, N. N.;
Prasad, A. R. Synthesis 2007, 1175. (k) Yadav, J. S.;
Srihari, P. Tetrahedron: Asymmetry 2004, 15, 81.
HRMS–FAB: m/z calcd for C H O Na: 263.1628; found:
1
4
24
3
2
63.1623.
Herbarumin III (7)
A soln of 16 (0.015 g, 0.062 mmol) and Grubbs II catalyst (0.006
mmol) in degassed anhyd CH Cl (25 mL) was refluxed for 16 h.
2
2
Then the mixture was quenched with ethyl vinyl ether (0.l mL) and
concentrated in vacuo. The residue was purified by column chroma-
tography (silica gel, PE–EtOAc, 92:8); this afforded pure 7.
(7) N-Acetylthiazolidinethione was synthesized by a protocol
similar to that given in the following: (a) Crimmins, M. T.;
Chaudhary, K. Org. Lett. 2000, 2, 775. For Crimmins’s
aldol approach, see: (b) Hodge, M. B.; Olivo, H. F.
Tetrahedron 2004, 60, 9397. (c) Crimmins, M. T.; King, B.
W.; Tabet, E. A.; Chaudhary, K. J. Org. Chem. 2001, 66,
894.
2
0
Yield: 89%; colorless liquid; [a]D +20.6 (c 0.50, CHCl3).
–
1
IR (neat): 3405, 2924, 1721, 1213, 1049, 760 cm .
1
H NMR (200 MHz, CDCl ): d = 0.88 (t, J = 7.0 Hz, 3 H), 1.22–1.43
3
(
m, 4 H), 1.71–1.83 (m, 2 H), 1.86–2.02 (m, 4 H), 2.14–2.43 (m, 3
Synthesis 2008, No. 12, 1938–1942 © Thieme Stuttgart · New York

1
942
J. S. Yadav et al.
PAPER
(
8) (a) Basha, A.; Lipton, M.; Weinreb, S. M. Tetrahedron Lett.
997, 4171. (b) Levin, J. I.; Turos, E.; Weinreb, S. M. Synth.
(10) Kiyooka, S.; Kuroda, H.; Shimasaki, Y. Tetrahedron Lett.
1986, 27, 3009.
1
Commun. 1982, 12, 989.
9) (a) Reiter, M.; Ropp, S.; Gouverneur, V. Org. Lett. 2004, 6,
(11) Jnanaga, J.; Hirata, K.; Saeki, H.; Katsuki, T.; Yamaguchi,
M. Bull. Chem. Soc. Jpn. 1979, 52, 1989.
(
9
1. (b) Lee, E.; Song, H. Y.; Kang, J. W.; Kim, D.-S.; Jung,
(12) (a) Fürstner, A.; Radkowaski, K. Chem. Commun. 2001,
671. (b) Fürstner, A.; Langemann, K. Synthesis 1997, 792.
C.-K.; Joo, J. M. J. Am. Chem. Soc. 2002, 124, 384.
Synthesis 2008, No. 12, 1938–1942 © Thieme Stuttgart · New York