Sarkomycin a methyl esters and functionalized cyclopentane blocks for brefeldin a

Article abstract of DOI:10.1134/S1070428012010022

Sarkomycin A methyl esters and functionalized cyclopentane blocks for brefeldin A were synthesized starting from diastereoisomeric (1R,2S)-and (1S,2R)-2-hydroxymethyl-N-[(1R)-1-phenylethyl]cyclopent-3-ene-1-carboxamides. Pleiades Publishing, Ltd., 2012.

Full text of DOI:10.1134/S1070428012010022

ISSN 1070-4280, Russian Journal of Organic Chemistry, 2012, Vol. 48, No. 1, pp. 8–17. © Pleiades Publishing, Ltd., 2012.
Original Russian Text © A.M. Gimazetdinov, G.V. Ishmurzina, M.S. Miftakhov, 2012, published in Zhurnal Organicheskoi Khimii, 2012, Vol. 48, No. 1,
pp. 16–25.
Sarkomycin A Methyl Esters and Functionalized Cyclopentane
Blocks for Brefeldin A
A. M. Gimazetdinov, G. V. Ishmurzina, and M. S. Miftakhov
Institute of Organic Chemistry, Ufa Research Center, Russian Academy of Sciences,
pr. Oktyabrya 71, Ufa, 450054 Bashkortostan, Russia
e-mail: bioreg@anrb.ru
Received May 14, 2011
Abstract—Sarkomycin A methyl esters and functionalized cyclopentane blocks for brefeldin A were synthe-
sized starting from diastereoisomeric (1R,2S)- and (1S,2R)-2-hydroxymethyl-N-[(1R)-1-phenylethyl]cyclopent-
3-ene-1-carboxamides.
DOI: 10.1134/S1070428012010022
Chiral cyclopentene blocks are key synthons for
the preparation of natural cyclopentanoids and their
analogs [1–3]. We previously described [4] a practical
procedure for the synthesis of individual vicinally
functionalized diastereoisomeric cyclopentenes I and
II which were used to develop rational synthetic
approaches to enantiomeric cyclosarkomycins [5]. Up
to now interest in sarkomycin A [6] and brefeldin A [7]
as antimicrobial, anticancer, and antiviral antibiotics
remains fairly strong. Studies are performed to im-
prove methods of their synthesis [8–12], and new
aspects of their application are revealed [13].
synthesis of enantiomeric sarkomycin A methyl esters
and most important cyclic precursors of brefeldin A.
The structures of the target products and the retro-
synthetic sequence starting from compounds I and II
are shown in Scheme 1.
We initially examined functionalization of the
double bond in lactone IX which was obtained by acid
hydrolysis of compound I in dioxane–9 N H2SO4 [4].
However, seemingly promising approaches to blocks
V–VIII directly from compound IX via epoxidation–
reduction to X, IV, and VI, reduction with BH3 and
oxidation to XI [14], and bromohydroxylation to XII
and XIII turned out to be inappropriate; all these reac-
tions led to the formation of isomer mixtures which
In the present work we demonstrated the possibility
of using compounds I and II as chiral templates by the
Scheme 1.
O
Me
O
Me
CH2
O
O
N
Ph
N
Ph
H
H
COOH
O
OH
OH
R
Sarkomycin A
III, IV
I
II
O
O
Me
HO
R
O
or
R
O
O
O
OH
(7S)-Brefeldin A
V, VI
VII, VIII
III, V, VIII, R = α-OH; IV, VI, VII, R = β-OH.
8

SARKOMYCIN A METHYL ESTERS
9
Scheme 2.
O
O
O
m-ClC6H4CO3H
CH2Cl2
LiAlH4, THF
80%
O
O
HO
O
+
O
HO
X, 60%
IV
1:1
VI
O
O
(1) BH3, THF
(2) NaOH, H2O2
O
O
HO
IX
XI, 92%
O
O
NBS, MeCN–H2O
90%
HO
O
Br
O
+
Br
HO
XIII
XII
1:1
cannot be separated by chromatography on silica gel
(Scheme 2).
trile–water was characterized by acceptable stereo- and
regioselectivity with predominant formation of bromo-
hydrins XIV and XV, respectively (Scheme 3).
An alternative version implied functionalization of
the double bond in monocyclic compounds I and II.
Unlike lactone IX, bromohydroxylation of I and II by
the action of N-bromosuccinimide (NBS) in acetoni-
Compounds XIV and XV were then subjected to
acid hydrolysis, and lactones XII and XVI thus ob-
tained were hydrodebrominated with Bu3SnH in the
Scheme 3.
O
Me
Me
Me
O
Me
NBS, MeCN–H2O
88%
N
H
Ph
Ph
Ph
Ph
N
H
Ph
Ph
Ph
Ph
+
Inseparable isomer mixture
HO
OH
OH
Br
I
XIV
4:1
O
O
Me
NBS, MeCN–H2O
88%
N
H
OH
N
H
OH
+
Inseparable isomer mixture
HO
Br
II
XV
4:1
O
O
Me
O
Me
NBS, MeCN–H2O
80%
N
H
N
N
Ph
H
+
H
HO
Br
OAc
OAc
OAc
Br
HO
XVII
XIX
2:1
XX
O
Me
O
Me
O
Me
NBS, MeCN–H2O
80%
N
N
N
Ph
H
H
+
H
HO
Br
OAc
OAc
OAc
Br
HO
XVIII
XXI
2:1
XXII
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 1 2012

GIMAZETDINOV et al.
10
Scheme 4.
O
Me
O
O
H2SO4, dioxane
Bu3SnH, PhH
88%
N
Ph
H
HO
HO
O
HO
O
94%
OH
Br
Br
XIV
XII
VI
VIII
III
O
Me
O
O
H2SO4, dioxane
94%
Bu3SnH, PhH
88%
N
Ph
H
HO
HO
O
HO
O
OH
Br
Br
XV
XVI
O
Me
O
O
H2SO4, dioxane
94%
Bu3SnH, PhH
88%
N
Ph
H
Br
Br
O
O
OAc
HO
HO
XIII
HO
XX
O
Me
O
O
H2SO4, dioxane
94%
Bu3SnH, PhH
88%
N
Ph
H
HO
HO
O
HO
O
OAc
Br
Br
XIX
XII
VI
O
Me
O
O
3 steps
66%
N
H
OAc
Ph
+
O
HO
O
HO
XVIII
XXIII
1:2
VIII
presence of AIBN in boiling benzene (Scheme 4); the
products, lactones VI and VIII had similar spectral
parameters, melting point 70–71°C, and opposite [α]D18
values, –59.8° (c = 1.017, CH2Cl2) (VIII) and +59.3°
(c = 1.245, CH2Cl2) (VI). According to published data
[15], the melting point of hydroxy lactone VI is 71°C,
[α]D20 = +61.2 (c = 2.64°, CH2Cl2).
Analogous bromohydroxylation of acetoxy deriva-
tives XVII and XVIII (prepared by acetylation of
hydroxy amides I and II) [16] resulted in the formation
of couples of stereo- and regioisomeric bromohydrins
XIX/XX and XXI/XXII at a ratio of 2:1 (Scheme 3).
The subsequent transformations afforded hydroxy
lactones III and VI and their enantiomers XXIII and
VIII (Scheme 4). These bicyclic hydroxy lactones are
important cyclopentane blocks possessing three chiral
centers. Enantiomers VI and VIII can be used in the
synthesis of brefeldin A, whereas lactones III and
XXIII are precursors of sarkomycin A.
A serious problem in the further steps leading to the
target structures was related to opening of the lactone
ring in compounds III (XXIII) and VI (VIII). The use
of benzenethiolate ion [1] and alkaline hydrolysis with
subsequent protection of the carboxy and hydroxy
groups via conversion into tert-butyl(dimethyl)silyl
ester (ether) [17] gave unsatisfactory results. We
succeeded in opening the lactone ring by the action of
thionyl chloride in boiling methanol; hydroxy lactones
III (XXIII) and VI (VIII) were thus converted in high
yield into methyl esters XXIV (XXV) and XXVI
(XXVII), respectively. The hydroxy group in XXIV
and XXV was protected by treatment with
t-BuMe2SiCl, and silyl ethers XXVIII and XXIX are
planned to be used in the synthesis of brefeldin A.
Esters XXVI and XXVII were oxidized with pyridi-
nium chlorochromate (PCC); the oxidation process
was accompanied by dehydrochlorination with forma-
tion of sarkomycin A methyl ester (XXX) and its
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 1 2012

SARKOMYCIN A METHYL ESTERS
11
Scheme 5.
O
O
O
SOCl2, MeOH
88%
t-BuMe2SiCl, CH2Cl2
OMe
Cl
OMe
Cl
HO
O
HO
O
95%
t-BuMe2Si
VI (VIII)
XXIV (XXV)
XXVIII (XXIX)
O
O
O
O
SOCl2, MeOH
88%
PCC, CH2Cl2
80%
H+/H2O [18]
52%
OMe
Cl
OMe
CH2
OH
O
CH2
HO
III (XXIII)
HO
HO
O
XXVI (XXVII)
XXX (XXXI)
(–)- or (+)-Sarkomycin A
[α]1D6 = –53.0°
O
O
PCC, CH2Cl2
75%
H+/H2O [14]
>50%
III (XXIII)
(–)- or (+)-Sarkomycin A
O
XXXII (XXXIII)
[α]1D6 = –363.1°
enantiomer XXXI. Direct oxidation of hydroxy lac-
tones III and XXIII with PCC gave stable sarkomycin
precursors, cyclosarkomycins XXXII and XXXIII,
which were synthesized by us previously from epimers
of III and XXIII at the hydroxy group [5]. Sarko-
mycin methyl esters XXX and XXXI, as well as com-
pounds XXXII and XXXIII, can be converted into
(–)- and (+)-sarkomycins by known methods [14, 18]
(Scheme 5).
and a solution of 1.25 ml (4.6 mmol) of Bu3SnH in
5 ml of benzene was added dropwise over a period of
4 h. The solvent was distilled off, and the residue was
purified by column chromatography on silica gel–KF
(10 wt %) using petroleum ether–ethyl acetate (1:3) as
eluent. Yield 0.29 g (88%), colorless crystals, Rf 0.3
(petroleum ether–ethyl acetate, 1:3), mp 52–54°C,
[α]D16 = +64.8° (c = 1.275, CH2Cl2). IR spectrum, ν,
cm–1: 3344 (O–H), 2966, 1743 (C=O), 1382, 1186,
1
1153, 1069, 992. H NMR spectrum, δ, ppm: 1.64–
EXPERIMENTAL
1.72 m (2H, 5-H, 6-H), 1.82–1.93 m (1H, 5-H), 1.98–
2.14 m (1H, 6-H), 2.32–2.40 br.s (1H, OH), 2.87–
2.97 m (1H, 3a-H), 3.03 t.d (1H, 6a-H, J = 3.36,
9.57 Hz), 4.26–4.36 m (2H, 3-H, 4-H), 4.60 d.d (1H,
3-H, J = 2.59, 9.57 Hz). 13C NMR spectrum, δC, ppm:
27.80 (C6), 34.30 (C5), 43.01 (C6a), 43.51 (C3a), 66.88
(C3), 73.84 (C4), 181.15 (C1). Mass spectrum, m/z
(Irel, %): 143 (100) [M + H]+, 125 (14.9). Found, %:
C 58.88; H 6.77. C7H10O3. Calculated, %: C 59.15;
H 7.04.
The IR spectra were recorded on a UR-20 spec-
trometer from thin films or suspensions in mineral oil.
The H and 13C NMR spectra were measured on
1
a Bruker AM-300 spectrometer at 300 and 75.47 MHz,
respectively, using CDCl3 as solvent and tetramethyl-
silane as internal reference. The mass spectra were
obtained on a Shimadzu LCMS-2010 EV instrument.
Thin-layer chromatography was performed on Sorbfil
plates. The optical rotations were measured on
a Perkin–Elmer 241 MS polarimeter. The purity of
the initial compounds was monitored by GLC on
a Chrom 5 chromatograph.
(3aS,5R,6aR)-5-Hydroxyhexahydro-1H-cyclo-
penta[c]furan-1-one (VI). a. Compound VI was syn-
thesized as described above for hydroxy lactone III
from 0.5 g (2.3 mmol) of bromohydrin XII. Yield
0.29 g (88%), colorless crystals, Rf 0.3, mp 69–70°C,
[α]D16 = –59.5° (c = 1.725, CH2Cl2). IR spectrum, ν,
cm–1: 3367 (O–H), 2954, 2922, 1743 (C=O), 1429,
(3aS,4R,6aR)-4-Hydroxyhexahydro-1H-cyclo-
penta[c]furan-1-one (III). A catalytic amount of azo-
bis(isobutyronitrile) (AIBN) was added to a solution of
0.5 g (2.3 mmol) of compound XIII in 15 ml of
benzene. The mixture was heated to the boiling point,
1
1384, 1199, 1141, 1101, 1037, 1008. H NMR spec-
trum, δ, ppm: 1.80 d (1H, 4-H, J = 14.23 Hz), 1.90–
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 1 2012

GIMAZETDINOV et al.
12
2.05 m (2H, 4-H, 6-H), 2.19 d (1H, 6-H, J = 13.71 Hz),
2.62–2.77 br.s (1H, OH), 2.92–3.03 m (2H, 3a-H,
6a-H), 4.18 d.d (1H, 3-H, J = 2.84, 9.05 Hz), 4.33–
4.42 m (1H, 5-H), 4.48 t.d (1H, 3-H, J = 2.07,
8.79 Hz). 13C NMR spectrum, δC, ppm: 36.65 (C6),
40.07 (C3a), 42.01 (C6a), 43.31 (C4), 73.15 (C3), 74.52
(C5), 181.52 (C1). Mass spectrum, m/z (Irel, %): 143
(100) [M + H]+, 125 (16.7). Found, %: C 58.99;
H 6.82. C7H10O3. Calculated, %: C 59.15; H 7.04.
mixture was stirred for 8 h at room temperature (TLC).
The mixture was then washed with 15 ml of a saturated
solution of Na2S2O3 and 15 ml of 5% aqueous solution
of NaHCO3, dried over MgSO4, and evaporated under
reduced pressure. The residue was subjected to chro-
matography on silica gel using petroleum ether–ethyl
acetate (1:1) as eluent to isolate two epimers at the
oxirane ring. Yield 0.21 mg (60%, Rf 0.2) and 0.14 mg
(30%, Rf 0.4), transparent viscous oily liquids. Major
isomer: [α]D16 = +31.0° (c = 0.93, CHCl3). IR spectrum,
ν, cm–1: 3405, 2924, 1751 (C=O), 1375, 1159, 1055,
b. A solution of 100 mg (7 mmol) of epoxide X in
5 ml of THF was added dropwise under argon to a sus-
pension of 80 mg (2 mmol) of LiAlH4 in 10 ml of
anhydrous THF, cooled to –78°C. The mixture was
stirred for ~2 h until the initial compound disappeared
(TLC). Excess LiAlH4 was decomposed by carefully
adding a 10% solution of H2SO4 at 0°C to pH ~7. The
organic phase was separated, and the aqueous phase
was extracted with ethyl acetate (3×10 ml). The ex-
tracts were combined with the organic phase, washed
with a solution of sodium chloride, dried over MgSO4,
and evaporated under reduced pressure. The residue
was purified by column chromatography on silica gel
using petroleum ether–ethyl acetate (1:3) as eluent.
Yield 86 mg (87%), mixture of regioisomeric alcohols
1
978, 854. H NMR spectrum, δ, ppm: 2.01–2.17 m
(1H, 5-H, J = 7.75, 14.66 Hz), 2.54 d (1H, 5-H, J =
14.78 Hz), 2.86–2.98 m (2H, 1b-H, 4a-H), 3.60 m
(pseudodoublet) (2H, 1a-H, 5a-H, J = 8.35 Hz),
4.43 d.d (1H, 2-H, J = 6.32, 9.18 Hz), 4.55 d (1H, 2-H,
J = 10.30 Hz). 13C NMR spectrum, δC, ppm: 31.01
(C5), 40.07 (C1b), 40.51 (C4a), 58.69 (C5a), 59.55 (C1a),
68.23 (C2), 179.12 (C4). Mass spectrum, m/z (Irel, %):
141 (100) [M + H]+, 80 (23.4). Found, %: C 59.75;
H 5.43. C7H8O3. Calculated, %: C 59.94; H 5.71.
(3aS,4S,5S,6aR)-4-Bromo-5-hydroxyhexahydro-
1H-cyclopenta[c]furan-1-one (XII). a. Compound
XIV, 1.7 g (5 mmol), was dissolved in 20 ml of di-
oxane, 10 ml of 9 N H2SO4 was added, and the mixture
was heated for 4 h under reflux (TLC) and evaporated.
The aqueous phase was extracted with diethyl ether
(3×20 ml), the combined extracts were dried over
MgSO4 and evaporated under reduced pressure, and
the residue was purified by chromatography on silica
gel using petroleum ether–ethyl acetate (1:1) as eluent.
Yield 1.03 g (94%), colorless crystals, Rf 0.65 (petrole-
1
IV and VI at a ratio of 1:1 (according to the H NMR
data), Rf 0.3.
(3aR,5S,6aS)-5-Hydroxyhexahydro-1H-cyclo-
penta[c]furan-1-one (VIII) was synthesized in a simi-
lar way from 0.35 g (1.61 mmol) of compound XVI.
Yield 0.2 g (88%), colorless crystals, Rf 0.3 (petroleum
ether–ethyl acetate, 1:3), mp 70–71°C, [α]D16 = +58.8°
(c = 1.245, CH2Cl2). IR spectrum, ν, cm–1: 3354
(O–H), 2956, 2922, 1745 (C=O), 1429, 1384, 1190,
1141, 1101, 1008. 1H NMR spectrum, δ, ppm: 1.83 d
(1H, 4-H, J = 13.99 Hz), 1.93–2.06 m (2H, 4-H, 6-H),
2.11–2.20 br.s (1H, OH), 2.25 d (1H, 6-H, J =
13.98 Hz), 2.98–3.07 m (2H, 3a-H, 6a-H), 4.21 d.d
(1H, 3-H, J = 2.55, 8.91 Hz), 4.40–4.45 m (1H, 5-H),
4.53 t.d (1H, 3-H, J = 2.14, 8.90 Hz). 13C NMR spec-
trum, δC, ppm: 36.83 (C6), 40.18 (C3a), 42.18 (C6a),
43.22 (C4), 73.37 (C3), 74.64 (C5), 181.57 (C1). Mass
spectrum, m/z (Irel, %): 143 (100) [M + H]+, 125 (12.3).
Found, %: C 58.83; H 6.77. C7H10O3. Calculated, %:
C 59.15; H 7.04.
um ether–ethyl acetate, 1:1), mp 79–81°C, [α]D16
=
–30.4° (c = 1.275, CH2Cl2). IR spectrum, ν cm–1: 3350
(O–H), 2962, 1757, 1734 (C=O), 1458, 1377, 1284,
1
1192, 1041, 991. H NMR spectrum, δ, ppm: 2.04 d
(1H, OH, J = 9.63 Hz), 2.26 d (1H, 6-H, J = 14.02 Hz),
2.64 d.d.d (1H, 6-H, J = 4.12, 9.80, 14.02 Hz), 3.20 t.d
(1H, 6a-H, J = 1.75, 9.90 Hz), 3.31–3.42 m (1H, 3a-H,
J = 9.35 Hz), 4.10–4.17 m (1H, 4-H), 4.32 d.d (1H,
3-H, J = 3.58, 9.63 Hz), 4.40–4.46 m (1H, 5-H), 4.51 t
(1H, 3-H, J = 9.62 Hz). 13C NMR spectrum, δC, ppm:
35.99 (C6), 42.25 (C6a), 48.44 (C3a), 58.00 (C4), 72.70
(C3), 79.20 (C5), 181.06 (C1). Mass spectrum, m/z
(81Br; Irel, %): 223 (10.3) [M + H]+, 141 (100). Found,
%: C 37.81; H 3.88; Br 35.89. C7H9BrO3. Calculated,
%: C 38.01; H 4.07; Br 36.20.
(1aR,1bS,4aR,5aS)-Hexahydro-4H-oxireno[3,4]-
cyclopenta[1,2-c]furan-4-one (X). A solution of
1.45 g (8.4 mmol) of m-chloroperoxybenzoic acid and
0.71 g (8.4 mmol) of NaHCO3 in 10 ml of methylene
chloride was added to a solution of 0.35 g (2.8 mmol)
of lactone IX in 10 ml of methylene chloride, and the
b. As described above for the hydrolysis of hydroxy
amide XIV, from 1.3 g (3.39 mmol) of amide XIX we
obtained 0.7 g (94%) of lactone XII, colorless crystals,
Rf 0.65 (petroleum ether–ethyl acetate, 1:1).
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 1 2012

SARKOMYCIN A METHYL ESTERS
13
c. N-Bromosuccinimide, 580 mg (3.2 mmol), was
added under stirring to a mixture of 200 mg
(1.6 mmol) of lactone X, 16 ml of acetonitrile, and
4 ml of water, and the mixture was stirred for 4 h at
room temperature (TLC). The mixture was then treated
with 10 ml of a saturated solution of Na2S2O3 and
stirred for 1 h, the organic solvent was evaporated, and
the residue was extracted with ethyl acetate (3×15 ml).
The combined extracts were dried over MgSO4 and
evaporated under reduced pressure, and the residue
was purified by column chromatography on silica gel
using petroleum ether–ethyl acetate (1:1) as eluent.
Yield 318 mg (90%), mixture of isomeric bromohy-
drins XII and XIII at a ratio of 1:1 (1H NMR), Rf 0.5.
3.36, 14.78 Hz), 3.87 d.d (1H, CHO, J = 3.10,
7.77 Hz), 4.35–4.41 m (1H, 3-H), 5.05 quint (1H,
CHPh, J = 7.24 Hz), 5.24–5.36 br.s (2H, OH), 7.08 d
(1H, NH, J = 6.94 Hz), 7.23–7.38 m (5H, Ph).
13C NMR spectrum, δC, ppm: 21.86 (CH3), 36.55 (C5),
46.05 (C1), 49.60 (CHPh), 54.85 (C2), 58.01 (C3),
61.33 (CH2O), 80.57 (C4); 126.12, 127.54, 128.75,
143.02 (Carom); 173.81 (C=O). Mass spectrum, m/z
(81Br; Irel, %): 344 (100) [M + H]+, 263 (72.4). Found,
%: C 59.42; H 5.54; Br 23.01; N 3.92. C17H20BrNO3.
Calculated, %: C 59.65; H 5.85; Br 23.39; N 4.09.
(1S,2R,3R,4R)-3-Bromo-4-hydroxy-2-hydroxy-
methyl-N-(1-phenylethyl)cyclopentanecarboxamide
(XV). From 3 g (12 mmol) of compound II we
obtained 0.72 g (18%) of an inseparable mixture of
isomeric bromohydrins (Rf 0.75, petroleum ether–ethyl
acetate, 1:1) and 2.88 g (70%) of compound XV as
a colorless crystalline substance, Rf 0.45 (petroleum
ether–ethyl acetate, 1:1), mp 99–101°C, [α]D16 = +75.9°
(c = 1.05, CH2Cl2). IR spectrum, ν, cm–1: 3311 (N–H,
O–H), 3064, 2954, 1772, 1708 (C=O), 1635, 1543,
(3aS,4S,5S,6aR)-5-Bromo-4-hydroxyhexahydro-
1H-cyclopenta[c]furan-1-one (XIII) was synthesized
as described above for lactone XII from 1.0 g
(2.6 mmol) of amide XX. Yield 0.54 g (94%), colorless
crystals, Rf 0.65 (petroleum ether–ethyl acetate, 1:1),
mp 81–83°C, [α]D16 = –74.8° (c = 1.0225, CH2Cl2). IR
spectrum, ν, cm–1: 3410 (O–H), 2924, 1737 (C=O),
1
1
1448, 1292, 1182, 1045, 700. H NMR spectrum, δ,
1440, 1381, 1301, 1182, 1001, 966. H NMR spec-
ppm: 1.48 d (3H, CH3, J = 6.84 Hz), 1.95 d.d (1H,
5-H, J = 2.8, 14.19 Hz), 2.28–2.40 m (1H, 5-H), 2.53–
2.68 m (1H, 2-H), 3.03 t.d (1H, 1-H, J = 3.92,
7.92 Hz), 3.47–3.53 br.s (1H, OH), 3.58 d.d (1H, 4-H,
J = 7.95, 11.05 Hz), 3.90–3.97 m (2H, CH2O), 4.34–
4.44 m (1H, 3-H), 5.06 quint (1H, CHPh, J = 7.35 Hz),
5.20–5.30 d (1H, OH, J = 9.12 Hz), 6.81 d (1H, NH,
J = 8.05 Hz), 7.24–7.38 m (5H, Ph). 13C NMR spec-
trum, δC, ppm: 21.63 (CH3), 36.33 (C5), 46.03 (C1),
49.39 (CHPh), 54.73 (C2), 57.41 (C3), 61.52 (CH2O),
80.51 (C4); 126.03, 127.46, 128.68, 142.54 (Carom);
173.60 (C=O). Mass spectrum, m/z (81Br; Irel, %): 344
(100) [M + H]+, 263 (66.3). Found, %: C 59.51;
H 5.58; Br 22.99; N 3.87. C17H20BrNO3. Calculated,
%: C 59.65; H 5.85; Br 23.39; N 4.09.
trum, δ, ppm: 2.18 br.s (1H, OH), 2.45 d.d.d (1H, 6-H,
J = 5.69, 9.70, 14.48 Hz), 2.64 d.d.d (1H, 6-H, J =
4.01, 5.82, 14.61 Hz), 3.23 t.d (1H, 6a-H, J = 3.49,
9.83 Hz), 3.32–3.41 m (1H, 3a-H), 4.32 d.d (1H, 3-H,
J = 5.43, 10.21 Hz), 4.33–4.39 m (2H, 3-H, 5-H, J =
4.92 Hz), 4.61 d.d (1H, 4-H, J = 2.58, 9.83 Hz).
13C NMR spectrum, δC, ppm: 36.60 (C6), 41.42 (C6a),
41.56 (C3a), 53.60 (C5), 66.46 (C3), 79.34 (C4), 179.88
(C1). Mass spectrum, m/z (81Br; Irel, %): 223 (9.1) [M +
H]+, 141 (100). Found, %: C 37.76; H 3.92; Br 35.94.
C7H9BrO3. Calculated, %: C 38.01; H 4.07; Br 36.20.
Compounds XIV and XV were synthesized in
a similar way.
(1R,2S,3S,4S)-3-Bromo-4-hydroxy-2-hydroxy-
methyl-N-(1-phenylethyl)cyclopentane-1-carbox-
amide (XIV). From 2.5 g (10 mmol) of amide I we
obtained 0.6 g (18%) of an inseparable mixture of un-
identified isomeric bromohydrins (Rf 0.75, petroleum
ether–ethyl acetate, 1:1) and 2.4 g (70%) of compound
XIV as a colorless crystalline substance, Rf 0.45 (pe-
(3aR,4R,5R,6aS)-4-Bromo-5-hydroxyhexahydro-
1H-cyclopenta[c]furan-1-one (XVI) was synthesized
as described above for lactone XII (a) from 2.0 g
(5.88 mmol) of compound XV. Yield 1.21 g (94%),
colorless crystals, Rf 0.65 (petroleum ether–ethyl
acetate, 1:1), mp 78–80°C, [α]D16 = +31.0° (c = 1.1725,
CH2Cl2). IR spectrum, ν, cm–1: 3352 (O–H), 3253,
2920, 1759, 1732 (C=O), 1436, 1394, 1286, 1180, 1041,
troleum ether–ethyl acetate, 1:1), mp 79–81°C, [α]D16
=
+16.0° (c = 0.986, CH2Cl2). IR spectrum, ν, cm–1: 3300
1
(N–H, O–H), 2970, 2875, 1751, 1637 (C=O), 1544,
989. H NMR spectrum, δ, ppm: 2.25 d (1H, 6-H, J =
1
1450, 1207, 1047, 700. H NMR spectrum, δ, ppm:
13.90 Hz), 2.62 d.d.d (1H, 6-H, J = 3.98, 9.73,
13.98 Hz), 3.21 t.d (1H, 6a-H, J = 1.69, 9.85 Hz),
3.34–3.46 m (2H, 3a-H, OH, J = 9.20 Hz), 4.09–
4.16 m (1H, 4-H), 4.32 d.d (1H, 3-H, J = 3.44,
9.44 Hz), 4.43–4.50 m (1H, 5-H), 4.55 t (1H, 3-H, J =
1.45 d (3H, CH3, J = 6.98 Hz), 1.98 d (1H, 5-H, J =
14.22 Hz), 2.29–2.43 m (1H, 5-H), 2.48–2.59 m (1H,
2-H), 3.05 t.d (1H, 1-H, J = 3.88, 8.01 Hz), 3.33 d.d
(1H, 4-H, J = 8.02, 11.38 Hz), 3.70 d.d (1H, CHO, J =
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GIMAZETDINOV et al.
14
9.54 Hz). 13C NMR spectrum, δC, ppm: 36.05 (C6),
42.20 (C6a), 48.46 (C3a), 57.86 (C4), 72.55 (C3), 79.30
(C5), 180.74 (C1). Mass spectrum, m/z (81Br; Irel, %):
223 (14.7) [M + H]+, 141 (100). Found, %: C 37.90;
H 3.79; Br 35.84. C7H9BrO3. Calculated, %: C 38.01;
H 4.07; Br 36.20.
127.84, 128.89, 142.00 (Carom); 170.51 (CH3C=O),
174.55 (NHC=O). Mass spectrum, m/z (81Br; Irel, %):
386 (100) [M + H]+, 368 (46.1), 304 (9.7). Found, %:
C 52.94; H 5.46; Br 20.42; N 3.45. C17H22BrNO4. Cal-
culated, %: C 53.13; H 5.73; Br 20.83; N 3.65.
[(1R,2R,3R,5S)-2-Bromo-3-hydroxy-5-{[(1R)-
1-phenylethyl]carbamoyl}cyclopentyl]methyl ace-
tate (XXI) and [(1R,2R,3R,5S)-3-bromo-2-hydroxy-
5-{[(1R)-1-phenylethyl]carbamoyl}cyclopentyl]-
methyl acetate (XXII) were synthesized in a similar
way from 1.5 g (6 mmol) of acetate XVIII.
[(1S,2S,3S,5R)-2-Bromo-3-hydroxy-5-{[(1R)-
1-phenylethyl]carbamoyl}cyclopentyl]methyl ace-
tate (XIX) and [(1S,2S,3S,5R)-3-bromo-2-hydroxy-
5{[(1R)-1-phenylethyl]carbamoyl}cyclopentyl]-
methyl acetate (XX) were synthesized as described
above for compounds XII and XIII from 2 g (7 mmol)
of acetate XVII.
Compound XXI. Yield 0.72 g (53%), colorless
crystals, Rf 0.35 (petroleum ether–ethyl acetate, 3:1),
mp 136–138°C, [α]D16 = +75.1° (c = 0.7, CH2Cl2). IR
spectrum, ν, cm–1: 3479 (N–H), 3311 (O–H), 2926,
1718, 1641 (C=O), 1548, 1465, 1257, 1031, 698.
1H NMR spectrum, δ, ppm: 1.42 d (3H, CH3CH, J =
6.92 Hz), 1.90 d (1H, 4-H, J = 14.16 Hz), 2.03 s (3H,
CH3C=O), 2.22–2.32 m (1H, 4-H, J = 7.55 Hz), 2.63–
2.72 m (1H, 1-H), 2.81 t (1H, 5-H, J = 7.87 Hz),
3.94 d.d (1H, CHO, J = 3.14, 8.81 Hz), 4.08 d.d (1H,
CHO, J = 9.12, 11.02 Hz), 4.27–4.39 m (2H, 2-H, 3-H,
J = 5.35, 11.33 Hz), 5.06 quint (2H, CHPh, OH, J =
7.24 Hz), 6.14 d (1H, NH, J = 6.61 Hz), 7.20–7.33 m
(5H, Ph). 13C NMR spectrum, δC, ppm: 20.86
(CH3C=O), 21.39 (CH3CH), 36.32 (C4), 46.91 (C1),
49.40 (CHPh), 52.42 (C5), 56.85 (C2), 63.32 (CH2O),
81.00 (C3); 126.10, 127.80, 128.90, 142.34 (Carom);
170.50 (CH3C=O), 172.95 (NHC=O). Mass spectrum,
m/z (81Br; Irel, %): 386 [M + H]+ (100), 304 (69.9).
Found, %: C 52.92; H 5.68; Br 20.47; N 3.59.
C17H22BrNO4. Calculated, %: C 53.13; H 5.73;
Br 20.83; N 3.65.
Compound XIX. Yield 1.43 g (53%), colorless
crystals, Rf 0.35 (petroleum ether–ethyl acetate, 3:1),
mp 93–95°C, [α]D16 = +12.7° (c = 1.035, CH2Cl2). IR
spectrum, ν, cm–1: 3313 (N–H, O–H), 2966, 1743,
1
1635 (C=O), 1543, 1373, 1147, 1031, 698. H NMR
spectrum, δ, ppm: 1.50 d (3H, CH3CH, J = 6.98 Hz),
1.79 s (3H, CH3C=O), 2.00 d (2H, 4-H, OH, J =
14.48 Hz), 2.31–2.37 m (1H, 4-H, J = 7.50 Hz), 2.64–
2.75 m (1H, 1-H), 2.90 t (1H, 5-H, J = 6.99 Hz),
3.82 d.d (1H, CHO, J = 9.31, 11.38 Hz), 3.94 d.d (1H,
CHO, J = 2.33, 8.80 Hz), 4.24 d.d (1H, 2-H, J = 5.43,
11.12 Hz), 4.27–4.42 m (1H, 3-H), 5.06 quint (1H,
CHPh, J = 6.98 Hz), 6.50 d (1H, NH, J = 7.50 Hz),
7.26–7.38 m (5H, Ph). 13C NMR spectrum, δC, ppm:
20.53 (CH3C=O), 21.86 (CH3CH), 36.39 (C4), 46.89
(C1), 49.52 (CHPh), 52.38 (C5), 56.75 (C2), 63.18
(CH2O), 81.12 (C3); 126.12, 127.83, 128.93, 142.42
(Carom); 170.41 (CH3C=O), 173.17 (NHC=O). Mass
spectrum, m/z (81Br; Irel, %): 386 (100) [M + H]+, 304
(65.7). Found, %: C 52.87; H 5.54; Br 20.51; N 3.49.
C17H22BrNO4. Calculated, %: C 53.13; H 5.73; N 3.65;
Br 20.83.
Compound XXII. Yield 0.35 g (27%), colorless
crystals, Rf 0.55, mp 118–120°C, [α]D16 = +79.0° (c =
1.023, CH2Cl2). IR spectrum, ν, cm–1: 3294 (N–H,
O–H), 2926, 1741, 1637 (C=O), 1367, 1234, 1043,
Compound XX. Yield 0.69 g (27%), colorless crys-
tals, Rf 0.55, mp 75–77°C, [α]D16 = –17.4° (c = 1.056,
CH2Cl2). IR spectrum, ν cm–1: 3279 (N–H, O–H),
2924, 1743, 1628 (C=O), 1363, 1234, 1060, 704.
1H NMR spectrum, δ, ppm: 1.53 d (3H, CH3CH, J =
6.85 Hz), 1.84 s (3H, CH3C=O), 2.52 d.d (1H, 4-H, J =
8.19, 16.15 Hz), 2.90 d.d.d (1H, 4-H, J = 4.43, 6.42,
15.93 Hz), 3.01–3.14 m (2H, 1-H, 5-H), 4.02 d.d (1H,
CHO, J = 8.18, 11.50 Hz), 4.21 d.d (1H, CHO, J =
3.32, 12.50 Hz), 4.27 d.d (1H, 2-H, J = 6.19, 11.50 Hz),
4.37 d (1H, 3-H, J = 6.64 Hz), 5.06 quint (1H, CHPh,
J = 7.08 Hz), 5.54 d (1H, OH, J = 12.28 Hz), 6.14 d
(1H, NH, J = 7.52 Hz), 7.28–7.38 m (5H, Ph).
13C NMR spectrum, δC, ppm: 20.62 (CH3C=O), 21.11
(CH3CH), 39.48 (C4), 43.05 (C1), 45.43 (C5), 49.59
(CHPh), 54.56 (C3), 61.37 (CH2O), 80.06 (C2); 126.11,
1
700. H NMR spectrum, δ, ppm: 1.42 d (3H, CH3CH,
J = 6.93 Hz), 2.01 s (3H, CH3C=O), 2.37 d.d (1H, 4-H,
J = 8.49, 16.04 Hz), 2.70 d.d.d (1H, 4-H, J = 4.09,
6.61, 16.36 Hz), 2.94–3.09 m (2H, 1-H, 5-H), 4.02–
4.27 m (4H, CH2O, 2-H, 3-H), 4.99 quint (1H, CHPh,
J = 6.93 Hz), 5.53 d (1H, OH, J = 11.01 Hz), 6.36 d
(1H, NH, J = 7.02 Hz), 7.19–7.31 m (5H, Ph).
13C NMR spectrum, δC, ppm: 20.89 (CH3C=O), 21.43
(CH3CH), 39.22 (C4), 42.86 (C1), 45.18 (C5), 49.53
(CHPh), 54.50 (C3), 61.18 (CH2O), 79.87 (C2); 125.99,
127.70, 128.80, 141.99 (Carom); 170.71 (CH3C=O),
174.47 (NHC=O). Mass spectrum, m/z (81Br; Irel, %):
386 (100) [M + H]+, 368 (60.4), 304 (8.0). Found, %:
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SARKOMYCIN A METHYL ESTERS
15
C 52.78; H 5.51; Br 20.63; N 3.54. C17H22BrNO4.
Calculated, %: C 53.13; H 5.73; Br 20.83; N 3.65.
Methyl (1S,2R,4R)-2-chloromethyl-4-hydroxy-
cyclopentanecarboxylate (XXV) was synthesized
from 0.37 g (2.6 mmol) of hydroxy lactone VIII. Yield
0.44 g (88%), transparent oily substance, Rf 0.4 (petro-
leum ether–ethyl acetate, 10:1), [α]D16 = +40.8° (c =
1.203, CH2Cl2). IR spectrum, ν, cm–1: 3414 (O–H),
2953, 1730 (C=O), 1436, 1375, 1201, 1170, 1103, 727.
1H NMR spectrum, δ, ppm: 1.42–1.48 br.s (1H, OH),
1.61 d.d.d (1H, 3-H, J = 5.13, 9.74, 13.56 Hz), 2.00 d.t
(1H, 5-H, J = 2.87, 14.41 Hz), 2.13 t.d (1H, 3-H, J =
7.56, 14.98 Hz), 2.34–2.43 m (1H, 5-H, J = 7.82 Hz),
2.48–2.57 m (1H, 2-H), 3.05 t.d (1H, 1-H, J = 3.15,
7.62 Hz), 3.53 d.d (1H, CHCl, J = 7.15, 10.68 Hz),
3.62 d.d (1H, CHCl, J = 7.32, 10.91 Hz), 3.72 s (3H,
OCH3), 4.33–4.40 m (1H, 4-H). 13C NMR spectrum,
δC, ppm: 39.25 (C5), 40.12 (C3), 45.32 (C2), 45.38 (C1,
CH2Cl), 52.16 (OCH3), 72.07 (C4), 176.48 (C=O).
Mass spectrum, m/z (35Cl; Irel, %): 193 [M + H]+ (100),
161 (15.4). Found, %: C 49.56; H 6.63; Cl 36.59.
C8H13ClO3. Calculated, %: C 49.87; H 6.75; Cl 36.88.
(3aR,4S,6aS)-4-Hydroxyhexahydro-1H-cyclo-
penta[c]furan-1-one (XXIII). Following the same
reaction sequence as in the synthesis of acetate XVII,
from compound XVIII we obtained colorless crystal-
line hydroxy lactones VIII (see above) and XXIII.
Compound XXIII. mp 51–53°C, [α]D16 = –64.0° (c =
1.025, CH2Cl2). IR spectrum, ν, cm–1: 3346 (O–H),
2962, 1749 (C=O), 1379, 1184, 1166, 1064, 992.
1H NMR spectrum, δ, ppm: 1.64–1.72 m (2H, 5-H,
6-H), 1.83–1.94 m (1H, 5-H), 1.97–2.12 m (1H, 6-H),
2.33–2.39 m (1H, OH), 2.87–2.96 m (1H, 3a-H),
3.03 t.d (1H, 6a-H, J = 3.62, 9.57 Hz), 4.26–4.35 m
(1H, 3-H, 4-H, J = 8.02, 9.57 Hz), 4.59 d.d (1H, 3-H,
J = 2.85, 9.83 Hz). 13C NMR spectrum, δC, ppm: 26.23
(C6), 34.29 (C5), 43.01 (C6a), 43.51 (C3a), 66.86 (C3),
73.84 (C4), 181.24 (C1). Mass spectrum, m/z (Irel, %):
143 (100) [M + H]+, 125 (17.2). Found, %: C 58.74;
H 6.94. C7H10O3. Calculated, %: C 59.15; H 7.04.
Methyl (1R,2R,3R)-2-chloromethyl-3-hydroxy-
cyclopentanecarboxylate (XXVI) was synthesized
from 0.21 g (1.48 mmol) of hydroxy lactone III. Yield
0.25 g (88%), transparent oily substance, Rf 0.4 (petro-
leum ether–ethyl acetate, 10:1), [α]D16 = –32.8° (c =
1.0, CH2Cl2). IR spectrum, ν, cm–1: 3446 (O–H), 2954,
1701 (C=O), 1436, 1375, 1211, 1170, 1147, 727.
1H NMR spectrum, δ, ppm: 1.58–1.68 m (1H, 5-H),
1.89–2.15 m (4H, 5-H, 4-H, OH), 2.34–2.45 m (1H,
2-H), 3.13 t.d (1H, 1-H, J = 3.30, 7.97 Hz), 3.64 d.d
(1H, CHCl, J = 8.52, 11.27 Hz), 3.72 s (3H, OCH3),
3.77 d.d (1H, CHCl, J = 7.42, 11.00 Hz), 4.23–4.28 m
(1H, 3-H). 13C NMR spectrum, δC, ppm: 28.15 (C5),
35.29 (C4), 41.59 (CH2Cl), 44.77 (C1), 51.13 (C2),
52.34 (OCH3), 73.83 (C3), 177.96 (C=O). Mass spec-
trum, m/z (35Cl; Irel, %): 193 (100) [M + H]+, 161
(22.9). Found, %: C 49.63; H 6.57; Cl 36.52.
C8H13ClO3. Calculated, %: C 49.87; H 6.75; Cl 36.88.
Methyl (1R,2S,4S)-2-chloromethyl-4-hydroxy-
cyclopentanecarboxylate (XXIV). A mixture of
0.42 g (2.96 mmol) of hydroxy lactone VI and 15 ml
of methanol was cooled to –30°C, 1.07 ml (14.8 mmol)
of thionyl chloride was added dropwise, and the mix-
ture was stirred for 3 h on heating under reflux. When
the initial compound disappeared (TLC), the solution
was evaporated under reduced pressure, and the
residue was purified by chromatography on silica gel
using petroleum ether–ethyl acetate (10:1) as eluent.
Yield 0.5 g (88%), transparent oily substance, Rf 0.4,
[α]D16 = –41.3° (c = 1.315, CH2Cl2). IR spectrum, ν,
cm–1: 3426 (O–H), 2952, 1736 (C=O), 1430, 1378,
1
1199, 1181, 1107, 727. H NMR spectrum, δ, ppm:
1.23–1.27 br.s (1H, OH), 1.62 d.d.d (1H, 3-H, J = 4.95,
9.90, 13.20 Hz), 2.02 d.t (1H, 5-H, J = 2.35, 14.57 Hz),
2.14 t.d (1H, 3-H, J = 7.70, 15.12 Hz), 2.36–2.45 m
(1H, 5-H, J = 7.97 Hz), 2.48–2.58 m (1H, 2-H),
3.04 t.d (1H, 1-H, J = 3.30, 7.42 Hz), 3.54 d.d (1H,
CHCl, J = 7.15, 11.00 Hz), 3.61 d.d (1H, CHCl, J =
7.42, J = 10.72 Hz), 3.73 s (3H, OCH3), 4.33–4.39 m
(1H, 4-H). 13C NMR spectrum, δC, ppm: 39.14 (C5),
40.10 (C3), 45.35 (C2), 45.40 (C1, CH2Cl), 52.07
(OCH3), 72.27 (C4), 176.23 (C=O). Mass spectrum,
m/z (35Cl; Irel, %): 193 (100) [M + H]+, 161 (18.9).
Found, %: C 49.62; H 6.52; Cl 36.47. C8H13ClO3. Cal-
culated, %: C 49.87; H 6.75; Cl 36.88.
Methyl (1S,2S,3S)-2-chloromethyl-3-hydroxy-
cyclopentanecarboxylate (XXVII) was synthesized
from 0.17 g (1.2 mmol) of hydroxy lactone XXIII.
Yield 0.2 g (88%), transparent oily substance, Rf 0.4
(petroleum ether–ethyl acetate, 10:1), [α]D16 = +33.6°
(c = 1.137, CH2Cl2). IR spectrum, ν, cm–1: 3452
(O–H), 2953, 1721 (C=O), 1436, 1375, 1212, 1166,
1
1144, 727. H NMR spectrum, δ, ppm: 1.57–1.67 m
(1H, 5-H), 1.88–2.16 m (4H, 5-H, 4-H, OH), 2.34–
2.45 m (1H, 2-H), 3.14 t.d (1H, 1-H, J = 3.47,
7.84 Hz), 3.63 d.d (1H, CHCl, J = 8.78, 11.03 Hz),
3.72 s (3H, OCH3), 3.76 d.d (1H, CHCl, J = 7.74,
11.00 Hz), 4.24–4.28 m (1H, 3-H). 13C NMR spec-
Compounds XXV–XXVII were synthesized in
a similar way.
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GIMAZETDINOV et al.
16
trum, δC, ppm: 28.01 (C5), 35.17 (C4), 41.64 (CH2Cl),
44.62 (C1), 51.17 (C2), 52.26 (OCH3), 73.69 (C3),
178.12 (C=O). Mass spectrum, m/z (35Cl; Irel, %): 193
(100) [M + H]+, 161 (18.8). Found, %: C 49.71;
H 6.62; Cl 36.64. C8H13ClO3. Calculated, %: C 49.87;
H 6.75; Cl 36.88.
25.66, 25.72, 25.78 [(CH3)3C]; 38.36 (C5), 39.95 (C3),
42.84 (CH2Cl), 44.37 (C2), 45.87 (C1), 51.73 (OCH3),
72.23 (C3), 174.03 (C=O). Mass spectrum, m/z (35Cl;
Irel, %): 306 (100) [M + H]+, 176 (19.9). Found, %:
C 54.48; H 8.64; Cl 11.28. C14H27ClO3Si. Calculated,
%: C 54.72; H 8.79; Cl 11.56.
Methyl (1R,2S,4S)-4-(tert-butyldimethylsilyloxy)-
2-(chloromethyl)cyclopentanecarboxylate
(XXVIII). A solution of 0.2 g (1 mmol) of hydroxy
ester XXIV in 3 ml of methylene chloride was added
under stirring to a mixture of 0.31 g (2 mmol) of tert-
butyl(chloro)dimethylsilane, 0.14 g (2 mmol) of imid-
azole, and 10 ml of methylene chloride. The mixture
was stirred for 4 h at room temperature (TLC) and
evaporated under reduced pressure, and the residue
was purified by column chromatography on silica gel
using petroleum ether–ethyl acetate (30:1) as eluent.
Yield 0.29 g (95%), colorless oily substance, Rf 0.6,
[α]D16 = +7.8° (c = 1.176, CH2Cl2). IR spectrum, ν,
cm–1: 2953, 1734 (C=O), 1436, 1363, 1255, 1105, 837,
777. 1H NMR spectrum, δ, ppm: 0.04 s [6H, (CH3)2Si],
0.88 s (9H, t-Bu), 1.70–1.79 m (1H, 3-H, J = 9.25 Hz),
1.93–2.08 m (2H, 3-H, 5-H), 2.15–2.22 m (1H, 5-H,
J = 7.70 Hz), 2.52 sext (1H, 2-H, J = 8.25 Hz),
2.90 d.d (1H, 1-H, J = 8.52, 15.59 Hz), 3.60 d.d (1H,
CHCl, J = 8.25, 10.72 Hz), 3.66–3.69 m (4H, OCH3,
CHCl), 4.23 quint (1H, 4-H, J = 6.33 Hz). 13C NMR
spectrum, δC, ppm: –4.86 [(CH3)2Si], 17.96 [(CH3)3C];
25.63, 25.69, 25.76 [(CH3)3C]; 38.24 (C5), 39.86 (C3),
42.79 (CH2Cl), 44.39 (C2), 45.82 (C1), 51.66 (OCH3),
72.16 (C3), 173.86 (C=O). Mass spectrum, m/z (35Cl;
Irel, %): 306 (100) [M + H]+, 176 (12.4). Found, %:
C 54.53; H 8.59; Cl 11.31. C14H27ClO3Si. Calculated,
%: C 54.72; H 8.79; Cl 11.56.
Methyl (1R)-2-methylidene-3-oxocyclopentane-
carboxylate (XXX). A solution of 0.16 g (0.83 mmol)
of hydroxy lactone XXVI in 5 ml of methylene chlo-
ride was added under stirring to 0.27 g (1.25 mmol) of
pyridinium chlorochromate in 5 ml of methylene
chloride. The mixture was stirred for 3 h at room tem-
perature (TLC) and filtered from inorganic precipitate,
the precipitate was washed with methylene chloride,
the filtrate was evaporated, and the residue was sub-
jected to chromatography on silica gel (petroleum
ether–ethyl acetate, 10:1). Yield 0.1 g (80%), trans-
parent oily substance, Rf 0.4, [α]D16 = +58.3° (c = 0.8,
CH2Cl2). IR spectrum, ν, cm–1: 2920, 2372, 1732
1
(C=O), 1438, 1205, 1181, 1097, 1043. H NMR spec-
trum, δ, ppm: 1.26–1.40 m and 1.60–1.67 m (1H each,
5-H), 2.16–2.42 m (2H, 4-H), 2.53–2.60 m (1H, 1-H),
3.76 s (3H, OCH3), 5.60 d (1H, CH2=, J = 1.94 Hz),
6.18 d (1H, CH2=, J = 2.12 Hz). 13C NMR spectrum,
δC, ppm: 23.11 (C5), 36.77 (C4), 49.29 (C1), 52.43
(OCH3), 120.51 (CH2=), 142.41 (C2), 175.75 (C=O),
211.61 (C3). Mass spectrum, m/z (Irel, %): 155 (100)
[M + H]+, 124 (7.3). Found, %: C 62.12; H 6.38.
C8H10O3. Calculated, %: C 62.34; H 6.49.
Compounds XXXI–XXXIII were synthesized in
a similar way.
Methyl (1S)-2-methylidene-3-oxocyclopentane-
carboxylate (XXXI) was synthesized from 0.19 g
(0.99 mmol) of compound XXVII. Yield 0.12 g (80%),
transparent oily substance, Rf 0.4 (petroleum ether–
ethyl acetate, 10:1), [α]D16 = –57.9° (c = 1.115, CH2Cl2).
IR spectrum, ν, cm–1: 2922, 2376, 1735 (C=O), 1438,
Methyl (1S,2R,4R)-4-(tert-butyldimethylsilyl-
oxy)-2-(chloromethyl)cyclopentanecarboxylate
(XXIX) was synthesized as described above for com-
pound XXVIII from 0.15 g (0.75 mmol) of hydroxy
ester XXV. Yield 0.22 g (95%), transparent oily sub-
stance, Rf 0.6 (petroleum ether–ethyl acetate, 30:1),
[α]D16 = –8.3° (c = 1.225, CH2Cl2). IR spectrum, ν,
cm–1: 2954, 1732 (C=O), 1436, 1360, 1261, 1101, 836,
777. 1H NMR spectrum, δ, ppm: 0.04 s [6H, (CH3)2Si],
0.87 s (9H, t-Bu), 1.70–1.71 m (1H, 3-H, J = 9.41 Hz),
1.92–2.07 m (2H, 3-H, 5-H), 2.16–2.22 m (1H, 5-H,
J = 7.34 Hz), 2.52 sext (1H, 2-H, J = 8.29 Hz),
2.90 d.d (1H, 1-H, J = 8.44, 15.23 Hz), 3.59 d.d (1H,
CHCl, J = 8.29, 10.93 Hz), 3.66–3.69 m (4H, OCH3,
CHCl), 4.24 quint (1H, 4-H, J = 6.74 Hz). 13C NMR
spectrum, δC, ppm: –4.85 [(CH3)2Si], 18.00 [(CH3)3C];
1
1203, 1181, 1099, 1036. H NMR spectrum, δ, ppm:
1.25–1.41 m and 1.60–1.68 m (1H each, 5-H), 2.17–
2.44 m (2H, 4-H), 2.52–2.59 m (1H, 1-H), 3.76 s (3H,
OCH3), 5.61 d (1H, CH2=, J = 2.19 Hz), 6.19 d (1H,
CH2=, J = 2.23 Hz). 13C NMR spectrum, δC, ppm:
23.03 (C5), 36.79 (C4), 49.24 (C1), 52.36 (OCH3),
120.48 (CH2=), 142.33 (C2), 175.82 (C=O), 211.76
(C3). Mass spectrum, m/z (Irel, %): 155 (100) [M + H]+,
124 (9.8). Found, %: C 62.08; H 6.24. C8H10O3. Cal-
culated, %: C 62.34; H 6.49.
(–)-(3aS,6aR)-Tetrahydro-1H-cyclopenta[c]-
furan-1,4(3H)-dione (XXXII) was synthesized from
90 mg (0.63 mmol) of hydroxy lactone III. Yield
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 1 2012

SARKOMYCIN A METHYL ESTERS
17
2. Crimmins, M.T., Tetrahedron, 1998, vol. 54, p. 9229.
3. Roberts, S.M., Santoro, M., and Sickle, E., J. Chem.
Soc., Perkin Trans. 1, 2002, p. 1735.
4. Gimazetdinov, A.M., Vostrikov, N.S., and Mifta-
khov, M.S., Tetrahedron: Asymmetry, 2008, vol. 19,
p. 1094.
5. Gimazetdinov, A.M., Gimazetdinova, T.V., and Mifta-
khov, M.S., Mendeleev Commun., 2010, vol. 20, p. 15.
6. Sung, V.S.-C., Antibiotics, 1967, vol. 1, p. 156.
67 mg (75%), transparent plates, mp 58–60°C, Rf 0.35
(petroleum ether–ethyl acetate, 1:1), [α]D16 = –363.1°
(c = 1.35, CH2Cl2). IR spectrum, ν, cm–1: 2953, 2924,
2852, 1757 (C=O), 1734 (C=O), 1456, 1379, 1174,
1
1124, 1026, 952. H NMR spectrum, δ, ppm: 2.18–
2.58 m (4H, 5-H, 6-H), 2.97–3.07 m (1H, 3a-H), 3.36–
3.44 m (1H, 6a-H), 4.39–4.51 m (2H, 3-H, J = 2.34,
7.59 Hz). 13C NMR spectrum, δC, ppm: 23.61 (C6),
36.55 (C5), 41.49 (C6a), 47.73 (C3a), 68.72 (C3), 178.39
(C1), 216.96 (C4). Mass spectrum: m/z 139 (Irel 100%)
[M – H]+. Found, %: C 59.81; H 5.55. C7H8O3. Cal-
culated, %: C 59.94; H 5.71.
7. Klausner, R.D., Donaldson, J.G., and Lippincott-
Schwartz, J., J. Cell. Biol., 1992, vol. 116, p. 1071.
8. Archambaud, S., Legrand, F., Collet, S., Aphecetche-
Juliene, K., Guingant, A., and Evain, M., Synlett, 2008,
p. 389.
9. Legrand, F., Archambaud, S., Aphecetche-Juliene, K.,
Collet, S., Guingant, A., and Evain, M., Eur. J. Org.
Chem., 2010, no. 7, p. 1364.
10. Martínez, A.G., Vilar, E.T., Fraile, A.G., Cerero, S.M.,
Osuna, S.O., and Maroto, B.L., Tetrahedron Lett., 2001,
vol. 42, p. 7795.
(+)-(3aR,6aS)-Tetrahydro-1H-cyclopenta[c]-
furan-1,4(3H)-dione (XXXIII) was synthesized from
120 mg (0.84 mmol) of hydroxy lactone XXIII. Yield
89 mg (75%), colorless crystalline substance, mp 57–
59°C, [α]D16 = +362.5° (c = 1.17, CH2Cl2). IR spectrum,
ν, cm–1: 2955, 2920, 2853, 1759 (C=O), 1733 (C=O),
1456, 1379, 1173, 1119, 1024, 952. 1H NMR spectrum,
δ, ppm: 2.17–2.57 m (4H, 5-H, 6-H), 2.97–3.07 m (1H,
3a-H), 3.37–3.45 m (1H, 6a-H), 4.40–4.51 m (2H, 3-H,
J = 2.12, 7.83 Hz). 13C NMR spectrum, δC, ppm: 23.60
(C6), 36.51 (C5), 41.45 (C6a), 47.71 (C3a), 68.67 (C3),
178.27 (C1), 216.92 (C4). Mass spectrum: m/z 139
(Irel 100%) [M – H]+. Found, %: C 59.73; H 5.61.
C7H8O3. Calculated, %: C 59.94; H 5.71.
11. Wang, Y. and Romo, D., Org. Lett., 2002, vol. 4,
p. 3231.
12. Wu, Y. and Gao, J., Org. Lett., 2008, vol. 10, p. 1533.
13. Anadu, N.O., Davisson, V.J., and Cushman, M., J. Med.
Chem., 2006, vol. 49, p. 3897.
14. Govindan, S.V., Hudlicky, T., and Koszyk, F.J., J. Org.
Chem., 1983, vol. 48, p. 3581.
15. Gais, H.J. and Lied, T., Angew. Chem., 1984, vol. 96,
This study was performed under financial support
by the Ministry of Education and Science of the
Russian Federation (state contract no. 14.740.11.0367).
p. 143.
16. Gimazetdinov, A.M. and Miftakhov, M.S., Russ. J. Org.
Chem., 2010, vol. 46, p. 528.
17. Tietze, L.F., Brashe, G., Grube, A., Boehnke, N., and
REFERENCES
Stadler, C., Chem. Eur. J., 2007, vol. 13, p. 8543.
1. Scarborough, R.M., Jr., Toder, B.H., and Smith, A.B. III,
18. Marx, J.N. and Minaskanian, G., J. Org. Chem., 1982,
J. Am. Chem. Soc., 1980, vol. 102, p. 3904.
vol. 47, p. 3306.
RUSSIAN JOURNAL OF ORGANIC CHEMISTRY Vol. 48 No. 1 2012