D-erythronolactone as a C4 building unit. Part 2.1 a short and efficient synthesis of both enantiomers of epi-muricatacin, a diastereoisomer of the native acetogenin from Annona muricata

Article abstract of DOI:10.1039/a607158i

Both enantiomers of epi-muricatacin (+)- and (-)-2 have been prepared from 2,3-O-isopropylidene-D-erythrose 7. The enantiomers (+)- and (-)-2 are obtained in good yields and with high diastereoisomeric and enantiomeric purity. The aim of the synthesis is to obtain both enantiomers of the target molecule from one chiral precursor. This was made possible by the reaction sequence for the introduction of the two different side chains being exchangeable.

Full text of DOI:10.1039/a607158i

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D-Erythronolactone as a C4 building unit. Part 2.1 A short and
efficient synthesis of both enantiomers of epi-muricatacin, a
diastereoisomer of the native acetogenin from Annona muricata
Andreas Gypser, Marcus Peterek and Hans-Dieter Scharf*
Institut für Organische Chemie der Rheinisch-Westfälischen Technischen Hochschule Aachen,
Prof.-Pirlet-Straβe 1, 52056 Aachen, Germany, Fax: ϩ49 241 8888 385
Both enantiomers of epi-muricatacin (ϩ)- and (Ϫ)-2 have been prepared from 2,3-O-isopropylidene-D -
erythrose 7. The enantiomers (ϩ)- and (Ϫ)-2 are obtained in good yields and with high diastereoisomeric
and enantiomeric purity. The aim of the synthesis is to obtain both enantiomers of the target molecule from
one chiral precursor. This was made possible by the reaction sequence for the introduction of the two
different side chains being exchangeable.
Introduction
Epi-Muricatacin 2 (Scheme 1) is the epimer of the naturally
occurring acetogenin muricatacin 1, which was extracted from
the seeds of Annona muricata.2 Muricatacin 1 is the simplest of
the known native acetogenins, bearing only two chiral centres
and having no tetrahydrofuran moiety unlike other members of
this class of natural products. The relative stereochemistry of
the diol moiety in 1 is threo. Both the natural product and its
unnatural epimer 2 are biologically active showing cytotoxicity
in KB and VERO cell lines.3
Scheme 2
Scheme 1
Muricatacin 1 has been synthesized by several groups
because it belongs to the highly interesting class of substituted
γ-lactones, which can be found in many natural products.2–9
Presently two syntheses of epi-muricatacin 2 are known,3,10 one
of them using a stereochemically unselective ketone reduction.3
In the course of our work on the use of erythro C4 building
units in natural product synthesis,1,11–13 we here present the syn-
thesis of both enantiomers of epi-muricatacin 2 starting with
2,3-O-isopropylidene--erythrose 7 which is easily accessible in
two steps from -isoascorbic acid 3 (Scheme 2).14,15
The synthesis of (Ϫ)-2 from 2,3-O-isopropylidene--
erythrose 7 is depicted in Scheme 3. Wittig reaction of 7 with
undecyl(triphenyl)phosphonium bromide 8 (from the reaction
of undecyl bromide with triphenylphosphine in refluxing tolu-
ene16) and potassium tert-butoxide in tetrahydrofuran leads to
the alcohol 9 (61%). The formation of the alkene is E-selective
(> 95:5 determined by 1H NMR). Compound 9 was then
oxidized with activated dimethyl sulfoxide according to the
method of Pfitzner and Moffat to the aldehyde 10 (88%).17,18
Subsequent Wittig reaction of this with the stabilized ylide
methyl (triphenylphosphoranylidene)acetate 11 in tetrahydro-
furan led to the diene 12 (57%). Hydrogenation of this on a
Pd/C contact afforded the saturated methyl ester 13 which was
deprotected under acidic conditions (THF, HCl, MeOH) and
cyclized to (Ϫ)-epi-muricatacin (Ϫ)-2. The ring closure to the
γ-lactone occurs immediately according to Baldwin’s rules.19
To synthesize the enantiomer (ϩ)-2 (Scheme 4), 2,3-O-
isopropylidene--erythrose 7 was first treated with methyl
(triphenylphosphoranylidene)acetate 11 in refluxing dichlo-
romethane to give the α,β-unsaturated ester 14 [60%; again
Results and Discussion
-Isoascorbic acid 3 was oxidized with aqueous hydrogen per-
oxide (2 equiv.) to give -erythronolactone 4 (77%). -
Erythronolactone 4 was then acetalized with a mixture of ace-
tone, 2,2-dimethoxypropane and catalytic amounts of toluene-
p-sulfonic acid to afford 2,3-O-isopropylidene--erythrono-
lactone 5 (76%). As a by-product we observed the formation of
2,3-O-isopropylidene--erythronic acid methyl ester 6a; the
acetonide-protected erythronic acid derivative 6b found by
Cohen et al.14,15 was not detected. Compound 5 was reduced
with diisobutylaluminium hydride in dichloromethane as a
solvent (yield 89%) to give, diastereoselectively, the β-anomer
(monitored by 1H NMR).
1
completely E-selective (determined by H NMR)]. In order to
establish the aliphatic side-chain of (ϩ)-2 the hydroxy group
was activated as a tosylate 15. The double bond was hydrogen-
ated on a Pd/C contact in ethanol under a hydrogen atmosphere
(5 bar) to 16; overall yield of 95% over two steps. The removal
J. Chem. Soc., Perkin Trans. 1, 1997
1013

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Scheme 3
of the double bond is necessary to avoid a side reaction of the
Michael system in the following cuprate addition. Alkylation of
the tosylate 16 with lithium di(undecyl)cuprate (prepared from
undecyllithium 17 and cuprous iodide) at Ϫ78 ЊC in diethyl
ether afforded the ester ent-13 (42%). Cyclization in THF with
catalytic amounts of aqueous hydrochloric acid yielded epi-
muricatacin (ϩ)-2 from ent-13 quantitatively, analogous to the
conversion of 13 into (Ϫ)-2.
Scheme 4
3 H, OCH3), 4.05 (d, J 6.0, 1 H, 2-H), 4.26 (d, J 5.0, 2 H, 4-H)
and 4.31 (dd, J 6.0, 5.5, 1 H, 3-H); δC(CDCl3) 25.1, 26.4 (2
CH3), 52.5 (OCH3), 65.3 (C-4), 71.0, 71.4 (C-3, C-2), 110.0
[C(CH ) ] and 172.7 (C᎐O).
᎐
3
2
(2R,3R)-2,3-O-Isopropylidene-D-erythrose 7
Our synthesis of both enantiomers of epi-muricatacin (ϩ)-2
and (Ϫ)-2 confirms the versatility of -erythronolactone as a C4
building unit as demonstrated by us earlier.1,11–13 By means of a
change in the sequence of side-chain introduction our strategy
leads to an efficient synthesis of both enantiomers 2 from one
chiral precursor.
To a solution of the protected -erythronolactone 5 (5.0 g, 32
mmol) in dichloromethane (100 ml) was added via a dropping
funnel a 1.0  solution of diisobutylaluminium hydride in
dichloromethane (50 ml, 50 mmol) added at Ϫ72 ЊC under an
inert atmosphere. The resulting mixture was stirred for 3 h at
Ϫ72 ЊC, after which methanol (16 ml) was to it cautiously, to
destroy the remaining diisobutylaluminium hydride. After
being warmed to room temperature, the reaction mixture was
poured into a mixture of ethyl acetate and water (1:1). The
mixture was acidified to pH 3 (monitored with a pH-meter)
with dilute sulfuric acid and the layers were separated. The
aqueous phase was extracted with ethyl acetate and the extract
evaporated to give the lactol 7 (4.5 g, 89%) as a pale yellow
solid, the spectroscopic data of which were identical with those
cited in the literature.1,14
Experimental
1H NMR: Varian VXR 300; 300 MHz, δ = 0 for TMS used as
internal standard, δ = 7.26 for CHCl3. 13C NMR: Varian VXR
300; 75 MHz, δ = 0 for TMS used as internal standard, δ = 77.0
for CHCl3. The multiplicity of the carbon nuclei was deter-
mined by the APT technique. Melting points are uncorrected:
Büchi melting point apparatus 510. Specific optical rotations:
Perkin-Elmer polarimeter 241. Column liquid chromato-
graphy: Merck Silica gel 60. Thin layer chromatography:
Merck Silica gel 60 F254 analytic aluminium plates. IR:
Perkin-Elmer PE 1750 FT. MS: Varian MAT 212 (normal con-
ditions: EI, 70 eV, 1 mA, 200 ЊC. CH analyses: Heraeus CHNO
Rapid.
Undecyl(triphenyl)phosphonium bromide 8
A solution of undecyl bromide (50 g, 0.21 mol) and triphenyl-
phosphine (56 g, 0.21 mol) in dry toluene (300 ml) was heated
under reflux for 48 h,16 and then evaporated. The remaining
solid 8 was dried in vacuo to give the title compound (106 g,
100%); δH (CDCl3) 0.88 (t, J 7.1, CH3), 1.20 (br m, 14 H, CH2),
1.63–3.70 (br m, 6 H, CH2) and 7.18–7.80 (br m, 15 H, Ar H);
δC(CDCl3) 14.1 (CH3), 22.6, 29.2, 29.2, 29.5, 30.3, 30.5, 31.2
(CH2), 125.3, 128.2, 129.0, 130.5, 130.6, 133.5, 133.7, 135.1,
135.1 and 137.7 (aromatic C).
(2R,3R)-O-Isopropylidene-D-erythronolactone 5
This compound was prepared (76%) from -isoascorbic acid 3
according to the procedure cited in the literature14,15; mp 66 ЊC
(lit.,14,15 68–68.5 ЊC); [α]D25 Ϫ103.4 (c 1.0 in H2O) {lit.,14 [α]2D5
Ϫ112 (c 1.5 in H2O)}; δH (CDCl3) 1.40, 1.49 [2 s, 6 H, C(CH3)2],
4.45 (d, J 2.4, 2 H, 4-H), 4.77 (d, 2 H, J 5.7, 2-H) and 4.90 (dd, J
5.7, 2.4, 1 H, 3-H); δC(CDCl3) 25.6, 26.8 (2 CH3), 70.3 (C-4),
(4R,5S)-2,2-Dimethyl-4-hydroxymethyl-5-[(E)-dodec-1-enyl]-
1,3-dioxolane 9
74.7, 75.6 (C-3, C-2), 114.0 [C(CH ) ] and 174.3 (C᎐O).
As a by-product we obtained methyl 2,3-O-isopropylidene-
erythronate 6a; δH (CDCl3) 1.35, 1.43 [2 s, 6 H, C(CH3)2], 3.80 (s,
A suspension of undecyl(triphenyl)phosphonium bromide 8
(28.1 g, 57 mmol) in dry tetrahydrofuran (100 ml) was cooled to
Ϫ78 ЊC and treated with potassium tert-butoxide (6.4 g, 57
᎐
3
2
1014
J. Chem. Soc., Perkin Trans. 1, 1997

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mmol). The orange solution was stirred at Ϫ20 ЊC for an ad-
ditional hour, after which a solution of the lactol 7 (3.0 g, 19
mmol) in dry tetrahydrofuran (10 ml) was added to it via a
dropping funnel. The cooling bath was removed and the reac-
tion mixture was stirred overnight. It was then treated with
water (50 ml) and diluted with diethyl ether (200 ml). The
phases were separated and the aqueous phase was extracted
with diethyl ether (× 3). The extract was dried (MgSO4) and
evaporated and the residue purified by column chromatography
using as eluent ethyl acetate–hexane (1:1) (Rf 0.23). Compound
9 was a yellow syrup (3.4 g, 61%); [α]2D0 Ϫ35.3 (c 1.13 in CHCl3);
157 (19), 156 (40) and 98 (100) (Found: C, 71.65; H, 10.48; M,
352.51. Calc. for C21H36O4: C, 71.55; H, 10.29%).
(4R,5S)-2,2-Dimethyl-4-methoxycarbonylethyl-5-dodecyl-1,3-
dioxolane 13
A 200-ml glass autoclave was charged with compound 12 (1.0 g,
2.8 mmol) as a solution in ethanol (100 ml) together with a
catalytic amount of palladium-on-charcoal (10%). After
hydrogenation under an atmosphere of hydrogen (5 bar), the
mixture was filtered through Celite® to remove the catalyst.
Evaporation of the filtrate yielded 13 as a colourless syrup (0.93
νmax(KBr)/cmϪ1 3481 (OH) and 1658 (C᎐C); δ (CDCl ) 0.88 (t,
g, 99%); νmax(KBr)/cmϪ1 1774 (C᎐O); δ (CDCl ) 0.88 (t, J 7.1,
᎐
᎐
H
3
H
3
J 6.4, 3 H, CH3), 1.27 (br m, 16 H, CH2), 1.39 [2 s, 6 H,
C(CH3)2], 2.08 (m, 2 H, CH2), 2.41 (br s, 1 H, OH), 3.55 (d, J
5.0, 2 H, CH2OH), 4.23 (dt, J 6.4, 5.0, 1 H, 4-H), 4.99 (ddd, J
CH3), 1.27 (br m, 22 H, CH2), 1.33, 1.42 [2 s, 6 H, C(CH3)2],
1.74–1.80, 2.42–2.66 (2 m, 4 H, CH2), 3.68 (s, 1 H, OCH3) and
4.05 (m, 2 H, CHO); δC(CDCl3) 14.1 (CH3), 22.7, 25.45, 26.0,
26.4, 28.56, 29.38–29.73, 30.6, 32.0 [14 CH2, 2 C(CH3)2], 51.6
(OCH3), 76.98, 77.96 (C-4, C-5), 107.6 [C(CH3)2] and 174.0
6.4, 7.7, 1.0, 1 H, 5-H), 5.43 (ddd, J 11.4, 8.7, 0.7, 1 H, CH᎐)
᎐
and 5.35 (ddd, J 11.4, 7.7, 1.1, 1 H, CH᎐); δ (CDCl ) 14.1 (CH ),
᎐
C
3
3
22.7, 27.9, 29.3, 29.4, 29.50, 29.57, 29.63, 29.65, 32.0 (9 CH2),
(C᎐O); m/z (%) 341 (26) [M ϩ Ϫ CH3], 239 (19), 81 (34), 74 (37)
᎐
᝽
25.3, 27.99 [C(CH3)2], 62.2 (CH2OH), 73.0, 78.5 (C-4, C-5),
and 55 (100) (Found: C, 71.01; H, 11.53; M, 356.54. Calc. for
108.5 [C(CH ) ], 124.4 and 135.5 (CH᎐); m/z (%) 298 (1) [M ϩ],
C21H40O4: C, 70.74, H, 11.31%).
᎐
3
2
᝽
238 (23), 223 (35), 97 (81) and 59 (100). C18H34O3 (298.46)
(Found: C, 72.12; H, 11.17; M, 298.46. Calc. for C18H34O3: C,
72.43; H, 11.48%).
(4R,5S)-2,2-Dimethyl-4-hydroxymethyl-5-[(E)-methoxy-
carbonylethenyl}-1,3-dioxolane 14
A solution of the protected -erythrose 7 (5.0 g, 31 mmol)
and methyl (triphenylphosphoranylidene)acetate 11 (15.5 g, 47
mmol) in dichloromethane (100 ml) was refluxed for 3 days
and then evaporated. The residue was extracted overnight
with pentane in a Soxhlet extractor after which the extract
was evaporated. The residue when chromatographed on silica
gel with ethyl acetate–hexane (1:1) gave 14 as a colourless
syrup (4.0 g 60%); [α] ϩ 13.2 (c 1.05 in CH2Cl2); νmax(neat)/
cmϪ1 3495 (OH), 1719 (C᎐O) and 1647 (C᎐C); δ (CDCl )
1.38, 1.54 [2 s, 6 H, C(CH3)2], 2.30 (br s, 1 H, OH), 3.45 (dd,
J 11.8, 5.2, 1 H, CH2OH), 3.60 (dd, J 11.8, 3.5, 1 H,
CH2OH), 3.73 (s, 3 H, OCH3), 4.57 (ddd, J 7.0, 5.2, 3.5, 1 H,
5-H), 5.60 (td, J 7.0, 1.6, 1 H, 4-H), 5.95 (dd, J 11.5, 1.3, 1 H,
(4S,5S)-2,2-Dimethyl-4-formyl-5-[(E)-dodec-1-enyl]-1,3-
dioxolane 10
Trifluoroacetic acid (0.3 ml) and pyridine (0.5 ml) were added to
a solution of compound 9 (2.3 g, 8 mmol) in a mixture of
dimethyl sulfoxide (15 ml) and dry toluene (15 ml). The result-
ing mixture was stirred for 5 min after which it was treated with
dicyclohexylcarbodiimide (4.9 g) and stirred overnight. After
this the mixture was filtered to remove precipitated dicyclo-
hexylurea, diluted with diethyl ether, washed with deionized
water (40 ml), dried (MgSO4) and evaporated. The residue was
purified by column chromatography to give the title compound
(2.0 g, 88%); νmax(KBr)/cmϪ1 1734 (C᎐O) and 1688 (C᎐C);
᎐
᎐
H
3
᎐
᎐
δH (CDCl3) 0.88 (t, J 6.6, 3 H, CH3), 1.27 (br m, 16 H, CH2),
1.44, 1.61 [2 s, 6 H, C(CH3)2], 2.08 (m, 2 H, CH2), 4.38 (dd, J
7.4, 3.4, 1 H, 4-H), 5.18 (td, J 7.4, 1.0, 1 H, 5-H), 5.34 (ddd, J
11.4, 7.4, 0.7, 1 H, C᎐H), 5.70 (ddd, J 11.1, 7.1, 1.0, 1 H, C᎐H)
C᎐CH) and 6.40 (dd, J 11.5, 7.0, 1 H, C᎐CH); δ (CDCl )
᎐ ᎐
C 3
24.7, 27.4 (CH3), 51.7 (OCH3), 61.5 (CH2OH), 74.8, 78.9 (C-
4, C-5), 108.9 [C(CH ) ], 120.6, 147.6 (C᎐C) and 166.4 (C᎐O);
᎐
᎐
3
2
m/z (%) 201 (34) [M ϩ Ϫ CH3], 141 (72) and 98 (90) (Found:
᎐
᎐
᝽
and 9.55 (d, J 3.4, 1 H, CHO); δC(CDCl3) 14.1 (CH3), 22.7, 24.7,
25.5, 28.1, 29.5, 29.62, 29.65, 32.0, 35.0 (9 CH2), 25.3, 27.5
[C(CH3)2], 74.6, 82.3 (C-4, C-5), 111.0 [C(CH3)2], 122.8, 136.8
(CH᎐) and 199.7 (C᎐O); m/z (%) 296 (2) [M ϩ], 239 (38), 209
C, 55.67; H, 7.45; M, 216.2. Calc. for C10H16O5: C, 55.55; H,
7.46%).
(4S,5S)-2,2-Dimethyl-4-tosyloxymethyl-5-[(E)-methoxy-
carbonylethenyl]-1,3-dioxolane 15
᎐
᎐
᝽
(26), 100 (100), 85 (74) and 83 (43). C18H32O3 (296.44) (Found:
C, 72.57; H, 10.44; M, 296.44. Calc. for C18H32O: 72.93, H,
10.88%).
Tosyl chloride (3.3 g, 17 mmol) was added to a stirred solution
of compound 14 (3.0 g, 14 mmol), triethylamine (2.8 g, 28
mmol) and N,N-dimethylaminopyridine (0.1 g, 1 mmol) in
dichloromethane (100 ml) at 0 ЊC in small portions. The mix-
ture was stirred for 1 h at 0 ЊC, allowed to warm to room tem-
perature and then stirred for additional 2 h. It was then diluted
with diethyl ether (150 ml) and washed with brine (× 2). The
aqueous layer was back-extracted with diethyl ether (2 × 100
ml). The combined organic layers were dried (MgSO4), filtered
and evaporated to yield the crude tosylate. This was chromato-
graphed on silica gel with ethyl acetate–hexane (1:1) to yield 15
as a colourless syrup (4.9 g, 96%); [α]2D0 ϩ 102.0 (c 0.94 in
(4R,5S)-2,2-Dimethyl-4-methoxycarbonylethenyl-5-[(E)-dodec-
1-enyl}-1,3-dioxolane 12
A solution of methyl (triphenylphosphoranylidene)acetate 11
(5.7 g, 17 mmol) was added to a solution of the aldehyde 10 (1.8
g, 6 mmol) in dry tetrahydrofuran (50 ml). After the solution
had been refluxed for 24 h it was diluted with deionized water
and diethyl ether and the phases were separated. The aqueous
phase was extracted with diethyl ether (× 3) and the combined
extracts were dried (MgSO4) and worked up. Column chroma-
tography then gave 12 (1.2 g, 57%) as a syrup; νmax(KBr)/cmϪ1
CH2Cl2); νmax(neat)/cmϪ1 3414, 3000, 2947, 1751 (C᎐O) and
᎐
1724 (C᎐O) and 1651 (C᎐C); δ (CDCl ) 0.88 (t, J 7.1, 3 H,
1598; δH (CDCl3) 1.33, 1.41 [2 s, 6 H, C(CH3)2], 2.44 (s, 3 H, aryl-
CH3), 3.71 (s, 3 H, OCH3), 3.83 (dd, J 10.4, 5.5, 1 H, CH2OTos),
4.01 (dd, J 10.4, 3.5, 1 H, CH2OTos), 4.64 (ddd, J 6.9, 5.5, 3.5, 1
H, 4-H), 5.57 (dd, J 6.9, 1.9, 1 H, 5-H), 5.83 (dd, J 11.5, 1.9, 1
᎐
᎐
H
3
CH3), 1.27 (br m, 16 H, CH2), 1.37, 1.42 [2 s, 6 H, C(CH3)2],
2.08–2.30, 2.42–2.66 (2 m, 2 H, CH2), 3.69, 3.74 (s, 3 H, OCH3),
4.71 (ddd, J 8.4, 7.05, 1.7, 1 H, 4-H), 5.05 (ddd, J 8.7, 6.7, 1.0, 1
H, 5-H), 5.31 (ddd, J 11.4, 7.4, 0.7, 1 H, 1-H), 5.65 (ddd, J 11.1,
H, CH᎐), 6.27 (dd, J 11.5, 6.9, 1 H, CH᎐), 7.34 (m, 2 H, ArH)
᎐
᎐
7.1, 1.0, 1 H, 1-H), 6.08 (dd, J 15.5, 1.7, 1 H, H CO C-CH᎐C)
and 7.77 (m, 2 H, ArH); δC(CDCl3) 21.6 (aryl CH3), 24.9, 27.2
᎐
3
2
and 6.77 (dd, J 14.8, 5.7, 1 H, H CO C-C᎐CH); δ (CDCl ) 14.1
(CH3), 51.8 (OCH3), 68.5 (CH2OTos), 74.6, 75.4 (C-4, C-5),
᎐
3
2
C
3
(CH3), 22.7, 24.7, 25.45, 25.52, 27.90, 27.94, 29.27, 29.38, 29.47,
29.51, 29.58, 29.64, 29.67, 32.0, 35.0 [2 C(CH3)2, 9 CH2], 51.6,
55.8 (OCH3), 74.35, 74.75, 75.51, 76.6 (CHO), 109.32
[C(CH3)2], 122.15, 122.22, 124.66, 124.80, 125.26, 135.1, 135.5,
144.5 (C᎐C) and 166.4 (C᎐O); m/z (%) 352 (3) [M ϩ], 239 (25),
109.6 [C(CH ) ], 121.7 (CH᎐), 128.0 (2 ArCH), 129.8 (2 ArC),
᎐
3 2
132.8 (ArC), 144.9 (ArC), 145.5 (CH᎐) and 165.9 (C᎐O); m/z (%)
᎐
᎐
370 (3) [M ϩ], 355 (28) [M ϩ Ϫ CH3], 295 (57), 155 (74) and 91
᝽
᝽
(100) (Found: C, 55.32; H, 6.03; M, 370.42. Calc. for
C17H22O7S: C, 55.12; H, 5.99%).
᎐
᎐
᝽
J. Chem. Soc., Perkin Trans. 1, 1997
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(4S,5S)-2,2-Dimethyl-4-tosyloxymethyl-5-methoxycarbonyl-
ethyl-1,3-dioxolane 16
in CHCl3)}; νmax(KBr)/cmϪ1 3422 (OH) and 1762 (C᎐O);
δH (CDCl3) 0.88 (t, J 6.4, CH3), 1.26 (br m, 22 H, CH2), 2.08–
᎐
Catalytic amounts of Pd/C were added to a solution of com-
pound 15 (3.0 g, 8 mmol) in ethanol (50 ml) and the hydrogen-
ation carried out under hydrogen (5 bar) for 24 h. The mixture
was then filtered through Celite® to remove the catalyst and
evaporated to yield 16 quantitatively as a colourless syrup (2.9
g, 99%); [α]D20 ϩ 11.4 (c 0.54 in CH2Cl2); νmax(Et2O)/cmϪ1 2950,
2.30, 2.42–2.66 (m, 5 H, CH2, CHOH), 3.94 (m, 1 H, CHOH),
4.44 (dt, J 7.1, 3.0, 1 H, CHO-lactone); δC(CDCl3) 14.1 (CH3),
21.1, 22.7, 25.7, 28.73, 29.36–29.65, 31.91, 31.92 (13 CH2), 71.4,
82.8 (C-3, C-4) and 177.5 (C᎐O); m/z (%) 284 (2) [M ϩ], 87 (23)
᎐
᝽
and 86 (100) (Found: C, 70.65; H, 10.98; M, 284. Calc. for
C17H32O3: C, 71.07; H, 11.34%).
2930 and 1720 (C᎐O); δ (CDCl ) 1.28, 1.32 [2 s, 6 H, C(CH ) ],
Compound ent-13 (0.11 g, 0.31 mmol) was treated with a
catalytic amount of aqueous hydrochloric acid in tetrahydro-
furan at room temperature for 2 h and then evaporated to dry-
ness. Recrystallisation of the residue from diethyl ether–
pentane yielded (ϩ)-2 as white crystals (0.09 g, 98%). The spec-
troscopic data are in agreement with that of (Ϫ)-2; [α]2D0 ϩ 31.5
(c 1.07 in CHCl3).
᎐
H
3
3 2
1.6–1.9 (m, 2 H), 2.45 (s, 3 H, aryl-CH3), 2.25–2.6 (m, 2 H), 3.68
(s, 3 H, OCH3), 3.95–4.25 (m, 4 H), 7.37 (m, 2 H, ArH) and 7.81
(m, 2 H, ArH); δC(CDCl3) 21.7 (CH3-aryl), 24.4 (CH2), 25.4,
27.9 (2 CH3), 30.8 (CH2), 51.7 (OCH3), 67.7 (CH2OTos), 74.6,
75.8 (C-4, C-5), 108.9 [C(CH3)2], 128.1, 129.9 (4 ArCH), 132.6
(ArC), 145.1 (ArC) and 173.6 (C᎐O); m/z (%) 357 (60)
᎐
[M ϩ Ϫ CH3], 143 (51) and 129 (100) (Found: C, 54.98; H,
᝽
6.61; M, 372.42. Calc. for C17H24O7S: C, 54.82; H, 6.49%).
Acknowledgements
Preparation of undecyllithium 17
We are grateful to the Fonds der Chemischen Industrie and the
Deutsche Forschungsgemeinschaft (Sonderforschungsbereich
380, Teilprojekt D) for the support of this work. The NMR
spectra were kindly recorded by Dr J. Runsink. We also thank
D. Gilliam for practical assistance.
Lithium powder (2.2 g, 310 mmol) was added to a solution of
undecyl chloride (24.8 g, 130 mmol) in pentane (50 ml) at 0 ЊC.
The resulting slurry was sonificated with ultrasound for 2 h at
0 ЊC. The yellowish solution containing 17 was then titrated
against diphenylacetic acid (0.74 mol lϪ1).
References
(4S,5R)-2,2-Dimethyl-4-methoxycarbonylethyl-5-dodecyl-1,3-
dioxolane ent-13
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Undecyllithium 17 in pentane (0.74 mol lϪ1; 7 ml, 5.2 mmol) was
added dropwise to a stirred slurry of purified cuprous iodide
(0.5 g, 2.6 mmol) in diethyl ether (25 ml) at Ϫ40 ЊC; the reaction
mixture turned black immediately. After complete addition of
the undecyllithium, the mixture was warmed to 0 ЊC to give a
clear black solution which was cooled to Ϫ78 ЊC and treated
with the tosylate 16 (0.5 g, 1.3 mmol) dissolved in diethyl ether
(5 ml), added dropwise. After 2 h the reaction was quenched
with saturated aqueous ammonium chloride at 0 ЊC. The
organic layer was separated, washed with brine (× 2); the com-
bined aqueous layers were then back-extracted once with
diethyl ether. The combined organic layers were dried (MgSO4),
filtered and evaporated to afford a colourless syrup which was
chromatographed on silica gel with diethyl ether–pentane (1:3)
to yield ent-13 as a colourless oil (0.17 g, 42%). The physical
properties and spectroscopic data are in agreement with those
of compound 13.
10 M. Saiah, M. Bessodes and K. Antonakis, Tetrahedron Lett., 1993,
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11 A. Gypser, 1995, Ph.D. Thesis, RWTH Aachen.
12 M. Flasche, Tetrahedron Asym., 1995, 6, 1543.
13 M. Flasche, 1994, Ph.D. Thesis, RWTH Aachen.
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(4R,5S)-(Ϫ)-epi-Muricatacin (؊)-2 and (4S,5R)-(ϩ)-epi-
muricatacin (ϩ)-2. Concentrated hydrochloric acid (5 ml) was
added to a solution of compound 13 (0.4 g, 1.2 mmol) in a
mixture of tetrahydrofuran (200 ml) and deionized water (60
ml); the reaction was monitored by TLC [hexane–ethyl acetate
(5:1)]. After completion of the reaction the mixture was
neutralized with sodium hydrogen carbonate and diluted with
diethyl ether. After separation of the phases, the aqueous layer
was extracted with diethyl ether (× 3). The combined extracts
were dried (MgSO4) and evaporated to give epi-muricatacin
(Ϫ)-2 as a colourless solid (0.3 g, 89%), mp 69–70 ЊC (lit.,3
69 ЊC); [α]2D0 Ϫ30.5 (c 1.87 in CHCl3) {lit.,3 [α]2D0 Ϫ32 (c 1.87
Paper 6/07158I
Received 21st October 1996
Accepted 18th November 1996
1016
J. Chem. Soc., Perkin Trans. 1, 1997