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Synthesis and absolute configuration of phomozin
Temzhedtvn Leffers, Vol. 35. No. 23, pp. 3917-3918, 1994 Eisevier Science Ltd Printedin GreatBritain oo40-4039/94 $7.00+0.00
Synthesis Nicolas
and Absolute
VicarP,
Jean-Yves
Configuration
Ortholand,
of Phomozin
Gilbert Y. Emeric,
Alfred Greiner+
Rhi3ne Fbuleac Agrdimie, Centre de Rcchutk de la Dargoire, BP9163 F 69263-Lyon CEDEX 09. France
phytotoxin phomozin has been unambiguously determined by
Ah&net: The ahlute
Eonfieuratian of the fmgal
PIwnwpsis h&a&i
is a fungus that causes necrosis and stem cankering of sunflower.
the synthesis of its two enantiomea
Phomozin 1 we
The structure of1 was determined
recently isolated from culture filtrates of this severe pathogen.*>
from
X-ray diffraction3 and other physical data, and by comparison with dimethyl glyceric acid and was identified as erythro .4 However,
according to the authors, the poor quality of crystals obtained did not allow them to
assign the absolute concretion enantiomets
with total confidence.
We thus considered
wish to report the absolute configuration
KzCO3,
acetone, dlux,
dioxolanone
5s (2S,3S) and
methodology.7
the
acid. We now
available ethyl orcelinate 2 by benzylation6
12h, 99%). alkaline hydrolysis (KOH, lZtOH/H~O, RT, 24h, 85%)
and treatment with oxaIy1 chloride (cat. Dh@, RT, toluene,
Homochiral
to synthesize
of 1 along with a facile synthesis of chiral phmzin.
The aromatic fragment 45 was obtained from commercially (PhCH2Br.
interesting
of erythro 3-(2’,4’-dihy~xy-6’-mthylbenzoyloxy)-2-hy~xy-2-~~ylbu~oic
10 mitt).
5b (2R.3R) were synthesized from lactic acid using the previously reported
3918
Sa (2S.3S) eryrhro 18 % overall
H
Rex7
OH Sb (2R3R) erythro 34 46 overall
lactic acid Me Coupling of the hindered diols Sa or 5b with 4 (ErjN, cat. DMAP,
CH2C12, OT,
run under saictly anhydrous conditions to minimize the formation of the remarkably Selective saponification
(NaOH, EtOH, Et20, 12h) and hydrogenolysis
10 min) has to be
stable anhydride of 3.
(Hz, Pd/C, EtOAc, 9 bars, Sh)
allows the isolation of the desired rargets.518
2
HO Me
H
H
HO
5a (2S.3S) Sb (2R,3R) Compounds 1 7a 7b
68 (2S,3S) 6b (2R,3R)
30% 20%
7a (2S,3S) 7b (2R.3R)
48% (2 steps) 42% (2 steps)
1.711 and 7b have the fqllowing specific rotations9 :
[a]*‘D= +28 (D20, c=O.316)’ [cc]% = +25,5 (D20. c=O.325) [a]+= -27 @20. ~0.325)
These data allow with total confidence the conclusion that Phowzin methylbenzoyloxy)-2-hydmxy-2-methylbutanoic
is (2S,3S) 3-(2’,4’-dihydroxy-6’-
acid.
Acknowledgment : The authors thank Prof J.Gor& (Universitd Claude Bernard. Lyon) for his interest in this work and the Minist& de la Recherche et de I’ Espace for financial support. References
and notes
Mazars, C.; Rossiguol, M.; Atuiol, P.; Klaebe, A. Phytochemistry 1990.29, 3441-3444. Mazars, C.; Canivenc, E.; Rossignol, M.; Auriol, P. Plant Science 1991,75, 155-160. Declercq, J.P.; K&be, A.; Rossignol, M.; Mazars, C. Acta Crystallogr., Sect C: 1991, C47,470-472. 1 is identified as “esythro (1 lS,lOR)” in Ref. 1 (corresponding to the X-ray diffraction atom labelling) but the PLUTO drawing represents the (11 S, 10s) enantiomer. All compounds gave satisfactory analyses. Hendrickson, J-B.; Ramsay, M.V.J.; Kelly, T.R. J. Am. Chem. Sot. 1972.94. 6834-6843. Greiner, A.; ortholand, J-Y. Tetrahedron Lett. 1992,33, 1897-1900. Spectral data were compatible with previously published datal. 7a: mp 89-92’C; *H NMR (250 MHz, D20): 6 6.20 (lH, s), 6.16 (1H. s), 5.38 (IH, q, J=6.5Hz), 2.34 (3H, s), 1.40 (3H, s), 1.32 (3H, d, J=6.5Hz); 13C NMR (62.5 MHz, RO): 6 182.5, 173.5, 164.4, 163.0, 146.4, 114.0, 109.2, 103.2. 80.2, 79.0, 25.6, 25.2, 17.3. Optical rotations were taken in QO in order to be consistent wifh the conditions of the original value.’
(Received in France 10 March 1994; accepted 5 April 1994)
Synthesis Nicolas
and Absolute
VicarP,
Jean-Yves
Configuration
Ortholand,
of Phomozin
Gilbert Y. Emeric,
Alfred Greiner+
Rhi3ne Fbuleac Agrdimie, Centre de Rcchutk de la Dargoire, BP9163 F 69263-Lyon CEDEX 09. France
phytotoxin phomozin has been unambiguously determined by
Ah&net: The ahlute
Eonfieuratian of the fmgal
PIwnwpsis h&a&i
is a fungus that causes necrosis and stem cankering of sunflower.
the synthesis of its two enantiomea
Phomozin 1 we
The structure of1 was determined
recently isolated from culture filtrates of this severe pathogen.*>
from
X-ray diffraction3 and other physical data, and by comparison with dimethyl glyceric acid and was identified as erythro .4 However,
according to the authors, the poor quality of crystals obtained did not allow them to
assign the absolute concretion enantiomets
with total confidence.
We thus considered
wish to report the absolute configuration
KzCO3,
acetone, dlux,
dioxolanone
5s (2S,3S) and
methodology.7
the
acid. We now
available ethyl orcelinate 2 by benzylation6
12h, 99%). alkaline hydrolysis (KOH, lZtOH/H~O, RT, 24h, 85%)
and treatment with oxaIy1 chloride (cat. Dh@, RT, toluene,
Homochiral
to synthesize
of 1 along with a facile synthesis of chiral phmzin.
The aromatic fragment 45 was obtained from commercially (PhCH2Br.
interesting
of erythro 3-(2’,4’-dihy~xy-6’-mthylbenzoyloxy)-2-hy~xy-2-~~ylbu~oic
10 mitt).
5b (2R.3R) were synthesized from lactic acid using the previously reported
3918
Sa (2S.3S) eryrhro 18 % overall
H
Rex7
OH Sb (2R3R) erythro 34 46 overall
lactic acid Me Coupling of the hindered diols Sa or 5b with 4 (ErjN, cat. DMAP,
CH2C12, OT,
run under saictly anhydrous conditions to minimize the formation of the remarkably Selective saponification
(NaOH, EtOH, Et20, 12h) and hydrogenolysis
10 min) has to be
stable anhydride of 3.
(Hz, Pd/C, EtOAc, 9 bars, Sh)
allows the isolation of the desired rargets.518
2
HO Me
H
H
HO
5a (2S.3S) Sb (2R,3R) Compounds 1 7a 7b
68 (2S,3S) 6b (2R,3R)
30% 20%
7a (2S,3S) 7b (2R.3R)
48% (2 steps) 42% (2 steps)
1.711 and 7b have the fqllowing specific rotations9 :
[a]*‘D= +28 (D20, c=O.316)’ [cc]% = +25,5 (D20. c=O.325) [a]+= -27 @20. ~0.325)
These data allow with total confidence the conclusion that Phowzin methylbenzoyloxy)-2-hydmxy-2-methylbutanoic
is (2S,3S) 3-(2’,4’-dihydroxy-6’-
acid.
Acknowledgment : The authors thank Prof J.Gor& (Universitd Claude Bernard. Lyon) for his interest in this work and the Minist& de la Recherche et de I’ Espace for financial support. References
and notes
Mazars, C.; Rossiguol, M.; Atuiol, P.; Klaebe, A. Phytochemistry 1990.29, 3441-3444. Mazars, C.; Canivenc, E.; Rossignol, M.; Auriol, P. Plant Science 1991,75, 155-160. Declercq, J.P.; K&be, A.; Rossignol, M.; Mazars, C. Acta Crystallogr., Sect C: 1991, C47,470-472. 1 is identified as “esythro (1 lS,lOR)” in Ref. 1 (corresponding to the X-ray diffraction atom labelling) but the PLUTO drawing represents the (11 S, 10s) enantiomer. All compounds gave satisfactory analyses. Hendrickson, J-B.; Ramsay, M.V.J.; Kelly, T.R. J. Am. Chem. Sot. 1972.94. 6834-6843. Greiner, A.; ortholand, J-Y. Tetrahedron Lett. 1992,33, 1897-1900. Spectral data were compatible with previously published datal. 7a: mp 89-92’C; *H NMR (250 MHz, D20): 6 6.20 (lH, s), 6.16 (1H. s), 5.38 (IH, q, J=6.5Hz), 2.34 (3H, s), 1.40 (3H, s), 1.32 (3H, d, J=6.5Hz); 13C NMR (62.5 MHz, RO): 6 182.5, 173.5, 164.4, 163.0, 146.4, 114.0, 109.2, 103.2. 80.2, 79.0, 25.6, 25.2, 17.3. Optical rotations were taken in QO in order to be consistent wifh the conditions of the original value.’
(Received in France 10 March 1994; accepted 5 April 1994)