CN103159773B - Polycyclic derivative with chiral spirolactone pyrrole ring structural fragment and synthetic method thereof - Google Patents
Polycyclic derivative with chiral spirolactone pyrrole ring structural fragment and synthetic method thereof Download PDFInfo
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- CN103159773B CN103159773B CN201310096957.6A CN201310096957A CN103159773B CN 103159773 B CN103159773 B CN 103159773B CN 201310096957 A CN201310096957 A CN 201310096957A CN 103159773 B CN103159773 B CN 103159773B
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- 0 C*=CC[C@](*[C@]1IC(C)=C)[C@](*)C1(*)C(C=CC(OC(C)=O)=CC*)=O Chemical compound C*=CC[C@](*[C@]1IC(C)=C)[C@](*)C1(*)C(C=CC(OC(C)=O)=CC*)=O 0.000 description 7
- VZGDOMSFYCUJPK-VEJGQTNOSA-N C[C@@](C1[C@](CC2)(C=C3)[O](C)C2=O)(C(OC)=O)NC[C@@H]1C3=O Chemical compound C[C@@](C1[C@](CC2)(C=C3)[O](C)C2=O)(C(OC)=O)NC[C@@H]1C3=O VZGDOMSFYCUJPK-VEJGQTNOSA-N 0.000 description 1
Abstract
The invention discloses a polycyclic derivative with a chiral spirolactone pyrrole ring structural fragment and a synthetic method thereof. The synthetic method comprises the following steps of: in an organic solvent, under inert gas shielding, based on imine derived from spiro hexyl dienone lactone and Glycine methyl ester as a raw material and a metal lewis acid/chiral ligand complex as a catalyst, adding carbonate or organic base; reacting at (-40)-20 DEG C; evaporating the solvent; and obtaining the target compound by column chromatography. The target compound obtained has bactericidal activity.
Description
Technical field
The invention belongs to Chiral polycyclic compou nd synthesis technical field, particularly relate to a kind of Polycyclic derivative and the synthetic method thereof with chiral spiro lactone pyrrole ring structure fragment.
Background technology
In recent years due to more and more discovery with biological functional activity polynuclear compound, make to increase the demand of the polynuclear compound with special construction thereupon, so it is important to synthesize various non-natural polynuclear compound meaning, and cause concern ((a) J.I.Halliday widely, M.Chebib, M.D.Mcleod, Aust.J.Chem.2010, 63, 808.(b) J.F.Huang, C.M.Orac, S.McKay, D.B.McKay, S.C.Bergmeier, Bioorg.Med.Chem.2008, 16, 3816.(c) D.Barker, D.H.-S.Lin, J.E.Carland, C.P.-Y.Chu, M.Chebib, M.A.Brimble, G.P.Savage, M.D.McLeod, Bioorg.Med.Chem.2005, 13, 4565.).
The Polycyclic derivative with chiral spiro lactone pyrrole ring structure fragment is the important compound of a class, is mainly used in medicine and bioactive compounds ((a) Trost, B.M.; Jiang, C.Synthesis2006,369.(b) Douglas, C.J.and Overman, L.E.Proc.Natl.Acad.Sci.U.S.A2004,101,5363.(c) Marti, C.; Carreira, E.M.Eur.J.Org.Chem.2003,2209.(d) Takagi, R.; Miyanaga, W.; Tojo, K.; Tsuyumine, S.; Ohkata, K.J.Org.Chem.2007,72,4117.)
Summary of the invention
The object of this invention is to provide the Polycyclic derivative that a class has chiral spiro lactone pyrrole ring structure fragment.
Another object of the present invention is to provide a kind of method that efficient synthesis has the Polycyclic derivative of chiral spiro lactone pyrrole ring structure fragment.
Another object of the present invention is to provide the application of the Polycyclic derivative with chiral spiro lactone pyrrole ring structure fragment.
The Polycyclic derivative with chiral spiro lactone pyrrole ring structure fragment provided by the invention, structural formula is as follows:
Structural formula (I-2):
Structural formula (II-1):
Structural formula (II-2):
Structural formula (III-1):
Structural formula (III-2):
Structural formula (IV-1):
Structural formula (IV-2):
Wherein,
R
1for to halobenzene base, adjacent halobenzene base, a halobenzene base, adjacent trihalogenmethyl phenyl, to trihalogenmethyl phenyl, to methyl-formiate phenyl, adjacent methyl-formiate phenyl, a methyl-formiate phenyl, p-nitrophenyl, O-Nitrophenylfluorone, phenyl, p-methylphenyl, o-methyl-phenyl-, 2-naphthyl, 1-naphthyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, cyclohexyl, cyclopentyl, C
1-C
9straight chained alkyl or C
1-C
9branched-chain alkyl;
R
2for hydrogen, benzyl, C
1-C
6straight chained alkyl or C
1-C
6branched-chain alkyl;
X is halogen;
N is 1 or 2.
Above-mentioned halogen can be fluorine, chlorine, bromine or iodine.
Above-mentioned R
1be preferably rubigan, Chloro-O-Phenyl, a chloro-phenyl-, to bromophenyl, o-trifluoromethyl phenyl, to methyl-formiate phenyl, p-nitrophenyl, phenyl, p-methylphenyl, o-methyl-phenyl-, 2-naphthyl, 2-furyl, 2-thienyl, cyclohexyl or isobutyl-.
Above-mentioned R
2be preferably hydrogen, methyl, ethyl, n-propyl, isobutyl-or benzyl.
Present invention also offers the synthetic method of above-claimed cpd, comprise step:
In organic solvent; under the protection of rare gas element; the imines derived with spiral shell cyclohexadienone lactone and glycine methyl ester is for raw material; with metal Lewis acids/chiral ligand complex for catalyzer; add carbonate or organic bases; react at-40 ~ 25 DEG C of temperature, boil off solvent, obtain target compound through column chromatography
or
or
For above-mentioned synthetic method, can carry out preferably following
1) above-mentioned organic solvent is methylene dichloride.
2) mol ratio of imines that above-mentioned spiral shell cyclohexadienone lactone and glycine methyl ester derive is 1:1.3.
3) above-mentioned metal Lewis acids/chiral ligand complex is adopted and is prepared with the following method:
Under room temperature, be not more than chiral ligand mole number by metal Lewis acids mole number and get metal Lewis acids and chiral ligand TF-Biphamphos is dissolved in organic solvent, through being obtained by reacting.
The complex compound of described metal Lewis acids/chiral ligand can be silver salt/TF-Biphamphos complex compound or mantoquita/TF-Biphamphos.
Publication number is CN101440037B, denomination of invention is 3,3 '-two bromo-4,4 ', 6, the structure of chiral ligand (S)-TF-BiphamPhos and (R) TF-BiphamPhos is disclosed in the Chinese patent of 6 '-four (trifluoromethyl) biphenyl-2,2 '-diamines and method for making thereof.
(S) structural formula of-TF-BiphamPhos is:
(R) structural formula of TF-BiphamPhos is:
In the structural formula of (S)-TF-BiphamPhos or (R) TF-BiphamPhos, R
1can be phenyl, 3,5-3,5-dimethylphenyls, 3,5-bis-trifluoromethyl or cyclohexyl; R
2can be hydrogen or bromine.
4) usage quantity of above-mentioned carbonate or organic bases is catalytic amount.
5) above-mentioned column chromatography take silica gel as stopping composition, with the mixed solvent of sherwood oil and ethyl acetate for eluent, and: the volume ratio of sherwood oil and ethyl acetate is 1:1.The target compound that above-mentioned synthetic method is obtained is placed in ethyl acetate solvent, with Rh/Al
2o
3and PtO
2for catalyzer, obtain the first kind derivative of target compound through hydrogenation
or
wherein, R
1, R
2, X, n the same target compound of definition.
By target compound obtained for above-mentioned synthetic method in methylene dichloride, under triethylamine alkaline condition, occur after Michael (Michael) reacts, to boil off solvent, obtain the Equations of The Second Kind derivative of target compound through column chromatography with thiophenol
or
wherein, R
1, R
2, X, n the same target compound of definition.
Fungicidal activity detection is carried out to the first kind derivative of target compound, target compound, the Equations of The Second Kind derivative of target compound, find that above-mentioned series has the equal tool fungicidal activity of Polycyclic derivative of chiral spiro lactone pyrrole ring structure fragment, can be used as the effective constituent of sterilant.
Compared with prior art, the present invention has following characteristics:
1) the inventive method synthesis is simple, and cost is low, and productive rate is high, and gained target compound corresponding selection is good, productive rate 65-90%, and corresponding selection is excessive >=and 90%;
2) adopt the Polycyclic derivative with spiro lactone pyrrole ring structure fragment of the series of new of the inventive method synthesis to have fungicidal activity, can be used as the effective constituent of sterilant;
3) complex compound of the catalyst metal Lewis acid/chiral ligand of the inventive method employing, shows the advantage that catalytic is fast and catalyst levels is low in the reaction.
Embodiment
For a better understanding of the present invention, below in conjunction with embodiment, the present invention is described further.
The structural formula of chiral ligand (the S)-TF-Biphamphos adopted in the following example is
the structural formula of chiral ligand (the R)-TF-Biphamphos adopted is
Embodiment 1
preparation
0.015mmol AgOAc and 0.017mmol (S)-TF-BiphamPhos is added in 25mL reaction tubes, under nitrogen protection, add 1mL methylene dichloride, stirred at ambient temperature 1 hour, then at 0 DEG C, add 0.39mmol2-(successively to chlorobenzene methene amido) methyl acetate, 0.30mmol cyclohexadienone butyrolactone, with 0.045mmol triethylamine, after stirring 18h, boil off solvent, product is through silica gel column chromatography (petrol ether/ethyl acetate 1/1), obtain white solid, productive rate 87%, fusing point 152 DEG C, the enantioselectivity excessive 97% of product, HPLC (Chiralcel AD-H, i-propanol/hexane=50/50, flowrate1.0mL/min, λ=210nm, t
r=10.19and25.53min), [α]
25 d=-147.2 (c0.67, CHCl
3),
1h NMR (CDCl
3, TMS, 300MHz) and δ 7.27 (m, 4H), 6.68 (d, J=10.2Hz, 1H), 5.85 (d, J=10.2Hz, 1H), 4.62 (d, J=7.8Hz, 1H), 4.13 (d, J=6.6Hz, 1H), 3.83 (s, 3H), 3.39-3.30 (m, 2H), 2.71-2.64 (m, 2H), 2.59-2.53 (m, 1H), 2.27-2.20 (m, 1H),
13cNMR (CDCl
3, TMS, 75MHz) and δ 194.6,174.7,171.9,147.8,135.9,133.6,130.0,128.9,128.4,80.5,65.3,62.9,53.7,52.8,49.6,36.5,27.5, IR (KBr) ν 3320,3015,2964,2922,1780,1725,1635,1527,1425,1191,1014,852,756,665cm
-1.HRMS calculated value for C
19h
18clNO
5+ H
+: 376.0950, observed value 376.0946.
Embodiment 2
preparation
0.015mmol AgOAc and 0.017mmol (S)-TF-BiphamPhos is added in 25mL reaction tubes, under nitrogen protection, add 1mL methylene dichloride, stirred at ambient temperature 1 hour, then at 0 DEG C, add the adjacent chlorobenzene methene amido of 0.39mmol2-(successively) methyl acetate, 0.30mmol cyclohexadienone butyrolactone, with 0.045mmol triethylamine, after stirring 18h, boil off solvent, product is through silica gel column chromatography (petrol ether/ethyl acetate 1/1), obtain white solid, productive rate 80%, fusing point 132 DEG C, the enantioselectivity excessive 95% of product, HPLC (Chiralpak AS-H, i-propanol/hexane=50/50, flowrate1.0mL/min, λ=210nm, t
r=21.11and38.99min.), [α]
25 d=-178.1 (c0.60, CHCl
3),
1h NMR (CDCl
3, TMS, 300MHz) and δ 7.49-7.45 (m, 1H), 7.40-7.37 (m, 1H), 7.25-7.22 (m, 2H), (6.80 d, J=10.2Hz, 1H), (5.88 d, J=10.2Hz, 1H), (4.81 d, J=7.2Hz, 1H), (4.14 d, J=9.0Hz, 1H), (3.82 s, 3H), 3.60-3.55 (m, 1H), 3.45-3.40 (m, 1H), (2.73-2.62 m, 2H), 2.43-2.34 (m, 1H), 2.25-2.18 (m, 1H),
13c NMR (CDCl
3, TMS, 75MHz) and δ 193.8,174.6,172.4,149.0,135.5,133.1,130.1,129.1,128.7,127.5,126.7,81.7,63.1,61.2,52.5,50.5,50.4,36.4,27.5, IR (KBr) ν 3345,3027,2955,2930,1762,1737,1613,1530,1437,1187,1018,862,756,735cm
-1.HRMSCalcd. calculated value C
19h
18clNO
5+ H
+: 376.0950, observed value 376.0946.
Embodiment 3
preparation
0.015mmol AgOAc and 0.017mmol (S)-TF-BiphamPhos is added in 25mL reaction tubes, under nitrogen protection, add 1mL methylene dichloride, stirred at ambient temperature 1 hour, then at 0 DEG C, add 0.39mmol2-(m-chloro benzylideneamino successively) methyl acetate, 0.30mmol cyclohexadienone butyrolactone, with 0.045mmol triethylamine, after stirring 18h, boil off solvent, product is through silica gel column chromatography (petrol ether/ethyl acetate 1/1), obtain white solid, productive rate 84%, fusing point 130 DEG C, the enantioselectivity excessive 94% of product, HPLC (Chiralpak AS-H, i-propanol/hexane=50/50, flowrate1.0mL/min, λ=210nm, t
r=27.81and41.90min.), [α]
25 d=-144.4 (c0.59, CHCl
3),
1h NMR (CDCl
3, TMS, 300MHz) and δ 7.32-7.24 (m, 4H), 6.71 (d, J=10.2Hz, 1H), 5.88 (d, J=10.2Hz, 1H), 4.59 (d, J=7.8Hz, 1H), 4.13 (d, J=6.6Hz, 1H), 3.83 (s, 3H), 3.37-3.32 (m, 2H), 2.71-2.64 (m, 2H), 2.56-2.50 (m, 1H), 2.27-2.19 (m, 1H),
13c NMR (CDCl
3, TMS, 75MHz) and δ 194.4,174.7,171.9,148.0,139.5,134.0,130.0,129.4,128.0,127.8,125.6,80.7,65.4,62.6,53.5,52.6,49.6,36.4,27.5, IR (KBr) ν 3320,3014,2920,2907,1752,1716,1603,1525,1456,1130,1025,862,756,635cm
-1.HRMS calculated value for C
19h
18clNO
5+ H
+: 376.0950, observed value 376.0946..
Embodiment 4
preparation
0.015mmol AgOAc and 0.017mmol (S)-TF-BiphamPhos is added in 25mL reaction tubes, under nitrogen protection, add 1mL methylene dichloride, stirred at ambient temperature 1 hour, then at 0 DEG C, add 0.39mmol2-(successively to trifluoromethyl benzylideneamino) methyl acetate, 0.30mmol cyclohexadienone butyrolactone, with 0.045mmol triethylamine, after stirring 18h, boil off solvent, product is through silica gel column chromatography (petrol ether/ethyl acetate 1/1), obtain white solid, productive rate 87%, fusing point 154 DEG C, the enantioselectivity excessive 96% of product, HPLC (Chiralpak AD-H, i-propanol/hexane=50/50, flow rate1.0mL/min, λ=210nm, t
r=7.18and16.49min), [α]
25 d=-112.0 (c0.60, CHCl
3),
1h NMR (CDCl
3, TMS, 300MHz) and δ 7.56 (d, J=8.1Hz, 1H), 7.46 (d, J=8.1Hz, 1H), 6.68 (d, J=10.2Hz, 1H), 5.84 (d, J=10.2Hz, 1H), 4.69 (d, J=7.2Hz, 1H), 4.17 (d, J=6.6Hz, 1H), 3.83 (s, 3H), 3.39-3.36 (m, 2H), 2.72-2.64 (m, 2H), 2.60-2.50 (m, 1H), 2.28-2.18 (m, 1H),
13c NMR (CDCl
3, TMS, 100MHz) and δ 194.3,174.7,171.9,147.9,141.6,129.9,127.9,125.2,125.1,80.5,65.3,62.7,53.5,52.7,49.7,36.4,27.5, IR (KBr) ν 3415,3086,2936,2905,1726,1700,1634,1503,1428,1122,1038,876,714,620cm
-1.HRMS calculated value for C
20h
18f
3nO
5+ H
+: 410.1213, observed value 410.1210.
Embodiment 5
preparation
0.015mmol AgOAc and 0.017mmol (S)-TF-BiphamPhos is added in 25mL reaction tubes, under nitrogen protection, add 1mL methylene dichloride, stirred at ambient temperature 1 hour, then at 0 DEG C, add 0.39mmol2-(successively to methyl-formiate benzylideneamino) methyl acetate, 0.30mmol cyclohexadienone butyrolactone, with 0.045mmol triethylamine, after stirring 18h, boil off solvent, product is through silica gel column chromatography (petrol ether/ethyl acetate 1/1), obtain white solid, productive rate 89%, fusing point 140 DEG C, the enantioselectivity excessive 96% of product, HPLC (Chiralpak AD-H, i-propanol/hexane=50/50, flow rate1.0mL/min, λ=210nm, t
r=14.78and32.53min.) [α]
25 d=-162.3 (c0.76, CHCl
3),
1h NMR (CDCl
3, TMS, 300MHz) and δ 7.98 (d, J=8.1Hz, 1H), 7.39 (d, J=8.1Hz, 1H), 6.69 (d, J=10.2Hz, 1H), 5.83 (d, J=10.2Hz, 1H), 4.68 (d, J=7.2Hz, 1H), 4.16 (d, J=6.6Hz, 1H), 3.90 (s, 3H), 3.84 (s, 3H), 3.39-3.37 (m, 2H), 2.72-2.64 (m, 2H), 2.58-2.48 (m, 1H), 2.27-2.20 (m, 1H),
13c NMR (CDCl
3, TMS, 100MHz) and δ 194.3,174.8,171.9,166.7,148.0,142.7,129.9,129.4,127.5,80.7,65.6,62.6,53.6,52.6,52.0,49.8,36.3,29.6,27.5, IR (KBr) ν 3386,3056,2985,2887,1755,1685,1606,1523,1428,1135,1038,876,755,689cm
-1.HRMS calculated value forC
21h
21nO
7+ H
+: 400.1397, observed value 400.1391.
Embodiment 6
preparation
0.015mmol AgOAc and 0.017mmol (S)-TF-BiphamPhos is added in 25mL reaction tubes, under nitrogen protection, add 1mL methylene dichloride, stirred at ambient temperature 1 hour, then at 0 DEG C, add 0.39mmol2-(p-nitrophenyl methene amido successively) methyl acetate, 0.30mmol cyclohexadienone butyrolactone, with 0.045mmol triethylamine, after stirring 18h, boil off solvent, product is through silica gel column chromatography (petrol ether/ethyl acetate 1/1), obtain white solid, productive rate 82%, fusing point 92 DEG C, the enantioselectivity excessive 98% of product, HPLC (Chiralpak IC, i-propanol/hexane=50/50, flow rate1.0mL/min, λ=210nm, t
r=28.84and32.69min.), [α]
25 d=-175.4 (c0.51, CHCl
3),
1h NMR (CDCl
3, TMS, 300MHz) and δ 8.17 (d, J=8.4Hz, 1H), 7.56 (d, J=8.4Hz, 1H), 6.70 (d, J=10.2Hz, 1H), 5.83 (d, J=10.2Hz, 1H), 4.76 (d, J=5.7Hz, 1H), 4.22 (d, J=6.3Hz, 1H), 3.83 (s, 3H), 3.41-3.38 (m, 2H), 2.74-2.67 (m, 2H), 2.61-2.54 (m, 1H), 2.31-2.24 (m, 1H),
13c NMR (CDCl
3, TMS, 100MHz) and δ 194.3,174.8,171.9,166.7,148.0,142.7,129.9,129.4,127.5,80.7,65.6,62.6,53.6,52.6,52.0,49.8,36.3,29.6,27.5, IR (KBr) 3426,3033,2958,2927,1745,1690,1643,1562,1252,1091,1014,880,756,668cm
-1.HRMS calculated value for C
19h
18n
2o
7+ H
+: 387.1198, observed value 387.1187.
Embodiment 7
preparation
0.015mmol AgOAc and 0.017mmol (S)-TF-BiphamPhos is added in 25mL reaction tubes, under nitrogen protection, add 1mL methylene dichloride, stirred at ambient temperature 1 hour, then at 0 DEG C, add 0.39mmol2-(benzylideneamino successively) methyl acetate, 0.30mmol cyclohexadienone butyrolactone, with 0.045mmol triethylamine, after stirring 18h, boil off solvent, product is through silica gel column chromatography (petrol ether/ethyl acetate 1/1), obtain white solid, productive rate 85%, fusing point 133 DEG C, the enantioselectivity excessive 97% of product, HPLC (Chiralpak AD-H, i-propanol/hexane=50/50, flowrate1.0mL/min, λ=210nm, t
r=11.78and22.31min.), [α]
25 d=-100.0 (c0.60, CHCl
3),
1h NMR (CDCl
3, TMS, 400MHz) and δ 7.31-7.28 (m, 5H), 6.68 (d, J=10.4Hz, 1H), 5.85 (d, J=10.4Hz, 1H), 4.64 (d, J=8.4Hz, 1H), 4.14 (d, J=7.2Hz, 1H), 3.84 (s, 3H), 3.38-3.35 (m, 2H), 2.70-2.63 (m, 2H), 2.57-2.52 (m, 1H), 2.45-2.19 (m, 1H),
13c NMR (CDCl
3, TMS, 100MHz) and δ 207.0,194.9,174.8,171.9,147.7,137.0,130.1,128.2,127.9,127.4,80.7,66.2,63.1,54.1,52.6,49.8,36.5,30.9,27.5, IR (KBr) ν 3400,3068,2958,2882,1784,1690,1612,1500,1450,1114,852,726,633cm
-1.HRMS calculated value for C
19h
19nO
5+ H
+: 342.1339, observed value 342.1336.
Embodiment 8
preparation
0.015mmol AgOAc and 0.017mmol (S)-TF-BiphamPhos is added in 25mL reaction tubes, under nitrogen protection, add 1mL methylene dichloride, stirred at ambient temperature 1 hour, then at 0 DEG C, add 0.39mmol2-(successively amino to methyl benzylidene) methyl acetate, 0.30mmol cyclohexadienone butyrolactone, with 0.045mmol triethylamine, after stirring 18h, boil off solvent, product is through silica gel column chromatography (petrol ether/ethyl acetate 1/1), obtain white solid, productive rate 81%, fusing point 136 DEG C, the enantioselectivity excessive 99% of product, HPLC (Chiralpak AD-H, i-propanol/hexane=50/50, flow rate1.0mL/min, λ=210nm, t
r=10.92and22.45min.), [α]
25 d=-117.5 (c0.73, CHCl
3),
1h NMR (CDCl
3, TMS, 400MHz) and δ 7.16 (d, J=8.0Hz, 1H), 7.11 (d, J=8.0Hz, 1H), 6.68 (d, J=10.4Hz, 1H), 5.86 (d, J=10.4Hz, 1H), 4.60 (d, J=8.0Hz, 1H), 4.10 (d, J=7.2Hz, 1H), 3.84 (s, 3H), 3.36-3.32 (m, 2H), 2.67-2.62 (m, 2H), 2.55-2.50 (m, 1H), 2.31 (s, 3H), 2.22-2.18 (m, 1H),
13c NMR (CDCl
3, TMS, 100MHz) and δ 195.1,174.8,172.0,147.7,137.6,133.8,130.2,129.0,127.3,80.8,66.2,63.2,54.3,52.6,49.8,36.6,27.5,21.1, IR (KBr) ν 3422,3109,2959,2901,1785,1610,1532,1411,1085,989,756,687cm
-1.HRMS calculated value for C
20h
21nO
5+ H
+: 356.1492, observed value 356.1492.
Embodiment 9
preparation
0.015mmol AgOAc and 0.017mmol (S)-TF-BiphamPhos is added in 25mL reaction tubes, under nitrogen protection, add 1mL methylene dichloride, stirred at ambient temperature 1 hour, then at 0 DEG C, add 0.39mmol2-(o-methyl-benzene methene amido successively) methyl acetate, 0.30mmol cyclohexadienone butyrolactone, with 0.045mmol triethylamine, after stirring 18h, boil off solvent, product is through silica gel column chromatography (petrol ether/ethyl acetate 1/1), obtain white solid, productive rate 88%, fusing point 155 DEG C, the enantioselectivity excessive 98% of product, HPLC (Chiralpak AD-H, i-propanol/hexane=50/50, flow rate1.0mL/min, λ=210nm, t
r=9.08and15.12min.), [α]
25 d=-178.7 (c0.53, CHCl
3),
1h NMR (CDCl
3, TMS, 300MHz) and δ 7.31-7.26 (m, 1H), 7.16 (m, 1H), 6.75 (d, J=10.2Hz, 1H), 5.83 (d, J=10.2Hz, 1H), 4.70 (d, J=7.5Hz, 1H), 4.09 (d, J=6.6Hz, 1H), 3.86 (s, 3H), 3.45-3.40 (m, 2H), 2.71-2.61 (m, 2H), 2.43-2.38 (m, 4H), 2.23-2.16 (m, 1H),
13c NMR (CDCl
3, TMS, 100MHz) and δ 194.7,174.7,171.9,148.4,135.8,135.1,130.3,130.2,127.6,125.8,125.4,81.1,62.8,62.7,52.6,52.4,50.1,37.0,27.5,19.7, IR (KBr) ν 3452,3219,2989,2911,1756,1600,1523,1423,1077,990,825,765,612cm
-1.HRMS calculated value .for C
20h
21nO
5+ H
+: 356.1495, observed value 356.1492.
Embodiment 10
preparation
0.015mmol AgOAc and 0.017mmol (S)-TF-BiphamPhos is added in 25mL reaction tubes, under nitrogen protection, add 1mL methylene dichloride, stirred at ambient temperature 1 hour, then at 0 DEG C, add 0.39mmol2-(2-naphthyl methylene successively amino) methyl acetate, 0.30mmol cyclohexadienone butyrolactone, with 0.045mmol triethylamine, after stirring 18h, boil off solvent, product is through silica gel column chromatography (petrol ether/ethyl acetate 1/1), obtain white solid, productive rate 82%, fusing point 154 DEG C, the enantioselectivity excessive 96% of product, HPLC (Chiralpak AD-H, i-propanol/hexane=50/50, flowrate1.0mL/min, λ=210nm, t
r=17.08and40.96min.), [α]
25 d=-67.3 (c0.40, CHCl
3),
1h NMR (CDCl
3, TMS, 300MHz) and δ 7.80-7.77 (m, 4H), 7.47-7.37 (m, 3H), (6.70 d, J=10.2Hz, 1H), (5.82 d, J=10.2Hz, 1H), (4.79 d, J=7.5Hz, 1H), (4.18 d, J=6.9Hz, 1H), (3.87 s, 3H), 3.45-3.41 (m, 2H), 2.71-2.63 (m, 2H), 2.56-2.49 (m, 1H), 2.25-2.22 (m, 1H),
13c NMR (CDCl
3, TMS, 75MHz) and δ 194.7,174.8,172.0,148.0,134.6,133.1,130.1,128.0,127.8,127.7,126.1,126.0,125.9,125.7,80.8,66.3,63.0,54.1,52.7,50.0,36.6,27.5, IR (KBr) ν 3412,3088,3030,2972,2900,1785,1613,1580,900,852,774,635cm
-1.HRMS calculated value for C
23h
21nO
5+ H
+: 392.1498, observed value 392.1492.
Embodiment 11
preparation
0.015mmol AgOAc and 0.017mmol (S)-TF-BiphamPhos is added in 25mL reaction tubes, under nitrogen protection, add 1mL methylene dichloride, stirred at ambient temperature 1 hour, then at 0 DEG C, add 0.39mmol2-(2-furfurylidene successively amino) methyl acetate, 0.30mmol cyclohexadienone butyrolactone, with 0.045mmol triethylamine, after stirring 18h, boil off solvent, product is through silica gel column chromatography (petrol ether/ethyl acetate 1/1), obtain yellow solid, productive rate 88%, fusing point 83 DEG C, the enantioselectivity excessive 96% of product, HPLC (Chiralpak AD-H, i-propanol/hexane=50/50, flowrate1.0mL/min, λ=210nm, t
r=13.17and17.08min.), [α]
25 d=-54.7 (c0.42, CHCl
3),
1h NMR (CDCl
3, TMS, 300MHz) and δ 7.35-7.33 (m, 1H), 6.67 (d, J=10.5Hz, 1H), 6.33-6.31 (m, 2H), 5.97 (d, J=10.5Hz, 1H), 4.72 (d, J=8.1Hz, 1H), 4.09 (d, J=6.3Hz, 1H), 3.82 (s, 3H), 3.35-3.32 (m, 2H), 2.69-2.51 (m, 3H), 2.27-2.18 (m, 1H),
13c NMR (CDCl
3, TMS, 100MHz) and δ 194.6,174.8,171.6,150.2,147.3,142.2,129.6,110.3,108.0,80.3,63.3,60.2,53.2,52.6,49.9,36.2,27.4, IR (KBr) ν 3400,3119,3020,2964,2898,1765,1622,1545,1307,904,852,753,688cm
-1.HRMS calculated value for C
17h
17nO
6+ H
+: 332.1137, observed value 332.1129.
Embodiment 12
preparation
0.015mmol AgOAc and 0.017mmol (S)-TF-BiphamPhos is added in 25mL reaction tubes, under nitrogen protection, add 1mL methylene dichloride, stirred at ambient temperature 1 hour, then at 0 DEG C, add 0.39mmol2-(2-thenylidene successively amino) methyl acetate, 0.30mmol cyclohexadienone butyrolactone, with 0.045mmol triethylamine, after stirring 18h, boil off solvent, product is through silica gel column chromatography (petrol ether/ethyl acetate 1/1), obtain yellow solid, productive rate 88%, fusing point 83 DEG C, the enantioselectivity excessive 93% of product, HPLC (Chiralpak AD-H, i-propanol/hexane=50/50, flowrate1.0mL/min, λ=210nm, t
r=12.59and23.28min.), [α]
25 d=-85.3 (c0.42, CHCl
3),
1h NMR (CDCl
3, TMS, 300MHz) and δ 7.22-7.20 (m, 1H), 7.00-6.95 (m, 2H), 6.66 (d, J=10.2Hz, 1H), 5.93 (d, J=10.2Hz, 1H), 4.92 (d, J=7.5Hz, 1H), 4.10 (d, J=6.0Hz, 1H), 3.83 (s, 3H), 3.35-3.33 (m, 2H), 2.67-2.53 (m, 3H), 2.27-2.17 (m, 1H),
13c NMR (CDCl
3, TMS, 100MHz) and δ 194.6,174.8,171.6,147.3,140.7,130.0,126.9,125.7,124.8,80.3,63.2,61.6,54.2,52.6,49.6,36.3,31.6, IR (KBr) ν 3326,3019,2964,2922,1735,1600,1522,1425,1091,1014,852,756,665cm
-1.HRMS calculated value for C
17h
17nO
5s+H
+: 348.0898, observed value 348.0900.
Embodiment 13
preparation
0.015mmol AgOAc and 0.017mmol (S)-TF-BiphamPhos is added in 25mL reaction tubes, under nitrogen protection, add 1mL methylene dichloride, stirred at ambient temperature 1 hour, then at 0 DEG C, add 0.39mmol2-(cyclohexylmethylene successively amino) methyl acetate, 0.30mmol cyclohexadienone butyrolactone, with 0.045mmol salt of wormwood, after stirring 18h, boil off solvent, product is through silica gel column chromatography (petrol ether/ethyl acetate 1/1), obtain white solid, productive rate 73%, fusing point 72 DEG C, the enantioselectivity excessive 98% of product, HPLC (Chiralpak AD-H, i-propanol/hexane=50/50, flowrate1.0mL/min, λ=210nm, t
r=8.83and16.42min.), [α]
25 d=+11.1 (c0.46, CHCl
3),
1h NMR (CDCl
3, TMS, 400MHz) and δ 6.79 (d, J=10.4Hz, 1H), 6.05 (d, J=10.4Hz, 1H), 3.91 (d, J=9.2Hz, 1H), 3.78 (s, 3H), 3.20-3.16 (m, 1H), (3.08-3.04 m, 1H), 2.93-2.84 (m, 1H), 2.74-2.57 (m, 2H), (2.36-2.29 m, 1H), 2.24-2.18 (m, 2H), 1.89-1.85 (m, 1H), (1.80-1.68 m, 5H), 1.62-1.56 (m, 1H), 1.31-1.09 (m, 2H), (1.06-0.92 m, 1H),
13c NMR (CDCl
3, TMS, 100MHz) and δ 195.6,174.6,173.0,149.2,130.7,82.3,70.3,61.8,52.5,51.4,50.4,38.4,36.4,31.2,27.6,26.4,25.8,25.6, IR (KBr) ν 3338,3002,2964,2878,1785,1653,1545,1433,1191,802,732,626cm
-1.HRMS calculated value for C
19h
25nO
5+ H
+: 348.1812, observed value 348.1806.
Embodiment 14
preparation
0.015mmol AgOAc and 0.017mmol (S)-TF-BiphamPhos is added in 25mL reaction tubes, under nitrogen protection, add 1mL methylene dichloride, stirred at ambient temperature 1 hour, then at 0 DEG C, add 0.39mmol2-(isobutylmethylene successively amino) methyl acetate, 0.30mmol cyclohexadienone butyrolactone, with 0.045mmol salt of wormwood, after stirring 18h, boil off solvent, product is through silica gel column chromatography (petrol ether/ethyl acetate 1/1), obtain yellow oily liquid, productive rate 78%, the enantioselectivity excessive 99% of product, HPLC (Chiralpak AS-H, i-propanol/hexane=50/50, flow rate1.0mL/min, λ=210nm, t
r=10.11and15.65min.), [α]
25 d=+51.7 (c0.46, CHCl
3),
1hNMR (CDCl
3, TMS, 400MHz) and δ 6.77 (d, J=10.4Hz, 1H), 6.08 (d, J=10.4Hz, 1H), 3.94 (d, J=8.0Hz, 1H), 3.79 (s, 3H), 3.43-3.40 (m, 1H), 3.24-3.22 (m, 1H), 3.05-3.01 (m, 1H), 2.68-2.63 (m, 2H), 2.42-2.38 (m, 1H), 2.21-2.16 (m, 1H), 1.82-1.78 (m, 1H), 1.49-1.45 (m, 1H), 1.27-1.22 (m, 1H), 0.93-0.91 (m, 6H),
13cNMR (CDCl
3, TMS, 100MHz) and δ 196.2,174.6,172.3,148.9,130.1,81.2,63.1,61.2,52.7,52.6,50.6,40.2,36.3,27.5,25.9,23.5,21.7, IR (KBr) ν 3389,3012,2967,2902,1788,1602,1500,1412,980,855,723,687,635cm
-1.HRMS calculated value forC
17h
23nO
5+ H
+: 322.1647, observed value 322.1649.
Embodiment 15
preparation
0.015mmol AgOAc and 0.017mmol (S)-TF-BiphamPhos is added in 25mL reaction tubes, under nitrogen protection, add 1mL methylene dichloride, stirred at ambient temperature 1 hour, then at 0 DEG C, add 0.39mmol2-(successively to chlorobenzene methene amido) methyl propionate, 0.30mmol cyclohexadienone butyrolactone, with 0.045mmol salt of wormwood, after stirring 18h, boil off solvent, product is through silica gel column chromatography (petrol ether/ethyl acetate 1/1), obtain white solid, productive rate 85%, fusing point 72 DEG C, the enantioselectivity excessive 99% of product, HPLC (Chiralpak AS-H, i-propanol/hexane=50/50, flowrate1.0mL/min, λ=210nm, t
r=13.30and21.18min.), [α]
25 d=-107.8 (c0.64, CHCl
3),
1h NMR (CDCl
3, TMS, 300MHz) and δ 7.31-7.27 (m, 4H), 6.52 (d, J=10.2Hz, 1H), 5.76 (d, J=10.2Hz, 1H), 4.78 (d, J=9Hz, 1H), 3.78 (s, 3H), 3.44-3.41 (m, 1H), 3.00 (d, J=7.5Hz, 1H), 2.65-2.79 (m, 3H), 2.29-2.24 (m, 1H), 1.61 (s, 3H),
13cNMR (CDCl
3, TMS, 100MHz) and δ 194.2,175.3,174.9,146.3,136.9,133.2,129.3,129.0,128.1,80.4,68.7,63.4,56.8,52.8,52.7,36.1,27.527.3, IR (KBr) ν 3340,3108,2984,2822,1775,1670,1580,1400,1052,900,852,620cm
-1.HRMS calculated value for C
20h
20clNO
5+ H
+: 390.1105, observed value 390.1103.
Embodiment 16
preparation
0.015mmol AgOAc and 0.017mmol (S)-TF-BiphamPhos is added in 25mL reaction tubes, under nitrogen protection, add 1mL methylene dichloride, stirred at ambient temperature 1 hour, then at 0 DEG C, add 0.39mmol2-(m-chloro benzylideneamino successively) methyl propionate, 0.30mmol cyclohexadienone butyrolactone, with 0.045mmol salt of wormwood, after stirring 18h, boil off solvent, product is through silica gel column chromatography (petrol ether/ethyl acetate 1/1), obtain white solid, productive rate 88%, fusing point 155 DEG C, the enantioselectivity excessive 98% of product, HPLC (Chiralpak AS-H, i-propanol/hexane=50/50, flowrate1.0mL/min, λ=210nm, t
r=12.28and26.48min.), [α]
25 d=-112.0 (c0.75, CHCl
3),
1h NMR (CDCl
3, TMS, 300MHz) and δ 7.36 (s, 1H), 7.27-7.24 (m, 3H), 6.56 (d, J=10.2Hz, 1H), 5.78 (d, J=10.2Hz, 1H), 4.75 (d, J=8.7Hz, 1H), 3.77 (s, 3H), 3.42-3.38 (m, 1H), 3.00 (d, J=7.2Hz, 1H), 2.79-2.65 (m, 3H), 2.28-2.22 (m, 1H), 1.61 (s, 3H),
13c NMR (CDCl
3, TMS, 100MHz) and δ 193.9,175.2,175.0,146.6,140.6,133.9,129.5,129.3,128.0,127.7,125.8,80.8,68.5,63.6,57.5,52.9,52.8,36.2,27.5,27.4, IR (KBr) ν 3350,3112,2985,2826,1760,1665,1575,1401,1055,876,754,640cm
-1.HRMS calculated value for C
20h
20clNO
5+ H
+: 390.1105, observed value 390.1103.
Embodiment 17
preparation
0.015mmol AgOAc and 0.017mmol (S)-TF-BiphamPhos is added in 25mL reaction tubes, under nitrogen protection, add 1mL methylene dichloride, stirred at ambient temperature 1 hour, then at 0 DEG C, add 0.39mmol2-(successively to trifluoromethyl benzylideneamino) methyl propionate, 0.30mmol cyclohexadienone butyrolactone, with 0.045mmol salt of wormwood, after stirring 18h, boil off solvent, product is through silica gel column chromatography (petrol ether/ethyl acetate 1/1), obtain white solid, productive rate 82%, fusing point 146 DEG C, the enantioselectivity excessive 98% of product, HPLC (Chiralpak IB, i-propanol/hexane=50/50, flow rate1.0mL/min, λ=210nm, t
r=10.26and12.70min.), [α]
25 d=-78.0 (c0.70, CHCl
3),
1h NMR (CDCl
3, TMS, 400MHz) and δ 7.57-7.49 (m, 4H), 6.54 (d, J=10.4Hz, 1H), 5.74 (d, J=10.4Hz, 1H), 4.84 (d, J=8.8Hz, 1H), 3.77 (s, 3H), 3.48-3.44 (m, 1H), 3.01 (d, J=7.6Hz, 1H), 2.74-2.66 (m, 3H), 2.29-2.23 (m, 1H), 1.63 (s, 3H),
13cNMR (CDCl
3, TMS, 100MHz) and δ 193.8,175.2,146.5,142.8,129.2,128.0,124.8,80.6,68.3,63.4,57.2,52.7,52.6,35.9,27.4,27.3, IR (KBr) ν 3415,3086,2936,2905,1726,1700,1634,1503,1428,1122,1038,876,714,620cm
-1.HRMS calculated value forC
21h
20f
3nO
5+ H
+: 424.1372, observed value 424.1366.
Embodiment 18
preparation
0.015mmol AgOAc and 0.017mmol (S)-TF-BiphamPhos is added in 25mL reaction tubes, under nitrogen protection, add 1mL methylene dichloride, stirred at ambient temperature 1 hour, then at 0 DEG C, add 0.39mmol2-(benzylideneamino successively) methyl propionate, 0.30mmol cyclohexadienone butyrolactone, with 0.045mmol salt of wormwood, after stirring 18h, boil off solvent, product is through silica gel column chromatography (petrol ether/ethyl acetate 1/1), obtain white solid, productive rate 87%, fusing point 122 DEG C, the enantioselectivity excessive 97% of product, HPLC (Chiralpak AD-H, i-propanol/hexane=50/50, flowrate1.0mL/min, λ=210nm, t
r=10.07and15.67min.), [α]
25 d=-57.8 (c0.65, CHCl
3),
1h NMR (CDCl
3, TMS, 300MHz) and δ 7.32-7.27 (m, 5H), 6.52 (d, J=10.2Hz, 1H), 5.75 (d, J=10.2Hz, 1H), 4.80 (d, J=9.3Hz, 1H), 3.80 (s, 3H), 3.47-3.42 (m, 1H), 3.03 (d, J=7.5Hz, 1H), 2.79-2.65 (m, 3H), 2.27-2.23 (m, 1H), 1.61 (s, 3H),
13cNMR (CDCl
3, TMS, 75MHz) and δ 194.6,175.3,175.0,146.1,137.7,129.4,128.0,127.7,127.5,80.4,69.0,64.3,56.8,53.3,52.8,36.2,27.5,27.1, IR (KBr) ν 3417,3056,2947,2804,1765,1677,1513,1470,1450,1000,852,726,644cm
-1.HRMS calculated value for C
20h
21nO
5+ H
+: 356.1485, observed value 356.1492.
Embodiment 19
preparation
0.015mmol AgOAc and 0.017mmol (S)-TF-BiphamPhos is added in 25mL reaction tubes, under nitrogen protection, add 1mL methylene dichloride, stirred at ambient temperature 1 hour, then at 0 DEG C, add 0.39mmol2-(successively amino to methyl benzylidene) methyl propionate, 0.30mmol cyclohexadienone butyrolactone, with 0.045mmol salt of wormwood, after stirring 18h, boil off solvent, product is through silica gel column chromatography (petrol ether/ethyl acetate 1/1), obtain white solid, productive rate 83%, fusing point 162 DEG C, the enantioselectivity excessive 98% of product, HPLC (Chiralpak AS-H, i-propanol/hexane=50/50, flowrate1.0mL/min, λ=210nm, t
r=9.73and19.17min.), [α]
25 d=-72.3 (c0.69, CHCl
3),
1h NMR (CDCl
3, TMS, 300MHz) and δ 7.20-7.18 (d, J=7.2Hz, 2H), 7.10-7.08 (d, J=7.2Hz, 2H), (6.52 d, J=10.2Hz, 1H), (5.76 d, J=10.2Hz, 1H), (4.76 d, J=9.3Hz, 1H), (3.79 s, 3H), 3.43-3.40 (m, 1H), 3.01 (d, J=7.2Hz, 1H), 2.78-2.68 (m, 4H), (2.30 s, 3H), 2.24-2.22 (m, 1H), 1.60 (s, 3H),
13c NMR (CDCl
3, TMS, 100MHz) and δ 194.6,175.2,174.9,146.1,137.4,134.3,129.5,128.8,127.5,80.4,69.2,64.3,56.9,53.4,52.9,36.2,27.5,27.0,21.1, IR (KBr) ν 3416,3022,2944,2815,1786,1655,1503,1422,1315,989,825,714,635cm
-1.HRMS calculated value for C
21h
23nO
5+ H
+: 370.1655, observed value 370.1649.
Embodiment 20
preparation
0.015mmol AgOAc and 0.017mmol (S)-TF-BiphamPhos is added in 25mL reaction tubes, under nitrogen protection, add 1mL methylene dichloride, stirred at ambient temperature 1 hour, then at 0 DEG C, add 0.39mmol2-(o-methyl-benzene methene amido successively) methyl propionate, 0.30mmol cyclohexadienone butyrolactone, with 0.045mmol salt of wormwood, after stirring 18h, boil off solvent, product is through silica gel column chromatography (petrol ether/ethyl acetate 1/1), obtain white solid, productive rate 85%, fusing point 63 DEG C, the enantioselectivity excessive 97% of product, HPLC (Chiralpak AS-H, i-propanol/hexane=50/50, flow rate1.0mL/min, λ=210nm, t
r=7.51and18.11min.), [α]
25 d=-120.0 (c0.24, CHCl
3),
1h NMR (CDCl
3, TMS, 300MHz) and δ 7.37 (s, 1H), 7.15-7.13 (m, 2H), 6.58 (d, J=10.2Hz, 1H), 5.74 (d, J=10.2Hz, 1H), 4.95 (d, J=8.7Hz, 1H), 3.81 (s, 3H), 3.48-3.45 (m, 1H), 3.04 (d, J=7.5Hz, 1H), 2.72-2.61 (m, 4H), 2.38 (s, 3H), 2.24-2.22 (m, 1H), 1.63 (s, 3H),
13c NMR (CDCl
3, TMS, 100MHz) and δ 194.3,175.1,175.0,146.8,136.0,135.8,130.2,129.6,127.4,125.8,125.6,80.8,68.6,60.4,57.8,52.9,52.2,36.7,27.6,27.0,20.0, IR (KBr) ν 3370,3055,2914,2826,1717,1626,1512,1436,1345,1212,825,714,656cm
-1.HRMS calculated value for C
21h
23nO
5+ H
+: 370.1656, observed value 370.1649.
Embodiment 21
preparation
0.015mmol AgOAc and 0.017mmol (S)-TF-BiphamPhos is added in 25mL reaction tubes, under nitrogen protection, add 1mL methylene dichloride, stirred at ambient temperature 1 hour, then at 0 DEG C, add 0.39mmol2-(2-furfurylidene successively amino) methyl propionate, 0.30mmol cyclohexadienone butyrolactone, with 0.045mmol salt of wormwood, after stirring 18h, boil off solvent, product is through silica gel column chromatography (petrol ether/ethyl acetate 1/1), obtain white solid, productive rate 81%, fusing point 63 DEG C, the enantioselectivity excessive 98% of product, HPLC (Chiralpak AS-H, i-propanol/hexane=40/60, flowrate0.8mL/min, λ=210nm), t
r=20.70and25.17min.), [α]
25 d=-55.0 (c0.19, CHCl
3),
1h NMR (CDCl
3, TMS, 300MHz) and δ 7.34 (s, 1H), 6.57 (d, J=11.2Hz, 1H), 6.31 (s, 2H), 5.89 (d, J=11.2Hz, 1H), 4.80 (d, J=8.7Hz, 1H), 3.78 (s, 3H), 3.44-3.41 (m, 1H), 2.98 (d, J=7.8Hz, 1H), 2.72-2.64 (m, 3H), 2.28-2.18 (m, 1H),
13c NMR (CDCl
3, TMS, 100MHz) and δ 194.0,175.2,174.6,151.0,146.6,141.9,128.8,110.3,107.6,80.4,68.9,58.4,57.0,52.8,52.5,36.1,27.4,27.1, IR (KBr) ν 3400,3056,2914,2856,1766,1611,1521,1426,1093,1015,853,757,650cm
-1.HRMS calculated value for C
18h
19nO
6+ H
+: 346.1292, observed value 346.1285.
Embodiment 22
preparation
0.015mmol AgOAc and 0.017mmol (S)-TF-BiphamPhos is added in 25mL reaction tubes, under nitrogen protection, add 1mL methylene dichloride, stirred at ambient temperature 1 hour, then at 0 DEG C, add 0.39mmol2-(benzylideneamino successively) methyl-butyrate, 0.30mmol cyclohexadienone butyrolactone, with 0.045mmol salt of wormwood, after stirring 18h, boil off solvent, product is through silica gel column chromatography (petrol ether/ethyl acetate 1/1), obtain white solid, productive rate 84%, fusing point 122 DEG C, the enantioselectivity excessive 97% of product, HPLC (Chiralpak AS-H, i-propanol/hexane=50/50, flowrate1.0mL/min, λ=210nm, t
r=9.85and25.36min.), [α]
25 d=-171.0 (c0.20, CHCl
3),
1h NMR (CDCl
3, TMS, 300MHz) and δ 7.37-7.24 (m, 5H), 6.51 (d, J=11.2Hz, 1H), 5.71 (d, J=11.2Hz, 1H), 4.68 (d, J=9.0Hz, 1H), 3.77 (s, 3H), (3.39-3.34 m, 1H), 3.01 (d, J=7.2Hz, 1H), 2.77-2.72 (m, 1H), 2.70-2.62 (m, 2H), (2.23-2.18 m, 1H), 2.16-2.08 (m, 1H), 1.79-1.72 (m, 1H), 0.91 (t, J=7.2Hz, 3H),
13c NMR (CDCl
3, TMS, 75MHz) and δ 194.8,175.5,174.6,146.0,145.5,138.0,129.3,128.1,127.8,80.6,73.4,64.3,56.2,53.5,52.6,36.3,32.6,27.6,8.7, IR (KBr) ν 3380,3026,2921,2811,1760,1622,1513,1470,1450,1120,852,726,630cm
-1.HRMS calculated value forC
21h
23nO
5+ H
+: 370.1652, observed value 370.1649.
Embodiment 23
preparation
0.015mmol AgOAc and 0.017mmol (S)-TF-BiphamPhos is added in 25mL reaction tubes, under nitrogen protection, add 1mL methylene dichloride, stirred at ambient temperature 1 hour, then at 0 DEG C, add 0.39mmol2-(benzylideneamino successively) methyl valerate, 0.30mmol cyclohexadienone butyrolactone, with 0.045mmol salt of wormwood, after stirring 18h, boil off solvent, product is through silica gel column chromatography (petrol ether/ethyl acetate 1/1), obtain white solid, productive rate 88%, fusing point 130 DEG C, the enantioselectivity excessive 97% of product, HPLC (Chiralpak AS-H, i-propanol/hexane=50/50, flowrate1.0mL/min, λ=210nm, t
r=8.47and19.37min.), [α]
25 d=-54.8 (c0.80, CHCl
3),
1h NMR (CDCl
3, TMS, 300MHz) and δ 7.36-7.26 (m, 5H), (6.50 d, J=7.2Hz, 1H), (5.71 d, J=7.2Hz, 1H), (4.69 d, J=9.0Hz, 1H), (3.76 s, 3H), 3.40-3.36 (m, 1H), 3.01 (d, J=7.5Hz, 1H), 2.80-2.73 (m, 1H), (2.70-2.64 m, 2H), 2.28-2.21 (m, 1H), 2.07-2.02 (m, 1H), (1.71-1.63 m, 1H), 1.53-1.51 (m, 1H), 1.17-1.15 (m, 1H), 0.93 (t, J=7.2Hz, 3H),
13c NMR (CDCl
3, TMS, 75MHz) and δ 194.6,175.3,174.9,146.1,137.7,129.4,128.0,127.6,127.5,80.4,69.0,64.4,56.8,53.3,52.8,36.2,27.5,27.1,19.4,14.0, IR (KBr) ν 3356,3020,2967,2902,1775,1612,1523,1433,1071,1020,852,756,636cm
-1.HRMS calculated value for C
22h
25nO
5+ H
+: 384.1813, observed value 384.1806.
Embodiment 24
preparation
0.015mmol AgOAc and 0.017mmol (S)-TF-BiphamPhos is added in 25mL reaction tubes, under nitrogen protection, add 1mL methylene dichloride, stirred at ambient temperature 1 hour, then at 0 DEG C, add 0.39mmol2-(benzylideneamino successively) isocaproic acid methyl esters, 0.30mmol cyclohexadienone butyrolactone, with 0.045mmol salt of wormwood, after stirring 18h, boil off solvent, product is through silica gel column chromatography (petrol ether/ethyl acetate 1/1), obtain white solid, productive rate 82%, fusing point 152 DEG C, the enantioselectivity excessive 94% of product, HPLC (Chiralpak AS-H, i-propanol/hexane=50/50, flow rate1.0mL/min, λ=210nm, t
r=6.33and8.21min.), [α]
25 d=+11.1 (c0.70, CHCl
3),
1h NMR (CDCl
3, TMS, 400MHz) δ 7.62 (d, J=7.6Hz, 2H), 7.38-7.36 (m, 2H), 7.29 (d, J=6.8Hz, 1H), 6.57 (d, J=10.0Hz, 1H), 5.98 (d, J=10.0Hz, 1H), 4.32 (d, J=10.0Hz, 1H), 3.80 (s, 3H), 3.37-3.33 (m, 1H), 3.17-3.08 (m, 1H), 2.79-2.74 (m, 2H), 2.59 (d, J=13.2Hz, 1H), 2.28-2.22 (m, 1H), 2.15-2.11 (m, 1H), 1.91-1.84 (m, 1H), 1.28-1.24 (m, 1H), 0.97 (d, J=6.8Hz, 3H), 0.82 (d, J=6.4Hz, 3H),
13c NMR (CDCl
3, TMS, 75MHz) and δ 197.7,175.5,175.2,145.9,141.3,129.9,128.6,127.8,127.7,82.0,68.5,60.7,59.6,55.6,53.4,51.2,29.4,28.0,25.8,24.6,22.7, IR (KBr) ν 3400,3031,2965,2880,1775,1612,1523,1433,1071,980,850,735,625cm
-1.HRMS calculated value for C
23h
27nO
5+ H
+: 398.1972, observed value 398.1962.
Embodiment 25
preparation
0.015mmol AgOAc and 0.017mmol (S)-TF-BiphamPhos is added in 25mL reaction tubes, under nitrogen protection, add 1mL methylene dichloride, stirred at ambient temperature 1 hour, then at 0 DEG C, add 0.39mmol2-(benzylideneamino successively) methyl phenylpropionate, 0.30mmol cyclohexadienone butyrolactone, with 0.045mmol salt of wormwood, after stirring 18h, boil off solvent, product is through silica gel column chromatography (petrol ether/ethyl acetate 1/1), obtain white solid, productive rate 89%, fusing point 138 DEG C, the enantioselectivity excessive 97% of product, HPLC (Chiralpak AS-H, i-propanol/hexane=50/50, flow rate1.0mL/min, λ=210nm, t
r=11.63and22.18min.), [α]
25 d=-29.2 (c0.68, CHCl
3),
1h NMR (CDCl
3, TMS, 300MHz) and δ 7.41-7.39 (m2H), 7.29-7.24 (m, 8H), 6.49 (d, J=10.2Hz, 1H), 5.69 (d, J=10.2Hz, 1H), 4.76 (d, J=9.3Hz, 1H), 3.60 (s, 3H), 3.46-3.40 (m, 1H), 3.27 (d, J=13.2Hz, 1H), 3.13 (d, J=13.2Hz, 1H), 3.11-3.08 (m, 1H), 2.88-2.78 (m, 1H), 2.72-2.63 (m, 2H), 2.32-2.18 (m, 1H),
13cNMR (CDCl
3, TMS, 75MHz) and δ 194.2,175.7,174.4,146.3,145.5,137.6,135.5,132.9,130.0,129.2,128.2,127.9,127.0,80.4,72.8,62.7,54.5,52.3,52.2,44.6,36.0,27.6, IR (KBr) ν 3426,3020,2965,2923,1737,1598,1523,1426,1092,1015,853,754,644cm
-1.HRMS calculated value for C
26h
25nO
5+ H
+: 432.1800, observed value 432.1806.
Embodiment 26
preparation
0.015mmol AgOAc and 0.017mmol (S)-TF-BiphamPhos is added in 25mL reaction tubes, under nitrogen protection, add 1mL methylene dichloride, stirred at ambient temperature 1 hour, then at 0 DEG C, add 0.39mmol2-(successively to chlorobenzene methene amido) methyl acetate, the iodo-4-phenyl of 0.30mmol3--1-oxygen spiral shell [4.5] decane-3, 6, 9-triolefin-2, 8-diketone, with 0.045mmol salt of wormwood, after stirring 18h, boil off solvent, product is through silica gel column chromatography (petrol ether/ethyl acetate 1/1), obtain white solid, productive rate 85%, fusing point 156 DEG C, the enantioselectivity excessive 96% of product, HPLC (Chiralpak AD-H, i-propanol/hexane=50/50, flow rate1.0mL/min, λ=210nm, t
r=14.93and21.86min.), [α]
25 d=-75.6 (c0.75, CHCl
3),
1h NMR (CDCl
3, TMS, 300MHz) and δ 7.51-7.46 (m, 5H), 7.34-7.24 (m, 4H), 6.36 (d, J=10.2Hz, 1H), 6.05 (d, J=10.2Hz, 1H), 4.69 (d, J=9.9Hz, 1H), 3.99 (d, J=4.8Hz, 1H), 3.84 (s, 3H), 3.32-3.22 (m, 2H),
13cNMR (CDCl
3, TMS, 75MHz) and δ 194.6,171.5,169.6,142.4,136.0,133.7,133.2,131.0,130.8,129.4,129.2,128.4,127.6,85.6,63.9,63.6,53.0,52.7,43.5, IR (KBr) ν 3450,3019,2964,2913,1756,1622,1531,1427,1014,920,852,756,620,490cm
-1.HRMS calculated value for C
25h
19clINO
5+ H
+: 576.0075, observed value 576.0069.
Embodiment 27
preparation
0.015mmol AgOAc and 0.017mmol (S)-TF-BiphamPhos is added in 25mL reaction tubes, under nitrogen protection, add 1mL methylene dichloride, stirred at ambient temperature 1 hour, then at 0 DEG C, add 0.39mmol2-(successively to bromobenzene methene amido) methyl acetate, 0.30mmol3-methoxyl group-2, 8-dioxy-1-oxygen spiral shell [4.5] decane-3, 6, 9-triolefin-4-methyl-formiate, with 0.045mmol salt of wormwood, after stirring 18h, boil off solvent, product is through silica gel column chromatography (petrol ether/ethyl acetate 1/1), obtain white solid, productive rate 80%, fusing point 161 DEG C, the enantioselectivity excessive 95% of product, HPLC (ChiralpakAS-H, i-propanol/hexane=50/50, flow rate1.0mL/min, λ=210nm, t
r=18.17and36.59min.), [α]
25 d=-170.6 (c0.51, CHCl
3),
1h NMR (CDCl
3, TMS, 400MHz) and δ 7.41 (d, J=8.4Hz, 2H), 7.33-7.27 (m, 2H), 6.14 (d, J=10.0Hz, 1H), 5.89 (d, J=10.0Hz, 1H), 4.71 (d, J=11.6Hz, 1H), 4.33 (s, 3H), 3.98 (d, J=6.0Hz, 1H), 3.81 (s, 3H), 3.75 (s, 3H), 3.71-3.69 (m, 1H), 3.58-3.53 (m, 1H),
13c NMR (CDCl
3, TMS, 100MHz) and δ 194.8,170.3,164.4,161.3,149.2,143.8,136.8,133.3,131.2,130.2,124.3,121.8,78.2,63.1,63.0,59.9,52.7,52.4,52.3,44.0, IR (KBr) ν 3318,3036,2914,2870,1760,1680,1513,1425,1091,852,756,665,550cm
-1.HRMS Calcd. calculated value C
22h
20brNO
8+ H
+: 506.0452, observed value 506.0445.
Embodiment 28
preparation
0.015mmol AgOAc and 0.017mmol (S)-TF-BiphamPhos is added in 25mL reaction tubes, under nitrogen protection, add 1mL methylene dichloride, stirred at ambient temperature 1 hour, then at 0 DEG C, add 0.39mmol2-(successively to chlorobenzene methene amido) methyl acetate, own [2.5] diene-1 of 0.30mmol3 ' H-volution, 1 '-cumarone-3 ', 4-diketone, with 0.045mmol salt of wormwood, after stirring 18h, boil off solvent, product is through silica gel column chromatography (petrol ether/ethyl acetate 1/1), obtain white solid, productive rate 89%, fusing point 155 DEG C, the enantioselectivity excessive 96% of product, HPLC (Chiralpak AD-H, i-propanol/hexane=50/50, flow rate1.0mL/min, λ=210nm, t
r=12.12and22.27min.), [α]
25 d=-291.0 (c0.69, CHCl
3),
1h NMR (CDCl
3, TMS, 300MHz) and δ 7.96 (d, J=7.5Hz, 1H), 7.74-7.72 (m, 1H), 7.62-7.59 (m, 1H), 7.38-7.35 (m, 2H), 7.30-7.28 (m, 3H), 6.35 (d, J=10.2Hz, 1H), 5.99 (d, J=10.2Hz, 1H), 4.71 (d, J=8.7Hz, 1H), 4.08 (d, J=6.0Hz, 1H), 3.69-3.63 (m, 2H), 3.54 (s, 3H),
13c NMR (CDCl
3, TMS, 100MHz) and δ 195.0,170.6,168.3,152.0,145.4,136.1,135.1,133.6,131.5,130.2,129.2,128.4,126.1,124.8,122.0,81.3,64.8,63.0,53.0,52.2,48.5, IR (KBr) ν 3382,3056,2989,2901,1722,1613,1523,1423,1096,900,813,753,665cm
-1.HRMS calculated value for C
23h
18clNO
5+ H
+: 424.0944, observed value 424.0946.
Embodiment 29
preparation
0.015mmol AgOAc and 0.017mmol (S)-TF-BiphamPhos is added in 25mL reaction tubes, under nitrogen protection, add 1mL methylene dichloride, stirred at ambient temperature 1 hour, then at 0 DEG C, add 0.39mmol2-(successively to chlorobenzene methene amido) methyl acetate, 0.30mmol1-oxygen spiral shell [5.5] dodecane-7, 10-diene-2, 9-diketone, with 0.045mmol salt of wormwood, after stirring 18h, boil off solvent, product is through silica gel column chromatography (petrol ether/ethyl acetate 1/1), obtain white solid, productive rate 78%, fusing point 152 DEG C, the enantioselectivity excessive 95% of product, HPLC (Chiralpak AS-H, i-propanol/hexane=50/50, flow rate1.0mL/min, λ=210nm, t
r=21.34and35.96min.), [α]
25 d=-153.0 (c0.91, CHCl
3),
1h NMR (CDCl
3, TMS, 300MHz) and δ 7.27-7.26 (m, 4H), 6.79 (d, J=10.2Hz, 1H), 5.89 (d, J=10.2Hz, 1H), 4.55 (d, J=7.8Hz, 1H), 4.13 (d, J=8.4Hz, 1H), 3.85 (s, 3H), 3.43-3.40 (m, 1H), 3.29-3.24 (m, 1H), 2.68-2.52 (m, 2H), 2.10-2.00 (m, 1H), 1.99-1.82 (m, 3H),
13c NMR (CDCl
3, TMS, 100MHz) and δ 194.5,172.4,168.3,149.2,135.7,133.3,129.6,128.6,128.2,80.0,65.7,62.0,53.9,52.5,51.0,36.3,29.1,16.2, IR (KBr) ν 3326,3019,2964,2922,1735,1600,1522,1425,1091,1014,852,756,665cm
-1.HRMS Calcd. calculated value C
20h
20clNO
5+ H
+: 390.1108, observed value 390.1103.
Embodiment 30
preparation
The product in 0.14mmol embodiment 1 is added, 5%mol Rh/Al in 25mL reaction tubes
2o
3with 5%mol PtO
2, add 2.5mL ethyl acetate, pass into the H of a pressure
2, stirred at ambient temperature 1 hour, boils off solvent, and product, through silica gel column chromatography (petrol ether/ethyl acetate 1/1), obtains white solid, productive rate 90%, fusing point 132 DEG C; Excessive 97%, HPLC (Chiralpak AD-H, i-propanol/hexane=50/50, flow rate1.0mL/min, λ=210nm, the t of enantioselectivity of product
r=13.77and15.29min.); [α]
25 d=-36.8 (c0.36, CHCl
3);
1h NMR (CDCl
3, TMS, 300MHz) and δ 7.39 (d; J=8.1Hz, 2H), 7.31 (d; J=7.8Hz, 2H), 4.54 (d; J=9.9Hz, 1H), 4.00 (d; J=6.6Hz, 1H), 3.86 (s; 3H), 3.41-3.34 (m, 1H); 3.09-3.04 (m, 1H), 2.98-2.88 (m; 1H), 2.63-2.57 (m, 2H); 2.15-1.99 (m; 4H), 1.76-1.71 (m, 1H);
13c NMR (CDCl
3, TMS, 75MHz) and δ 208.8,174.8,170.9,135.5,133.7,128.6,128.2,84.1,63.1,62.6,56.4,52.5,50.4,36.4,32.3,27.7; IR (KBr) ν 3421,3015,2965,2880,1765,1523,1435,1071,913,852,753,625cm
-1.HRMS calculated value for C
19h
20clNO
5+ H
+: 378.1106, observed value 378.1103.
In the present embodiment, Rh/Al
2o
3refer to that Rh load is at Al
2o
3on, Rh/Al
2o
3and PtO
2mixing plays katalysis, Rh/Al jointly
2o
3and PtO
2consumption be 5% of the molar weight of substrate.
Embodiment 31
preparation
0.015mmol AgOAc and 0.017mmol (S)-TF-BiphamPhos is added in 25mL reaction tubes, under nitrogen protection, add 1mL methylene dichloride, stirred at ambient temperature 1 hour, then at 0 DEG C, add 0.39mmol2-(successively to chlorobenzene methene amido) methyl acetate, 0.30mmol cyclohexadienone butyrolactone, with 0.045mmol triethylamine, after stirring 12h, add 0.33mmol triethylamine and 0.33mmol thiophenol again, after stirring reaction 12h, boil off solvent, product is through silica gel column chromatography (petrol ether/ethyl acetate 1/1), obtain white solid, productive rate 92%, fusing point 138 DEG C, the enantioselectivity excessive 97% of product, HPLC (Chiralpak AD-H, i-propanol/hexane=50/50, flow rate1.0mL/min, λ=210nm, t
r=9.83and12.12min.), [α]
25 d=-116.5 (c0.50, CHCl
3),
1hNMR (CDCl
3, TMS, 400MHz) and δ 7.46 (d, J=7.2Hz, 2H), 7.33-7.26 (m, 7H), 4.61-4.55 (m, 3H), 4.06 (d, J=6.8Hz, 1H), 3.67 (s, 3H), 3.48-3.43 (m, 1H), 3.25-3.21 (m, 1H), 2.70-2.63 (m, 2H), 2.53-2.46 (m, 2H), 2.24-2.17 (m, 1H), 1.88-1.83 (m, 1H),
13c NMR (CDCl
3, TMS, 75MHz) and δ 206.5,174.4,170.4,135.3,133.7,133.1,132.6,128.9,128.6,127.9,127.6,86.7,62.8,62.3,56.3,52.4,49.9,48.4,44.6,28.8,28.0, IR (KBr) ν 3415,3030,2970,2913,1775,1513,1435,1090,1014,835,756,680,625cm
-1.HRMS Calcd. calculated value for C
25h
24clNO
5s+H
+: 486.1146, observed value 486.1136.
The productive rate of embodiment 1-31 gained compound and corresponding selection is excessive is shown in Table 1.
The productive rate of table 1 embodiment gained compound and enantiomeric excess
Embodiment 32
Fungicidal activity detects
Liquor strength 50ppm, made agar block is got with the 5mm device that fans the air, dividing chooses into each culture dish, if blank, it is cultivated 48-72 hour constant incubator 27 DEG C, check bacterial plaque diameter, inhibiting rate=(contrast bacterial plaque diameter-sample bacterial plaque diameter)/contrast bacterial plaque diameter × 100%, does a repetition simultaneously.Measurement result is in table 2.
Solubility promoter: dimethyl methyl phthalein amine; Emulsifying agent: tween-80; Obtain solution: sterilized water.Wherein, dimethyl methyl phthalein amine/H
2o=1/1000; Emulsifying agent/H
2o=5/1000 (weight percent).
The bacteriostasis rate of table 2 the compounds of this invention
Claims (10)
1. have the Polycyclic derivative of chiral spiro lactone pyrrole ring structure fragment, it is characterized in that, its structural formula is the one in following structural formula:
Structural formula (I-1):
Structural formula (I-2):
Structural formula (II-1):
Structural formula (II-2):
Structural formula (III-1):
Structural formula (III-2):
Structural formula (IV-1):
Structural formula (IV-2):
Wherein,
R
1for to halobenzene base, adjacent halobenzene base, a halobenzene base, adjacent trihalogenmethyl phenyl, to trihalogenmethyl phenyl, to methyl-formiate phenyl, adjacent methyl-formiate phenyl, a methyl-formiate phenyl, p-nitrophenyl, O-Nitrophenylfluorone, phenyl, p-methylphenyl, o-methyl-phenyl-, 2-naphthyl, 1-naphthyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, cyclohexyl, cyclopentyl, C
1-C
9straight chained alkyl or C
1-C
9branched-chain alkyl;
R
2for hydrogen, C
1-C
6straight chained alkyl or C
1-C
6branched-chain alkyl;
X is halogen;
N is 1 or 2.
2. there is the Polycyclic derivative of chiral spiro lactone pyrrole ring structure fragment as claimed in claim 1, it is characterized in that:
Described R
1for rubigan, Chloro-O-Phenyl, a chloro-phenyl-, to bromophenyl, o-trifluoromethyl phenyl, to methyl-formiate phenyl, p-nitrophenyl, phenyl, p-methylphenyl, o-methyl-phenyl-, 2-naphthyl, 2-furyl, 2-thienyl, cyclohexyl or isobutyl-.
3. there is the synthetic method of the Polycyclic derivative of chiral spiro lactone pyrrole ring structure fragment, it is characterized in that, comprise step:
In organic solvent; under protection of inert gas; the imines derived with spiral shell cyclohexadienone lactone and glycine methyl ester is for raw material; with metal Lewis acids/chiral ligand complex for catalyzer; add carbonate or organic bases; react at-40 ~ 25 DEG C of temperature, boil off solvent, obtain target compound through column chromatography
(I-1),
(I-2),
(II-1),
(II-2),
(III-1),
(III-2),
(IV-1) or
(IV-2),
Wherein,
R
1for to halobenzene base, adjacent halobenzene base, a halobenzene base, adjacent trihalogenmethyl phenyl, to trihalogenmethyl phenyl, to methyl-formiate phenyl, adjacent methyl-formiate phenyl, a methyl-formiate phenyl, p-nitrophenyl, O-Nitrophenylfluorone, phenyl, p-methylphenyl, o-methyl-phenyl-, 2-naphthyl, 1-naphthyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, cyclohexyl, cyclopentyl, C
1-C
9straight chained alkyl or C
1-C
9branched-chain alkyl;
R
2for hydrogen, C
1-C
6straight chained alkyl or C
1-C
6branched-chain alkyl;
X is halogen;
N is 1 or 2.
4. synthetic method according to claim 3, is characterized in that:
The mol ratio of the imines that described spiral shell cyclohexadienone lactone and glycine methyl ester derive is 1:1.3.
5. synthetic method according to claim 3, is characterized in that:
Described metal Lewis acids/chiral ligand complex is adopted and is prepared with the following method:
Under room temperature, be not more than chiral ligand mole number by metal Lewis acids mole number and get metal Lewis acids and chiral ligand TF-Biphamphos is dissolved in organic solvent, through being obtained by reacting.
6. synthetic method according to claim 5, is characterized in that:
The complex compound of described metal Lewis acids/chiral ligand is silver salt/TF-Biphamphos complex compound or mantoquita/TF-Biphamphos.
7. have the first kind derivative compound of the Polycyclic derivative of chiral spiro lactone pyrrole ring structure fragment, it is characterized in that, its structural formula is the one in following structural formula:
(V-1),
(V-2),
(VI-1),
(VI-2),
(VII-1),
(VII-2) or
(VIII-1),
(VIII-2),
Wherein,
R
1for to halobenzene base, adjacent halobenzene base, a halobenzene base, adjacent trihalogenmethyl phenyl, to trihalogenmethyl phenyl, to methyl-formiate phenyl, adjacent methyl-formiate phenyl, a methyl-formiate phenyl, p-nitrophenyl, O-Nitrophenylfluorone, phenyl, p-methylphenyl, o-methyl-phenyl-, 2-naphthyl, 1-naphthyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, cyclohexyl, cyclopentyl, C
1-C
9straight chained alkyl or C
1-C
9branched-chain alkyl;
R
2for hydrogen, C
1-C
6straight chained alkyl or C
1-C
6branched-chain alkyl;
X is halogen;
N is 1 or 2.
8. first kind derivative according to claim 7, is characterized in that:
Described R
1for rubigan, Chloro-O-Phenyl, a chloro-phenyl-, to bromophenyl, o-trifluoromethyl phenyl, to methyl-formiate phenyl, p-nitrophenyl, phenyl, p-methylphenyl, o-methyl-phenyl-, 2-naphthyl, 2-furyl, 2-thienyl, cyclohexyl or isobutyl-.
9. have the Equations of The Second Kind derivative of the Polycyclic derivative of chiral spiro lactone pyrrole ring structure fragment, it is characterized in that, its structural formula is the one in following structural formula:
(V-3),
(V-4),
(VI-3),
(VI-4),
(VII-3),
(VII-4),
(VIII-3) or
(VIII-4),
Wherein,
R
1for to halobenzene base, adjacent halobenzene base, a halobenzene base, adjacent trihalogenmethyl phenyl, to trihalogenmethyl phenyl, to methyl-formiate phenyl, adjacent methyl-formiate phenyl, a methyl-formiate phenyl, p-nitrophenyl, O-Nitrophenylfluorone, phenyl, p-methylphenyl, o-methyl-phenyl-, 2-naphthyl, 1-naphthyl, 2-furyl, 3-furyl, 2-thienyl, 3-thienyl, cyclohexyl, cyclopentyl, C
1-C
9straight or branched alkyl;
R
2for hydrogen, C
1-C
6straight chained alkyl or C
1-C
6branched-chain alkyl;
X is halogen;
N is 1 or 2.
10. the compound described in claim 1,2,7,8 or 9 is as the application of the effective constituent of bactericide.
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| US20060004079A1 (en) * | 2004-06-08 | 2006-01-05 | Manam Rama R | Anti-bacterial and anti-cancer spiro beta-lactone/gamma-lactams |
| WO2010135914A1 (en) * | 2009-05-26 | 2010-12-02 | Syngenta Participations Ag | New spiroheterocyclic furan and thiofuran dione derivatives |
| EP2532660A1 (en) * | 2007-08-03 | 2012-12-12 | Pfizer Products Inc. | Synthetic intermediates prepared using a 2-deoxyribose-5-phosphate aldolase (DERA) chemoenzymatic process |
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2013
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| US20060004079A1 (en) * | 2004-06-08 | 2006-01-05 | Manam Rama R | Anti-bacterial and anti-cancer spiro beta-lactone/gamma-lactams |
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| WO2010135914A1 (en) * | 2009-05-26 | 2010-12-02 | Syngenta Participations Ag | New spiroheterocyclic furan and thiofuran dione derivatives |
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