JPH03275677A - Production of new cyclobutane derivative - Google Patents
Production of new cyclobutane derivativeInfo
- Publication number
- JPH03275677A JPH03275677A JP7202490A JP7202490A JPH03275677A JP H03275677 A JPH03275677 A JP H03275677A JP 7202490 A JP7202490 A JP 7202490A JP 7202490 A JP7202490 A JP 7202490A JP H03275677 A JPH03275677 A JP H03275677A
- Authority
- JP
- Japan
- Prior art keywords
- group
- carbon atoms
- substituted
- alkyl group
- protected
- Prior art date
- Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
- Pending
Links
- 125000001995 cyclobutyl group Chemical class [H]C1([H])C([H])([H])C([H])(*)C1([H])[H] 0.000 title claims abstract description 7
- 238000004519 manufacturing process Methods 0.000 title claims description 8
- 150000001875 compounds Chemical class 0.000 claims abstract description 35
- 125000000217 alkyl group Chemical group 0.000 claims abstract description 21
- 229910052760 oxygen Inorganic materials 0.000 claims abstract description 14
- 125000002768 hydroxyalkyl group Chemical group 0.000 claims abstract description 12
- 229910052717 sulfur Inorganic materials 0.000 claims abstract description 12
- 125000003903 2-propenyl group Chemical group [H]C([*])([H])C([H])=C([H])[H] 0.000 claims abstract description 8
- 125000003545 alkoxy group Chemical group 0.000 claims abstract description 8
- 125000002947 alkylene group Chemical group 0.000 claims abstract description 6
- 238000007363 ring formation reaction Methods 0.000 claims abstract 2
- 125000004432 carbon atom Chemical group C* 0.000 claims description 43
- 229910052739 hydrogen Inorganic materials 0.000 claims description 12
- 239000001301 oxygen Substances 0.000 claims description 12
- 239000001257 hydrogen Substances 0.000 claims description 11
- MYMOFIZGZYHOMD-UHFFFAOYSA-N Dioxygen Chemical compound O=O MYMOFIZGZYHOMD-UHFFFAOYSA-N 0.000 claims description 9
- 125000004434 sulfur atom Chemical group 0.000 claims description 9
- 125000004435 hydrogen atom Chemical class [H]* 0.000 claims description 7
- 229910052799 carbon Inorganic materials 0.000 claims description 6
- 125000003178 carboxy group Chemical group [H]OC(*)=O 0.000 claims description 6
- 239000000126 substance Substances 0.000 claims description 6
- OKTJSMMVPCPJKN-UHFFFAOYSA-N Carbon Chemical compound [C] OKTJSMMVPCPJKN-UHFFFAOYSA-N 0.000 claims description 5
- 125000002837 carbocyclic group Chemical group 0.000 claims description 5
- 125000000623 heterocyclic group Chemical group 0.000 claims description 5
- 125000001570 methylene group Chemical group [H]C([H])([*:1])[*:2] 0.000 claims description 5
- QVGXLLKOCUKJST-UHFFFAOYSA-N atomic oxygen Chemical compound [O] QVGXLLKOCUKJST-UHFFFAOYSA-N 0.000 claims description 3
- NINIDFKCEFEMDL-UHFFFAOYSA-N Sulfur Chemical compound [S] NINIDFKCEFEMDL-UHFFFAOYSA-N 0.000 claims 1
- 125000004429 atom Chemical group 0.000 claims 1
- 239000011593 sulfur Substances 0.000 claims 1
- -1 (substituted) methylene Chemical group 0.000 abstract description 15
- 238000009833 condensation Methods 0.000 abstract description 5
- 230000005494 condensation Effects 0.000 abstract description 5
- 239000003905 agrochemical Substances 0.000 abstract description 3
- 239000003153 chemical reaction reagent Substances 0.000 abstract description 3
- 239000003814 drug Substances 0.000 abstract description 3
- 239000002994 raw material Substances 0.000 abstract description 3
- 238000000034 method Methods 0.000 abstract description 2
- 238000002360 preparation method Methods 0.000 abstract description 2
- 229940079593 drug Drugs 0.000 abstract 1
- 239000000796 flavoring agent Substances 0.000 abstract 1
- 235000019634 flavors Nutrition 0.000 abstract 1
- 239000000463 material Substances 0.000 abstract 1
- ZEUTWAOYDYRJPP-MMQJMDILSA-N methyl (1r,6s,7r,8r)-6-butylsulfanyl-7-(2-oxo-1,3-oxazolidine-3-carbonyl)bicyclo[4.2.0]octane-8-carboxylate Chemical compound O=C([C@H]1[C@@H]([C@H]2CCCC[C@]21SCCCC)C(=O)OC)N1CCOC1=O ZEUTWAOYDYRJPP-MMQJMDILSA-N 0.000 abstract 1
- RTZKZFJDLAIYFH-UHFFFAOYSA-N Diethyl ether Chemical compound CCOCC RTZKZFJDLAIYFH-UHFFFAOYSA-N 0.000 description 12
- YXFVVABEGXRONW-UHFFFAOYSA-N Toluene Chemical compound CC1=CC=CC=C1 YXFVVABEGXRONW-UHFFFAOYSA-N 0.000 description 9
- XEKOWRVHYACXOJ-UHFFFAOYSA-N Ethyl acetate Chemical compound CCOC(C)=O XEKOWRVHYACXOJ-UHFFFAOYSA-N 0.000 description 6
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 6
- 230000003287 optical effect Effects 0.000 description 6
- 239000002904 solvent Substances 0.000 description 5
- 239000003054 catalyst Substances 0.000 description 4
- 150000001930 cyclobutanes Chemical class 0.000 description 4
- 150000002431 hydrogen Chemical class 0.000 description 4
- WEVYAHXRMPXWCK-UHFFFAOYSA-N Acetonitrile Chemical compound CC#N WEVYAHXRMPXWCK-UHFFFAOYSA-N 0.000 description 3
- UHOVQNZJYSORNB-UHFFFAOYSA-N Benzene Chemical compound C1=CC=CC=C1 UHOVQNZJYSORNB-UHFFFAOYSA-N 0.000 description 3
- 239000002841 Lewis acid Substances 0.000 description 3
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 3
- 150000007517 lewis acids Chemical class 0.000 description 3
- 125000002496 methyl group Chemical group [H]C([H])([H])* 0.000 description 3
- 239000000203 mixture Substances 0.000 description 3
- 239000002808 molecular sieve Substances 0.000 description 3
- TVMXDCGIABBOFY-UHFFFAOYSA-N octane Chemical compound CCCCCCCC TVMXDCGIABBOFY-UHFFFAOYSA-N 0.000 description 3
- 239000003208 petroleum Substances 0.000 description 3
- URGAHOPLAPQHLN-UHFFFAOYSA-N sodium aluminosilicate Chemical compound [Na+].[Al+3].[O-][Si]([O-])=O.[O-][Si]([O-])=O URGAHOPLAPQHLN-UHFFFAOYSA-N 0.000 description 3
- FYGHSUNMUKGBRK-UHFFFAOYSA-N 1,2,3-trimethylbenzene Chemical compound CC1=CC=CC(C)=C1C FYGHSUNMUKGBRK-UHFFFAOYSA-N 0.000 description 2
- 238000005160 1H NMR spectroscopy Methods 0.000 description 2
- 229940126062 Compound A Drugs 0.000 description 2
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 2
- YNQLUTRBYVCPMQ-UHFFFAOYSA-N Ethylbenzene Chemical compound CCC1=CC=CC=C1 YNQLUTRBYVCPMQ-UHFFFAOYSA-N 0.000 description 2
- NLDMNSXOCDLTTB-UHFFFAOYSA-N Heterophylliin A Natural products O1C2COC(=O)C3=CC(O)=C(O)C(O)=C3C3=C(O)C(O)=C(O)C=C3C(=O)OC2C(OC(=O)C=2C=C(O)C(O)=C(O)C=2)C(O)C1OC(=O)C1=CC(O)=C(O)C(O)=C1 NLDMNSXOCDLTTB-UHFFFAOYSA-N 0.000 description 2
- IMNFDUFMRHMDMM-UHFFFAOYSA-N N-Heptane Chemical compound CCCCCCC IMNFDUFMRHMDMM-UHFFFAOYSA-N 0.000 description 2
- OFBQJSOFQDEBGM-UHFFFAOYSA-N Pentane Chemical compound CCCCC OFBQJSOFQDEBGM-UHFFFAOYSA-N 0.000 description 2
- JUJWROOIHBZHMG-UHFFFAOYSA-N Pyridine Chemical compound C1=CC=NC=C1 JUJWROOIHBZHMG-UHFFFAOYSA-N 0.000 description 2
- WYURNTSHIVDZCO-UHFFFAOYSA-N Tetrahydrofuran Chemical compound C1CCOC1 WYURNTSHIVDZCO-UHFFFAOYSA-N 0.000 description 2
- 238000009835 boiling Methods 0.000 description 2
- 125000000484 butyl group Chemical group [H]C([*])([H])C([H])([H])C([H])([H])C([H])([H])[H] 0.000 description 2
- 150000002148 esters Chemical class 0.000 description 2
- 239000003205 fragrance Substances 0.000 description 2
- 239000000543 intermediate Substances 0.000 description 2
- 239000003446 ligand Substances 0.000 description 2
- 125000001160 methoxycarbonyl group Chemical group [H]C([H])([H])OC(*)=O 0.000 description 2
- 239000012046 mixed solvent Substances 0.000 description 2
- PSHKMPUSSFXUIA-UHFFFAOYSA-N n,n-dimethylpyridin-2-amine Chemical compound CN(C)C1=CC=CC=N1 PSHKMPUSSFXUIA-UHFFFAOYSA-N 0.000 description 2
- LTEDQKPGOZDGRZ-UHFFFAOYSA-L propan-2-olate;titanium(4+);dichloride Chemical compound Cl[Ti+2]Cl.CC(C)[O-].CC(C)[O-] LTEDQKPGOZDGRZ-UHFFFAOYSA-L 0.000 description 2
- LGXAANYJEHLUEM-UHFFFAOYSA-N 1,2,3-tri(propan-2-yl)benzene Chemical compound CC(C)C1=CC=CC(C(C)C)=C1C(C)C LGXAANYJEHLUEM-UHFFFAOYSA-N 0.000 description 1
- DHWYCCUUWKEGOF-UHFFFAOYSA-N 1-butylsulfanylcyclohexene Chemical compound CCCCSC1=CCCCC1 DHWYCCUUWKEGOF-UHFFFAOYSA-N 0.000 description 1
- 238000001644 13C nuclear magnetic resonance spectroscopy Methods 0.000 description 1
- 125000004217 4-methoxybenzyl group Chemical group [H]C1=C([H])C(=C([H])C([H])=C1OC([H])([H])[H])C([H])([H])* 0.000 description 1
- 125000004172 4-methoxyphenyl group Chemical group [H]C1=C([H])C(OC([H])([H])[H])=C([H])C([H])=C1* 0.000 description 1
- 101150041968 CDC13 gene Proteins 0.000 description 1
- 108700018454 CDC15 Proteins 0.000 description 1
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 238000005481 NMR spectroscopy Methods 0.000 description 1
- VYPSYNLAJGMNEJ-UHFFFAOYSA-N Silicium dioxide Chemical compound O=[Si]=O VYPSYNLAJGMNEJ-UHFFFAOYSA-N 0.000 description 1
- PMZURENOXWZQFD-UHFFFAOYSA-L Sodium Sulfate Chemical compound [Na+].[Na+].[O-]S([O-])(=O)=O PMZURENOXWZQFD-UHFFFAOYSA-L 0.000 description 1
- FAPWRFPIFSIZLT-UHFFFAOYSA-M Sodium chloride Chemical class [Na+].[Cl-] FAPWRFPIFSIZLT-UHFFFAOYSA-M 0.000 description 1
- 229910021626 Tin(II) chloride Inorganic materials 0.000 description 1
- 229910021627 Tin(IV) chloride Inorganic materials 0.000 description 1
- HEDRZPFGACZZDS-MICDWDOJSA-N Trichloro(2H)methane Chemical compound [2H]C(Cl)(Cl)Cl HEDRZPFGACZZDS-MICDWDOJSA-N 0.000 description 1
- 125000004453 alkoxycarbonyl group Chemical group 0.000 description 1
- 125000005336 allyloxy group Chemical group 0.000 description 1
- AZDRQVAHHNSJOQ-UHFFFAOYSA-N alumane Chemical class [AlH3] AZDRQVAHHNSJOQ-UHFFFAOYSA-N 0.000 description 1
- 125000003118 aryl group Chemical group 0.000 description 1
- 125000001797 benzyl group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])* 0.000 description 1
- 125000000051 benzyloxy group Chemical group [H]C1=C([H])C([H])=C(C([H])=C1[H])C([H])([H])O* 0.000 description 1
- 125000001584 benzyloxycarbonyl group Chemical group C(=O)(OCC1=CC=CC=C1)* 0.000 description 1
- 150000001721 carbon Chemical class 0.000 description 1
- 101150081467 cdc15 gene Proteins 0.000 description 1
- 239000007810 chemical reaction solvent Substances 0.000 description 1
- JNGZXGGOCLZBFB-IVCQMTBJSA-N compound E Chemical compound N([C@@H](C)C(=O)N[C@@H]1C(N(C)C2=CC=CC=C2C(C=2C=CC=CC=2)=N1)=O)C(=O)CC1=CC(F)=CC(F)=C1 JNGZXGGOCLZBFB-IVCQMTBJSA-N 0.000 description 1
- FEWQWVKYZVOEAS-UHFFFAOYSA-N cyclobut-2-en-1-ylidenemethanone Chemical compound O=C=C1CC=C1 FEWQWVKYZVOEAS-UHFFFAOYSA-N 0.000 description 1
- 239000012024 dehydrating agents Substances 0.000 description 1
- YNLAOSYQHBDIKW-UHFFFAOYSA-M diethylaluminium chloride Chemical compound CC[Al](Cl)CC YNLAOSYQHBDIKW-UHFFFAOYSA-M 0.000 description 1
- JGHYBJVUQGTEEB-UHFFFAOYSA-M dimethylalumanylium;chloride Chemical compound C[Al](C)Cl JGHYBJVUQGTEEB-UHFFFAOYSA-M 0.000 description 1
- 150000002009 diols Chemical class 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 239000004210 ether based solvent Substances 0.000 description 1
- 125000003754 ethoxycarbonyl group Chemical group C(=O)(OCC)* 0.000 description 1
- 125000001495 ethyl group Chemical group [H]C([H])([H])C([H])([H])* 0.000 description 1
- 125000000816 ethylene group Chemical group [H]C([H])([*:1])C([H])([H])[*:2] 0.000 description 1
- 238000007710 freezing Methods 0.000 description 1
- 230000008014 freezing Effects 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 125000002887 hydroxy group Chemical group [H]O* 0.000 description 1
- 239000012280 lithium aluminium hydride Substances 0.000 description 1
- CRGZYKWWYNQGEC-UHFFFAOYSA-N magnesium;methanolate Chemical compound [Mg+2].[O-]C.[O-]C CRGZYKWWYNQGEC-UHFFFAOYSA-N 0.000 description 1
- 125000000956 methoxy group Chemical group [H]C([H])([H])O* 0.000 description 1
- MDZWGXVLSWCFDR-WDEREUQCSA-N methyl (1r,4s)-2-butyl-3-methylsulfanyl-4-(2-oxo-1,3-oxazolidine-3-carbonyl)cyclobut-2-ene-1-carboxylate Chemical compound COC(=O)[C@H]1C(CCCC)=C(SC)[C@@H]1C(=O)N1C(=O)OCC1 MDZWGXVLSWCFDR-WDEREUQCSA-N 0.000 description 1
- 239000008363 phosphate buffer Substances 0.000 description 1
- 238000003672 processing method Methods 0.000 description 1
- LVTJOONKWUXEFR-FZRMHRINSA-N protoneodioscin Natural products O(C[C@@H](CC[C@]1(O)[C@H](C)[C@@H]2[C@]3(C)[C@H]([C@H]4[C@@H]([C@]5(C)C(=CC4)C[C@@H](O[C@@H]4[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@@H](O)[C@H](O[C@H]6[C@@H](O)[C@@H](O)[C@@H](O)[C@H](C)O6)[C@H](CO)O4)CC5)CC3)C[C@@H]2O1)C)[C@H]1[C@H](O)[C@H](O)[C@H](O)[C@@H](CO)O1 LVTJOONKWUXEFR-FZRMHRINSA-N 0.000 description 1
- UMJSCPRVCHMLSP-UHFFFAOYSA-N pyridine Natural products COC1=CC=CN=C1 UMJSCPRVCHMLSP-UHFFFAOYSA-N 0.000 description 1
- 238000001228 spectrum Methods 0.000 description 1
- 235000011150 stannous chloride Nutrition 0.000 description 1
- 238000003756 stirring Methods 0.000 description 1
- 239000004575 stone Substances 0.000 description 1
- 239000000725 suspension Substances 0.000 description 1
- YLQBMQCUIZJEEH-UHFFFAOYSA-N tetrahydrofuran Natural products C=1C=COC=1 YLQBMQCUIZJEEH-UHFFFAOYSA-N 0.000 description 1
- 238000004809 thin layer chromatography Methods 0.000 description 1
- 150000003606 tin compounds Chemical class 0.000 description 1
- HIAIVILTZQDDNY-UHFFFAOYSA-J tin(4+);trifluoromethanesulfonate Chemical compound [Sn+4].[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F.[O-]S(=O)(=O)C(F)(F)F HIAIVILTZQDDNY-UHFFFAOYSA-J 0.000 description 1
- AXZWODMDQAVCJE-UHFFFAOYSA-L tin(II) chloride (anhydrous) Chemical compound [Cl-].[Cl-].[Sn+2] AXZWODMDQAVCJE-UHFFFAOYSA-L 0.000 description 1
- HPGGPRDJHPYFRM-UHFFFAOYSA-J tin(iv) chloride Chemical compound Cl[Sn](Cl)(Cl)Cl HPGGPRDJHPYFRM-UHFFFAOYSA-J 0.000 description 1
- 150000003609 titanium compounds Chemical class 0.000 description 1
- XJDNKRIXUMDJCW-UHFFFAOYSA-J titanium tetrachloride Chemical compound Cl[Ti](Cl)(Cl)Cl XJDNKRIXUMDJCW-UHFFFAOYSA-J 0.000 description 1
- 238000005406 washing Methods 0.000 description 1
Abstract
Description
【発明の詳細な説明】
［産業上の利用分野］
本発明は、単環のシクロブタン誘導体及びシクロブタン
環を含む縮合環の、更には光学活性なこれら化合物の製
造法に関する。DETAILED DESCRIPTION OF THE INVENTION [Industrial Application Field] The present invention relates to monocyclic cyclobutane derivatives and condensed ring compounds containing a cyclobutane ring, and also to methods for producing these optically active compounds.
［従来の技術］
シクロブタン誘導体及びシクロブタン環を含む縮合環は
、試薬、医薬品、農薬、香料等或い（よこれらの製造原
料或いは中間体として有用である。[Prior Art] Cyclobutane derivatives and condensed rings containing a cyclobutane ring are useful as reagents, pharmaceuticals, agricultural chemicals, fragrances, etc., or as raw materials or intermediates for their production.
［発明が解決しようとする課題］
これら、シクロブタン誘導体及びシクロブタン環を含む
縮合環は、製造が困難であり、特に実用的な光学活性な
これら化合物の製造法は皆無である。[Problems to be Solved by the Invention] These cyclobutane derivatives and fused rings containing a cyclobutane ring are difficult to produce, and there is no particularly practical method for producing these optically active compounds.
［課題を解決するための手段］
本発明は、一般式（１）
は独立に水素、炭素数１から５のアルキル基、保護され
た炭素数１から５のヒドロキシアルキル基または、炭素
数１から５のアルコキシ基、または炭素数１から５の、
アリル基置換アルコキシ基を示すかまたは、Ｒ３と８４
が結合して３員環から３０員環の炭素環または複素環を
示す。Ａは置換基を有するまたは無置換の炭素数２から
５のアルキレン基を、Ｙは酸素またはイオウ原子を、Ｚ
は置換または無置換メチレン基または酸素またはイオウ
原子を示す］
で表されるシクロブタン誘導体及び一般式（１）で表さ
れる化合物の一般式（１１）
１から５の、アリル基置換アルキル基を示し、Ｒ２は水
素、炭素数１から５のアルキル基、保護された炭素数１
から５のヒドロキシアルキル基または保護されたカルボ
キシル基を示し、Ｒ３及びＲ４［式中８２は水素、炭素
数１から５のアルキル基、保護された炭素数１から５の
ヒドロキシアルキル基または保護されたカルボキシル基
を示し、Ａは置換基を有するまたは無置換の炭素数２か
ら５のアルキレン基を、Ｙは酸素またはイオウ原子を、
２は置換または無置換メチレン基または酸素またはイオ
ウ原子を示す］
で表わされる化合物と一般式（ＩＩＩ ）［式中８１は
炭素数１から５のアルキル基、炭素数１から５の、アリ
ル基置換アルキル基を示し、Ｒ３及び８４は独立に水素
、炭素数１から５のアルキル基、保護された炭素数１か
ら５のヒトＯキシアルキル基または、炭素数１から５の
アルコキシ基、または炭素数１から５の、アリル基置換
アルコキシ基を示すかまたは、Ｒ３と８４が結合して３
員環から３０員環の炭素環または複素環を示す。］で表
わされる化合物を縮合環化する事を特徴とする製造法に
関する。[Means for Solving the Problems] The present invention provides that the general formula (1) is independently hydrogen, an alkyl group having 1 to 5 carbon atoms, a protected hydroxyalkyl group having 1 to 5 carbon atoms, or a protected hydroxyalkyl group having 1 to 5 carbon atoms. 5 alkoxy group, or 1 to 5 carbon atoms,
Represents an allyl group-substituted alkoxy group, or R3 and 84
are combined to represent a 3- to 30-membered carbocyclic or heterocyclic ring. A is a substituted or unsubstituted alkylene group having 2 to 5 carbon atoms, Y is an oxygen or sulfur atom, and Z
represents a substituted or unsubstituted methylene group or an oxygen or sulfur atom] General formula (11) of a cyclobutane derivative represented by and a compound represented by general formula (1) 1 to 5 represents an allyl group-substituted alkyl group , R2 is hydrogen, alkyl group having 1 to 5 carbon atoms, protected 1 carbon number
5 represents a hydroxyalkyl group or a protected carboxyl group, R3 and R4 [wherein 82 is hydrogen, an alkyl group having 1 to 5 carbon atoms, a protected hydroxyalkyl group having 1 to 5 carbon atoms, or a protected represents a carboxyl group, A represents a substituted or unsubstituted alkylene group having 2 to 5 carbon atoms, Y represents an oxygen or sulfur atom,
2 represents a substituted or unsubstituted methylene group, oxygen or sulfur atom] and a compound represented by the general formula (III) [wherein 81 is an alkyl group having 1 to 5 carbon atoms, an allyl group having 1 to 5 carbon atoms] represents an alkyl group, R3 and 84 are independently hydrogen, an alkyl group having 1 to 5 carbon atoms, a protected human Ooxyalkyl group having 1 to 5 carbon atoms, an alkoxy group having 1 to 5 carbon atoms, or 1 to 5 carbon atoms; to 5 represents an allyl-substituted alkoxy group, or R3 and 84 are bonded to form 3
Indicates a 30- to 30-membered carbocyclic ring or a heterocyclic ring. This invention relates to a production method characterized by condensing and cyclizing a compound represented by the following.
本発明によれば、従来製造が困難であったシクロブタン
誘導体が簡便に、更には光学活性にも製造できる。According to the present invention, cyclobutane derivatives, which have conventionally been difficult to produce, can be easily produced, and further, optically active derivatives can be produced.
一般式（１１）で表される化合物と一般式（Ｉｌｌ ’
）で表される化合物を縮合触媒を用いて反応すると、触
媒の種類によりラセミ体のあるいは光学活性な一般式（
１）で表されるシクロブタン化合物が高収率で得られる
。この反応に於ける縮合触媒としては、例えばルイス酸
あるいはルイス酸と当量または過剰量のリガンドを組合
わせたものが挙げられる。ルイス酸としては、例えば四
塩化チタン、ジクロロジイソプロポキシチタンなどのチ
タン化合物、二塩化スズ、四塩化スズ、二価スズトリフ
ラート等のスズ化合物、塩化ジメチルアルミニウム、塩
化ジエチルアルミニウム等のアルミニウム化合物等が挙
げられる。リガンドとしては立体的に込み合ったジオー
ル類が好ましく、例えば（２Ｓ、３Ｓ）−２，３−０−
（＋−フェニルエチリデン）−１，１，４，４−テトラ
フェニル−１゜２、３．４−ブタンテトラオール（化合
物Ａ）、（２Ｒ，３Ｒ） −２，３−０−（１−フェニ
ルエチリデン） −１，＋、 ４．４−テトラフェニ
ル−１、２，３，４−ブタンテトラオール（化合物Ｂ）
、（２Ｓ、３Ｓ）−２，３−０−ベンジリデン−１゜＋
、 ４．４−テトラフェニル−１，２，３，４−ブタ
ンテトラオール（化合物Ｃ）、（２Ｒ，３Ｒ）−２，３
−０−ベンジリデン−１，１，４，４−テトラフェニル
−１，２，３，４−ブタンテトラオール（化合物Ｄ）、
（２Ｓ、３Ｓ） −２，３−Ｏ−（１−フェニルエチリ
デン）ｌ、 １．４゜４−テトラキス（４−メトキシ
フェニル）−１゜２、３．４−ブタンテトラオール（化
合物Ｅ）、（２Ｒ，３Ｒ） −２，３−０−（１−フェ
ニルエチリデン） −１，１，４，４−テトラキス（４
−メトキシフェニル） −１，２，３，４−ブタンテト
ラオール（化合物Ｆ）或はこれらの化合物のラセミ体等
の分子内に５員環以上の環、好ましくは５−８員環を有
し、その環をはさんで両側に水酸基の結合した基を有す
るもの等が挙げられる。Compounds represented by general formula (11) and general formula (Ill'
) is reacted with a condensation catalyst to form a racemic or optically active general formula (
The cyclobutane compound represented by 1) is obtained in high yield. The condensation catalyst used in this reaction includes, for example, a Lewis acid or a combination of a Lewis acid and an equivalent or excess amount of a ligand. Examples of Lewis acids include titanium compounds such as titanium tetrachloride and dichlorodiisopropoxytitanium, tin compounds such as tin dichloride, tin tetrachloride, and divalent tin triflate, and aluminum compounds such as dimethylaluminum chloride and diethylaluminum chloride. Can be mentioned. As the ligand, sterically crowded diols are preferred, such as (2S,3S)-2,3-0-
(+-phenylethylidene)-1,1,4,4-tetraphenyl-1゜2,3,4-butanetetraol (compound A), (2R,3R) -2,3-0-(1-phenyl ethylidene) -1,+, 4,4-tetraphenyl-1,2,3,4-butanetetraol (compound B)
, (2S,3S)-2,3-0-benzylidene-1°+
, 4.4-tetraphenyl-1,2,3,4-butanetetraol (compound C), (2R,3R)-2,3
-0-benzylidene-1,1,4,4-tetraphenyl-1,2,3,4-butanetetraol (compound D),
(2S, 3S) -2,3-O-(1-phenylethylidene)l, 1.4゜4-tetrakis(4-methoxyphenyl)-1゜2,3.4-butanetetraol (compound E), (2R,3R) -2,3-0-(1-phenylethylidene) -1,1,4,4-tetrakis(4
-methoxyphenyl) -1,2,3,4-butanetetraol (compound F) or a racemate of these compounds, etc., has a 5-membered ring or more, preferably a 5-8 membered ring, in the molecule. , and those having groups with hydroxyl groups bonded to both sides of the ring.
般式（１１）で示される化合物と一般式（Ｉｌｌ ）で
示される化合物の使用割合は前者１当量に対し後者０、
１から５当量好ましくは、０．５から２当量である。縮
合触媒の使用量は一般式（０）の化合物１当量に対しｏ
、ｏｏｔから２当量好ましくは０．０１当量から１．２
当量である。この反応に於て、反応系中にモレキュラー
シーブス４Ａなどの脱水剤を加えることにより反応がよ
り効率よく進行することがある。反応の溶媒としては、
例えばペンタン、ヘキサン、ヘプタン、石油エーテル、
ベンゼン、トルエン、エチルベンゼン、トリメチルベン
ゼン、トリイソプロピルベンゼン等の炭化水素系溶媒、
フロン等のハロゲン化炭素系溶媒、エーテル、テトラヒ
ドロフラン等のエーテル系溶媒、アセトニトリル等の溶
媒及びこれらの混合溶媒が挙げられ、反応温度は、反応
溶媒の凝固点から沸点程度がよく、好ましくは、−５０
℃から３０℃位がよい。例えば、Ｒ２がメトキシカルボ
ニル基、ＡがＣＨ２ＣＨ２、Ｙが酸素、２が酸素である
一般式（１１）の化合物（１当量）及び、Ｒ１がメチル
基、Ｒ３が水素である一般式（Ｉｌｌ ）の化合物（１
゜２５当量）を、縮合触媒としてジクロロジイソプロポ
キシチタン（０，＋０当量）及び（２Ｓ、 ３Ｓ）−
２，３−Ｏ−（１−フェニルエチリデン）−１，１，４
，４−テトラフェニル−１，２，３゜４−ブタンテトラ
オール（化合物Ａ）（０，ｚ当量）を組み合わせた物を
用い、モレキュラーシ−ブス４Ａを加え、石油エーテル
−トルエン混合溶媒中、０℃で反応させることにより（
３Ｓ、 ４Ｓ）−３−メトキシカルボニル−１−メチ
ルチオ−４−（オキサゾリジン−２−オン−３−イル）
カルボニル−１−シクロブテンが高化学収率、高光学収
率で得られる。また、上記反応において一般式（ＩＩ＋
）で表される化合物としてＲ１がメチル基、Ｒ３がブ
チルである化合物を用いれば、 （３Ｒ，４Ｓ）−２
−ブチル−３−メトキシカルボニル−１−メチルチオ−
４−（オキサゾリジン−２−オン−３−イル）カルボニ
ル−１−シクロブテンが高化学収率、高光学収率で得ら
れる。The ratio of the compound represented by the general formula (11) and the compound represented by the general formula (Ill) is 1 equivalent of the former to 0 of the latter,
1 to 5 equivalents, preferably 0.5 to 2 equivalents. The amount of condensation catalyst used is o per equivalent of the compound of general formula (0).
, 2 equivalents from oot, preferably 0.01 equivalents to 1.2 equivalents
It is equivalent. In this reaction, the reaction may proceed more efficiently by adding a dehydrating agent such as molecular sieves 4A to the reaction system. As a solvent for the reaction,
For example, pentane, hexane, heptane, petroleum ether,
Hydrocarbon solvents such as benzene, toluene, ethylbenzene, trimethylbenzene, triisopropylbenzene,
Examples include halogenated carbon solvents such as chlorofluorocarbons, ether solvents such as ether and tetrahydrofuran, solvents such as acetonitrile, and mixed solvents thereof, and the reaction temperature is preferably from the freezing point to the boiling point of the reaction solvent, preferably -50
The temperature is preferably between ℃ and 30℃. For example, a compound (1 equivalent) of the general formula (11) where R2 is a methoxycarbonyl group, A is CH2CH2, Y is oxygen, and 2 is oxygen, and a compound of the general formula (Ill) where R1 is a methyl group and R3 is hydrogen. Compound (1
25 equivalents), dichlorodiisopropoxytitanium (0,+0 equivalents) and (2S, 3S)- as condensation catalysts.
2,3-O-(1-phenylethylidene)-1,1,4
,4-tetraphenyl-1,2,3゜4-butanetetraol (compound A) (0,z equivalent) was used in combination with molecular sieves 4A, and in a mixed solvent of petroleum ether and toluene. By reacting at 0℃ (
3S, 4S)-3-methoxycarbonyl-1-methylthio-4-(oxazolidin-2-one-3-yl)
Carbonyl-1-cyclobutene is obtained in high chemical and optical yields. Furthermore, in the above reaction, the general formula (II+
) If a compound in which R1 is a methyl group and R3 is a butyl group is used, (3R,4S)-2
-butyl-3-methoxycarbonyl-1-methylthio-
4-(oxazolidin-2-one-3-yl)carbonyl-1-cyclobutene is obtained in high chemical and optical yields.
本発明化合物に於てＲＩ Ｒ２Ｒ’によって示される
炭素数１から５のアルキル基としては、例えばメチル基
、エチル基、ブチル基等のアルキル基が挙げられ、炭素
数１から５の、アリル基置換アルコキシ基としては、例
えばベンジル基、４−メトキシベンジル基等の芳香族環
で置換された炭素数１から５のアルキル基が挙げられる
。また、保護された炭素数１から５のヒトＯキシアルキ
ル基としでは、例えばベンジルオキシメチル基、アセチ
ルオキシメチル基、ｔ−ブチルジフェニルシリルオキシ
メチル基等が挙げられる。保護されたカルボキシル基と
しては、例えばメトキシカルボニル基、エトキシカルボ
ニル基等のようなアルコキシカルボニル基や、ベンジル
オキシカルボニル基の７ラルキルオキシカルボニル基等
が挙げられる。Examples of the alkyl group having 1 to 5 carbon atoms represented by RI R2R' in the compound of the present invention include alkyl groups such as a methyl group, ethyl group, butyl group, and allyl groups having 1 to 5 carbon atoms. Examples of the alkoxy group include an alkyl group having 1 to 5 carbon atoms substituted with an aromatic ring such as a benzyl group and a 4-methoxybenzyl group. Further, examples of the protected human O-oxyalkyl group having 1 to 5 carbon atoms include a benzyloxymethyl group, an acetyloxymethyl group, and a t-butyldiphenylsilyloxymethyl group. Examples of the protected carboxyl group include alkoxycarbonyl groups such as methoxycarbonyl group and ethoxycarbonyl group, and 7-ralkyloxycarbonyl group such as benzyloxycarbonyl group.
炭素数１から５のアルコキシ基としては、例えばメトキ
シ基、アリルオキシ基等が挙げられ、炭素数１から５の
、アリル基置換アルコキシ基としては、例えばベンジル
オキシ基、４−メトキシベンジルオキシ基、ｔ−ブチル
ジフェニルシリルオキシ基等が挙げられる。Examples of the alkoxy group having 1 to 5 carbon atoms include methoxy group and allyloxy group, and examples of the allyl-substituted alkoxy group having 1 to 5 carbon atoms include benzyloxy group, 4-methoxybenzyloxy group, t -butyldiphenylsilyloxy group and the like.
［実施例］
次に、実施例を挙げて本発明化合物の製造について具体
的に説明する。[Example] Next, the production of the compound of the present invention will be specifically explained with reference to Examples.
実施例１゜
（＋） −（ＩＲ，６Ｓ、 ７Ｒ，８Ｒ） −６−ｎ
−ブチルチオ−８−メトキシカルボニル−７−（オキサ
ゾリジン−２−オン−３−イル）カルボニルビシクロ［
４，２，０１オクタンの製造アルゴン雰囲気中、ジクロ
ロジイソプロポキシチタン（１１１，２５ｍｇ、０．４
６９５ｍｍ。Example 1゜(+) -(IR, 6S, 7R, 8R) -6-n
-butylthio-8-methoxycarbonyl-7-(oxazolidin-2-one-3-yl)carbonylbicyclo[
Preparation of 4,2,01 octane Dichlorodiisopropoxy titanium (111,25 mg, 0.4
695mm.
１）及び（２Ｒ，３Ｒ）−２，３−０−（１−フェニル
エチリデン） −１，１，４，４−テトラフェニル−１
，２，３，４−ブタンテトラオール（化合物Ｂ）（２７
６，５０ｍｇ、０．５２３ｍｍｏｌ）にトルエン（４ｍ
ｌ）を加え、室温で３０分間攪拌する。更に、加熱乾燥
した粉末モレキュラーシーブス４Ａ （２００ｍｇ））
及び石油エーテル（沸点〜８０℃、４ｍ１）及び３−
［（Ｅ）−３−（メトキシカルボニル）プＯベノイル］
−オキサゾリジン−２−オン（８５，３５ｍｇ、０゜４
２８５ｍｍｏ Ｉ）を加え０℃に冷却する。この懸濁液
に１−ｎ−ブチルチオシクロヘキセン（１１９，８０ｍ
ｇ、０．７０３ｍｍｏｌ）の石；由エーテル溶液（１，
５ｍ１）を加えた後、０℃で２日間攪拌する。反応液に
０．２Ｍ−リン酸緩衝液（ｐＨ７，０）を加え反応を停
止し、無機物をセライトを用いて濾去した後、有機物を
酢酸エチルで抽出する。抽出液は飽和食塩水で洗浄後、
無水硫酸ナトリウムで乾燥した後、減圧下溶媒を溜去す
る。残渣は、薄層クロマトグラフィー（酢酸エチル：ヘ
キサン＝１“＋、ｖ／ｖ）で精製しく＋）（Ｉ Ｒ，６
Ｓ、 ７Ｒ，８Ｒ） −６−ｎ−ブチルチオ−８−メ
トキシカルボニル−７−（オキサゾリジン−２−オン−
３−イル）カルボニルビシク０ ［４，２，０］オクタ
ン（１５１，４０ｍｇ９６％）を得る。1) and (2R,3R)-2,3-0-(1-phenylethylidene)-1,1,4,4-tetraphenyl-1
,2,3,4-butanetetraol (compound B) (27
6,50mg, 0.523mmol) to toluene (4m
Add l) and stir at room temperature for 30 minutes. Furthermore, heat-dried powdered molecular sieves 4A (200 mg))
and petroleum ether (boiling point ~80°C, 4ml) and 3-
[(E)-3-(methoxycarbonyl)benoyl]
-Oxazolidin-2-one (85.35 mg, 0°4
Add 285 mmol I) and cool to 0°C. This suspension was added to 1-n-butylthiocyclohexene (119,80m
g, 0.703 mmol) of stone; ether solution (1,
After adding 5 ml), the mixture was stirred at 0°C for 2 days. The reaction was stopped by adding 0.2M phosphate buffer (pH 7.0) to the reaction solution, the inorganic substances were filtered off using Celite, and the organic substances were extracted with ethyl acetate. After washing the extract with saturated saline,
After drying over anhydrous sodium sulfate, the solvent was distilled off under reduced pressure. The residue was purified by thin layer chromatography (ethyl acetate:hexane = 1"+, v/v) (I R, 6
S, 7R, 8R) -6-n-butylthio-8-methoxycarbonyl-7-(oxazolidin-2-one-
3-yl)carbonylbicyclo[4,2,0]octane (151,40 mg 96%) is obtained.
’Ｈ−ＮＭＲ（ＳＯＯＭ）Ｉ’ｚＦＴ、 ＣＤＣ１５）
ろ：０、８７ （３Ｍ、 ｔ、 Ｊ＝２．９）１ｚ
） 。'H-NMR(SOOM)I'zFT, CDC15)
Ro: 0, 87 (3M, t, J=2.9) 1z
).
１、３０−１．６２ （１１）１． ｍ） 。1, 30-1.62 (11) 1. m).
１、９１１．９８ （＋Ｈ，ｌ） 。1,911.98 (+H, l).
２．４７（Ｉ）Ｉ、ｄｄｄ、Ｊ＝６．１．８．４． Ｎ
、２１（ｚ）。2.47(I) I, ddd, J=6.1.8.4. N
, 21(z).
２、６６ （ＩＨ，ｄｄ、 Ｊ＝４．９．１０．０Ｈｚ
）。2,66 (IH, dd, J=4.9.10.0Hz
).
２．７２（ＩＨ，ｄｄｄ、Ｊ＝６．４．８．４．１＋、
２Ｈ２）。2.72 (IH, ddd, J=6.4.8.4.1+,
2H2).
３．３４（＋Ｈ，ｔ、ＪｌＩＩＯ，０Ｈｚ）。3.34 (+H, t, JlIIO, 0Hz).
３、６２ （３Ｈ，ｓ）。3,62 (3H,s).
３．８８（Ｈｌ、ｄｄｄ、Ｊ＝５．０．９．０． ＋１
．０Ｈ１）。3.88 (Hl, ddd, J=5.0.9.0. +1
．． 0H1).
４、 Ｇｏ （ＩＨ，ｑ、 Ｊ＝９．０Ｈ２） 。4. Go (IH, q, J=9.0H2).
４、１２−４．４０ （２Ｈ，ａ＋） 。4, 12-4.40 (2H, a+).
４．７７（ＩＨ，ｄ、Ｊ＝１０．０Ｈｚ）。4.77 (IH, d, J=10.0Hz).
”Ｃ−ＮＭＲ（＋２５Ｍ）ＩｘＦＴ、ＣＤＣ１３）
６：＋３．５．２０．９．２１．０．２２１．２２．５
．２７．７．２９．０゜３＋、０．３６．６．３９．５
．４２．７．４５．５．５＋、２．５Ｌ７゜６１．８．
１５３．０．１６９．７．１７３．０゜［α］ Ｄ＋７
？、２°（ｃ １．１３． ＣＨ２Ｃｌ２）。”C-NMR (+25M) IxFT, CDC13)
6: +3.5.20.9.21.0.221.22.5
．． 27.7.29.0°3+, 0.36.6.39.5
．． 42.7.45.5.5+, 2.5L7゜61.8.
153.0.169.7.173.0° [α] D+7
? , 2° (c 1.13. CH2Cl2).
本化合物の光学純度は以下のようにして決定した。即ち
、本化合物をメタノール中０℃でマグネシウムメトキシ
ドで処理し、（Ｉ Ｒ，６Ｓ、 ７ Ｒ。The optical purity of this compound was determined as follows. That is, this compound was treated with magnesium methoxide in methanol at 0° C. to give (IR, 6S, 7R).
８Ｒ）−６−ｎ−ブチルチオ−７，８−ビスメトキシカ
ルボニルカルボニルビシクロ［４，２，０］オクタンへ
導いた後、エーテル中水素化リチウムアルミニウムで還
元し、（ＩＲ，６８，７Ｆ１．８Ｒ）−６−ｎ−ブチル
チオ−７，８−ビスヒドロキシメチルピシク［：ｌ ［
４，２，Ｏｌオクタンを得る。これを常法（（Ｒ）−ａ
−メトキシ−〇−トリフルオロメチルーフェニルアセチ
ルクロリド（（Ｒ）−ＭＴＰＡＣｌ ）、 ジメチル
アミノピリジン（ＤＭＡＰ）／ピリジン（ｐｙｒ））に
従いビス（Ｒ）−ＭＴＰＡエステルに導いた。8R) -6-n-Butylthio-7,8-bismethoxycarbonylcarbonylbicyclo[4,2,0]octane, which was then reduced with lithium aluminum hydride in ether (IR,68,7F1.8R) -6-n-butylthio-7,8-bishydroxymethylpisic [:l [
4,2,Ol octane is obtained. This is done in the usual manner ((R)-a
-Methoxy-〇-trifluoromethyl-phenylacetyl chloride ((R)-MTPACl), dimethylaminopyridine (DMAP)/pyridine (pyr)) to yield bis(R)-MTPA ester.
このビス（Ｒ）−ＭＴＰＡエステルと、表記化合物のラ
セミ体より同様に導いたビス（Ｒ） −ＭＴＰＡｍステ
ルの５００ＭＨｚ−ＮＭＲの比較により、本化合物の光
学純度は、〉９８％ｅｅであると決定した。By comparing 500 MHz-NMR of this bis(R)-MTPA ester and bis(R)-MTPAm ester similarly derived from the racemic form of the title compound, the optical purity of this compound was determined to be >98% ee. did.
実施例２゜
（Ｉｓ、２Ｒ，３Ｒ）−１−エチルチオ−３−メチル−
３−メトキシカルボニル−７−（オキサゾリジン−２−
オン−３−イル）カルボニルシクロブタン
１−ｎ−ブチルチオシクロヘキセンの代わりに２−エチ
ルチオブＯペンを用いる以外は、実施例１と同様に処理
し、（ＩＳ、２Ｒ，３Ｒ）−１−エチルチオ−３−メチ
ル−３−メトキシカルボニル−７−（オキサゾリジン−
２−オン−３−イル）カルボニルシクロブタン及び（Ｉ
Ｒ，２Ｒ，３Ｒ）−１−エチルチオ−３−メチル−３−
メトキシカルボニル−７−（オキサゾリジン−２−オン
−３−イル）カルボニルシクロブタンの混合物（７２：
２８．７０％）を得る。Example 2゜(Is, 2R, 3R)-1-ethylthio-3-methyl-
3-methoxycarbonyl-7-(oxazolidine-2-
(IS,2R,3R)-1-ethylthio-3 -Methyl-3-methoxycarbonyl-7-(oxazolidine-
2-one-3-yl)carbonylcyclobutane and (I
R,2R,3R)-1-ethylthio-3-methyl-3-
Mixture of methoxycarbonyl-7-(oxazolidin-2-one-3-yl)carbonylcyclobutanes (72:
28.70%).
’Ｈ−ＮＭＲ（５００Ｍｌ（ｚＦＴ、ｃＤｃ１３）
５：Ｌ １９ （３ｘ０．２８Ｈ，ｔ、 Ｊ＝１．４Ｈ
２）。'H-NMR (500Ml (zFT, cDc13)
5:L 19 (3x0.28H,t, J=1.4H
2).
Ｌ ２５ （３ｘ０．７２Ｈ，ｔ、 Ｊ＝、７．４Ｈ１
）。L 25 (3x0.72H, t, J=, 7.4H1
).
Ｌ ３３（３ｘ０．７２Ｈ，ｓ）。L 33 (3x0.72H, s).
Ｌ ６９ （３Ｘ０．２８）１． Ｓ） 。L 69 (3X0.28)1. S).
２、１７ ［１ｘＯ，７２Ｈ，ｄｄ、 Ｊ＝１．０．９
．３Ｈｚ）。2, 17 [1xO,72H,dd, J=1.0.9
．． 3Hz).
２．３３（ＩｘＯ，２１１Ｈ，ｄｄ、Ｊ＝３．８．８．
３８Ｚ）。2.33 (IxO, 211H, dd, J=3.8.8.
38Z).
２、４５−２．８５ （３Ｈ，ｍ） 。2, 45-2.85 (3H, m).
３、６２ （ＩｘＯ，７２）１． ｑ、 Ｊ＝９．３）
＋２）。3,62 (IxO,72)1. q, J=9.3)
+2).
３、６６ （３）１． ｓ）。3, 66 (3) 1. s).
３．８９（ＩｘＯ，２ｇ）１．ｄｔ、Ｊ＝８．３．
＋０．２）１ｚ）。3.89 (IxO, 2g)1. dt, J=8.3.
+0.2)1z).
３、９５−４．１２ （２Ｈ，ｍ） 。3, 95-4.12 (2H, m).
４、３７−４．４６ （２１（、ｍ） 。4, 37-4.46 (21 (, m).
４、６０ （ＩｘＯ，２８Ｈ，ｄ、 Ｊ：１１．３Ｈｚ
）。4,60 (IxO,28H,d, J:11.3Hz
).
５、 Ｇｏ （ＩｘＯ，７２１（、ｄ、 Ｊ＝９．３）
＋１１゜この混合物各々の相対立体配置は、２次元スペ
クトルＣ０８Ｙ及びＮ０ＥＳＹにより決定した。5, Go (IxO,721(,d, J=9.3)
+11° The relative configuration of each of this mixture was determined by two-dimensional spectra C08Y and NOESY.
また、光学純度は実施例１と同様にビス（Ｒ）−ＭＴＰ
Ａエステルに導き測定したところ、主成績体が９８５％
ｅｅ、異性体が７９％ｅｅであった。In addition, the optical purity was the same as in Example 1.
When the A ester was introduced and measured, the main product was 985%.
ee, isomer was 79% ee.
実施例３゜
以下の表に本発明化合物の製造例を示す（実施例１の化
合物も含む）。記載以外の条件、処理方法は実施例１と
同じである。光学純度は、実施例１と同様に決定した。Example 3 The following table shows production examples of the compounds of the present invention (including the compound of Example 1). Conditions and processing methods other than those described are the same as in Example 1. Optical purity was determined in the same manner as in Example 1.
［効果］
一般式（１）で表される化合物を立体特異的に製造する
ことができた。これらの化合物は、光学活性であるので
、試薬、医薬品、農薬、香料等或いはこれらの製造原料
或いは中間体として有用である。[Effect] The compound represented by the general formula (1) could be stereospecifically produced. Since these compounds are optically active, they are useful as reagents, pharmaceuticals, agricultural chemicals, fragrances, etc., or raw materials or intermediates for their production.
Claims (2)
から５の、アリル基置換アルキル基を示し、Ｒ＾２は水
素、炭素数１から５のアルキル基、保護された炭素数１
から５のヒドロキシアルキル基または保護されたカルボ
キシル基を示し、Ｒ＾３及びＲ＾４は独立に水素、炭素
数１から５のアルキル基、保護された炭素数１から５の
ヒドロキシアルキル基または、炭素数１から５のアルコ
キシ基、または炭素数１から５の、アリル基置換アルコ
キシ基を示すかまたは、Ｒ＾３とＲ＾４が結合して３員
環から３０員環の炭素環または複素環を示す。Ａは置換
基を有するまたは無置換の炭素数２から５のアルキレン
基を、Ｙは酸素またはイオウ原子を、Ｚは置換または無
置換メチレン基または酸素またはイオウ原子を示す］ で表されるシクロブタン誘導体(1) General formula (I) ▲There are mathematical formulas, chemical formulas, tables, etc.▼(I) [In the formula, R^1 is an alkyl group with 1 to 5 carbon atoms, 1 carbon number
5 represents an allyl-substituted alkyl group, R^2 is hydrogen, an alkyl group having 1 to 5 carbon atoms, a protected alkyl group having 1 carbon number
5 represents a hydroxyalkyl group or a protected carboxyl group, R^3 and R^4 are independently hydrogen, an alkyl group having 1 to 5 carbon atoms, a protected hydroxyalkyl group having 1 to 5 carbon atoms, or It represents an alkoxy group having 1 to 5 carbon atoms, or an allyl group-substituted alkoxy group having 1 to 5 carbon atoms, or a 3- to 30-membered carbocyclic or heterocyclic ring in which R^3 and R^4 are combined. Shows a ring. A is a substituted or unsubstituted alkylene group having 2 to 5 carbon atoms, Y is an oxygen or sulfur atom, and Z is a substituted or unsubstituted methylene group or an oxygen or sulfur atom] A cyclobutane derivative represented by
護された炭素数１から５のヒドロキシアルキル基または
保護されたカルボキシル基を示し、Ａは置換基を有する
または無置換の炭素数２から５のアルキレン基を、Ｙは
酸素またはイオウ原子を、Ｚは置換または無置換メチレ
ン基または酸素またはイオウ原子を示す］ で表わされる化合物と一般式（III） Ｒ＾３ＣＨ＝ＣＲ＾４ＳＲ＾１（III） ［式中Ｒ＾１は炭素数１から５のアルキル基、炭素数１
から５の、アリル基置換アルキル基を示し、Ｒ＾３及び
Ｒ＾４は独立に水素、炭素数１から５のアルキル基、保
護された炭素数１から５のヒドロキシアルキル基または
、炭素数１から５のアルコキシ基、または炭素数１から
５の、アリル基置換アルコキシ基を示すかまたは、Ｒ＾
３とＲ＾４が結合して３員環から３０員環の炭素環また
は複素環を示す。］で表わされる化合物を縮合環化する
事を特徴とする一般式（ I ） ▲数式、化学式、表等があります▼（ I ） ［式中Ｒ＾１は炭素数１から５のアルキル基、炭素数１
から５の、アリル基置換アルキル基を示し、Ｒ＾２は水
素、炭素数１から５のアルキル基、保護された炭素数１
から５のヒドロキシアルキル基または保護されたカルボ
キシル基を示し、Ｒ＾３及びＲ＾４は独立に水素、炭素
数１から５のアルキル基、保護された炭素数１から５の
ヒドロキシアルキル基または、炭素数１から５のアルコ
キシ基、または炭素数１から５の、アリル基置換アルコ
キシ基を示すかまたは、Ｒ＾３とＲ＾４が結合して３員
環から３０員環の炭素環または複素環を示す。Ａは置換
基を有するまたは無置換の炭素数２から５のアルキレン
基を、Ｙは酸素またはイオウ原子を、Ｚは置換または無
置換メチレン基または酸素またはイオウ原子を示す］ で表されるシクロブタン誘導体の製造法(2) General formula (II) ▲There are mathematical formulas, chemical formulas, tables, etc.▼ (II) [In the formula, R^2 is hydrogen, an alkyl group having 1 to 5 carbon atoms, or a protected hydroxyalkyl group having 1 to 5 carbon atoms. group or protected carboxyl group, A is a substituted or unsubstituted alkylene group having 2 to 5 carbon atoms, Y is an oxygen or sulfur atom, and Z is a substituted or unsubstituted methylene group, oxygen or sulfur. [indicates an atom] A compound represented by the general formula (III) R^3CH=CR^4SR^1 (III) [In the formula, R^1 is an alkyl group having 1 to 5 carbon atoms, 1 carbon number
5 represents an allyl-substituted alkyl group, R^3 and R^4 are independently hydrogen, an alkyl group having 1 to 5 carbon atoms, a protected hydroxyalkyl group having 1 to 5 carbon atoms, or a protected hydroxyalkyl group having 1 to 5 carbon atoms. to 5 alkoxy group, or an allyl group-substituted alkoxy group having 1 to 5 carbon atoms, or R^
3 and R^4 combine to represent a 3- to 30-membered carbocyclic or heterocyclic ring. General formula (I) characterized by condensed cyclization of a compound represented by [In the formula, R^1 is an alkyl group having 1 to 5 carbon atoms, carbon Number 1
5 represents an allyl-substituted alkyl group, R^2 is hydrogen, an alkyl group having 1 to 5 carbon atoms, a protected 1-carbon alkyl group
5 represents a hydroxyalkyl group or a protected carboxyl group, R^3 and R^4 are independently hydrogen, an alkyl group having 1 to 5 carbon atoms, a protected hydroxyalkyl group having 1 to 5 carbon atoms, or It represents an alkoxy group having 1 to 5 carbon atoms, an allyl-substituted alkoxy group having 1 to 5 carbon atoms, or a 3- to 30-membered carbocyclic or heterocyclic ring in which R^3 and R^4 are combined. Shows a ring. A is a substituted or unsubstituted alkylene group having 2 to 5 carbon atoms, Y is an oxygen or sulfur atom, and Z is a substituted or unsubstituted methylene group or an oxygen or sulfur atom] A cyclobutane derivative represented by manufacturing method
Priority Applications (3)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7202490A JPH03275677A (en) | 1990-03-23 | 1990-03-23 | Production of new cyclobutane derivative |
| US07/657,463 US5250697A (en) | 1990-03-01 | 1991-02-19 | Cyclobutane derivatives |
| EP91102806A EP0444597A1 (en) | 1990-03-01 | 1991-02-26 | Novel cyclobutane derivative |
Applications Claiming Priority (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| JP7202490A JPH03275677A (en) | 1990-03-23 | 1990-03-23 | Production of new cyclobutane derivative |
Publications (1)
| Publication Number | Publication Date |
|---|---|
| JPH03275677A true JPH03275677A (en) | 1991-12-06 |
Family
ID=13477431
Family Applications (1)
| Application Number | Title | Priority Date | Filing Date |
|---|---|---|---|
| JP7202490A Pending JPH03275677A (en) | 1990-03-01 | 1990-03-23 | Production of new cyclobutane derivative |
Country Status (1)
| Country | Link |
|---|---|
| JP (1) | JPH03275677A (en) |
-
1990
- 1990-03-23 JP JP7202490A patent/JPH03275677A/en active Pending
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