LV10781B - Macrolides - Google Patents

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Publication number
LV10781B
LV10781B LVP-93-1233A LV931233A LV10781B LV 10781 B LV10781 B LV 10781B LV 931233 A LV931233 A LV 931233A LV 10781 B LV10781 B LV 10781B
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LV
Latvia
Prior art keywords
hanpmmep
6bitb
rpynny
μπμ
moryt
Prior art date
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LVP-93-1233A
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English (en)
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LV10781A (lv
Inventor
Derek R Sutherland
Oswy Z Pereira
Hazel M Noble
Michael V J Ramsay
John B Ward
Neil Porter
Richard A Fletton
Edward P Tiley
David Noble
Original Assignee
American Cyanamid Co
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Priority claimed from GB868613790A external-priority patent/GB8613790D0/en
Priority claimed from GB868625854A external-priority patent/GB8625854D0/en
Priority claimed from GB878708423A external-priority patent/GB8708423D0/en
Application filed by American Cyanamid Co filed Critical American Cyanamid Co
Publication of LV10781A publication Critical patent/LV10781A/lv
Publication of LV10781B publication Critical patent/LV10781B/lv

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Classifications

    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07D—HETEROCYCLIC COMPOUNDS
    • C07D493/00—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system
    • C07D493/22—Heterocyclic compounds containing oxygen atoms as the only ring hetero atoms in the condensed system in which the condensed system contains four or more hetero rings
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N43/00—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds
    • A01N43/90—Biocides, pest repellants or attractants, or plant growth regulators containing heterocyclic compounds having two or more relevant hetero rings, condensed among themselves or with a common carbocyclic ring system
    • A—HUMAN NECESSITIES
    • A01—AGRICULTURE; FORESTRY; ANIMAL HUSBANDRY; HUNTING; TRAPPING; FISHING
    • A01N—PRESERVATION OF BODIES OF HUMANS OR ANIMALS OR PLANTS OR PARTS THEREOF; BIOCIDES, e.g. AS DISINFECTANTS, AS PESTICIDES OR AS HERBICIDES; PEST REPELLANTS OR ATTRACTANTS; PLANT GROWTH REGULATORS
    • A01N49/00—Biocides, pest repellants or attractants, or plant growth regulators, containing compounds containing the group, wherein m+n>=1, both X together may also mean —Y— or a direct carbon-to-carbon bond, and the carbon atoms marked with an asterisk are not part of any ring system other than that which may be formed by the atoms X, the carbon atoms in square brackets being part of any acyclic or cyclic structure, or the group, wherein A means a carbon atom or Y, n>=0, and not more than one of these carbon atoms being a member of the same ring system, e.g. juvenile insect hormones or mimics thereof
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P31/00—Antiinfectives, i.e. antibiotics, antiseptics, chemotherapeutics
    • A61P31/04—Antibacterial agents
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H19/00—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof
    • C07H19/01—Compounds containing a hetero ring sharing one ring hetero atom with a saccharide radical; Nucleosides; Mononucleotides; Anhydro-derivatives thereof sharing oxygen

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  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Organic Chemistry (AREA)
  • Health & Medical Sciences (AREA)
  • General Health & Medical Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • Agronomy & Crop Science (AREA)
  • Environmental Sciences (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Dentistry (AREA)
  • Plant Pathology (AREA)
  • Pest Control & Pesticides (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Molecular Biology (AREA)
  • Insects & Arthropods (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Genetics & Genomics (AREA)
  • Animal Behavior & Ethology (AREA)
  • General Chemical & Material Sciences (AREA)
  • Biotechnology (AREA)
  • Medicinal Chemistry (AREA)
  • Biochemistry (AREA)
  • Oncology (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Communicable Diseases (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Saccharide Compounds (AREA)
  • Organic Low-Molecular-Weight Compounds And Preparation Thereof (AREA)

Description

1 1 LV 10781 MAKPOJIMflHbIE COEflMHEHMfl
HacTomnee M3o6peTeHMe othocmtch k ηοβνμ οοθαμηθημαμ -aHTMānoTUKaM, κ npoi^eccaM nojiyMeHMH 3tmx coeAUHeHMii, a TaK>Ke κ φθρΜθμβΒΤΜΗΘΟΚΜΜ Κ0ΜΠ03Μψ1ΗΜ, COAepJKaUļMM 3ΤΜ ΟΟΘΑΜΗΘΗΜΗ. B HameM Πβτθητηομ onncaHun w 2166436 (BennKo6pnTaHnn) Mbi onncbieaeM nonyHeHMe AhtuSmotmkob S541, KOTopbie MoryT 6biTb oTfle/ieHbi ot npoflyKTOB φβρΜβΗΤ3ί1ΜΜ ηοβνχ Streptomyces sp. ABTopbi HacToaLLļero M3o6peTeHMfl oTKpbmn euļe OflHy rpynny COeflMHeHMM, XapaKTepM3yeMblX aHTMČHOTMHeCKOM aKTMBHOCTbK), M KOTOpbie MoryT 6biTb nonyHeHbi nyTeM ΧΜΜΜΗθοκοίί μοα^Φμιο^μ Ahtm6motmkob S541.
TaK, Β C00TB6TCTBMM C OflHMM M3 βΟΠβΚΤΟΒ, HaCTOflLiļee Μ3θ6ρβΤΘΗΜΘ b ocoSeHHOCTM OTHOCMTcn κ coeflMHeHMflM, xapaKTepn3yeMbiM φορ&ψποίί I:
2 Μ Κ ΜΧ COJlflM, rfle R1 npeflCTaenfleT οοδοίί μθτμπ-, 3τμπ - μγμ M3onponnnrpynny, R2 npeflCTaBnaeT co6oii θτομ eoflopofla, Ci-8anKmibHyio rpynny m/im C3.8 anKeHM/ibHy»o rpynny, OR3 - npeflCTaBJifleT co6oii rnflpoKCnnbHyio rpynny μπμ 3aMeujeHHyK) rnflpoKCM/ibHyK> rpynny, coAep>Kaunyio flo 25 θτομοβ yrnepofla, m rpynna = NOR2 ηθχοαμτοα b E - κοΗφΜ^ρθψΜ.
TepMMH "ajiKMnbHa«" mjim "anKeHM/ibHan”, OTHOCfliiļMMcn κ rpynne \λπ\λ nacTM rpynnbi b οοβΑΜΗβΗΜηχ, xapaKTepn3yeMbix φopMyno^ί I, 03HaMaeT, hto flaHHan rpynna ΗΒπηβτοη ζιμηθμηομ μπμ pa3BeTBJieHHoii. B τβχ cnyMaax, Korfla R2 b οοθαμηθημαχ, xapaKTepn3yeMbix φopMyπo¢ί I, npeflCTaBJineT οοδοίί Ci-8anKnnbHyK) rpynny, to HanpMMep, OHa Μθ>κβτ 6biTb MeTunbHOM rpynnoū, 3TM/ibHoii rpynnoM, HopM-nponnjībHoii rpynnofi, M3onponnnbHoii rpynnoū, HopM-6yTnnbHoii rpynnoM, M3o6yTwibHoii rpynnoii min TpeT-6yTnnbHoii rpynnoii m, npeflnoHTMTenbHo, OHa ηβ/ιηβτοΒ MeTunbHoii rpynnoū. B τβχ cnyMaflx, Korfla R2 πρβΑοτβΒίΐηβτ co6oii C3.8anKeHnnbHyio rpynny, to OHa μο>κθτ, nanpMMep, BBJiHTbCfl a/īnmībHoii rpynnoM. B τβχ cjiyMaflx, KorAa rpynna OR3 b οοβΑΜΗβΗκηχ, xapaKTepn3yeMbix φopMyπoίί ( I ), ΑΒπηβτοίΐ 3aMemeHHoū γμαροκομ^βηομ rpynnoii, to OHa Μθ>κβτ npeACTaB/iflTb co6om a4nnoKCnrpynny, τ.β. rpynny, xapaKTepn3yeMyK> φορινψπβΜΜ -OCOR4, OCO2R4 mjim -OCSOR4 (γαθ R4 npeACTaenaeT co6oū βΐΊΜφθΤΜΜβαψΚ), apani^aTMseci<yio μπμ apoMaTMMecic/K) rpynny, TaKy»o xax HanpMMep, anKMnbHan rpynna, ajiKeHMJībHan rpynna, a/iKMHmībHafl rpynna, LļMKnoariKMribHaii rpynna, apa/iKMJībHan rpynna mjim apmībHan rpynna), a τθίοκβ Μθ>κβτ npeACTaBnnTb οοδοίί φopM^1πoκc^1Γpyππy; rpynny, xapaicrepM3yeMyK) φopMy/loίί -OR5 (γαθ R5 ecTb xax 6bino y«a3aHO Bbiiue Ann R4), rpynny, xapaiaepii3yeMyK) φopMyJ^oM -OSO2R6 (γαθ R6 npeACTaBJineT οοδοίί CManKnnbHyio rpynny mjim C6-ioapmibHyio rpynny), 4MKnnHecKyK) mjim aiļMKnMHecKy»o a4eTajibOKcnrpynny, rpynny, xapaKTepn3yeMyio φopMyπo^ί 0C0(CH2)nC02R7 (γαθ R7 πρβΑΟτβΒ/ιηβτ co6oii aTOM BOAopoAa mjim rpynny, ιοκ 6bmo yKa3aHo Bbiiue a^p R4, a n paBHneTcn 0, 1 μπμ 2) min rpynny, xapaKTepn3yeMyio φopMyJ^o^ί OCONR8R9 3 3LV 10781 ( rfle R8 m R9 MoryT Kax<AbiM, He3aBMCMMo Apyr ot Apyra, abaaTbcn stomom BOflopofla mam Ci^ aJiKn/ibHOM rpynnoM, T.e., HanpMMep, MeTMAbHOM rpynnoM). B τθχ cnyMajļx, Korfla R4 mam R5 npeflCTaBnneT co6om a/iKtuibHbie rpynnbi, το ohm Μοιγτ ABAATbcn, HanpMMep, Ci-sa/iKMJībHbiMH rpynnaMM, T.e. MeTmībHoii rpynnoM, STMAbHOM rpynnoiit HopM-nponMAbHOii rpynnoii, M3onponn/ibHOM rpynnoM, HopM-6yTMAbHOM rpynnoū, M3o6yTMAbHOM rpynnoM, TpeT-6yTnnbHOM rpynnofi mam HopM-renTMAbHofi rpynnoū m npn θτομ a/iKMJībHbie rpynnbi MoryT τθιοκθ ABAATbcn 3aMemeHHbiMM. B τβχ cnyHaflx, Korfla R4 ΑΒΑΑβτοη 3aMei±ļeHHOM aAKMAbHOM rpynnoM, to 3Ta rpynna μο>κθτ 6biTb 3aMeLLļeHa, HanpMMep, oahmm mam HecKonbKMMM, HanpMMep, AsyMA MJ1M TpeMfl 3T0M3MM ΓβΑΟΓβΗΘ (ΗβΠρΜΜβρ, 3T0M3MM XAOpa MAM 6pOMa) MJ1M Kap6oKCnrpynnoM, Ci^aJiKOKcnrpynnoM, (τ.β. μθτοκομ-, 3To«CMrpynnoM), φeHOκc^1ΓpyππoM mam CMAMAOKCMrpynnoii. B τβχ cnyHanx, xorAa R5 npeACTaBnneT co6om 3aMemeHHyio anKMAbHyio rpynny, 3Ta rpynna Μ0>κβτ 6biTb 3aMeiAeHa c noMOiiļbio LļMKnoa/iKM/ibHoii rpynnbi, τβκοΐί, Kax HanpMMep, LļMKnonponMnbHan rpynna. B τβχ cnyManx, KorAa R4 mam R5 nenatoTcn anKeHMAbHOM μπμ a/iKMHMJībHOM rpynnaMM, to ohm Moryr 6biTb, HanpMMep, C2.eanKeHMAbHOM rpynnofi, τθκομ, iok HanpMMep, a/iriMJībHan rpynna mam C2-8anKMHMAbHaA rpynna. B τβχ cnyManx, KorAa R4 mam R5 πρθαοτθβααιοτ co6om LļMKnoanKMAbHbie rpynnbi, to ohm MoryT npeACTaB/iHTb co6om, HanpMMep, C3-iiiļMicnoaAKMnbHbie rpynnbi, iame Ka« C3-7MMKnoanKMAbHbie rpynnbi, T.e., HanpMMep, LļMKAoneHTMAbHbie rpynnbi. B τβχ cnyHanx, KorAa R4 mdm R5 πρβΑοτβΒηηιοτ co6om anKMnbHbie rpynnbi, to ohm npeAnoHTMTenbHo οοΑβρχοτ ot 1 ao 6 θτομοβ ymepoAa b anKMAbHOM οοκοπκβ m apMAbHan rpynna mam apMAbHbie rpynnbi MoryT npeACTaenflTb co6om κβρδομΜΚΑΜΜβοκΜβ rpynnbi mam ΓβτβρομΜΚΑΜΜβοκΜβ rpynnbi, m coAepjKauļMe npeAnoHTMTeAbHO ot 4 ao 15 θτομοβ yrnepoAa, T.e., HanpMMep, cfjeHMAbHbie rpynnbi. ilpMMepaMM TaKMx rpynn αβαακ)τοα Φθημα-Ci-6aAKMAbHbie rpynnbi, t. e., HanpMMep, 6eH3MAbHbie rpynnbi. 4 B Tex cnyHaflx, Korfla R4 n/in R5 npeACTaBHHK>T οοδοίί apnnbHbie rpynnbi, to ohh MoryT aermTbca Kap6oiļHKTMMecKHMn nnn ΓβτβρομΜΚΠΜΜθοκΜΜΜ rpynnaMn n npeflnoMTMTenbHO coflep>KaTb ot 4 flo 15 θτομοβ yrnepofla n MoryT, HanpuMep, npeACTaBnaTb οοδοίί φβΗΜ/ΐΒ^ιο rpynny. B τβχ cnyManx, KorAa R4 co,qep>Km cnnnjiOKOH3aMecTHTejib, to cnnnjibHa« rpynna Μ0>κβτ BicmonaTb b ce6a Tpn rpynnbi, KOTopbie Μοιγτ nBrmTbcn oflUHaKOBbiMH nnn pa3nnHHbiMH n BbičpaHHbiMM H3 rpynnbi, BKnKDHaioiiļeti b ce6n anKnnbHyio, anKaHnnbHyio, anKOKcniļnKnoanKnnbHyK), apa/iKMJibHyK), apnnbHyio nnn apnnoKcnrpynribi. TaKne rpynnbi MoryT 6biTb T3KMMM >ΚΘ, KaK 6blJ10 yKa3aHO BbILUe fl/lfl R4 H, Β 0C06eHH0CTM, 3TO OTHOCMTcn κ MeTnnbHon, TpeT-6yTmibHoii nnn Φθημπβηομ rpynnaM. XapaKTepHbiMn npninepaMn τβκηχ cnnnnoKcnrpynn nenaiOTca
TpnMeTnncnnnnoKcnrpynna n TpeT-6yTnnAnMeTnncnnnnoKcnrpynna. B Tex cnyManx, κογαθ -OR3 πρβΑοτβΒηηβτ οοδοίί rpynny, c xapaicrepM3yeMyK) φορι\^ηοή -OSO2R , to OHa μοκθτ, HanpnMep, npeflCTaBJiflTb οοδοίί MeTnncyr^oHMnoKcnrpynny nnn napa- τonyoπcyJ^bφoH^t/^oκc^lΓpyππy. Β τβχ cnyMaax, κογαθ -OR πρβΑΟτβΒηηβτ οοδοίί ΑηκηηΜβο^ιο aiļeTanb0Kcnrpynny, to 3Ta rpynna μο>κθτ nMeTb, HanpnMep, ot 5 flo 7 KODbLļeBblX ΗΠβΗΟΒ H ΜΟ>ΚβΤ npeflCTaBfmTb οοδοίί, HanpklMep,
TeTparnAponMpaHMnoKcnrpynny. Β τβχ cnyHaax, κογαθ OR3 πρβΑΟΤβΒηηβτ οοδοίί rpynny, xapaKTepn3yeMyK> φopMynoίί OCO(CH2)n CO2R7, to OHa Μθ>κβτ, HanpnMep, flB/iflTbCfl rpynnoii1 xapaKTepM3yeMoii φopMynaMn 0C0C02R7a nnn φopMynoή 0C0CH2CH2C02R7a, γαθ R7a npeACTaB/ιηβτ οοδοίί θτομ BOAopoAa nnn Ci-4anKnnbHyio rpynny, τ.β . HanpnMep, MeTnnbHyfo rpynny, nnn 3TMJibHyK) rpynny.
Conn, KOTopbie MoryT 6biTb nonyneHbi c πθΜθίψ»ιο οοβΑΜΗβΗΜίί, xapaKTepn3yeMbix φopMynoίί I, coAep>KauļMe KncnoTHy*o rpynny, npeACTaBfiiiiOT οοδοίί conu c οοηοβθημρμμ, t. e., HanpnMep, conu uļenoHHbix ΜβτβηηοΒ, τ. e. TaKne κθκ conu Ηβτρηη nnn Kanna. 5 5 LV 10781 B οοθαμηθημλχ, xapaKTepn3yeMbix tpopMynoii I, rpynna R1 npeflnoMTMTenbHO flon>KHa npeflCTaBnnTb co6oii M3o-nponn/ibHyK) rpynny. rpynna OR3 npeflnoHTMTe/ibHO npeflCTaB/ifieT co6om μθτοκομ-Kap6oHM/iOKCnrpynny mjim, b ocočeHHocTM, aiļeT0Kcnrpynny, MeT0Kcnrpynny mjim OKCnrpynny. B ο6ιαθμ cnyMae οοθαμηθημβ, xapa«Tepu3yeMbie φopMyπo¢! (I), b KOTopbix OR npeACTaBJiHeT co6oii 0Kcnrpynny, ββπβ»οτοβ B OCOSeHHOCTM npeAnOMTMTeJlbHbIMM. Ba)KHblMM ΟΟβΑΜΗΘΗΜΒΜΜ, nonyMeHHblMV1 B COOTBeTCTBMM C HaCTOflllļMM Μ3θ6ρΘΤβΗΜβΜ, BBJ1BI0TCH ΤΘ coeAUHeHMii, xapaxTepn3yeMbie φopMyno^i ( 1 ), b κοτορωχ npeACTaB/ιηβτ co6oii M30-nponmibHyio rpynny, R πρθαοτθβπβθτ co6oii MeTM/ibHyK) rpynny 3 m OR npeACTaBnfleT co6oū 0Kcnrpynny, ai4eT0Kcnrpynny min MeTOKCMKap6oHMnoKCiirpynny.
Kax 6bmo yKa3aH0 paHee, οοθαμηθημβ, BBJii»K)U4Mec« πρβΑΜβτοΜ HacToamero Μ3θ6ρβτβΗΜη, MoryT 6biTb ncno/ib30BaHbi b «anecTBe aHTM6MOTMKOB. CoeAMHeHMB, BBJIBKDUļMeCB ΠρβΑΜΘΤΟΜ HaCTOBU4ero Μ3θ6ρβΤΘΗΜΒ, TaiOKe MOryT 6blTb MCn0Jlb30BaHbl B ΚΘΜΘΟΤΒβ npOMe>KyTOMHblX ΟΟΘΑΜΗΘΗΜΜ ΠρΜ ΠΟΙψΜΘΗΜΜ ΑΡΥ™Χ a«TMBHblX COeAMHeHMM. Β ΤΘΧ CJiyHaHX,
KorAa coeAMHeHMii, ββιιβιοιαμθοη πρθαμθτομ HacTomnero Μ3ο6ρβτβΗΜίΐ, ncnojib3yioTca β «anecTBe npoMe>KyTOMHbix οοθαμηθημμ, το - OR3 rpynna ΜΟ>ΚβΤ BB/lBTbCB 3aLLļMLL(eHHOM ΓΜΑΡΟΚΟΜΠΒΗΟΜ rpynnOM Μ ΑδΗΗΟβ M3o6peTe'Hne β οοο6θηηοοτμ othocmtcb k τθκμμ 3ammneHHbiM coeAMHeHMBM. Ηθο6χοαμμο noAMepKHyTb, mto TaKaa rpynna AOfi>KHa o6naAaTb MMHMMyMOM AononHUTenbHoii φyHκ^MOHa.ΠbHocτM c τθμ, mo6bi M36e>KaTb AonoJiHMTenbHbix μβΗτροβ peaKLjMM μ αογοκηθ 6biTb τθκομ, HTo6bi ΒΒΠΒ/IOCb B03M0>KHblM OCyU4eCTBMTb H3 ΗΘΘ ΟβΠβΚΤΜΒΗΟΘ ρβΓΘΗβρΜρΟΒβΗΜβ rnApoKcmībHoii rpynnbi. (IpuMepaMM 3ainnmeHHbix rMAPOKcmibHbix rpynn, BB/iBiOTCB χοροιυο M3BecTHbie rpynnbi, KOTopbie onncbiBaraTca, HanpMMep, b κημγθ “ Protective Groups in Organic Chemistry” by Theodora W. Greene (Wiley Interscience, new York 1981) and “Protective Groups in Organic Chemistry” by J. F. W McOmic (Plenum Press, London 1973). npMMepaMM OR3 3aiiļnmeHHbix rnApoKcnnbHbix rpynn BB/intoTcn φeHoκc^1a^eoκc^1Γpyππbl, cnnnnoKCMaiļeTOKCMrpynnbi (τ.β. HanpMMep, 6
TpMMeTnncmiMnoKCMaiļeTOKCMrpynna m TpeT-6yTmi/ļMMeTnncnnnnoKCM-aiļeT0Kcnrpynna), m cmjim/iokcm - rpynnbi, rame κβκ HanpuMep: τρμμθτμπ-cnnnnoKCnrpynna m TpeT-6yTnnflMMeTMJicMJiMjioKcnrpynna.
CoeAUHeHMfl, HBnnioiUMecH πρθαμθτομ HacTOjnnero μ3ο6ρθτθημπ, coAepMomne TaKMe rpynnbi, 6yAyT b ochobhom HaxoAMTb πρμμθηβημθ b «anecTBe npoMex<yTOHHbix οοθαμηθημμ. flpyrne rpynnbi, TaKMe κβκ aiļeTOKCM-rpynnbi, MoryT cny)KMTb b κθμθοτβθ 3amMineHHbix rMAP0KcmibHbix rpynn, ho MoryT τθιοκθ npMcyTCTBoeaTb b LļeneBbix aKTMBHbix οοθαμηθημηχ. Οοθαμηθημα, nBJiRtoiiļnecfl πρβΑΜβτοΜ HacToniAero M3o6peTeHMfl, xapaKTepn3yiOTC« 3ητμ6μοτμηθο<ομ aKTMBHOCTbK), t. e., HanpuMep, npOTUBOre/lbMMHTHOM (npOTMBOrnMCTHOM) aKTMBHOCTbK), ΗΘΠρΜΜβρ, ΠρΟΤΜΒ ΗΘΜ3Τ0Α0Β, Μ, B ΟΟΟδβΗΗΟΟΤΜ, 3TM ΟΟΘΑ^ΗΘΗΜΗ Xapa«T6pM3yiOTCH ΘΗΤΜ-3HAOnapa3MTMHeCKOM M aHTM-3KTOnapa3MTMMeCKOM aKTMBHOCTbK). 3KTonapa3MTbi m 3Hflonapa3MTbi πορβχοιοτ πκ>ΑβΜ μ μηο>κθοτβο pa3J1MHHblX >KMBOTHblX Μ, B OC06eHHOCTM, OHM nopa>KaK)T Ce/lbCKO-X03HMCTBeHHblX )KMBOTHblX, Τ3ΚΜΧ KaK CBMHbM, OBlļbl, KpynHblM poraTbIM CKOT, a Tax<e A^Mb (t. e., HanpMMep, xyp, μηαιοιιιθκ), noiuaAeM, κροπμκοβ, πτμα μ AOMaUJHMX >KMBOTHblX Τ3ΚΜΧ KaK CO@aKM, KOLUKM, ΜΟρΟΚΜΘ CBMHKM, ΧΟΜΗΚΜ Μ T. fl. napa3MTMHecKafl ΜΗφθκμΜΗ b >KMBbix opraHM3Max πρμβοαμτ k 3ηθμμμ m noīepe sēca, mto ββπηθτοη β3>κηομ πρμμμηομ 3KOHOMMMecKMX noTepb bo BCeM MMpe. ΠρΜΜθρβΜΜ ΒΜΑΟΒ 3Hfl0napa3MT0B, nopa>KaiOll4MX ΤΘΚΜΧ >KMBOTHblX μ/μπμ πκιαθμ, HBJinKJTCH Ancylostoma, Ascaridia, Ascaris, Aspicularis, Brugia, Bunostomum, Capillaria, Chabertia, Cooperia, Cyathostomes, Dictyocaulus, Dirofilaria, Dracunculus, Enterobius, Gastrophiius, Haemonchus, Heterakis, Hyostongylus, Loa, Metastongylus, Necator, Nematodirus, Nematospiroides, Nippostrongylus, Oesophagostomum, Onchocerca, Ostertagia, Oxyuris, Parafilaria, Parascaris, Probstmayria, Strongylus, Strongyloides, Syphacia, Thelagia, Toxascaris, Toxocara, Trichonema, Trichostrongylus, Trichinella, Trichuris, Triodontophorus, Uncinaria m Wuchereria. (IpMMepaMM 3KAonapa3MTOB, nopax<aK)inMx >κμβοτηβιχ μ/μπμ πιοαθμ, BBnflioTCfl apTponoAHbie 3KAonapa3MTbi, Tāme KaK ManauļMe, KycaK)LLļMe 7 7LV 10781
HaceKOMbie, MflCHbie Myxn, 6noxn, buum, KpoBOcocyuļne HaceKOMbie, icneiiļn n Apyrne flByxKpbi/ibie HaceKOMbie. npHMepaMM Τ3ΚΜΧ 3KT0napa3HT0B, nOpa>KaK)lJ4MX >KMBOTHblX h/mjim mofleii, nermioTCfl Ambylomma, Anopheles, Boophilus, Chorioptes, Culexpipiens, Culliphore, Demodex, Damalinia, Dermatobia, Haematobia, Haematopinus, Haematophysalis, Hyaloma, Hypoderma, lxodes, Linognathus, Lucilia, Melophagus, Oestrus, Otobius, Otodectes, Psorergates, Stomoxys m Tabanus.
CoeAMHeHMH, αβπηιοιαμθοα πρβΑΜβτοΜ HacTonmero Μ30δρβτβΗΜΛ, BBJlJHOTCfl θφφβΚΤΜΒΗΗΜΜ ΚβΚ ΠρΜ MCn0J1b30BaHHM ΜΧ “β Πρθ6κρΚβ", ΤΘΚ Μ B >κμβομ opraHM3Me προτιΐΒ ιιικροκοΐΌ cneKTpa 3Hfl0napa3HT0B Μ 3KTOnapa3HTOB. AHTM6MOTMMeCKa?l aKTMBHOCTb, COeflMHeHMii, HBnfUOIHMXCfl πρβΑΜβτοΜ HacToaiAero Μ3θ6ρβτβΗΜΒ, Μθ>κβτ 6biTb, HanpMMep, npOAeMOHCTpHpOBaHa Β φΟρΜΘ HX aKTMBHOCTH K CB060AH0>KHByiAHM
HeMaTOflaM, τθκμμ κθκ Caenorhabditis elegans m Nematospiroides dubius.
Ba>KHblM aKTHBHbIM COeAHHeHMeM, flBJIfllOlAMMCfl ηρβΑΜβΤΟΜ HacTOsuļero Μ3ο6ρβτβΗΜΗ, BB/ineTCH coeAMHeHne, xapaTepn3yeMoe φopMyJ^o^ί (I), β κοτοροίί: R1 npeACTaB/iaeT co6oū MeTiinbHyio rpynny, R2 npeACTaBnneT co6oii MeTn/ibHyio rpynny m OR3 πρβΑοτθΒΠΗβτ co6ofi MeTOKCM-rpynny. flpyrHM B3>KHblM aKTHBHbIM ΟΟβΑΜΗβΗΜβΜ, HB/lHHDliļMMCH ΠρβΑΜβΤΟΜ HacTOHinero μ3ο6ρθτθημη, ΗΒΠΗβτοπ coeAMHeHMe, xapaiepn3yeMoe φopMyno^ί I, β κοτοροπ: R1 ηρβΑοτθΒΠΗβτ coāoii 3Tn/ibHyKD rpynny, R2 npeACTaBnfleT co6oii MeTM/ibHyio rpynny m OR3 npeACTaeJiBeT co6om rnApoKCnnbHyio rpynny. B oco6eHHOCTM Ba>KHbiM a«TMBHbiM coeAHHeHMeM, BBJiHioiiļiiMCfl πρβΑΜβτοΜ HacTOHiAero μ3ο6ρθτθημη, ηβπηθτοη coeAHHeHMe, xapaTepM3yeMoe φopMyJ^o^ί (I), β κοτοροϋ: R1 npeACTaenaeT co6oii M3onponnnbHyio rpynny, R2 πρβΑΟΤθΒπηβτ co6oii MeTnnbHyio rpynny m OR3 npeACTaBJiaeT co6oii rnAPOKCnnbHyK) rpynny. 8 Οοθαμηθημθ, xapaTepM3yeMoe φορΜγ/ιοΛ (I), b κοτοροϋ: R1 npeflCTaB/i«eT co6oPi M3onponrni-rpynny, R2 npeflCTaBnneT co6oii MeTMjibHyio rpynny m OR3 npeACTaBnneT co6om rnApoKCnnbHyK) rpynny, npeflCTaB/iaeT co6oh θκτμβηοθ οοθαμηθημθ προτΜΒ ujupoKoro Anana30Ha 3Hflonapa3moB m 3KT0napa3MT0B. TaK, HanpMMep, 6bino ycTaHOBJieHo, mto οοθαμηθημθ, yKa3aHHoe Bbiiue, HB/ineTcn aKTMBHbiM πρΜ πρμμθηθημμ b >kmbom opraHM3Me προτΜΒ napa3MTMMecKnx HeMaTOflOB, τθκμχ Kax Ascaris, Cooperia curticei, Cooperia arcophora, Cyathostanes, Dictyocaulus viviparus, Dirofilaria immitis, Gastophilus, Haemonchus contortus, Nematodirus battus, Nematodirus hilvetianus, Nematodirus spathiger, Hematospiroides dubius, Hippostrongylus braziliensis, Oesophaostomum, Onchocera gutturosa, Ostertagici circumeineta, Ostertagia ostertagi, Oxyuris equi, Parascaris eguorum probstmayrici, Strongylus edentatus, Strongylus vulgaris, Triadortophorus u Uncinarici stenocephala, a TaioKe προτΜΒ napa3MTMMecKMx αμημηοκ, ryceHMLļ, H6C0T0HHbix Knemeii, 6nox, Βΐυβίί τ3κμχ K3K Amblyomma hebracum, Anopheles stevensi, Boophilus dicolarartus, Boophilus microplus, Chorioptes ovis, Culexpipiens molestus, Damalinia bovis, Dermatobia, Haematopinus, Hypoderma, Linognathus vituli, Lucilia sericata, Psoroptes ovis, Phipicephalus appendicularis m Sacroptes.
CoeflMHeHMfl, flBJlfllOLLļMeCfl ΠρβΑΜΘΤΟΜ HaCTOflUļerO Μ3θ6ρΘΤΘΗΜΗ, τθιοκθ moo/t 6biTb ncnonbaoBaHbi b κθηθοτβθ μηοθκτμαμαοβ, aKapMiļMfloe m HeMaTOLļUflOB AJm yHMHTO>KeHMfi HaceKOMbix b cejibCK0MX03HMCTBe, b necHOM xo3flūcTBe, Ha nnaHTaiļnqx φpyκτoBblx AepeBbee, a τθιοκθ b o6u4ecTBeHHbix μθοτθχ m Ha οκπθαθχ. HaceKOMbie, >KHBymne b ποηκθ mjim Ha cejibCK0X03«iicTBeHHbix KynbTypaxt βκπιομθη 3naKH, (τθκμθ ksk HanpMMep: niiieHMlļa, HHMeHb, M3MC M pMC), ΧΠΟΠΗΘΤΗΜΚ, ΤθδθΚ, OBOU4M, ΤΘΚΜΘ K3K HanpMMep: coa, φpyκτbl) τθκμθ κθκ Aphis fabae, Aulacorthum circumflexum, Myzus persicae, Nephotettix cineticeps, Nilpan/ata lugens, Panonychus ulmi, Phorodon humuli, Phyllocoptruta oleivora, Tetranychus urticae, a τβιοκβ HaceKOMbie BMfla Trialeuroides; ηθμθτοαη τθκμθ κθκ πρθαοτθβμτθπμ βμαθ Aphelencoides, Globodera, Heterodera, Meloidogyne u Panagrellus; Lepidoptera τθκμθ κθκ Heliothis, Plutella m Spodoptera, a τθιοκθ aojiiohocmkm, 9 9 LV 10781
TaKne κθκ Anthonomus grandīs n Sitophilus granarius; MyMHbie >κγκΜ TaKne κβκ Tribolium castaneum, Myxn TaKne κβκ Musca domestica, Mypaebn, TepMnTbi TaKne KaK Pear Psylla\ Trips tabacr, TapaKaHbi, τβκηβ κβκ Blatella germanica n Periplaneta americana, a TaioKe μοοκητν TaKne κβκ Aedes aegypti. B οοοδβΗΗοετη KaK ycTaHOBnnn 3anBHTenn HacTomiļero η3θ6ρβτβΗη«, coeflnHeHne, ΠΒΠΑίοΐΑββοπ πρβΑΜβτοιη HacTonmero Η3θ6ρβτβΗηπ, n xapaTepn3yeMoe φορΛ/ψποή (I), b κοτοροή: R1 npeflCTaBnneT co6on n3o-nponnnbHyK> rpynny, R npeflCTaBnneT co6on MeTnnbHyio rpynny n 3 OR πρβΑοτβΒπηβτ co6on rnApoKcnnbHyto rpynny, ηβτιηβτοη atanBHbiM no οτηοιιιθηηκ) κ Tetranychus urticae, HaxoA«iAHXcn HanncTBe φρβΗ^οκηχ 6o6ob, ηροτηΒ Mysus persicae, HaxoAfliHHXcn Ha nncTbnx κητβήοκοή KanycTbi, ηροτηΒ Heliothis virescens, HaxoA«LL|nxcn Ha /incTb«x xnonMaTHnKa, ηροτηΒ Nilaparvata lugens, ηθχοαηιαμχοπ Ha ροοτκβχ pnca, ηροτηΒ Mūsa domestica, HaxoAflii|nxcn B πηβοτηκοΒωχ κοροδοπκθχ, b KOTopbie noMeiiļeH pacTBop caxapa n xnonHaTo6yMa>KHafl npaara, προτηβ Blatella germanica, HaxoA«mnxcfl b n/iacTHKOBbix κοροδοπκβχ c KycoHKaMn nninn, προτηβ Spodoptera exique ηθχοααιμμχοα Ha ηηοτβηχ χποπΜβΤΗηκβ η προτηβ Meloidogyne incognita.
CoeAMHeHnn, «BnnKJUļnecn πρβΑΜβτοΜ HacToamero η3θβρβτβΗηπ, τθιοκβ Moryr 6biTb ncnonb3oeaHbi b KasecTee Φυηγμαηαοβ, HanpnMep, προτηβ LUTaMa enfla Candida sp. τβκηχ κβκ Candida albicans n Candida glabrata η προτηβ Αροχοκβββιχ τρηδκοβ τβκηχ KaK Saccharomyces carlsbergensis. B οοοτθβτοτβηη c HacTomuHM η3θ6ρβτβΗηβΜ 3anBnTenn HacTomAero η3θ6ρβτβΗηπ, co3Aann οοβΑΜΗβΗηπ, xapaTepn3yeMbie φορΛ/^ποή ( I ), κβκ 6bmo yKa3aHO Bbiiue, n KOTopbie MoryT 6biTb ncnonb3oeaHbi e KanecTee βΗτηδηοτηκοβ. B οοοθβΗΗοοτη 3τη coeAUHeHna MoryT 6biTb ncno/ib3oeaHbi AJin πβπβΗηη η/ιη ο6ρβ6οτκη χοιβοτηηχ η ηκ>ΑβΜ. 3apax<eHHbix 3HAonapa3nTaMn, 3tcronapa3HTaMn n/nnn nnecHeBbiMn ηΗφβκμηηνιη, a τβιοκβ 6biTb ncnonb3oeaHbi e cenbCKOM χο3ηήοτββ, necHOM xo3nncTee, aji* οδρββοτκη πηβΗΤβμηή, e KasecTBe πβοτημηΑοβ ρ,ηη yHHHTO>KeHnfl 10
HaceKOMbix, a τθιοκθ b κθμθοτβθ aKapmļMAOB μ ηθμθτοαμαοβ. 3tm οοθαμηθημα TaioKe Μοιγτ 6biTb Mcnonb30BaHbi b ο6ιαθμ cnyHae b κθμθοτβθ necTMLļUflOB fl/ia yHnmo>KeHMfl ηθοθκομηχ m b flpymx cnyHaax, HanpuMep, b xpaHnnmiļax, 3flaHM«x m flpyrnx o6uļecTBeHHbix MecTax o6maHnn HaceKOMbix. B ο6ιαθμ cnyMae stu οοθαμηθημη Moryr 6biTb πρμμθηθηη HenocpeflCTBeHHO β,ηη opraHM3Ma oSmaHun 3tmx napa3HTOB (τ.β. opraHM3Ma >ΚΜΒΟΤΗΟΓΟ ΜΠΜ ΜΘ/ΙΟΒΘΚΘ, MJ1M ρθΟΤΘΗΜΒ, MJ1M OBOLiļeM ) M/1M 3TM ΟΟΘΑΜΗΘΗΜΒ
MoryT 6biTb npuMeHeHbi no MecTy o6nTaHnn, nnčo ηθποορθαοτβθηηο Ha οθμμχ Hace«oMbix.
CoeflHHeHHfl, nBrmtoinneca πρθαμθτομ HacTomi^ero Μ3ο6ρθτθημη, TaioKe MoryT 6biTb npuroToenenbi flnn πρμμθηθημη nio6biM yflo6HbiM cnoco6oM flnn nocneflyK)mero Mcnonb30BaHMa b BeiepMHapnn μπμ MefluiļMHe, μ TaKMM o6pa30M HacToauLļee μ3ο6ρθτθημθ othocmtch τθιοκθ k cfcapMaiļeBTHHecKMM κομπο3μι4μαμ, coAep>KaLiļMM οοθαμηθημθ, ηβπηιοιαθθοη πρβΑΜΘΤΟΜ HacTomnero μ3ο6ρθτθημ* μ κοτορΗβ npuroAHbi pj\?\ ncnonb30BaHMSR b BeTepnHapnn μπμ μθαμι4μηθ. TaKne κομπο3Μ4μμ MoryT 6biTb npuroTOBJieHbi A-πη Mcnonb30BaHMfl oSbiHHbiM o6pa30M c noMouļbio οαηογο μπμ ηθοκοπβκμχ npMroAHbix ηοομτθπθμ μπμ pa36aBMTeneM. ΚθΜΠ03Μί1ΜΜ, ΠΒΠΠΙΟΙΑΜΘΟΠ ΓφΘΑΜΘΤΟΜ Η30ΤΟίΗΑ6Γ0 Μ3θ6ρβΤΘΗΜΠ, BKJIlOHaiOT Β ce6n ΤΘΚΜΘ φΟρΜΗ, KOTOpbie Β ΟΟΟδβΗΗΟΟΤΜ npMrOTOBneHbl ΑΠ« napeHTepanbHoro bboas, βκπιοηθη ββοα b MonoHHyio >xene3y, a τθιοκθ Κ0ΜΠ03Μ11ΜΜ, ΠρΘΑΗ33Η3ΜΘΗΗΝΘ ΑΠΠ Opa/lbHOrO, peKTanbHOrO, ΤΟΠΜΜΘΟΚΟΓΟ, BHyTpnyMMHanbHoro, μμππθητμροβθηηογο, οΦτθπβμμηθοκογο πρμμθηθημμ, ΠρΜΜΘΗΘΗΜΠ ΗβρΘ3 HOC ΜΠΜ reHMTO-ypMHanbHOfO πρΜΜΘΗΘΗΜΠ. ΟΟΘΑΜΗΘΗΜΗ, ΠΒΠΠΙΟΙΑΜΘΟΗ ΠρβΑΜΘΤΟΜ ΗβΟΤΟΠΙΑΘΓΟ Μ3θ6ρβΤΘΗΜΠ Moiyr 6biTb npuroTOBneHbi α*ιη Mcnonb30BaHMfl β βθτθρμηθρμμ utīm MeAULļHHe nyTeM μηϊθκι1ΜΜ, m ohm MoryT 6biTb πρμγοτοβπθηβι β φορΜβ θαμημηηηχ A03npoBOK, b aMnynax μπμ β APymx θμκοοτπχ, οοαθρχοιιιμχ eAHHMMHyio A03y. μπμ β κοητθμηθρθχ, coAep>KamMx MHoropa3oeyio A03y, b cnynae ηθο6χοαμμοοτμ k τθκμμ κομπο3Μ4μπμ Μοιγτ 6biTb Ao6aeneHbi KOHcepeaHTbi. Κομπο3μι1μμ, npeAHa3Ha4eHHbie απη MH-beKiļMM, MoryT 6biTb npuroTOBneHbi β φορΜβ cycneH3MM, pacTBopoe μπμ 3MynbcnM b boahom Hocmene, μπμ c noMOiiļbio ηοομτθππ, ηθ βοαν, m ohm MoryT coAep>KaTb LV 10781 Π areHTbi, cnoco6cTByK)inne o6pa30BaHMK) KOMno3nnnii, t. e. rame κθκ cycneAnpyK)U4Me, CTa6nnM3npyK>iAMe, 3MMynbrMpyK>mne, conK>6nnn3npy-(OLLļne m/m/im AMcneprnpyioiiļMe areHTbi. AnbTepHaTMBHo, atcruBHbm MHrpeflueHT μο>κθτ 6biTb npuroToeneH β φορΜβ CTepuribHoro nopotuKa on* nocneAyiouļero BHeceHnn b npuroAHbiii Hocme/ib, TaKOM κθκ HanpMMep CTepunbHaa, ηθ coAepaouļan nuporeHOB, BOAa, m sto πρΜΓΟΤΟΒηβΗΜβ npOM3BOAHTC« nepeA ΠρΜΜΘΗΘΗΜβΜ. K MacrmHbiM ηοομτθαλμ οτηοοβτοη MHoroaTOMHbie cnupTbi M mx cjio>KHbie 30npbi, lame κβκ cno>KHbie rnmjepMHOBbie οφκρω, «McnoTbi )κμρηογο pnAa. pacTmenbHbie Macna, τθκμθ κθκ HanpMMep apaxncoBoe Macno, Macno οθμθμθκ χηοπΗβτΗΜίο mjim φρβκίΐΜΟΗΜροΒθΗΗΟβ Macno KOKOcoeoro opexa, MUHepanbHbie TaKne κβκ HanpuMep >kmakmm πβρβφΜΗ, Μ30ΠΡ0ΠΜΠ MMpMCTaT Μ 3ΤΜΠ0Πβ3Τ, a ΤβΙΟΚβ ΑΡΥΓΜβ 3Η3Π0ΓΜΜΗΒΙΘ οοθαμηθημα. flpyrne Hocmenu, coAepKaiiļne Maiepnaribi, Tāme kbk φΟρΜΘΑΒ mMLļepMHa, ΠΡΟΠΜΑΘΗ ITlMKOnb, ΓΠΜΚΟΠΜ ΠΟΑΜ3ΤΜΠΘΗ3, 3ΤβΗ0η ΜΠΜ mMκoφypoπ τβιοκβ MoryT 6biTb ncnonb30BaHbi. OčbNHbie HenoHoreHHbie, KaTMOHHbie un μ θημοηηβιθ noBepxHOCTHO-aKTMBHbie areHTbi MoryT 6bm» ncnonb30BaHbi nn6o no OAHOMy, rm6o β οομθτθημμ APyr c ApyroM npti ηρΜΓΟΤΟΒΠΘΗΜΜ Κ0ΜΠ03ΜμΜΜ. Κομπο3Μ4ΜΜ, npeAHa3HaneHHbie α-Π* BeTepMHapHoro πρμμθηθημρ, MoryT 6biTb τβιοκβ npuroTOBneHbi β φορΜβ MH-betoļHM β,ηπ ββοαθ β MonoMHyio x<ene3y, κβκ o6ecneMMBaK>mne ΜβΑπβΗΗΟΘ BbiAeneHne βκτμβηογο KOMnoHema (npeAHa3HaHeHHbie pj\n A^nienbHoro B03AeMCTBMn), Tax m Ha ocHoee, 6bicTpo BbiAenmomeii aKTMBHbiii κομποηθητ. 3τμ κομπο3μαμμ woryT npeACTaBnnTb co6om CTepn/ibHbie pacTBopbi nnn cycneH3nn β BOAHbix mpm MacnaHbix ηοομτθπβχ, κοτορωβ npn ηθο6χοαμμοοτμ οοΑβρχοτ cryiAaiOLiļMii μπμ cycneHAnpyK)iAMM areHT, τβκοίί κβκ HanpMMep μηγκμμ mpm τββρΑωϋ πβρβφΜΗω, πΗβ/ηΐΗωίί bock, 12-okcμ CTeapnH, rnAPoreHe3npoBaHHoe KacTopoBoe Macno, cīeapaTbi anioMMHMH Mnn rnui^epnn MOHOCTeapaT. 06bHHO HeMOHoreHHbie, KaTMOHHbie v\m aHMOHHbie noBepxHOCTHO-aKTMBHbie eeuļecTBa Moryr 6biTb ncnonb30BaHbi nn6o no OAHOMy, nn6o β οομθτθημμ Apyr c ApyroM npn πρΜΓΟτοβηβΗΜΜ κομπο3μαμμ. 12 Οοθαμηθημα, nennioiJUMecfl npeflMeTOM ΗβετοηιμβΓο Μ3θβρβτβΗΜΛ τβιοκβ MoryT 6biTb npMMeHeHbi fina BeTepMHapHoro MnM μθαμαμηοκογο Η33Η3ΗΘΗΜί1 B φθρΜΘ, ΠρΜΓΟΑΗΟΜ A™ OpanbHOlO ΠρΜΜΘΗΘΗΜΑ, T. β. B BMfle pacTBopoe, cnponoB, 3Mynbcnii mjim cycneH3MM, nn6o b φορΜβ cyxoro nopoiiiKa nocneAy>oii^ero CMeiūMBaHMa c boaom MnM αρΥΓμμ πρμγοαηνμ HocmeneM nepeA πρμμθηθημθμ, npn ηθο6χοαμμοοτμ, c Ao6aeneHMeM OKpaujiiBaioiAero MnM apoMaTM3Mpyiomero areHTOB. TeepAbie κομπο3μμμμ, τθκμθ KaK, HanpMMep, τββηβτκΜ, Kancynbi, neneuiKM, luapMKM, nacTbi, nopoLUKM, rpanynbi npeABapmejibHO cMeinaHHbie roTOBbie φορΜω, MoryT TaioKe 6biTb Mcnonb30BaHbi. TeepAbie μ >κμακμθ κομπο3μι1μμ, npeAHa3HaMeHHbie pj\n opanbHoro πρμμθηθημα, MoryT 6biTb nonyMeHbi b COOTBeTCTBMM C ΜβΤΟΑΘΜΜ, ΧΟρΟΙϋΟ M3BeCTHblMM CneLļManMCTaMM B A3HH0M oSnacTM. TaKne κομποθμαμμ MoryT τβιοκβ coAepx<aTb οαμη μπμ HecKonbKO φθρΜθμβΒΤΜΜβοκΜ npMroAHbix ηοομτθπθμ MnM HanonHMTeneM, κοτορωβ ΜΟΓγΤ HaXOAMTbCfl B ΤΒβρΑΟΜ MnM JKMAKOM φθρΜΘ. ΠρΜΜβρθΜΜ φθρΜΘΙ^βΒΤΜΜβΟΚΜ ΠρΜΓΟΑΗΝΧ HOCMTeneM, npeAHa3HaseHHblX A/1fl ncnonb30BaHwn b τβθραηχ γοτοββιχ φορΜβχ, ηβηηιοτοη CBfl3biBaK>mne areHTbi, τ. e. τθκμθ κθκ HanpMMep, npeABapMTenbHO >KenaTMHM3MpoBaHHbiM MaMCOBbiii KpaxMan, ποηΜΒΜΗΜηπΜρροηΜΑΟΗ MnM οκομπροπμπμθτμπ-iļenniono3a, HanormmenM, τθκμθ κθκ HanpMMep, naKT03a, mmkpo-KpMdajiMsecKafl 4enniono3a μπμ φοοφθτ KanbījMn, ny6pMKaHTbi, τθκμθ κθκ HanpMMep, CTeapaT ΜΘΓΗΜΗ, TanbK MnM flByOKMCb ΚρβΜΗΜΗ, Αβ3ΜΗΤΘφ3ΗΤΒΙ, τθκμθ κθκ HanpMMep, KapTc^enbHbiM KpaxMan μπμ ηθτρμμ γ/ιμκοπθτ KpaxMana, MnM yena>KHHK)i±ļMe areHTbi, τθκμθ κθκ HanpMMep, cynbφaτ naypnna ηθφμβ. Ta6nemi MoryT 6biTb ποκρωτω c noMOLiļbio μθτοαοβ, χοροιυο M3eecTHbix cneiļManMCTaM b abhhom oānacTM. npMMepaMM φθρΜθμβΒΤΜΗβΟΚΜ npMrOAHblX npMCaAOK, A^B MCnonb30BaHMn npM ηρΜΓΟΤΟΒηβΗΜΜ >KMAKMX rOTOBblX φθρΜ, HBnflKDTCa cycneHAMpy»oiAMe areHTbi, τθκμθ κθκ HanpMMep, cnpon cop6nTa, MeTMnL^enniono3a MnM rMAporeHM3MpoeaHHbie nMiiļeebie >KMpbi, 3MynbrMpyioiiļMe areHTbi, τθκμθ kqk HanpMMep, ηβμΜΤΜΗ MnM aKaiļMH, 6e3BOAHbie HOCMTenM, τθκμθ KaK HanpMMep, Macno MMHAann, MacnnHbie cno>KHbie ΘφΜρω MnM 3TMnoBbiM cnMpT, m KOHcepBaHTbi, τθκμθ κθκ HanpMMep, 13 13 LV 10781 μθτμπ - MnM nponnnnapa-OKCn6eH3oaTbi min cop6MHOBan κμοποτθ, τθιοκθ b τθκμθ roTOBbie φορΜΗ MoryT 6biTb BicrnoHeHbi cTa6miM3MpyioinMe m como6miM3MpyioinMe areHTbi. nacTbi, npeAHa3HaMeHHbie flna opanbHoro πρμμθηθημπ, MoryT 6biTb npurOTOB^eHbl B COOTBeTCTBMM C ΜΘΤΟΑΘΜΜ, ΧΟρΟΟΙΟ M3BeCTHblMM cnei^nanncTaM b αθηηομ oSnacTM. llpMMepaMM npMeMneMbix φθρΜθμβΒΤΜΜβοκΜ npnroflHbix αοΘθβοκ, npeAHa3HaneHHbix A^m ncnonb30BaHnn npn πρμμθηθημμ nacToo6pa3Hbix κομπο3μαμμ, nenaiOTcn cycneHAnpyiou4Me min reneo6pa3ytoiAne areHTbi, τθκμθ xax HanpMMep, AHCTeapaT θπιομμημη nnn rnflporeHM3npoBaHHoe KacTopoBoe Macno; Ancneprnpy»oiAMe arem-bi, τθκμθ κθκ HanpMMep, nonMCopSaTbi, 6e3BOAHbie HocMTenu, τθκμθ κθκ HanpMMep, apaxMCOBoe Macno, MacnnHbie cno>KHbie 3φΜρω, γπμκοπμ MnM MaKporonM; CTa6MnM3MpyK)LAMe m conio6MnM3Mpyioii4Me areHTbi. Οοθαμηθημα, nennioiAMecfl πρθαμθτομ Haoromnero μ3ο6ρθτθημα τθιοκθ ΜΟΓγτ 6biTb πρμμθηθημ b βθτθρμηθρηβιχ μβηηχ nyTeM ββθαθημη μχ β ΑΗΘΒΗΟΜ ΠΜφΘΒΟΜ paiļMOH, Κ3Κ B TBepAyiO, ΤΘΚ Μ Β >KMAKyiO nMIAy, Τ. Θ. Κ3Κ HaCTb ΑΗΘΒΗΟΜ A03bl Μη Μ C ΠΜΤΒΘΒΟΜ ΒΟΑΟΜ. Οοθαμηθημπ, nenatoiAMecn πρθαμθτομ HacTonuļero μ3ο6ρθτθημη ΤΘΙΟΚΘ MOryT 6blTb ΒΒΘΑΘΗΒΙ OpanbHO Ann BeTepMHapHblX μβηβΜ Β φορΜΘ >κμακομ A03bi neKapcTBa, τθκομ κθκ pacTBop, cycneH3M« MnM AMcnepcMn 3ΚΤΜΒΗ0Γ0 ΜΗΓρΘΑΜΘΗΤΘ ΒΜΘΟΤΘ C φθρΜθμβΒΤΜΗΘΟΚΜ npMIOAHblM ΗΟΟΜΤβηβΜ MnM HanonHMTeneM. Οοθαμηθημλ, nenflioiAMecn πρθαμθτομ HacToniAero μ3ο6ρθτθημ« τθιοκθ MoryT, HanpMMep, 6biTb npMroToeneHbi β φορΜβ οβθηθμ, τ. θ. Αθ3ΜροΒθκ, οοαθρχοιαμχ oGbNHbie MaTepManbi, Mcnonb3yeMbie πρΜ Μ3ΓΟΤΟΒΠΘΗΜΜ ΟΒΘΗΘΜ, ΠρΘΑΗ33Η3ΗΘΗΗΝΧ 11Π9\ BeTepMH3pHblX MnM μθαμαμηοκμχ μβηβίί MnM β φορΜΘ neccapMM, τ. e., HanpMMep, coAep>Kau4MX MaTepnanbi, Mcnonb3yeMbie απη μ3γοτοβπθημπ o6biKHOBeHHbix neccapMM.
CoeAMHeHMn, jranmoiAMecn πρθαμθτομ HacTonmero μ3ο6ρθτθημ« MoryT 6biTb, Mcnonb3oeaHbi A^a τοπμηθοκογο πρμμθηθημπ, b BeTepMHapHbix MnM μθαμι4Μηθκμχ μβηηχ β φορΜΘ Ma3eū, κρβΜΟΒ, nocbOHOB, ujaMnyHeM, ποροΐϋκοΒ, aapo3oneM, κομπο3Μ3ΜΜ Ann μθκθημη MnM Kanenb, HanpMMep, rna3Hbix Kanenb MnM HocoBbix Kanenb. Ma3M MnM KpeMbi MoryT 6biTb, 14
HanpMMep, npuroTOBneHbi c noMouļbio boahom μπμ MacnnHOM ocHOBbi c ΑοδβΒπβΗΜβΜ npnroAHbix cryuļatoiAnx m/mnu reneo6pa3yioii4Mx areHTOB. Ma3M ρ,ηη ma3Horo πρμμθηθημα MoryT 6biTb npon3BeAeHbi no CTepmībHoii ΤβΧΗΟηΟΓΜΜ C MCnOnbSOBaHMeM CTepmibHblX ΚΟΜΠΟΗβΗΤΟΒ. ΚθΜΠ03ΜμΜΜ, npeAHa3HaMeHHbie a^i* πρΜΜβΗβΗΜη nyTeM nonnea ποΒβρχΗοοτΜ, MoryT 6biTb npuroTOBneHbi Α-π* BeTnpnHapHbix Lļeneii c ncno/ib30BaHneM opraHMMecKnx pacTBopMTeneii \λπ\λ b φορΜβ cycneH3MM, m MoryT coAep>KaTb areHTbi, KOTopbie ycKopntOT npoMecc aACop6LļMM nepe3 xo>Ky, μ θτμ κομπο3μι1μμ τβιοκβ MoryT coAep>KaTb areHTbi, KOTopbie o6ecneHMBa»OT conio6MJiM3aAM>o, CTa6nnn3aLļMKD nnn KOHcepeaLjMto, hjim τθμ mjim HHbiM cnoco6oM ynymuaK)T xapaiorepMCTMKM xpaHeHM« m/mjih npocTOTbi ΠρΜΜβΗβΗΜΑ.
JlocbOHbi ΜΟΓγτ 6biTb npuroTOBneHbi Ha boahom Mnn MacnflHoii οοηοβθ m, b o6iiļeM cnyMae, Aonx<Hbi coAep»<aTb oamh nnn HecKOJibKo 3MynbmpyK)U4Mx θγθητοβ, CTa6nnn3amipyK5LiļMX θγθητοβ, AMcneprMpyioinMx areHTOB, cycneHAMpyK>mnx θγθητοβ, crymaK)iAnx areHTOB min OKpaLunBaK>mnx areHTOB. ΠοροιυκΜ MoryT 6biTb npMroToeneHbi c noMoiiļbK) ηιοδοτο πρμγοαηογο nopoiuKoo6pa3Horo ocHOBaHMn. Kannu MOiyr 6biTb nonyneHbi c noMouļbio βοαηογο Unu 6e3BOAHoro ocHOBaHHH m Tax >xe εοΑβρχοτ oahh Unu HecKonbKO AHcneprnpyiOLAHx areHTOB, CTa6nnn3a4npyi0Li4Mx areHTOB, AMcneprnpyioiAMx areHTOB Unu cycneHAnpyK3iiļnx areHTOB. Ohm MoryT τβιοκβ C0Aep>KaTb KOHcepeaHT. flnn πρΜΜβΗβΗΜη nyTeM MHranmļHH οοθαμηθημη, HBnniouļHecn πρβΑΜβτοΜ HacTosuLļero Μ3θ6ρβτβΗΜ3 MoryT 6biTb, McnonbaoeaHbi Ann BeTepnHapHbix mnu μθαμι4μηοκμχ iļeneii b φορΜβ pacnbīneHHoro ποτοκβ. 06uļan AneBHan A03MpoBKa οοθαμηθημμ, nBnfnouļnxcn πρβΑΜβτοΜ HacTomnero M3o6peTeHnn Moiyr 6biTb m ncnonb3yeMan xax b BeTepnHapHbix, τθκ m b μθαμαμηοκμχ μβηηχ, Aon>KHa ηθχοαμτβοη b Anana30He οτ οαηογο ao 2000 μκγ/κγ >κμβογο eeca, npeAnoHTMTenbHO b Awana30He οτ 5 ao 800 μκγ/κγ >κμβογο Beca, h 3Ta A03a μο>κθτ 6biTb pa3AeneHa Ha MHAMBMAyanbHūie A03bi, npMHMMaeMbie, HanpMMep, οτ 1 ao 4 pa3 b AeHb. Ηθο6χοαμμο noAMepKHyTb, hto A03npoBKa 6yAeT 3aBMceTb οτ B03pacTa μ οοοτοηΗΜη 6onbHoro, 15 15 LV 10781 opraHM3Ma, noAeepraeMoro πθηθημιο, cnoco6a ββοαθ npenapaia n bmas ΠρΜΜβΗΒβΜΟΜ ΓΟΤΟΒΟΜ φΟρΜΝ. fl03Mp0BKM βΠ* ΑβΗΗΟΓΟ OpraHM3Ma ΜΟΓγΤ 6biTb onpeAeneHbi μοχοαη m3 o6bNHbix coo6pa>KeHMM, HanpMMep, πγτβΜ cpaBHeHMfl aKTMBHocieii α^ηηογο οοθαμηθημα m M3BecTHoro areHTa-3ητμ6μοτμκ3.
CoeAUHeHMfl, BBriBiouļMecB πρβΑΜβτοΜ HacTonmero Μ3θδρβτβΗΜη Moryr 6biTb, Mcnonb3oeaHbi πιο6ημ o6biHHbiM cnoco6oM πρ m cenbCKoxo3fliicTBeHHOM μπμ caAOBOM πρΜΜβΗβΗΜΜ, μ τθκμμ o6pa30M HacTOflunee Μ3θ6ρβτβΗΜβ ΒκπιοΗββτ b ce6n ece τβ κομπο3μαμμ, C0Aep>KaLqne οοθαμηθημη, αβπηιοιαμθοη πρβΑΜβτοΜ HacTonmero M3o6peTeHna, KOTopbie npuroAHbi ρ,ηη ncnonb30BaHna b cenbCKOM xo3«iicTBe m npn οβρθδοτκβ cafloe nnaHTaiļuPi. Tāme γοτοβηθ 0opMbi BKJiKJMatOT b ce6fl 6e3BOAHbie MnM >κμακμθ κομπο3Μ4μμ, HanpMMep, AycTbi, ocHOBaHMH, coAepx<aiiļne AycTbi μπμ KOHiļeīpaTbi; ποροιυκΜ, BK/iranan pacTBopMMbie μπμ ysna>KHBeMbie ποροιυκΜ; rpaHynbi, BiouoMatoiAMe MMKporpaHy/ibi m AHcneprnpyeMbie rpaHynbi; TeKyHMe κομπο3μι1μμ; 3MynbCMM, τθκμθ κθκ HanpMMep, pa36aeneHHbie 3MynbCMM μπμ 3MynbrMpyeMbie koh LļeHTpaTbi; nonMBOHHbie pacTeopbi, Tāme ksk HanpMMep, pacTBOpbi απfl o6pa6oT«M κορΗβΜ m ceM«H; pacTBopbi ana ποπμβκμ οθμηη; MacnBHbie KOHi\eHTpaTbi; pacTBopbi Macen; TaKMe κθκ HanpMMep, MH-beKLļMM A/ifl no/iMBKM CTe6neii; κομπο3μι1μμ α-πη pacnbmeHMn, oxypMBaHMn m o6pa6oTKM TyMaHOM.
B οβιμβΜ cnynae TaKMe πρΜΓ0Τ0Β/ιβΗΜ« 6yAyT BīcnfonaTb b ce6n coeAMHeHMe, CB«3aHHoe c npMroAHbiM HocMTeneM μπμ pa36aeMTeneM. TaKMe HOCMTenM μογ>τ npeACTaenaTb co6om >κμακμθ MnM TBepAbie Maiepnanbi m npeAHa3HaHeHbi A-πη τογο, mo6bi cnocoācTBOBaTb πρΜΜβΗβΗΜίο οοθαμηθημη πμ6ο nyreM AMcneprMpoeaHMn ero TaM, γαθ oho aojdkho 6biTb πρΜΜβΗβΗο, jim6o nyTeM co3A3Hmh πρΜΓΟτοΒηβΗΜη, κοτοροβ Μθ>κβτ 6biTb nonyMeHo nonb30BaieneM m nepepaāoTaHo b AncneprMpoBaHHyio κομπο3μι1μ»ο. TaKMe πρΜΓΟτοΒηβΗΜη χοροωο M3BecTHbi cneijManMCTaM b AaHHOM oānacTM m MoryT 6biTb nonyneHbi c noMOUļbio o6biHHbix μθτοαοβ, τθκμχ κθκ HanpMMep, CMeuieHMe μΛμίμ pa3MenbHeHMe θκτμβηογο MHrpeAMeHTa MnM MHrpeAMeHTOB 16 ΒΜβετβ c HOcmejieM min pa36aBMTeneM, τβκμμ, κβκ HanpuMep, TeepAbiū HocnTenb, pacTBopmenb noBepxHOCTHO-aKTMBHbiii areHT. npurOflHblMM TBepflbIMM HOCMTenflMM MCnonb30BaHMfl B ΓΟΤΟΒΗΧ φορΜθχ, t3khx, Kax HanpuMep, AycTbi, rpaHy/ibi μπμ ποροιυκνι, MOiyr flBnnTbCfl Maiepnanbi, Bbi6paHHbie vi3 rpynnbi, BKn»oMatouļeii b ce6n, HanpuMep, npupoAHbie MMHepanbHbie HanonHMTenM, jame kqk α^τομητ, TanbK, Kao/iMHm, ΜΟΗΤΜορκπηοΗΜΤ, προφΜΠΜτ min aTTanynbrnT. BbicoKOAUcnepcHan KpeMHeean KMcnoTa linu BbicoKOAMcnepmpoBaHHbie a6cop6eHTHbie nonMMepbi Μοιγτ, b cnynae ηθο6χοαμμοοτμ, 6biTb AočaBneHbi b κομπο3Μ1μιο. rpaHy/ikipOBaHHbie HOcmeJiH, oānaAaioiAMe aAcop6LļnoHHoii cnocoSHOCTbio, KOTopbie ΜΟΓγτ 6biTb ncnonb30BaHbi, Moryr npeACTaBJimb co6om xax nopticrbie MaTepnanbi, τθκμθ κθκ HanpuMep, neM3a, pa3MenbMēHHbifi KMpnim, cemionm μπμ δβΗΤΟΗΜτ, mjim HenopMCTbie MaTepnanbi, τθκμθ iok Kanbīļm h/im necoK. npnroAHbie npeABapuTe/ibHo rpaHynnpoBaHHbie Maiepnajibi, KOTopbie MoryT 6biTb ncnonb30BaHbi, v\ KOTopbie MoryT HMeTb opraHimecKyio μπμ HeopraHMHecKyio npnpoAy, npeACTaB/uiKDT co6oū αοπομμτ m pa3MenbMeHHbie οοτθτκμ pacTeHMū. npHrOAHbIMH paCTBOpmenflMM PJ\n MCnOnb30BaHHfl B KaneCTBe HOCHTeneii hjih pa36aBMTeneii nennioTCfl apoMaTMHecKMe yrjieeoAopoAbi, CnnpTbl H mUKOJlM HJIH HX npOCTbie 3φΜρΒΙ, CnO>KHbie 3φΜρω, KeTOHbl, aMHAbi khcjiot, cunbHbie nonapHbie ochob3hm?i, πρκ ηθο6χοαμμοοτμ anoKCHAHpoBaHHbie pacTHTenbHbie Macna h βοαθ. 06bNHbie HeHHOreHHbie, KaTMOHHbie H/lMaHHOHHbie ΠΟΒβρΧΗΟΟΤΗΟ-aKTUBHbie areHTbi, TaKne κβκ HanpuMep, 3TOKcnnnpoBaHHbie anKMnbHbie φβΗΟΠΒΐ h cnupTbi, cojiii me/iOHHbix MeiannoB Unu U4enoHH03eMenbHbix MeiannoB anκ^1n6eH3oncynbφoHOBb^x KMcnoT, nnΓHOcynbφOHOBbιx kmchot Unu cynbφoHaτbl nonnMepHbix φβΗοηοβ, KOTopbie o6naAK)T xopouunMH 3MynbrnpyKDU4HMH, AHCneprnpyKDlAHMM H/Mnn yBn3)KHHK)LL4HMM CBOMCTBaMM, MoryT TaioKe 6biTb ncnonb30BaHbi, nw6o b hmctom bha©, nn6o b coHeTaHMM, b yKa3aHHbix κοΜΠθ3Ημπηχ. CTa6nnn3aTopbi, areHTbi, npenflTCTByK>mne cnnnaHwo; areHTbi, npennTCTByKHAne neHoo6pa30BaHwo; areHTbi-peryn«Topbi b«3koctm, HanonHMTenH h aAre3MBbi, φοτοοτ36ιιηΜ33τορΒΐ, a TaioKe yAo6peHim, 17 17LV 10781 nmneBbie CTMMynaTopbi m flpyrne aKTMBHbie cy6cTaHi4MM, MoryT 6biTb, b cnyMae ηθο6χοαμμοοτμ, BBefleHbi b κομπο3μι4μμ. Οοθαμηθημα, nBJifltouļnecfl npeflMeTOM HacTomiļero μ3ο6ρθτθημη, TaioKe MoryT 6biTb ΠρΜΓΟΤΟΒ/ieHbl B ΟΜΘΟΜ C flpyrHMM MHCeKTMLļHAaMM, aKapmļMflaMM m HeMaTOLļMflaMM. B y«a3aHHbix πρμγοτοβπθημαχ κοΗμθΗτρβψΊΛ aKTUBHoro Maiepnana b oāuļeM cnyqae αοτοκηθ HaxoAMTbCfl b Anana30He ot 0,01 ao 99 % BecoBbix, m, 6onee npeAnoHTMTenbHO, b Anana30He ot 0,01 ao 40 % eecoBbix. npoMbiLuneHHbie npoAyKTbi b οδφβΜ cnyqae προμ3βοαητοη β φορΜβ KOHLļeHTpnpoBaHHbix κομπο3μι1μμ, KOTopbie αογοκηβι 6biTb pa36aBneHbi, npn ΜΧ ΠρΜΜΘΗΘΗΜΜ, AO, HanpMMep, 0,001-0,0001 % ΒΘΟΟΒΗΧ. ΚΟΠΜΗΘΟΤΒΟ ΠρΜΜβΗΗΘΜΟΓΟ ΟΟΘΑΜΗΘΗΜΑ 33BMCMT ΟΤ μβΠΟΓΟ ρί>Α3 φβκτοροΒ, κοτορωβ αοπ>κηη 6biTb yMTeHbi, η κ ημμ othochtch: βμα HaceKOMoro μ CTeneHb 3apax<eHMfl. Οαηοκο, β ο6ιαθμ cnyHae, pacxoA, paBHbiii β Awana30He οτ 10 r/ra ao 10 κτ/ra, ηβπαθτοη npuroAHbiM, npeAnoMTMTe/ibHO npMMeHATb β κοπμμθοτβθ ot 10 γ/κγ ao 1 κτ/ra απ* yHMMTO>KeHM« Knemefi m HaceKOMbix, μ β κο/ιμμθοτβθ ot 50 r/ra ao 10 κτ/ra A/lfl yHMHTO>KeHMH HeMaTOAOB.
CoeAUHeHMfi, ABJiniomiiecfl πρθαμθτομ HacTomiļero Μ3ο6ρθτθημη, MoryT 6biTb ββθαθημ wm πρμμθηθην β οομθτθημμ c ApyrMMM aKTMBHbiMM MHrpeAneHTaMM. Β οοο6θηηοοτμ οοθαμηθημη, ηβ·πηκ)ιαμθοα πρβΑΜβτοΜ HacTOfUAēro μ306ρθτθημη, MoryT 6biTb BBeAeHbi nnn npMMeneHbi b COMeTaHMM C APyrMMM M3BeCTHb!MM npOTMBOrejlbMMHTHblMM ripenapaTaMM. l1yTeM oOteAUHeHMfl οοθαμηθημμ, αβπηιοιαμχοη πρθαμθτομ HacTOflUļero Μ3θ6ρβΤΘΗΜΑ, C APy™MM npOTMBOrejlbMMHTHblMM npenapaTaMM M0>K6T 6blTb paciunpeH οπβκτρ ΜΗφβκψιοΗΗωχ 3a6oneBaHMii, Bbi3BaHHbix napa3MTaMM, c KOTopbiMM npeACTaBrraeTCfl B03M0>KH0CTb ycneujHO OopOTbCfl. TaK, ΜΟ)ΚβΤ 6biTb peann30BaHa B03M0>KH0CTb ycneniHoii 6opb6bi προτκβ napa3MTMMeCKMX ΜΗφβΚμΜΜ, ΠΟ OTHOliieHUlO K KOTOpbIM OTAeilbHbie npenapaTbi OKa3bieaK3Tcfl ηθ3ΦΦθκτμβη^μμ μπμ o6naAaiOT TonbKO HaCTHHHOM aKTMBHOCTbK).
CoeAMHeHnn, nenjitoiAMecn πρθαμθτομ HacTomnero μ3ο6ρθτθημη, Μοιγτ 6biTb nonyMeHbi c πομοιαμο cnoco6oB, κοτορωβ 6yAyT onncaHbi 18 flanee. B οοοτβθτότβμμ c ηθκοτορβιμμ M3 3Tmx cnoco6oB npeflCTaBJineTCfl Heo6xo/ļMMbiM 3auļmnTb rn,qpoKCMnbHyio rpynny, HaxoflnmyK>CB b 5-Πθησ>ΚβΗΜΜ B MCXOflHOM ΜΘΤθρΜΘΠΘ ΠβρβΑ ΤΘΜ, KaK OCyLLļeCTBHTb onncbiBaeMyio ρββκμΜίο. B t3khx cnyHaflx Aanee μο>κθτ OKa3aTbcn Heo6xoflHMbiM o6ecneMHTb οηητμθ 3auļMTbi 3Toii rMApoKCMnbHoii rpynnbi, c LļenbK) προΒΘΑβΗΜπ peataļMM, npn3BaHHoii no/iyMMTb iļeneBoe οοθαμηθημθ, BBnniOLAeecH πρθαμθτομ HacTonmero M3o6peTeHHfl, Μοιγτ 6biTb ncnoiib30BaHbi AJ™ 3tmx μΘ/ιβΡί, m 3tm cnoco6bi, Hanpmviep, onncaHbi b ynoMRHyToii Bbiiue κημγθ TpnHa n Μθκ-Αμμ. B cooTBeTCTBMM c oahmm M3 acneKTOB HacTonmero μ3ο6ρθτθημη 3aflBme/ib pa3pa6oTan cnocoč ( A ) πογ^μθημα οοθαμηθημμ, xapaKTepn3yeMbix φοριν^ποΜ ( I ), κοτορπίί 3aKjnoMaeTCfl b peaKLļnn Me>KAy coeAviHeHMeM, xapaKTepn3yeMbiM φορι^/ιο^ (II): o
OR (II)
nocneAyK)iLļHM οηατμθμ 3ammbi α-πη οοθαμηθημα, xapaKTepn3yeMoro φορινψποΜ ( I ), b κοτοροΜ OR3 - npeACTaB/ifleT co6oū 3amm±ļeHHyio 19 19 LV 10781 rn,qpoKcmibHy»o rpynny, m, b cnyHae ηθο6χοαμμοοτμ, c nocjieAyiomMM o6pa3oeaHneM conn.
PeaKLļnn oKCMMupoBaHUfi μο>κθτ 6biTb ocymecTBneHa b boahom mjim 6e3BOflHOM peaKLļkioHHoti cpefle, ο6ηηηο ripu TeMnepaiypax b flnana30He ot -2 flo +100°C, T.e. Hanpuviep, ot -10 ao +50°C. npeACTaenaeTCfl yAo6HbiM ncnonb30BaTb peareHT, xapaKTepn3yeMbiM φopMyπo¢ί H2NOR2 b φορΜβ cojim, HanpMMep πρμοοθαμηθηηομ conn ΚΜοηοτω, τβκοίί xax ΓΜΑΡοχηορίΊΑ- B Tex cnyMasRx, kotas TaKan conb ncnonb3yeTcsi, to peaKLļna μοκθτ 6biTb npoeeASHa b npncyTCTBnn areHTa, CBH3biBaK>mero KncnoTy.
PacTBopMTenflMM, κοτορωβ MoryT 6biTb ncnonb30BaHbi, «ermiOTCfl BOAa h CMeiiiMBatoiAneca c boaom pacTBopuTenu, TaKne xax cnupTbi, HanpuMep, μθτθηοπ min 3TaHon, aMMAbi, τθκμθ Kax HanpviMep, N,N-ΑΜΜΘΤΜΠφΟρΜΘΜΜΑ. N.N-AMMeTMnaLļeTaMMA ΜΠΜ ΓΘΚΟβΜΘΤΜΠφΟΟφΟρθΜΜΑ, npocTbie οφΜρΝ, TaKne KaK npocTbie αμκπμμθοκμθ οφκρω, τ. e. TeTparMApcx£ypaH wnw α^οκοθη m aiļnnoBbie προοτωβ 3φΜρω, τθκμθ κθκ AMMeTOKcusTaH nnw προοτοϋ α^τμποβημ 3φκρ, HMTpmībi, TaKMe Kax HanpuMep, aiļeTOHMTpun, cyr^0Hbi, τθκμθ κβκ HanpuMep, γθπογθημ-poeaHHbie yrneBOAopoAbi, τ. e. HanpuMep, ΜβΤΜ/ιβΗΧ/ιορΜΑ m cno>KHbie 3φΜρω, TaKne KaK STunaiļeTaT, a Taione ομθομ, cocTonmne M3 Aayx m 6onee Τ3ΚΜΧ pacTBopuTeneii. B Tex cnyManx, κογαθ ncnojib3yeTcn BOAHan cpeAa ρ,ηη προβθαθημη peaKiļnn, το peaKiļMOHHaa cpeAa oābiHHO μο>κθτ 6biTb 6yφep^ιpoBaHa c noMoiiļbto cooTBeTCTByioiAeii κιιαιοτω, οοηοβθημη mtih 6yφepH0Γ0 pacTBopa AO BeriMMMHbi BOAopoAHoro noKa3aTejiH, paBHoro ot 2 ao 9 βΑ· pH. K npuroAHbiM KucnoTaM othochtch MMHepa/ibHbie KucnoTbi, τθκμθ KaK xnopncTOBOAopoAHan KMcnoTa mui cepHaa KMcnoTa, m KapOoHOBan κμοποτθ, Taxan KaK HanpiiMep, yKcycHan κμοποτθ. Πρμγοαηνμμ οοηοβθημημμ nenatoTcn KapāoHaTbi v\ 6w<ap6oHaTbi ιαθπομηνχ ΜβτβιιποΒ, Taxne xax 6nKap6oHaT HaTpua; γμαροοκμομ, τθκμθ κθκ HanpuMep rnApooKMCb Ηθτρκη n KapāoKcmiaTbi uļenoHHbix μθτθπποβ, τθκμθ KaK Hanpuviep, ai4eTaT Ηβτρι/ΐΛ. npnroAHbiM 6yφepHblM pacTBopoM «Βηηβτοη pacTBop, coctojuahm H3 aqeTaTa Ηβτρκη m yKcycHofi ΚΜοηοτω. 20
Οοθαμηθημη, xapaKTepn3yeMbie φορΜγηοιί ( II ), BBJiaiOTCfl nn6o M3BeCTHblMM ΟΟΘΑΜΗΘΗΜΑΜΜ, KOTOpbie yKa3aHbl B ΠθΤΘΗΤΗΟΜ OnMCaHHM
BenMKoāpmaHmi Na 2176182, min MoryT 6biTb nonyHeHbi m M3Becmbix coeflMHeHMii, onncbiBaeMbix b αθηηομ τβκετβ, c ncno/ib30BaHneM CTaHflapTHbix npoiļeAyp. B cooTBeTCTBMM c ApyrnM acneKTOM HacTofliAero μ3ο6ρθτθημη 3aflBMTenn npefl/iaraiOT emē oamh cnoco6 ( B ) pj\s\ no/iyMeHiifl οοθαμηθημμ, xapaKTepi43yeMbix φοριν^Γίοίί ( I ), b κοτορωχ R npeflciaBJifleT co6oii Ci-8anKMnbHyio rpynny min C3^ariKeHMjibHyio rpynny m OR3 -npeflCTaBnneT co6oā 3aMemeHHyto rnflpoKcnnbHyK> rpynny, m otot cnoco6 3aKni04aeTCfl b peaKiļnn Me>Kfly coeflMHeHneM, xapaicrepM3yeMbiM φopMynoM (I), b κοτοροΜ OR3 -npeACTaB/ifleT co6om rnApoKcmibHyio rpynny, m peareHTOM, φyHK^Me^ί κοτοροΓΟ fiermeTcn npeepaLiļeHMe rMflpoKcmībHoPi rpynnbi b 3aMemeHHyK> rnAP0KCMnbHyio rpynny, c nocneAyioiAMM, b cnyqae ηθο6χοαμμοοτμ, o6pa30BaHneM conn. ΑμΜΠΜρΟΒβΗΜΘ, φορΜΜ,ΠΜρΟΒβΗΜβ, CyJ^bφOH^1pOBaH^1e, 3ΤΘρΜφΜ-KaLļMfl, cunupoBaHue mjim peaKLļHfi o6pa30BaHH» aiļeTana MoryT 6biTb προΒβΑβΗΗ c noMombK) o6biHHbix MeTOflOB, κβκ 6yAeT yxa3aHO Aa/iee.
Tax HanpMMep, peaioļMH aLļM/iMpoBaHMfl μο>κθτ 6biTb npoeefleHa c ncnonb30BaHneM aiļM^npy(OLAero areHTa, TaKoro xax HanpMMep, KMcnoia, xapaxTep.M3yeMafl φοριν^ποίί R4COOH mjim peaKiļMOHHOcnoco6Hoe npon3BOAHoe 3Tom KMcnoTbi, τβκοβ K3K HanpMMep, ranonAaHrnApnA KucnoTbi, t. e. τθκομ κθκ HanpMMep, xnopaHrnApnA KucnoTbi; θηγμαρ^Α mjim aKTMBMpOBaHHbIM CHO>KHblM 3φΜρ, MJIM peaKLļMOHHOCnOCOāHOe npOH3BOflHOe Kap6oHOBOM κμοποτη, MMeioiiļeM φορν^^ R4OCSOH. B peaK4Mflx aLjMJiMpoBaHMfl, Mcnonb3yK)LLļMX ra/iOMAaHrMAPMAbi kmcjiot m aHrnAPMAbi, MoryT, b cnyMae ηθο6χοαμμοοτμ, 6biTb ncnonb30BaHbi ycnoBMfl, b οοοτβθτοτβμμ c KcrropbiMii npncyTCTByeT areHT, CBfl3biBaK>mMM KncnoTy, τθκο m Kax HanpMMep, τρθτμηηβιμ 3mhh (τ.β. HanpMMep,
TpM3THnaMMH, ΑΚΜβΤΜΠΘΗΜηΜΗ MJIM ΠΜρΜΑΜΗ ), ΗβΟρΓΘΗΜΜβΟΚΜβ OCHOBaHMfl (TaKne Kax HanpMMep, Kap6oHaT KanbLļMH mjim 6nKap6oHaT Haipnn), m 4MKJiMMecKne paAMKanbi TaKne Kax ημ3ιιιμθ okmcm 1,2-anKnneHa (T.e. 21 21LV 10781
HanpMMep, OKMCb 3ΤΜ/1βΗ3 MJ1M OKMCb ΠρΟΠΜΓΙβΗθ), B KOTOpblX ra/IMfl, CBn3biBaK)iiļMii Boflopofl, BbiflejineTcn b pe3y/ibTaTe peaKLļUM aiļMJinpoBaHMB.
PeaKiļnn aiļMnMpoeaHMB, Mcnonb3yiomaR KucnoTbi, οδωΗΗΟ flon>KHa npoBOflMTbCfl b npncyTCTBMM KOHfleHCMpytoiiļero areHTa, HanpMMep, KapāoAMMMMfla, τθκογο κβκ HanpMMep, N.N’-AMiļMKnoreKCM/iKapeoMMA mom N-3TMn-N'-y-flMMeTMnaMMHonponMnKap6oflMMMMfl; KapāoHMribHoro coeflMHe- hmr, TaKoro κβκ Kap6oHMnflMMMMfla3on μπμ conefi M30Kca3ona, τθκομ κθκ HanpMMep, nepxnopaT N-3TMn-5<fc>eHMnM30Kca3ona. AKTMBMpoBaHHbm c/io)KHbiM 3φΜρ μο>κθτ 6biTb yAo6Ho nonyneH no MecTy c Mcnonb3oeaHMeM, HanpMMep, 1-0KCM6eH3OTpMa3ona β πρμο^πότβμμ KOHAeHCMpyK)inero areHTa, κβκ 6bino yKa3aHO Bbliue. AjībTepHaTMBHo aKTMBMpoeaHHbiM cnoKHbiM 3φπρ μο>κθτ 6biTb nonyMeH 3apaHee.
PeaKLļMB aLļMJiMpoBaHMH, Μο>κβτ 6biTb npoBefleHa β boahom μπμ b 6e3BOAHOM peaKLļMOHHOM cpefle oGbiHHO npM TeMnepaiypax b Anana30He ot -20 flo +100, t. e., HanpMMep, οτ-1- ao +50 °C.
PeaKLļMH φΟρΜΜΠΜρΟΒΘΗΜΗ ΜΟ)ΚβΤ 6blTb ΠρΟΒβΑβΗβ C MCnonb30BaHMeM 3ΚΤΜΒΜρ0Β3ΗΗ0Γ0 ΠΡΟΜ3ΒΟΑΗΟΓΟ MypaBbMHOM KMCilOTbl, TaKoii KaK HanpMMep, Ν-φορΜΜη MMMAa3on μπμ θηγμαρμα
MypaBbMHoyKcycHOM KMcnoTbi, b o6bNHbix ycnoBM«x peaKLjMM.
PeaKiļMn cynbφoHMnMpoBaHMfl Μθ>κβτ 6biTb ocymecTBneHa c noMOLLļbKD peaKiļMOHHOcnocoāHoro npoM3BOAHoro cynbφoκMcnoτbι, xapaiaepM3yeMoro φopMyπoM R6S03H, τθκογο κβκ HanpMMep, cynbφoHMnΓanMA, t. e. HanpMMep, χηορΜΑ R6S02CI, μπμ cyπbφoHOBblM 3ΗΓΜΑΡΜΑ· PeaKLļMH CynbφOHM/^MpOBaHMy^ ΠρβΑΠΟΗΤΜΤβΠΒΗΟ npOBOAMTCB B npMcyTCTBMM πρμγοαηογο areHTa, CBfl3biBaioiAero KMcnoTy, Kax 5bmo yKa3aHO Bbliue.
PeaKiļMfl ΒτβρΜφΜκβμΜΜ Μ0>κβτ 6biTb ocymecTBneHa c Mcnonb30BaHMeM peareHTa, xapaiaepM3yeMoro φopMynoM R5Y (γαθ R5 ecTb KaK 6bino yKa3aHO Bbliue, a Y npeACTaenaeT co6om OTLijennflK>myK> rpynny, TaKyto KaK χπορ, δροΜ μπμ moa μπμ ΓMAPOκap6MncynbφoHMnoκcMΓpyππyl T3Kyio KaK MeTMncyr^OHMnoKCM - μπμ τοηΜηονπΒφοΗΜηοκοΜ μπμ ranoanKaHOMnoKCMrpynny, TaKyio κθκ AnxnopaLļeiaTOKCM). 3Ta peaKiļMfl 22 Μοκβτ 6biTb npoeeAeHa πγτβΜ o6pa30BaHMH ajiKoronaTa MarHMH c ncno/ib30BaHMeM peareHTa rpMHbnpa, TaKoro kqk HanpMMep, ranufla ΜβΤΜΑΜΘΓΗΜΛ, ΤΘΚΟΓΟ K3K MOAMA ΜβΤΜηΜ3ΓΗΜΗ, ΜΠΜ C MCn0/lb30BaHMeM ra/iMAa TpManKMncMnMnMeTMnMarHMn, TaKoro KaK HanpMMep, χηορΜΑ TpHMeTHJicmimiMeTUJiMarHun c nocneAyK>meM o6pa6oTKoii peareHTOM, MMeiOllļMM φορΜγηγ R5Y.
AnbTepHaTMBHO peaKiļMn μομθτ 6biTb npoeeAeHa b npMcyTCTBMM cojim cepe6pa, τβκοίί KaK OKMCb cepe6pa, nepxnopaT cepe6pa, Kap6oHaT cepe6pa, carmLļuriaT cepe6pa m mx CMeceii, m 3Ta cMCTeMa μο>κθτ 6biTb b OCOGeHHOCTM ΠρΜΓΟΑΗΟΜ B ΤΘΧ CJiyMaflX, KOrAa npoiļecc 3ΤβρΜφΜΚ811ΜΜ npoBOflmcfl c ncnonb30BaHneM ranufla ajiKiiiia, T.e. HanpMMep μοαμαθπ μθτμαθ.
PeaKLļMfl 3ΤβρΜφΜΚ3ίΐΜΜ μο>κθτ 6biTb yAo6HO npoeeAeHa b pacTBopmejie, τθκομ KaK npocToii 3φΜρ, T.e. HanpMMep, AH3TnnoBbiii npOCTOH 3φπρ. 06pa30BaHne aneTann μοϊκθτ 6biTb ocyiiļecTBneHO 3a cneT peaKLļMM c IļHKTIMMeCKHM MJ1H aiļUKTlHMeCKHM npOCTbIM BMHMAOBblM 3φΜρθΜ. 0TOT ΜβΤΟΑ nenneTcn b οοο6θηηοοτμ npnroAHbiM απ* nonyHeHnn προοτωχ TeTparnAponnpaHMnoBbix 3φΜροβ, c ncnonb30BaHneM b KanecTBe peareHTa AMruApormpaHa, mam 1-anKOKcnanKnnoBbix npocTbix 3φΜροβ, τβκΜχ KaK 1-3T0KCnajiKHA0Bbiii npocToPi 3φΜρ, c Mcnonb30BaHneM b KanecTBe peareHTa npocToro' anKHJīBMHHJioBoro 30npa. 3Ty peaKiļmo iļenecoo6pa3HO npOBOflMTb B npHCyTCTBHH CMAbHOrO ΚΜΟΑΟΤΗΟΓΟ KaTaJlH3aTOpa, HanpMMep, MMHepanbHOM KMcnoTbi, τθκομ KaK cepHan KMcnoTa, mjim b npMcyTCTBMM opraHMHecKOM ογπΒφοκΜοηοτΒΐ, TaKOM KaK HanpMMep, napa-
Tonyoncyr^OKMcnoTa, b HernApoKcmībHOM, npaKTMMecKM ne coAepjKauļMM BOAbi, pacTBOpMTene.
PacTBopMTennMM, κοτορπβ Μοιγτ 6biTb Mcnonb3oeaHbi npM προΒβΑβΗΜΜ yKa3aHHbix Bbiiue peaKL|MM, nenmoTcn κθτοην (HanpMMep, aiļeTOH), θμμαη, T.e. HanpMMep, Ν,Ν-ΑΜΜβτΜηφορΜβΜΜΑ, mam Ν,Ν-AMMeTMnaiļeTaMMA Μη μ ΓβκοθΜβτΜηφοοφορβΜΜΑ), προοτωβ 3φΜρω (τ.β. HanpMMep, ΑΜκπΜΗβοκΜβ mam npocTbie 3φΜρω, TaKMe κθκ HanpMMep, τeτparMAPoφypaH Mnn AMOKcaH, μ aiļMKAVMecKMe npocTbie 3φΜρω, TaKMe KaK 23 23 LV 10781 ΑΜΜβΤ0Κ0Μ3Τ3Η M/1M flM3TmiOBblM npOCTOM 3φΜρ), HMTpMAbl (ΗΘΠρΜΜβρ, aLļeTOHMTpun), ymeBOflopoflbi τθκμθ κθκ HanpMMep, ranoreHMpoeaHHbie yrneBOflopoAbi (HanpMMep, ΜβΤΜηβΗχπορηΑ), m cno>KHbie 3φΜρω, TaKMe κβκ HanpMMep, 3Tnnaiļ6TaT, a τθιοκθ CMecM, οοστοηίΑΜβ M3 flByx μπμ HecKonbKMX τ3κμχ pacTBopmeneii.
PeaKiļMfl cminpoBaHMn μο>κθτ 6biTb ocymecTBjieHa nyTeM B3anMOfleiicTBM5ļ c ranMAOM cM/iujia (t. e. HanpMMep, χ/ιορμαομ), npeAnoHTMTenbHo b npMcyTCTBMM οοηοβθημμ, TaKoro, κβκ HanpMMep, ΤρΜ3ΤΜ/13ΜΜΗΜΜΜΑ330η3 M/1M ΠΜρΜΑΜΗ, C MCn0J1b30BaHMeM paCTBOpMTeilfl, TaKoro, KaK HanpMMep, ΑΜΜβτΜ/ιφορΜθΜΜΑ-
PeaKAMfl KapOaMOM/iMpoBaHMn, no3BonHK>uļan nonyMMTb coeAMHeHMe, xapaiaepM3yeMoe φopMynoM ( I ) β κοτοροΜ OR npeACTaenaeT co6om rpynny, xapaiaepM3yeMyK) φopMyJ^oM OCONR8R9, Μθ>κβτ 6biTb ocyiiļecTBJieHa nyieM Β33ΜΜ0ΑβΜ0ΤΒΜη c npMroAHbiM aLļMJiMpytouļMM (t. e. Kap6aMOM/inpyK)LLļMM) areHTOM. Πρμγοαηβιμμ Kap6aMOMnMpyiou4MMM areHTaMM, KOTopbie MoryT 6biTb Mcnonb3oeaHbi α*ιη nony»HeHMn οοθαμηθημμ, B KOTOpblX OAMH M3 R8 M R9, ΠρβΑΟΤΘΒΠηβΤ COSOM ΘΤΟΜ BO/ļOpOJļa, a APyrOM AB/ifieTcn C-ManKMnbHOM rpynnoM, ηΒΠίΐκίτοη M30LļMaHaTbi, xapaKTepM3y-eMbie φopMynoM R10NCO (γαθ R10, npeACTaenneT co6om Ci^anKnnbHyK) rpynny). PeaKiļMn Kap6aMOMnMpoeaHMH Aon>KHa, κβκ npeACTaBrmeTcn Lļenecoo6pa3HbiM, npoBOAMTbcn b npMcyTCTBMM pacTBopMTenn μπμ cviecu pacTBopMTeneti, Bbi6paHHbix M3 rpynnbi, BKnioMajomen b ce6n yrneeoAopOAbi (HanpMMep, apoMaTMMecKMe yrneBOAopoAbi, τθκμθ κθκ 6eH3on μπμ Tonyon), ranoreHMpoBaHHbie yrneBOAopoAbi (HanpMMep, τθκμθ κθκ ΑΜχηορΜβτθΗ), aMMAbl (TaKMe ΚΘΚ HanpMMep, φορΜΘΜΜΑ μπμ ΑΜΜβΤΜΠφΟρΜΘΜΜΑ), cno>KHbie 3φΜρω (HanpMMep, τθκμθ xax 3TMJiaLļeTaT), npocTbie 3φπρΒΐ (HanpMMep, TaKMe KaK LļMKJiMHecKMe npocTbie 3φΜρΜ, τ.β. TeTparMApc^ypaH μπμ AMOKcaH), κβτοΗω (TaKMe KaK HanpMMep, aijeTOH), cynbφoκcMAbι (τ.β. TaKMe KaK HanpMMep, ΑΜΜβτΜ/^ηΒφοκεΜΑ) μπμ cMecM stmx pacTBopMTeneii. 3Ta ρββκμΜη Μθ>κβτ 6biTb npoeeAeHa npn TeMnepaiypax b Anana30He ot -80°C ao TeMnepaTypbi tohkm κμπθημπ peaKLļMOHHOM CMecM, HanpMMep ao 100 °C, m npeAnoHTMTenbHo b Anana30He ot -2 ao +30 °C. 24
PeaKLļMM Kap6aM0MJinpoBaHMfl, μο>κθτ cnoco6cTBoeaTb npncyTCTBne ocHoeaHHfl, TaKoro, KaK HanpMMep, τρβτΜΗΗΟβ opraHunecKoe οοηοβθημθ, T.e. HanpMMep, TpM-/HM3UJMM 3ΠΚΜΠ/3ΜΜΗ, T. θ. Η3ΠρΜΜβρ, TpM3TMJ13MMH. flpyrnM npnroflHbiM Kap6aMOiiJiMpyK)i^HM θγθητομ nenneTca iļnaHOBan Kucnoia, Koropan oābiMHo μο>κθτ 6biTb npoM3Be,qeHa no MecTy, HanpMMep M3 LļMaHaia menoHHoro MeTanna, τθκογο KaK HanpMMep 4M3H3t Η3τρΜΛ, μ 3tom peaKiļMM cnoco6cTByeT npMcyTCTBMe KMcnoTbi τβκοϋ, KaK HanpMMep CM/ibHaa opraHMMecKan KMcnoia, TaKan KaK TpM0TopyKcycHan KMcnoTa. LļMaHOBaa κμοποτθ 3φφβκτΜΒΗ0 cooTBeTCTByeT οοθαμηθημημ Μ30ΐ1Μ3Η3Τ3, yKa3aHHbiM BbiLue, b KOTopbix R10, npeACTaB/iaeT co6om BOflopofl μ τθμ caMbiM cnoco6cTByeT npeBpatiļeHMto οοθαμηθημμ, xapaKrepM3yeMbix φopMynoM ( II ), HenocpeACTBeHHo b mx Kap6aMOM/iOKCM-aHanorM (T.e. οοθαμηθημα, xapaKTepM3yeMbie φopMynoM ( I ), b κοτοροίί OR3 npeACTaBfiiieT co6om rpynny, OCONH2).
AnbTepHaTMBHo Kap6aMOMJiMpoeaHMe Μ0>κβτ 6biTb ocymecTBJieHO nyTeM peaKLļMM c Φοογθηομ mjim Kap6aM0HMjiAMMMMAa30/i0M c nocneAyKDLiļeM peaKLļMeM c θμμμβκομ μπμ πρμγοαηβιμ 3aMeuļeHHbiM 3MMH0M, ΠρΜ ΗβΟδΧΟΑΗΜΟΟΤΜ Β ΒΟΑΗΟΜ ΜΠΜ 6β3ΒΟΑΗΟΜ peaKLļMOHHOM ΟρβΑβ. 06pa30BaHne οοθαμηθημμ, xapaiaepM3yeMbix φopMynoM ( I ), β KOTopbix OR3 πρβΑΟτβΒηηβτ co6om rpynny xapaKTepM3yeMyio φopMyJ^oM 0C0(CH2)nC02R7 Μθ>κβτ 6biTb οδβοπβΗβΗΟ nyTeM θαμ/ιμροβθημη cooTBeTCTBytomero 5-OKCMCoeAHHeHMH c noMoiLļbto KMcnoTbi, xapaiaepM3yeMOM φopMy/lOM H02C(CH2)nC02R7 mjim eē peaKAMOHHO-Cnoeo6HblM npOM3BOAHblM, B COOTBeTCTBMM C npOlļeAypOM aiļMflMpOBaHMH, yKa3aHHOii Bbiiue. B COOTBeTCTBMM C APyrMM aCneKTOM HaCTOHLLļerO Μ3θδρβΤβΗΜΗ 3a«BMTenb npeAnaraeT eunē oamh cnoco6 ( C ) απη nonyMeHM« οοθαμηθημμ, xapaiaepM3yeMbix φopMyπoM I, β κοτοροΜ R npeACTaermeT co6om aTOM BOAopoAa, m OR3 πρβΑΟτβΒΠΑβτ co6oii 3aMeiiļeHHyK) rMAPOKCMnbHyro rpynny, m ^τepMφM^Mpyιoι^MM areHTOM R Υ (γαθ R πρβΑΟτββ/ΐΒβτ co6oii Ci.8anKMJibHy»o rpynny, mjim C3.8ajiKeHM/ibHyK> rpynny, μ Y ecTb KaK 6bino yKa3aHO Bbiiue); πρΜ ηθο6χοαμμοοτμ ocyiAecTBJineTcn cHHTMe 3auļMTbi α*ιη 25 LV 10781 οοθαμηθημη, xapaKTepM3yeMoro cpopMynoii I, b κοτοροΜ OR3 πρβΑΟΤβΒπηβτ cočon 3aLLļmneHHyK) rnflpoKcmibHyKD rpynny n Aanee, npn Heo6xoAHMocTM, npon3BOAHTcn o6pa30BaHne conn.
PeaKLļMH 3ΤΘρΜφΜΚ311ΜΜ ΜΟ>ΚΘΤ 6blTb ΠρΟΒΘΑΘΗΘ, HanpnMep, nyTeM o5pa3oeaHMfl anKoronma Mamna c Mcnonb3oeaHMeM peatauBa rpnHbapa, TaKoro xax rannA MeTnnMamnn, T.e. HanpnMep, noA^Aa MeTnnMarHna, c nocneAyK)iiļeii o6pa6oTKon peareHTOM R2Y. AnbTepHaTHBHO 3Ta peaKLļnn Μθ>κβτ 6biTb προΒΘΑβΗθ, b npncyTCTBnn conn cepe6pa, τβκοη, κβκ HanpnMep, okucb cepeāpa, nepxnopaT cepe5pa nnn cannijnnaT cepeāpa nnn nx cMecen, nnn b npncyTCTBnn ocHoeaHMjļ, τθκογο xax HanpnMep, KapSoHaT Kanna nnn rnApnA HaTpna. Ρββκμηη Βτβρηφηκβμηη μο>κθτ 6biTb npoeeAeHa, b opraHHaecKOM pacTeopnTene, b t3kom Kax HanpnMep, προοτοή 3φηρ, T.e. AM3TnroBbin npocron 3φηρ, τeτparnAPoφypaH nnn AnoKcaH nnn b aMnAe, τθκομ κθκ HanpnMep ΑΜΜβτηηφορΜβΜηΑ nnn ΓβκοθΜβτηηφοοφορΗωή TpnaMnA nnn CMecn Taxnx pacTBopnTenen npn TeMnepaiype OKpy>Ka(omen cpeAbi. Πρη τβκηχ ynoenax κοΗφηΓγρβμηη OKcnMMHorpynnbi npaiannecKn ocTaeTca Ηβη3ΜΘΗΗθή nocne npoeeAeHna peaKLļnn ΒτβρηφηκθΑΗη. B οοοτΒβτοτΒηη c APyrnM acneicTOM HacToamero Η3θδρβτβΗΗΗ 3aaenTenb npeA-naraeT eiiļe oahh cnoco6 (D) A^a nonyHeHna coeAMHeHnn, xapaiaepn3yeMbix φορΜ^ποη 1, b κοτοροΜ OR3 npeACTaenaeT co6on rnApoKcnnbHyK> rpynny, n KOTopbiii 3ai<niOMaeTcn b BoccTaHOBneHnn coeAnHeHna, xapaKTepn3yeMoro φopMynoH (III) NOR2
(III) 26 c nocneflytoiiļMM o6pa30BaHneM, b cnynae ηθο6χοαμμοοτμ, coneii.
PeaKiļMfļ BOccTaHOBJieHiin μοϊκθτ 6biTb ocymecTBneHa c noMoiiļbK) BoccTaHaBnnBaK3LLļero areHTa, KOTopbiii ηβπαθτο?ι οποοο6ηβιμ κ οτβρβο-ceneKTMBHOMy βοοοτ3ηοβπθημκ) 5-κβτο rpynnbi. K npnroflHbiM βο<χτ3Η3Β.πμ-eaioinMM aremaM OTHocmcfl 6opornflpnflbi, TaKne KaK āopornflpnflbi uļenoHHbix MeTannoe (HanpMMep, 6opornflpnfl Hapnn) m πμτμμ amoKCM-ajlKDMMHMM rMflpMAbl, ΤβΚΜβ xax nMTMM TpM6yTOKCMa/lK)MMHMMrMAPMA·
PeaKiļMH Mcnonb3yiomafl 6opornApnflHbiiī βοοοτθηθβπμβθιοιαμμ areHT, ΜΜββΤ M8CT0 B npMCyTCTBMM paCTBOpMTe/lfl, ΤΘΚΟΓΟ KaK ΘΠΚβΗΟΠ, T. β. HanpMMep, Μ30-ΠρθΠΜηθΒΗΜ ΟΠΜρΤ Μ/1Μ M30-6yTMn0BblM ΟΠΜρΤ, OāblMHO npM TeMnepaiype b Awana30He ot - 30 ao + 40 °C, t. e. HanpMMep, 0°C.
PeaKiļMn, BKntoMatoujafl ncnonbsoeaHue jihthm ajiKOKCMamoMMHMM-rMAPHAa, μμθθτ MecTO b npMcyTCTBMM pacTBopMTenn, TaKoro KaK HanpMMep προοτοΜ 3φΜρ, τ. e. HanpMMep, TeTparMApoc{)ypaH μπμ AnOKcaH, μ μο>κθτ 6biTb npoeeAeHa npn TeMnepaTypax b Anana30He ot - 78 ao 0 °C. ripoMe>KyTOHHbie οοθαμηθημα, xapaKTepM3yeMbie <t>opMyjioii (III), MoryT 6biTb no/iyHeHbi M3 5,23-AMKeTOHa, xapaKTepM3yeMoro 0opMynoii (IV) o
nyTeM o6pa6oTKM oahmm 3KBMBaneHTHbiM κοπμηθοτβομ peareHTa H2NOR2 (γαθ R ecTb κβκ 6bino yKa3aHo paHee) c Mcnonb30BaHMeM ycnoBMM peaKiļMM OKCMMMpoBaHMfl, yKa3aHHbix paHee α-π* nonyMeHnn οοθαμηθημμ, xapaKTepM3yeMbix φopMynoM I.
CoeAMHeHMfl, xapaKTepM3yeMbie φopMyJ^OM (I ), MoryT 6biTb nonyneHbi nyieM οκΜοηβΗΜΗ οοθαμηθημη, xapaicrepM3yeMoro φopMynoM (V) 27 27 LV 10781
OH
3Ta peaKiļMH Μθ>κβτ 5biTb ocyu4ecTB/ieHa c noMOUļbio oKMcnnioinero areHTa, npeAHa3HaneHHoro fl/in npeBpauļeHMfl btopmhhom γμαροκομπβηομ rpynnbi, b pe3ynbTaie nero προμ3βοαμτοη οοθαμηθημθ, xapaicrepM3yeMoe 4)opMynoM (VI). K npurOflHblM OKMCJIflKJlAMM ΘΓβΗΤΘΜ OTHOCHTCH XHHOHbl B npk1CyTCTBMM BOflbl, Τ.β. HanpMMep, 2,3-AMXJlOpO-6,6-AMl4MaHO-14- 6θη3οχμηοη mjim 2,3,5,6-TeTpaxnopo-1,4-6eHX0XMH0H, OKMCJi«K)mne arembi, co,qep>KaLLļMe xpoM / 6-tm Ba/ieHTHbiii /, t. e. Tāme κθκ flnxpoMaT ηθτρμη mjim nMpMflMHHa MJIM TpeXOKMCb ΧρΟΜΘ B nupMflMHe, npeflnOHTme/lbHO B npncyTCTBMM KaTann3aTopa nepeHoca φθ3Η; okmcjihioiamm areHT, coflep>KaLiļMii 4-x BaneHTHbiM MapraHeiļ, t. e. HanpMMep, flByoKMCb MapraHiļa b flnx/iopMeTaHe; N-ranocyKiļMHMMMfl, t. e. HanpMMep, N-x/iopocyKLļMHMMMA mjim N-6poMocyKiļMHMMMfl; αμ8κομ]^πβΦοκομα, t. e. HanpMMep, AMMeTM/icyjib4>OKCMfl, b npncyTCTBnn aKTMBMpyiOLLļero areHTa, τθκογο xax HanpMMep, N,N,-Amļm<noreKcmiKap6oAMMMMfl utīm aijMJi ra/iMAa τθκογο κθκ HanpMMep, OKcaiinnxjiopnA, hjim κομππθκο, coAepjKamMM πμρμαμη m TpexoKMCb cepbi.
PeaKLļMH ΜΟ>ΚΘΤ 6blTb ΠρΟΒΘΑβΗΘ θφφβΚΤΜΒΗΟ B ΠρΜΓΟΑΗΟΜ pacTBopMTene, κοτορωίί μοκθτ 6biTb BbiāpaH M3 rpynnbi, βκπιοη3Κ)ιαθμ b ce6n κθτοη, τθκοίί κβκ HanpMMep, βμβτοΗ; προοτοίί 3φΜρ, τθκομ κθκ HanpMMep, AH3TMJiOBbiM προοτοίί 3φΜρ, αμοκοθη Μ/ΊΜ τeτpaΓMApoφypaH; 28 yrneBOAopoA, τθκομ κθκ HanpMMep, reKcaH; ranoreHMpoBaHHbiii yr/ieBOflopofl, τβκοίί KaK HanpMMep, χηοροφορΜ μπμ μθτμπθηχπορμα; μπμ cjiOMHbm 3φΜρ, T3K0M κβκ HanpMMep, 3MnaLļeTaT mjim 3aMeuļeHHbiM aMM/ļ, HanpMMep, /1ΜΜβτΜϋφορΜ3ΜΜΑ. Κομ6μη31(μμ t3kmx pacTBopMTeneii jim6o b hmctom BMAe, /im6o c boaom TaiOKe MOiyr 6biTb Mcno/ib30BaHbi. Bbi6op pacTBopMTenji 6yAeT 3aBMceTb ot TMna OKMcnHtoLiļero areHTa,
Mcnonb3yeMoro b peaKLļMM KOHBepcMM. 3τθ peaKiļMn Μθ>κβτ 6biTb προθθΑβΗθ npM TeMnepaiypax b AMana30He ot - 80 °C ao + 50 °C.
CoeAMHeHM«, xapaicrepM3yeMbie φopMyπoM (V), MoryT 6biTb nonyHeHbi, HanpMMep, nyTeM BbipauļMBaHMn Streptomyces Hermoarchaensis Na CIB 12015 (3ano>KeHHoro 10 οβΗτηδρη 1984 roAa β Ποοτοηηηβιμ Φοηα KynbTyp HaiļMOHanbHoro Φοηαθ npoMbnuneHHbix μ μοροκμχ δβκτβρΜίί, MCcneAOBaTenbCKan CTaHiļMn ToppM, A6epAMH, CoeAMHeHHoe KoponeBCTBo) μγμ ero MyTaHTa c M3onMpoeaHMeM οοθαμηθημη ot nonyneHHoro τθκμμ o6pa30M φβρΜβΗΤ3ΐ4Μ0ΗΗ0Γ0 0ynbOHa.
OpraHM3M Streptomyces Hermoarchaensis μο>κθτ 6biTb BbipaiiļeH c nOMOLLļblO 06bl4HblX ΜβΤΟΑΟΒ, T. β. B npMCyTCTBMM cnoco6Hbix K accMMMiīnLļMM mctomhmkob ymepofla, a30Ta m MMHepanbHbix coneM. Cnoco6Hbie κ accMMMnniļMM mctomhmkm yrnepoAa, a30Ta m MMHepanoB MoryT 6biTb npeACTaB/ieHbi β βμαθ jim6o npocTbix, γμ6ο β βμαθ κομπ/ιθκοηνχ nMTaTenbHbix BemecTB, κβκ HanpMMep, οπμοθηο β Π3τθητηομ οπμοθημμ BenMKoāpMTaHMM Na 2166436. Πρμγοαηθη cpeAa, coAep>KauļaH yKa3aHHbie BeuļecTBa, onMcaHa β ΠρΜΓΟτοβηβΗΜΜ Na 1, npeACTaB/ieHHOM Aanee.
BbipamHBaHMe opraHM3Ma Streptomyces Hermoarchaensis b oāiiļeM cnyMae Aon>KHO ocyiAecTBnnTbcn npM TeMnepaType b Anana30He ot 20 ao 50 °C μ πρβΑποΜΤΜΤβΠΒΗΟ b Anana30He ot 25 ao 40 °C m npM stom npeACTaBnneTcn ΗβοδχοΑΜΜΗΜ, 4To6bi ocyuļecTBrmnacb aapaiļMH m nepeMeujMBaHMe, HanpMMep, nyreM βοτρηχμβθημη \λπ\λ pa3MeiuMBaHMH. CpeAa μοϊκθτ 6biTb nepBOHananbHO noABepmyTa MHOKynMpoBaHMto c noMOiiļbK) He6onbiuoro KonMnecTBa cnopynMpoBaHHOM cycneH3MM MMKpoopraHM3MOB, ho c τβΜ, 4To6bi M36e>KaTb 33Aep>KKy β ροοτβ, BereTaTMBHbiii MHOKyn«T opraHM3Ma Μ0>κβτ 6biTb npMroToeneH nyTeM 29 29 LV 10781 HHOKynnpoBaHn« He6onbujoro KonnnecTBa KynbTypHoii cpeflbi co cnopoBon φορΜοίί opraHM3Ma, m eereiaTMBHbiM nHOKynaT, nonyHeHHbin τθκμμ o6pa30M, Μ0)κβτ 6biTb nepeeefleH b φβρΜβΗΤΗνιο cpefly κηκ, mto 6onee npeflnoHTMTenbHO, Ha 0flHy nnn HecKO/ibKO CTafluii noceea, Ha κοτορωχ AanbHeūujnn ροοτ μμθθτ μθοτο nepe/ļ nepeHOCOM b ocHOBHy»o φβρΜβΗτβι^ΜΟΗΐ^ιο cpefly. OepMeHTaLļna b οθιμβΜ cnyHae Aon>KHa npoBOflMTbCH npn eennwnHax BOAopoflHoro noKa3aienn b flnana30He ot 2,5 AO 8,5 θα. pH.
OepMeHTaiļMfl μοϊκθτ npoeoAMTbcn b TeseHne nepnoAa βρθμθημ ot 2 AO 10 ΑΗβίί, HanpuMep, 5 αηθμ. Οοθαμηθημα, xapaicrepn3yeMbie φορ&ψηοή (V), MoryT 6biTb οταθπθηβι ot nonyMeHHoro τθκμμ o6pa30M ecero, φβρΜβΗτβΜΜΟΗΗΟΓο 6ynbOHa nyTeM o6biHHbix μθτοαοβ οταθπθημλ n pa3AeneHna. npn stom MoryT 6biTb ncnonb30BaHbi caMbie pa3Hoo6pa3Hbie μθτοα^ι φρθΚψ^ΟΗΜρΟΒβΗΜΑ, ΤΘΚΜΘ ΚΘΚ ΗΘΓφΜΜθρ, aACOp6lļMfl-3nK)MpOBaHMe, oca>KAeHMe, φρθκι^ηοΗΗθη KpncTannn3aLļnn η θκοτρβκμηη pacTBopnTena, KOTOpbie MOryT KOMāUHMpoeaTbCa pa3nMHHblMM nyTflMM. 3KCTpaKl4Hfl pacTBopMTeneM η χροΜβτοφθφηη, κβκ 6bmo ycTaHOBneHo, nenatoTca Han6onee npnroAHbiM cnocoSoM οτΑβηβΗηη n pa3AeneHna coeAMHeHnn. npnroAHbin μθτοα ποίψΜθΗΜΑ coeAnHeHnn, xapaiaepn3yeMbix φopMyπoiί (V), HCnOJ1b3ytOLLļMŪ 3TM ΠρομβΑΥΡΗ, yKa3aH B ΠρΜΓΟΤΟΒ/ΙΘΗΜΜ Na 1, onncbieaeMOM Aanee. B οοοτΒΘτοτΒΜΜ c eoļe oahmm acneKTOM HacToamero η3θ6ρβτθΗηη 3aaBnTenn npeAnarafOT cnocoā (E) AJifl nonyMeHna οοθαμηθημμ, xapa«Tepn3yeMbix φορι^ηοή ( I ), b κοτορωχ OR3 npeACTaejiaeT co6on rnAPOKcmibHyK) rpynny, n KOTopbiii 3aicniOMaeTCfl b tom, mto ocyu4ecTBnaeTca CHflTMe 3amnTbi y cooTBeTCTByfOLLļero coeAMHeHMii, xapaiaepM3yeMoro φορι^ηοή ( I ), b κοτοροΜ OR3 npeACTaBJiiieT co6on 3au|MLi)eHHyto rnAPOKcmibHyK) rpynny, κβκ 6bino onncaHO Bbiiue.
TaK HanpMMep, aiļnnbHaa rpynna, Taran xax aiļeTnn-rpynna Μ0>κβτ 6biTb yAaneHa nyTeiu οοηοβηογο rnAponn3a, T.e. HanpMMep, c ncnonb30BaHneM rkiApooKMCM HaTpua nnn Kanna b boahom pacTBope cnnpTa; nnn c noMombio κμοποτηογο rnAPonn3a, HanpnMep, c ncnonb30BaHneM 30 KOHLļ6HTpi4pOB3HHOM cepHoii KucnoTbi b μθτθηοπθ. ALļeTanbHbie rpynnbi, TaKne KaK TeTparMAPonMpaHMn, MoryT 6biTb y/ļaneHbi, HanpMMep, nyTeM ncnonb30BaHnn κμοιοτηογο rnflponn3a, t. e. c ncnonb30BaHneM KMcnoTbi, τθκομ, KaK HanpMMep, yKcycHan μπμ τpMφτopyκcycHan KMcnoTa, mjim pa36aBJieHHOM MMHepanbHoii KMcnoTbi. CM/iMJībHbie rpynnbi MoryT 6biTb yflaneHbi c Mcnonb30BaHneM mohob φτορΜ/ļa (HanpMMep, M3 ΤβΤρ33ΠΚΜ/13Μ0ΗΜΜφΤ0ρΜ/13, ΤΘΚΟΓΟ, KaK ΤβΤρθ-ΗΟρΜ-δ^ΓΓΜΠβΜΟΗΜΜφΤΟρΜΑ), φτορΜβθ BOflopofla b BOflHOM βμβτοΗΜτρΜηβ ΜΠΜ κΜαιοτβ, τ3κομ KaK napa-To;iyon cynbφoκMCnoτa (HanpMMep, b MeTaHone). ApM/iMeTM/ibHbie rpynnbi MoryT 6biTb yflaneHbi nyTeM οδρβδοτκΜ kmchotom JlbiOMca, (HanpMMep, τρΜφτορΜΑ δορβ/θφπρβτ) b npMcyTCTBMM TMona (TaKoro KaK HanpMMep, OTaHTMon) b πρμγοαηομ pacTBopMTene, τθκομ κβκ αμχπορμθτθη, ηρπ κομη3τηομ TeMnepaType.
ConM KMcnoT, xapaiaepM3yeMbie φopMyπoM ( I ), MoryT 6biTb nonyHeHbi c noMoiAbio o6biHHbix μθτοαοβ, HanpMMep, nyTeM οδρβδοτκΜ KMcnoTbi ocHOBaHMeM μπμ nyTeM npeepaiiļeHMn oahom cojim b APyry»o 3a cneT MOHOo6MeHa.
HacTOflLiļee Μ3θδρβτβΗΜβ Aanee MnniocTpMpyeTcn, ho He orpaHMMMeaeTcn yKa3biBaeMbiMM Aanee ΠρΜΓοτοΒηβΗΜΗΜΜ m flpMMepaMM, b kotopwx TeMnepaTypbi yKa3aHbi b °C, “L" 03HaMaeT πμτρ m EtOH- 03Ha4aeT 3TaHon. B npMBOAMMblX ΑβΠββ ΓΙρΜΙΌΤΟΒΑβΗΜΗΧ Μ ΠρΜΜθρθΧ ΟΟβΑΜΗβΗΜΗ nOMMeHOB3Hbl KaK npOM3BOAHbie M3BeCTHblX φθΚΤΟρΟΒ, φθΚΤΟρΟΒ A, B, C Μ D. Φβκτορ A npeACTaenaeT co6om coeAMHeHMe, xapaKTepM3yeMoe φopMynoM ( VI ), b κοτοροΜ R1 npeACTaenneT co6om μθτμπ m R3 npeACTaBnneT co6oii boaopoa; μ φθκτορ D πρβΑοτβΒηηβτ co6om coeAMHeHMe, xapaiorepM3yeMoe φopMynoM ( VI ), b κοτοροΜ R1 npeACTaenfleT co6om θτμπ m R3 πρβΑΟΤθΒΠΗβτ co6oii boaopoa; 31 LV 10781 OH H3C-
(VI)
Πρμγοτοβ/ιθημθ 1-5-κθτο OaKTOPa A
Cnopbi Streptomyces thermoarchaensis NCIB 12015 6bmn HHOKynnpoBaHbi Ha CKOiueHHbiii orap, M3roTOB/ieHHbiii H3 cne,qyiOLUMX κομποηθητοβ: Γ/Γ1 Αροχοκθβομ SKCTpaKT (Oxoid L 21) 0.5 Co/iOAOBbiA 3KCTpaKT (Oxoid L 39) 30 MMKOJiorMsecKMM πβπτοΗ (Oxoid L 40) 5 Arap Ns 3 (Oxoid L 13) 15 flncTMnnpoBaHHan BOfla o6teMOM flo 1 Jimpa, BOflopoflHbm noKa3aie/ib paeeH 5,4 θα pH m noABeprarmcb MHOKynnpoBaHmo npn TeMnepaType 28 °C B ΤΘΗΘΗΜΘ 10 flHefi.
Co3peBiuan «ynbTypa Ha ckolu6hhom arape flanee noKpbiBa/iacb 6 μπ 10 % pacTBopa rrmiļepMHOBoro pacTBopa m 3aieM 3aHnmanocb CTeprnibHbiM MHCTpyMeHTOM C ΤΘΜ, MT06bl pa3pblXJlMTb Cnopbl H ΜΜμΘΠΜΜ. AjlMKBOTHbie Aonn, o6"beMOM 0,4 μπ, nonyHeHHoū cycneH3MM cnop nepeHocnnncb b 32 CTepMJībHbie nonunponuneHOBbie προδκρκΜ, KOTopbie 3θτβΜ 3anapnBanncb (3ananBajnncb) m xpaHnnncb b βτΜοοφβρβ napoB jkmakoio a30Ta ao τθχ nop, noKa ηθ B03HMKana Heo6xoflMMOCTb b mx Mcnojib30BaHMM. flee KOn6bi SpneHMeiiepa eMKocTbio 250 mji, coflepjKaoļue 50 m/i. 3aceHHHoii cpeflbi, 6bmn npuroTOBneHbi cne,qyK)iiļMM o6pa30M: Γλ'1 fl-riiK)K03a 15,0 mnuepMH 15 ΠβΠΤΟΗ COM 15 XJ10PMfl H3TPMH 3,0 yrneKMcnbiM KajībUMM 1.0 AMCTMji/iMpOBaHHaa BOfla ΛΟ 1 ji (BenuMMHa BOflopoflHoro noKa3aTejia cpeflbi nepBOHaManbHO 6bma paBHa 6,7 efl. pH, KOTopaa 3areM flOBOAnnacb ao 7,0 eA. pH c noMoiAbto βοαηογο pacTBopa γμαροοκμομ HaTpua nepeA o6pa6oTKoti b aBTOKJiaee. BenumiHa BOAopoAHoro noKa3aienn cpeAbt nocne o6pa6oTKM b aBTOKJiaee 6bina paBHa 7,3 eA- pH.). Ka)KAan H3 κοπ6 noABepranacb MHOKynnpOBaHnio c noMombio 0,2 mji. cycneH3HM cnop, B3STOM H3 προβΜροκ. flanee Kon6bi noAsepranMCb MHKy6ai4MM npw TeMnepaiype 28 °C b τβΜΘΗΜβ 3-χ αηθη b uuetiKepe, epaina»omeMCH co CKopocTbK) 250 o6/mmh ( c AMβΜβτροΜ opSHTanbHoro epameHMfl, paBHbiM 50 mm ).
CoAep>KaHMe o6enx koji6 6bmo Mcnonb3oeaHO A^a MHOKynMpoBaHMH φβρΜβΗΤ311ΜΟΗΗθΛ ΘΜΚΟΟΤΜ ( θ6ΐ>έΜΟΜ 70 A ), ΟΟΑβρΧΟίμβίί 40 JIMTpOB TOM >κθ caMoti cpeAbi, c AoSaBiieHMeM ποιίΜπροπΜΠΘΗβ 2000 (0,06% OS’bēMa/OČ'bēMHblM). ΓΙΟΠΜΠρΟΠΜΠΘΗ 2000 6blJ! ΑΟδθΒΠβΗ, KaK 3TO ηθοΘχοα^μο πρΜ προββΑβΗΜΜ npoLļecca φβρΜβΗΤθμΜΜ α^η κοπτροπΗ neHoo6pa3oeaHMH. npopecc φβρΜβΗτβψΊΜ npoBOAMncn npM TeMnepaType 28 °C npn nepeMeujMBaHMM m aapaijMM, ΑοοτβτοΗΗωχ α^>* τογο, mto6w o6ecneMMTb noAAep>KaHMe ypoBH« pacTBopeHHoro KMcnopOAa Bbiuie, ηθμ 30 % HacbimeHMn. CnycTH 24 Mača φβρΜβΗΤθμΜΜ nopiļMM 6ynbOHa eMKOCTbto 9 ΠΜτροΒ 6bina 3arpyx<eHa b φβρΜβΗτβρ ο6τ>θμομ 700 πμτροβ, coAepjKauļMM 450 πμτροβ cpeAbi, πογ^μθηηομ cneAy»oaļMM o6pa30M: 33 33 LV 10781 Γη'1 fl-l71K)K03a 2,8 ConoAOBbiM AeKCTpMH(Mfl30E) 27,8 ApKacoM-50 (Avka Oy 50) 13,9 Me/iacca (MepHan naTOKa) 1,7 K2HP04 1.0 CaC03 1,39 Cmjimkoh-525 (Dow Carning) 0,06% θ6ΐ>έΜΗΙ»ΙΧ/θ6τ>βΜΗΜΜ riepefl CTepmiM3aiļnefi eenMHMHa BOflopoflHoro noKa3aTe/wi flOBOflunacb flo 6.5 βΑ· pH. npoAecc φβρΜΘΗΤθμΜΜ npoBOAMJicfl ripu TeMnepaType 28 °C ripu nepeMeiiiMBaHMM n aapaiļMM. npoTMBOBcneHMBatomnM npenapaT-ΠΟΑΜΠρΟΠΜΠΘΗ 2000 A06aBnflJlCfl B COOTBeTCTBMM C Tpe60BaHHflMM, M BenuMMHa βοαοροαηογο noKa3aTena CHM>Ka/iacb ρ,ο 7.2 βΑ· pH nyieM Ao6aBneHnn pacTBopa cepHoii KucnoTbi ao τβχ nop, nona He nponcxoAnno co3peBaHne KynbTypbi. ΦβρΜβΗΤθμΜΡΐ c co3peBaHneM KynbTypbi npon3oujjia Mepe3 5 ΑΗβίί.
BynbOH, b KOJiMMecTBe 450 n, 6bm noABepmyT οοβθτπθημκ) b μθΗτρΜφγΓθ Tuna “ΒβοτφβΠΜΗ KA25” n ociaTOMHbiii, o6pa3y»oiAniicn CBepxy b pe3ynbTaTe oicramanm, Maiepna/i 3aMeHRnca βοαομ, b οδ-beMe 20 AMTpOB. H3BJieweHHblii KTieTOMHblii MaTepna/1, B ΚΟΠΜΗβΟΤΒβ 25.5 Γ, noABepranca nepeMeujtiBaHmo b τβΗβΗΜβ 1 Mača b CMecme/ie Tuna “CmībBepcoH, ΜθΑβ/ib BX” c Mcnonb3oeaHneM αο^τθτομηογο KonuMecTBa 3TaHona c πο/ψΜβΗΜβΜ b pe3yxibTaTe MaTepnan očiumm ο6τ»θμομ 75 ηΜτροΒ. noAyMeHHa« cycneH3na noABepranacb φκπΒτρβΑΜΜ, μ τββρΑωΜ ocTaTOK noBTopHO 3KCTparnpoea^cfl μθτθηοπομ, b KOJiMMecTBe 35 ηΜτροΒ, m φΜΑΒΤρΟΒβ/ΙΟΛ. 06l>eAMHeHHblM φΜ/lbTpaT, B ΚΟΠΜΜβΟΤΒβ 87 ΠΜΤρΟΒ, pa36aBJifl;icfl βοαομ b κοπμμθοτβθ 40 /i, v\ 3KCTparnpoBancfl Aanee neiponeiiHbiM 3φΜροΜ, b κοπμμθοτβθ 30 ϋΜτροβ, MMeiOLLļMM TeMnepaTypy 60-80 °C. CnycTn 30 MMHyT φθ3Βΐ pa3Aermnncb Ha ^eHτp^ιφyΓe Tuna "ΒβοτφβπΜΜ MEMI256” m hvdkhhh MeTanonbHan dpa3a noABepranacb noBTopHOMy 3KCTparnpoBaHMK) πβτροπβίίΗωΜ 3φιιροΜ, b κοπμμθοτβθ 30 jimpoB, ΜΜβΚ)ΐΐ1ΜΜ TeMnepaTypy 60-80 °C, nocne Ao6aB/ieHM« BOAbi b 34 ΚΟΠΜΗΘΟΤΒΘ 40 ΠΜΤρΟΒ. ΠΟΟΠΘ ρβ3ΑβΠΘΗΜΠ ΗΜ)ΚΗΠΠ φ83θ ΠΟΒΤΟρΗΟ noABepranacb 3KCTpampoBaHM»o neTponeiiHbiM 3φΜροΜ, b κοπμηθοτβθ 30 χίΜτροΒ, μμθκ)ι±|μμ TeMnepaiypy 60-80 °C. 06beAMHeHHbie φθ3Ν πβτροηβΜΗΟΓΟ ΘφΜρβ, oātēMOM 85 πητροβ, noABepranMCb KOHAeHTpupoBaHMK) πγτβΜ TpexKpaTHoro nponycKaHMfl nepe3 BbinapMeaTenb ππθηοηηογο TMna φιιρΜΗ ur^ayAep 8.8-12-27" (AaeneHMe napoe 0,1 6apa, TeMnepaTypa napoe 20 °C, TeMnepaTypa napa 127 °C). ΚοΗμβΗτρβτ, b ο6τ>θμθ 9 ΠΜτροβ, noABepranca cyiiiKe c Mcnonb3oeaHMeM cynbφaτa HaTpufl, b κοπμηθοτβθ 2 κγ, m Aanee noABeprancn κοηαθητρμροβθημιο npM ποημ>κθηηομ αββπθημμ npM TeMnepaType 40 °C c noMOLLļbio Bpauļa»omeroc5i ππθηοηηογο BbinapMBaTenn.
Macnoo6pa3HbiM οοτθτοκ, β κοπμηθοτβθ 130 r, noABeprancn pacTBopeHMio β χποροφορΜβ c nonyHeHneM MaTepuana β ο6τ>θμθ 190 mn, κοτορωίί 33τθμ nponycKancn nepe3 KonoHKy TMna “MepcK-7734”, 3anonHeHHy>o AByOKMCblO κρθμημη-60 (200 x 4 cm), pa3MeuļeHHOM b χποροφορΜβ. KonoHKa noABepranacb npoMbieaHMio χποροφορΜΟΜ (500 μπ) m Aanee npoM3BOAnnocb 3πιομροβ3ημθ CMecbto, οοοτοπιαθμ M3 χποροφορΜβ μ 3TMnaL|eTaTa ( 3:1 ) μ φρβκμΜΜ c npuMepHbiM ο6ι»θμομ, paBHbiM 40 μπ, co6MpanMCb nocne OT6opa npeAujecTBy»oiiļero οδΤίθΜθ, paBHoro 1400 μπ.
OpaKLjMM Ns Na 32-46 noABepranMCb ομθιιιμβ3ημκ) m BbinapMeaHMio c nonyne.HMeM b pe3ynbTaTe Macna, β κοπμηθοτβθ 21,2 r. ΦρβκμΜΜ Na Na 47-93 noABepranMCb ομθιπθημκ) m BbinapMBanncb c nonyneHMeM b pe3ynbTaTe Macna, β κοπμηθοτβθ 20,1 r, κοτοροθ noABepranocb pacTBopeHMK) β ομθομ, οοοτοπιαθμ M3 χποροφορΜβ μ STMnaiļeTaTa (β ΟΟΟΤΗΟΙΙΙΘΗΜΜ 3:1) ΑΟ o6-beMa, paBHoro 50 ΜΠ. 3τβ CMeCb 38ΤΘΜ BBOAMnaCb β KonoHKy TMna “Μθροκ - 7734", 3anonHeHHyK) AayoKMCb»o φθμημπ-60 (200 χ 4 cm), HaxoAnuļeMca β ομθομ, οοοτοπιαθμ M3 χποροφορΜβ μ 3TMnai4eTaTa β οοοτηοιπθημμ 3:1, μ φρβκμΜΜ c npMMepHbiM ο6τ»θμομ, paBHbiM 40 μπ, coSMpanMCb nocne npeAwecTByiomero οτβορβ φρβκμΜΜΜ β κοπμηθοτβθ 1400 μπ. ΦρβκμΜΜ Na Na 22-36 coeAMHnnMCb μ noABepranMCb BbinapMBaHMio c nonyneHMeM Macna, β κοπμηθοτβθ 3,1 r, κοτοροθ Aanee AoāaBnnnocb κ Macny, nonyHeHHOMy M3 φρβκι^ΜΜ Na Na 32 - 46 M3 nepeoii κοποηκμ. 06"beAHHeHHbie Macna noABepranMCb pacTBopeHMK) β κμπβιαθμ 35 35 LV 10781 ΜβτβΗΟΐιβ (4 mji) m 3aTeM AoSaB/iHJiMCb κ ropjmeMy nponaH-2-ony, B KormsecTBe 20 mji, m flanee noflBepranncb KpMCTa/iM3anMM.
MaTOHHbifi pacTBop nocne KpMCTani43a4MM noflBepranca BbinapMBaHMto c ποπγΗβΗΜβΜ b pe3ynbTaTe Mac/ia, κοτοροβ pacTBopanocb b paBHOM 06-bēvie μθτμπθηχπορμαθ, m no/iyHeHHafl CMecb 3arpyx<a/iacb b KonoHKy ( 30 x 2,2 cm ) THfia "MepK Kn3enbrenb 60” (cmto Na 70 - 230 no ACTM, api\ Na 7734), coflepx<amyfo μθτμ/ιθηχτιορμα. C/iom npoMbieancn M6TnneHXJiopnflOM b KonMMecTBe, paBHOM #ByM 06-bēMaM cjioh h 3aTeM noflBepra/icn antoMposaHHio CMecb to, cocTOflineii M3 χ/ιοροφορΜβ m 3TnnaqeTaTa, b οοοτηοιιιθημμ 3:1, b κοπΜΗβοτΒβ, paBHOM fleyM oStēMaM cnon. BbinapMBaHMe amoaTa πο3βοπμτιο nonyHHTb Macno, κοτοροβ noflBepranocb pacTBopeHHto β μθτθηοπθ m 3aTeM noflsepranocb npenapaTHBHOMy >KMAKOCTHOMy χρΟΜβΤΟΓρθφΜρΟΒΘΗΜΙΟ C BbICOKOM pa3peujatomeM cnoco6HOCTbio Ha ycTaHOBKe “ΟφβρΜοορδ S5 ODS-2” (250 x 20 mm Phase Sep. Ltd ). Πορψικ o6pa3Lļa, o6tēMOM 5 mji nepeKaMHBariHCb HacocoM β κοηοΗκγ β τθηθημθ nepnoAa βρθμθημ, paBHoro 1 MHHyTe m coflep>KHMoe κοποηκμ noABepranocb anioMpoBaHMio cMecbio, C0CT0HLL(6M H3 aLļeOHHTpHJia 14 BOAbl, B COOTHOUjeHMH 7.3 npi4 CJieflyK)lAHX ycnoBnnx:
BpeMa Β MMHYTax nogana (mji/mmh) 0,00 0,00 BpeMfl BBOfla 1.00 0,00 1,10 30,00 39,90 30,00 40,00 35,00 75,00 35,00
MaTepi4a/i, κοτορωίί 6bm anioMpoBaH 143 kotiohkm npenapaTMBHoro >KI4flOCTHOfO Χρ0Μ3Τ0φ3φ3 C BbICOKOM pa3peilJaiOLAeM CnOCOOHOCTbK), noABeprancn MccneAOBaHMio μθτοαομ yJ^bτpaφnoJ^eτoBo^ί αιβισροοκοπΜΜ Πρΐ4 AJlHHe BOJIHbl, paBHOM 238 Η3ΗΟΜβΤρθΒ. B pe3y/ibTaTe BbinapMBaHMfl ο6έιΘΑΜη6ηηβιχ φρβκμΜΜ c πμκομ 3/iiOMpoBaHM«, MM6BUJMM μθοτο Ha 33,4 ΜΜΗγτβ, 6bi/io nojiyMeHo coeAMH6HM6, yKa3aHHoe β 3aronoBKe, β κοπμηθοτβθ 34 μγ, β βμαθ τβθραογο Marepmna. 36 E.l. Macc-cneiorpocKormii no3Bo/inna o6Hapy>KMTb MoneKynnpHbiM moh npn 610 m flana xapaKTepncTMMecKne ockohkm npH: 592, 574, 556, 422, 259 m 241. ΠΡΜΜΕΡ Na 1
23/Ε/-Μθτοκοημμμηο Φθκτορ A lai 5.23-ϋπκβτο Φθκτορ A
Oxiia)KAeHHbiū /ibflOM pacTBop, nonyHeHHbiM M3 KOHLļeHTpupoBaHHOū CepHOM KMCHOTbl B ΚΟΠΜΜΘΟΤΒΘ 1,2 ΜΠ ΑΜΧρΟΜΘΤΘ ΗβΤρΜΠ B ΚΟΠΜΜΘΟΤΒΘ 120 ΜΓ Β BOfle, Β ΚΟΠΜΜΘΟΤΒΘ 2 ΜΠ, fl06aB/lΠΠΜ Β ΤΘΜΘΗΜΘ 15 MMHyT Κ oxjia>KfleHHOMy nbflOM pacTBopy 5-κβτο Φβκτορ Α (β κοπμηθοτβθ 200 μγ) μ cynb0aiy κμοπογο TeTpa6yTmiaMOHMfl, β κοπμηθοτβθ 15 μγ, β STMnaijeTaTe, Β ΚΟΠΜΗΘΟΤΒΘ 4 ΜΠ, ΠρΜ ΜΗΤΘΗΟΜΒΗΟΜ ΠθρΘΜΘΙΠΜΒβΗΜΜ. CnyCTfl OflUH HaC, nonyMeHHan cMecb noABepranacb pa36aeneHMio STMnaiļeTaTOM m opraHimecKan 0a3a npoMbieanacb HacbimeHHbiM βοαημμ pacTBopoM 6nKap6oHaTa ηθτρμη. BbicyiueHHan opraHMHecKan φβ3β flanee Bbinapneanacb m nonyMeHHan CMona onMujanacb nyTeM χροΜθτοΓρβφΜροΒβΗΜΑ Ha “MepK Kn3enbrenb 60”, cmto Na 230-400, b κοπμηθοτβθ 100 μπ. B pe3y/ibTaie antoMposannn c noMou^bK) 10 % pacTBopa 3TnnaiļeTaTa β αμχπορμθτβηθ 6bmo nonyHeHo οοθαμηθημθ, yKa3aHHoe b 3aronoBKe β βμαθ πθπθβοκθπτομ neHbi, κοπμηθοτβθ 86 μγ; δ ( CDCL3) BKHKDHana 6,57 ( MyjibTnrmeT, 1H ), 2.50 ( ομηγπθτ, 2H ), m 1.89 (MynbTnrmeT, 3H).
/β/ 5-ΚΘΤΟ. 23 /E/-MeTOKCHMMMHO Φβκτορ A B ΟΟΟΤΒΘΤΟΤΒΜΜ C 3TMM ΠρΜΜβρΟΜ 5,23-ΑΜΚΘΤΟ ΦβΚΤΟρ Α Β ΚΟΠΜΗβΟΤΒΘ 475 ΜΓ, ΓΜΑΡΟΧΠΟρΜΑ ΜΘΤ0Κ0ΜΠ3ΜΜΗ3, Β ΚΟΠΜΜΘΟΤΒΘ 69 ΜΓ Μ 6e3BOAHbiM θμβτθτ ΗβτρΜΠ, β κοπμηθοτβθ 175 μγ, noABepranMCb pacTBOpeHMio β μθτθηοπθ. CnycTn 1,5 naca βηα6ρ>κμβ3ημπ πρκ κομηθτηομ TeMnepaType, pacTBop BbiAep>KMBancn β τθηθημθ 16 nacoB πρΜ TeMnepaType -18 °C, pa35aBnancn 3TMnai4eTaTOM m TinaTenbHO
npOMblBanCH OAHOHOpManbHOM ΧΠΟρΜΟΤΟΒΟΑΟρΟΑΗΟΜ ΚΜΟΠΟΤΟΜ, BOAOM M
pacconoM. BbicymeHHan opraHMMecKan φθ38 noAeepranacb χροΜ3τοφ3φΜροΒ3ΗΜΚ) c Mcnonb30BaHMeM “Μβροκ KM3enbrenb 60”, CMTO 37 37 LV 10781
Na 230 - 400, b κο/ιμηθοτβθ 120 mji. B pe3ynbTaie θπιομροβθημλ kojiohkm CMecbio, cocToniiļeii M3 reKcaHa m 3TnnaiļeTaTa, b εοοτΗοιυβΗΜΜ 4:1, 6bmo nonyMeHO οοθαμηθημθ, yKa3aHHoe b 3aro/ioBKe b βμαθ >κθπτομ neHbi, b KOiiMMecTBe 225 μγ / α /21D + 80 °C ( c 1.20, CHCI3), Xmax ( EtOH ) 241 Η3Η0Μβτρ ( ε 27,500 ), vmax ( CHBr3), 3530, 3460 ( OH ) 1708 (C = O), 1676 ( C = C - C= ), 986 ( C - O ), δ ( CDCL3) BKniOMana 6,58 ( CMHmeT, 1H ), 3.84 ( CMHmeT, 4H ), 3.80 ( CMHmeT, 1H ), 3.58 ( MynbTnruieT, 1H ), 3,30 (ay6neT 14,1H ), 1,00 (ay6jieT 6,3H ), 0,96 (fly6neT 6,3H ), 0,92 (fly6/ieT 6,3H ).
/ C / 23 / E /-MeTOKCHHMHHO ΦβΚΤΟΡ A /1/ Bopornflpnfl HaTpua, b κοπμμθοτβθ 6,5 μγ floāaBnnncn κ oxna>KAeHHOMy jibaom pacTBopy 5 - κβτο, 23 / E / -μθτοκομμμμηο Φβκτορ Α / 83 μγ / b M3onponaHO/ie / 20 μγ /. noJiyHeHHafl b pe3yjibTaTe CMecb >Ke/iToro LļBeTa noABepranacb nepeMeiuMBaHMK) b τθηθημθ 35 MMHyT b jie/ļ^HoPi βθηηθ, 3βτβΜ pa36aBJiRnacb 3TnnaneTaTOM m Ti^aTenbHo npoMbieanacb oflHOHopMajībHOii xjiopmctoboaopoahom kmcjiotom, boaom m pacconoM. BbicyweHHafl opraHMHecKaa (paaa AaJiee Bbinapneanacb m nonyMeHHaa b pe3yjibTaTe cMona >κθπτογο iļBeia noABepra/iacb ομμοτκθ nyTeM χρ0Μ3Τ0Γρ3φΜρ0Β3ΗΜ3 Μβρβ3 "Μβρκ «M3ejibrejib 60", cmo Na 230 - 400, b KonunecTBe 60 mji. 3ūK)npoBaHne coAep>KMMoro kojiohkm ocyiAecTB/iiinocb CMecbio, cocTomiļeii M3 reKcaHa n 3TnnaiļeTaTa b cooTHOLueHMM 2:1, hto Π03ΒΟΠΜΠΟ nonyHMTb coeAMHeHne, yKa3aHHoe b 3aronoBKe b βμαθ wejiTOM πθηβι, b κοπμηθοτβθ 58 μγ. B pe3yjibTaTe Kpmrannma^m M3 reKcaHa 6bino nojiyneHO coeAMHeHne, yKa3aHHoe b 3aro/iOBKe, MMetoiiļee TeMnepaTypy tohkm ruiaBJieHMfl, paBHy»o 203 °C, / α /21D + 133 °C (fi 1.12, CHCI3), ( EtOH ) 244 HaHOMeTpa ( ε 26,200), δ ( CDCL3) BKritonaJia 4,29 ( τρΜπηβτ 7,1 H ), 3.84 ( CMHmeT, 3H ), 3,29 (Ay6JieT 15.1H). (II) PacTBop 5-κβτο, 23 / Ε / - μθτοκομμμμηο Oaiaop Α, b κοπΜΗβοτΒβ 50 μγ b 6θ3βοαηομ τeτpaΓMApoφypaHe, b κοπμμθοτβθ 1 mji, AoGaBrmncfl κ oxna>KAeHHOMy ao TeMnepaiypb« -78 °C pacTeopy tmapmas jimtmm τρΜΟ-τρβτ-6yTOKCM a/iiOMMHMfl b κοπΜΗβοτΒβ 261 μγ, b 6θ3ΒΟαηομ τeτpaΓMApoφypaHe, 38 β κοηΜΜΘΟΤΒβ 3 μπ. CnycTH 0,75 naca Bbiflep>KMBaHMfl πρΜ TeMnepaType -78 °C no/iyMeHHbiii pacTBop pa36aBrm/ica STunaijeTaTOM β κοπμηθοτβθ 30 μπ \λ fla/iee TiiļaTenbHO npoMbiBajica 0,5 HopMa/ibHOM xnopMCTOBOflopoflHoii kmcjiotoū m BOfloii. BbicyiueHHaa opraHMMecKaa 0a3a noflBepranacb BbinapuBaHuto n nonynpoAyKT - CbipeLļ noABeprajica ομμοτκθ nyieM χροΜθτοΓρβφΜροΒθΗΜΑ Ha “Μβρκ Kn3e.ribrenb 60", cmo Nfl 230 - 400. 3jnonpoBaHne ocyinecTBnflnocb 25% STunaLļeTaTOM β γθκοθηθ c nonyHeHMeM b pe3ynbTaie οοθαμηθημη, yKa3aHHoro b 3aronoBKe, b bha© neHbi 6enoro μβθτβ / α /2^ + 128 °C (c 0.95, CHCI3), δ ( CDCL3 ) βκ/ιιοηθη 4,29 (τρκππβτ 7,1H ), 3.84 ( ομηγπθτ, 3H ), 3,29 (Ay6neT 15,1H). ΠΡΗΜΕΡ2
23 / E /-MeTOKCHHMHHO Φβκτορ A. 5 - auetaT B cooTBeTCTBMM c 3tmm npMMepoM 6θ3βοαηημ pacTBop aLļeiaTa Haipnn b κοπμμθοτβθ 2,8 r β βοαθ (15 μπ) αο6θβπηπμ κ pacTBOpy 25-κβτο OaicTop Α, 5-aiļeTaia (β κοπμηθοτβθ 3,13 r, npuMep Nfl 18 β Πθτθητηομ onncaHun ΒθπμκοΘρμτθημμ Ns 2176182) b μθτθηοπθ m Aanee Ao6aeniuiM ΓΜΑΡΟχποριίΑ MeTOKCnaMUHa, β κοπμηθοτβθ 3,01 r. nonyHeHHbiii t3kmm o6pa30M pacTBop noABeprancn nepeMetuMBanvuo β τθμθημθ 1,5 naca npn TeMnepaiype 20 °C, pa36aermncfl STunaiļeTaTOM m TinaTenbHO npoMbieancn 0,5 HOpMaHbHOM ΧΠΟρΜΟΤΟΒΟΑΟρΟΑΗΟίί KMCHOTOM, BOAOPi m pacconoM. BbicymeHHa« opraHMMecKan φ838 Bbinapneanacb ao ποητμ cyxoro cocToaHMB, m neHa 6enoeaToro LļeeTa 6bma noABepmyTa οημοτκθ nyTeM χροΜ3τθΓρ3φΜροΒ3ΗΜη Ha "MepK KM3enbrenb 60”, cmto Nfl 230 - 400, 600 mji. 3nK)npoBaHne κοποηκμ ocymecTBnHnocb cviecbio, οοοτοηιαθμ M3 reKcaHa m STM/iaiļeTaTa β οοοτηοιιιθημμ 4:1, hto πο3Βοπμπο nonyMMTb οοθαμηθημθ, yKa3aHHoe β 3aronoBKe ββμαθ 6θο1βθτηομ πθην, β κοπμμθοτβθ 2,14 r, / α /21d + 128 °C ( c 1.35, CHCI3), Xmax ( EtOH ) 244 H3HOM6Tpa ( ε max 27,250 ), vmax ( CHBr3), 3460, 3480 ( OH ) 1733 (aiļeTaT), 1715 (C = O), 995 ( C - O ), ( CDCL3) BīcniOMan b ce6n 5,5 - 5,6 ( MynbTiinneT, 2H ), 3.84 ( ομηγπθτ, 3H ), 3.29 (Ay6neT 15,H ), 2.16 ( ομηγπθτ, 3H ). 39 39 LV 10781 ΠΡΜΜΕΡ 3
/ 23 / E /-okchhmhho Φθκτορ A, 5 - auetaT
PeaKLļnn 25-κθτο Φβκτορ A, 5-aneTaTa c γμαροχπορμαομ rnflpoKCM/iaMMHa 6bma ocymecTB/ieHa b οοοτβθτοτβμμ c μθτοαμκομ, aHa^orMMHOiS onncaHoii Bbiiue b ΠρΜΜβρβ 1. rionynpoflyKT - cbipeiļ 6bm noABepmyT οημοτκθ nyTeM χροΜθτοφβφΜροΒβΗΜη »a na “MepcK Kn3enbrejib 60”, cmto Nq 230 - 400. Ilpoiļecc antoMpOBaHUB ocymecTBnHjicn CMecbio, cocTomiļeii M3 aTnnaLļeTaTa u aiļeTOHMTpuna β οοοτηοοιθημμ 4:1, c nonyMeHueM b pe3y/ibTaie οοθαμηθημη, yKa3aHHOro b 3aronoBKe, β bmag 6eciļBeTHoii πθηη, / α /21D + 132 °C ( c 1.01, CHCI3), Xmax( EtOH ) 244 H3H0M6Tpa ( 8max 27,800 ), vmax ( CHBr3), 3565, 3470 (OH) 1732 (aLļeTaT), 1712 (C = O), 993 ( C - O ), δ ( CDCL3) BicmoMan 8.12 ( ομηγπθτ, 1H ). 5,5 -5,6 ( MyjibTnn.neT, 2H ), 3.42 (Ay6neT 15,1H ), 2.16 ( οιηπιθτ, 3H ). ΠΡΜΜΕΡ 4
/ 23 / E /-ΜβτοκοΗΗΜΗΗΟ Oairrop A
PacTBop npoAyKTa, πο/ψηθηηοιό β cooTBeTCTBMM c ΠρΜΜβροΜ 2, b KonMHecTBe 1,88 r, β μθτθηοπθ noABepra/icn oxna>KAeHHK) β πθααηομ βθηηθ h 3βτβΜ npon3BOAnnocb Ao6aB/ieHne oAHOHopMa/ibHoro βοαηογο pacTeopa TMAPOOKMCH HaTpHfl B ΚΟΠΜΜβΟΤΒβ 5,6 MJ1, H nOJiyMeHHbM T3KHM 06pa30M pacTBop noABepra/icn nepeMeujHBaHmo b neA^Hoii 6aHe β τθηθημθ 1,5 Mača. rionyMeHHbiii pacTBop pa35aBjinncfl STunaiļeTaTOM m TtiļaTejibHO npoMbieancn 0,5 HopManbHOM xjiopmctoboaopoahom khcjiotoh, boaom pacconoM. BbicyiueHHan opraHHMecKan φθ3θ Bbinapnea/iacb, h o6pa30BaBLijancn neHa oMnuļanacb nyTeM χροΜβτοφθφΜροΒθΗΜη Ha "MepcK Kn3enbrenb 60”, cmto Ns 230 - 400. B pe3ynbTaTe 3/iionpoBaHMfl coAep>KMMoro κοηοΗΚΜ cMecbro, cocTomnefi M3 reKcaHa m 3TnnaLļeTaTa b cooTHoiueHHM 2:1, 6bina nonyMeHa 6ecLļBeTHan neHa, b κο/ιμμθοτβθ 1,429 r. (locne KpncTannn3aiļnn M3 reKcaHa 6bino nonyMeHO οοθαμηθημθ, yKa3aHHoe b 3aronoBKe β mmctom βμαθ, MMeramee teMnepaTypy tomkm nnaBneHHn, 40 paBHyio 203 °C, / α /2^ + 132 °C ( c 1.21, CHCI3 ), Xmax ( EtOH ) 244 H3H0M6Tpa ( emax 29,200 ), v max( CHBr3), 3540 ( OH ) 1708 ( C = O ), δ ( CDCL3) BKniOMan 4,29 ( τρΜππβτ 7, 1H ), 3.84 ( ΟΜΗΓ,πβτ: 3H ), 3,29 (Ay6neT 15:1H). ΠΡΜΜΕΡ5
123 / E /-MeTOKCHHMHHO Φβκτορ A B pe3ynbTaie rnflponn3 npoflyi<Ta, nonyMeHHoro b ΠρΜΜβρβ 3. b ΟΟΟΤΒβΤΟΤΒΜΜ C ΜβΤΟΑΜΚΟΜ, ΟΠΜΟΘΗΗΟΜ B ΠρΜΜβρβ 3, 6bin no/iyMeH npOflyKT, KOTopbiM noflBeprancfl χροΜ3τοΓρ3φπροΒ3ΗΜ>ο HB “MepcK KM3e.nbre.nb 60”, cmto Na 230 - 400, b κοπμμθοτβθ 400 μπ. Ilocjie 3/nonpoBaHMfl CMecM, cocTomiļeii M3 reKcaHa n 3Tnnai4eTaia b cooTHOiueHMM 1:1, 6bino πο/ψΗβΗΟ 21 οοββΜΗβΗΜβ, yi<a3aHHoe b 3aronoBKe β βμαθ Θθοιβθτηομ neHbi, / α / ο + 140 °C ( £ 1.24, CHCI3), Xmax ( EtOH ) 244 HaHOMeTpa ( smax 26,700), v max ( CHBr3 ), 3565, 3490 ( OH ) 1710 ( C = O ), 994 ( C-0 ), 6 ( CDCL3 ) BKniOMan 8,11 ( cnHrner. 1H ), 4,29 ( τρΜπηβτ 7:1H ), 3,41 (Αγ6/ιβτ 15:1H ). flPHMEP 6
/ 23 / E /-3TOKCMMMHHO OaKTOP A
PacTBop 6θ3βοαηογο aiļeiaTa ΗβτρΜη, β κοπμμθοτβθ 140 μγ, β βοαθ, β KonuMecTBe 3 μπ, Ao6aBJiBJicn κ pacTeopy 23-κβτο Φβκτορ Α, β KommecTBe 200 μγ, ( nonyHeHHOMy, κβκ yKa3aHO β ΠρΜΜβρβ 23, β ΠβΤβΗΤΗΟΜ OriMCaHMM ΒβΠΜΚΟδρΜΤΘΗΜΜ Na 2176182 ) Μ ΓΜΑρΟΧΠΟρΜΑβ STOKCMaMMHa, Β ΚΟΠΜΜββΤΒβ 126 ΜΓ, Β ΜβΤβΗΟΠβ, Β ΚΟΠΜΗββΤΒβ 20 MJ1. CnycT« 2 naca BbiAep>KMBaHMB πρΜ TeMnepaType 20 °C nojiyHeHHbiM pacTBop pa36aBJiBJicn c noMoiiļbio npodoro 3φΜρβ (40 μπ) m npoMbieancn boaom. BbicyujeHHaa opraHMHecKaa φβ3β Bbinapneanacb, m o6pa30BaBUJMMCii b pe3ynbTaTe npoAyicr, npeACTaBnaioiiļMM co6om neHy 6enoBaToro iļeeTa, OMMinancn nyTeM χροΜβτοΓρβφΜροΒθΗΜΗ Ha "MepcK KM3enbrenb 60", cmto Na 230 - 400, β κοπΜΜββτββ 90 μπ. B pe3ynbTaTe 3/llOMpOBaHMfl ΟΟΑβρ>ΚΜΜΟΓΟ KOJIOHKM C nOMOUļblO CMeCM, COCTOflULieM M3 3TM/iai4eTaTa m reKcaHa b cooTHOiueHMM 1:2, 6bino nonyMeHO βοβΑΜΗβΗΜβ, 41 41 LV 10781 yxa3aHHoe b 3aronoBKe b βμαθ 6θο^βθτηομ neHbi, b κοπμηθοτβθ 189 μγ; /α/2^ + 125 °C (c 100, CHCI3), Xmax ( EtOH ) 244 H3H0M6Tpa ( Emax 28,200 ), vmax ( CHBr3 ), 35400, 34800 (OH) 1705 (C=0), 994 (C-O), δ ( CDCL3 )
BtcmoMan 3,40 (τριιππθτ: 7:1H), 4,10 ( κβμητθτ 7:2H ), 3,31 ( fly6neT 15:1 H), 1,21 (τρΜΠ/ιβτ: 7:3H).'
CoeflMHeHMfl 7, 8 m 9 6binn nonyMeHbi aHanorMMHbiM o6pa30M M3 23-κβτο Oaicrop A m cooTBeTCTByK>mero npuroflHoro a/iKOKCnaMMHa. ΠΡΜΜΕΡ7
/ 23 / E /-amiHjioKCHHMHHO Oaicrop A /a/21D + 124 °C (c 117, CHCI3), Xmax(EtOH) 244 HaHOMeipa ( Emax 28,400 ), vmax ( CHBr3), 35500, 34900 ( OH ) 1708 ( C = O ), 990 (C-0 ), δ ( CDCL3 ) BīcntOMan b ce6a 5,98 ( MynbTnn^eT, 1H ), 5,28 ( abomhom fly6/ieT 17,2:1H), 5,15 ( aboūhom Ay6neT 97,2:1H), 4,5-4,7( MyjibTnnneT, 2H ), 4,29 (TpunneT: 7:1H), 3,36 ( Ay6neT 14,1H), coeAMHeHiie 6bino nojiyMeHO M3 rnAPOxJiopnAa a/i/imioKCMaMHHa. ΠΡΜΜΕΡ8
/ 23 / E /·Μ3ΟΠΡΠΜ/1ΟΚ0ΜΜΜΗΗΟ Φ3ΚΤΟΡ A
Iol^o + 116 °C (c 0.97, CHCI3), Xmax ( EtOH ) 244 HaHOMBTpa ( emax 25000.), vmax( CHBr3), 3550, 3490 (OH) 1708 ( C=0 ), 992 (C-O), δ (CDCL3) BKnroMan b ce6a 4,2-4,4 ( MynbTnnneT, 2H ), 3,30 (Ay6neT 14:1 H ), 1,21 ( Ay6/ieT 7,3H ), 1,20 ( Ay6neT 7, 3H), 3T0 coeAMHeHne 6bi.no nonyHeHO M3 rnApoxnopnAa H3onponnnoKcnaMMHa. ΠΡ1ΛΜΕΡ 9
/ 23 / E /-hopm-6vtovchhmhho OaKTOP A /a/21D + 115 °C (c 1.00, CHCI3), Xmax( EtOH ) 244 HaHOMeipa ( Emax 31,800 ), vmax( CHBr3), 3540, 3460 ( OH ), 1708 ( C=0 ), 992 ( C - O ), δ ( CDCL3) BKfiKDHan 4,28 ( τρκππθτ 6, 1H ), 4,03 ( MyjibTnn.neT, 2H ), 396 42 (fly6neT 14, 1H), 0,9-1,1 ( MynbTnn.neT, 15H ), οοθαμηθημθ 6bino nonyMeHO m rnflpoxnopnAa HopM. 6yTOKCnaMMHa. ΠΡΜΜΕΡ 10
/ 23 / E /-ηορμ-μθτοκοηημηηο Φβκτορ A. 5 aueTaT / I / B cooTeeTCTBHH c 3thm npMMepoM npoM3BOflMnocb αο68βπθημθ 3-x MonnpHoro pacTBopa HOflMfla μθτμπμβγημη b προετοΜ 3φΜρβ. b κοπμμθοτβθ 0,16 μπ, κ nepeMeuuaHHOMy pacTBopy npoflyKTa, nonyMeHHoro b npHMepe Na 3, b κοπμμθοτβθ 120 μγ., b 6θ3ΒΟαηομ γθκοθμθτμπΦοοΦορηομ TpkiaMHfle, b κοπμμθοτβθ 5 Μη, b βτΜοοφβρΘ a30Ta. flanee npon3BOflnnocb Ao6aBneHne μοαμθτθηθ, b κοπμμθοτβθ 0,09 μπ. h cnycTa oamh Mac noflBepranacb pa36aBneHMK> θτμπθαθτθτομ, b κοπμμθοτβθ 30 μπ. m flanee TīflaTenbHO npoMbieanocb 2-x HopManbHOM χπορμοτοβοαοροαηομ kmchotom m BOflOM.BbicyiueHHan opraHMMecKaa φθ3θ nofleepranacb BbinapMBaHMK) m o6pa30BaBLiiancsR cMona nofleepranacb ομμοτκθ χρομθτογρθΦμροβθημθμ Ha “MepK Kn3enbrenb 60”, cmto Na 230 - 400, b κοπμμθοτβθ 80 μπ. B pe3ynbTaTe θπιομροβθημπ οοαθρ>κμμογο κοποηκμ 6bino nonyMeHO ΟΟΘΑΜΗΘΗΜΘ, yKa3aHHOe B 3aronOBKe, ΑΠΗ OntOMpOBaHMn MCnonb30BanaCb CMecb, cocTOiuiļan M3 reKcaHa m sTMnaiļeTaTa, b οοοτηοιπθημμ 2:1, npoAyKT npeflCTaBnnn co6om 6enyio neHy, /a/2^ + 123 °C (c 1.25, CHCI3), X.max ( EtOH ) 245 ΗθΗΟΜβτροΒ ( emax30,300 ); Cneicrp παθρηομθγημτηογο pe30HaHca 6bin οπμοθη paHee b ΠρΜΜβρβ Na 2. (II) npoflyKT, nonyMeHHbiii b npMMepe 3, b κοπμμθοτβθ 0,082 r., noflBeprancn pacTBopeHMio b προοτοΜ 3φΜρβ b κοπμμθοτβθ 10 μπ, coflepjKaifleM OKMCb cepe6pa, b κοπμμθοτβθ 0,4 r., b οβθ>κθπρμγοτοβπθηηομ pacTBope (boahom) HMTpaTa cepe6pa μ b 2M pacTBope γμαροοκμομ ηθτρμη. nonyMeHHan CMecb noABepranacb πθρθμθιπμβθημκ) πρΜ κομηθτηομ TeMnepaType b τθμθημθ fleyx Macoe, nocne μθγο npOM3BOflMnacb φΜΠΒτρθμΜπ m pacTBopMTenb BbinapMBancn c nonyMeHMeM b pe3ynbTaTe nonynpoflyKTa-Cbip4a b φορΜβ CMonbi ϊκθπτογο αβθτθ. 3tot οοτθτοκ nofleeprancfl ομμοτκθ nyTeM npenapaTMBHoro χροΜθτοΓρβφΜροΒβΗΜη b τοηκμχ οποπχ Ha “ Μβρκ 5717" πρΜ θπιομροβθημμ CMecbio, cocTonmeii H3 ΑΜΧΠ0ρΜΘΤ3Η3 M aiļeTOHa B ΟΟΟΤΗΟΙΠΘΗΜΜ 25; 1. OCHOBHan nonoca 43 43 LV 10781 ((JjpaKLļMfi) 3KCTparnpoBanacb, noABepranacb BbinapMBaHmo c nony4eHMeM b pe3ynbTaie οοθαμηθημη, yKa3aHHoro b 3aronoBKe, b κοαμμθοτβθ 0,059 r. Cneiorp flflepHO-MamuTHoro pe30HaHca 6bm yKa3aH Bbirne b ΠρΜΜθρβ 2. ΠΡΗΜΕΡ 11
/ 23 / E /-MefOKCHHMHHO OaKTOP A. 5 MeTMJiKap6oMaT
MeTMn Μ3011Μ3Η3Τ, Β ΚΟ/ΙΜΜΘΟΤΒΘ 0,13 Μη., 125 ΜΓ. Μ ΤρΜΟΤΜΠΘΜΜΗ, 2 Kannu, AoāaBnanMCb κ pacTBopy 23/Ε/-μθτοκο4μμμηο Oaicrop Α, β ΚΟηΜΗΘΟΤΒβ 350 Μη., Β 6β3ΒΟΑΗΟΜ ΑΜΜβΤΜηφΟρΜΘΜΜΑβ, Β ΚΟηΜΗβσΤΒΘ 0,75 Μη. Kon6a c nonyMeHHoii τθκμμ o6pa30M CMecbto ηηοτΗΟ 3aKpbieanacb μ Harpeeanacb β τβΜβΗΜβ 5,5 naca πρκ TeMnepaType 80 °C m ripu nepeMeiiJMBaHMM. nony4eHHan tbkum o6pa30M cMecb BbīnMBanacb β βοαυ, b KonuMecTBe 50 Μη. m flanee 3Ta CMecb cpunbTpoBanacb nepe3 KM3enbryp. OdnbTpoBanbHan neneujKa npoMbieanacb boaom, b KonimecTBe 150 Μη. m Aanee aKCTparupoBanacb c ΑΜχηορΜβτβΗΟΜ, β κοηΜΗβοτΒβ 75 Μη. nonyMeHHbiii sKCTpaKT cyujnncfl c noMOLiļbio cynb(fcaTa Mamnn m noABeprancn KOHiļeHTpupoBaHMK) c nonyMeHneM b pe3ynbTaie neHbi >Kēmoro iļBeia, KOTopan noABepranacb ομμοτκθ Ha xpoMaTorpa0MHecKofi κοηοΗκβ, 3anonHeHHOii cenMKareneM, npn cpeAHeM AaeneHMM (τβ 125 Γ.,“Μβρκ Kn3enbrenb 60", cmo Na 230 - 400. B pe3ynbTaTe amonpoBaHun CMecbio,.cocTonu4eM M3 rekcaHa m amnaueTaTa, b cooTHOLueHnn 1:1, 6bino nonyneHo coeAMHeHne, yKa3aHHoe b 3aronoBKe, β βμαθ neHbi 5enoro LļBeTa μ β κοπμμθοτβθ 206 μγ. /a/21D + 99 °C ( c 0,55, CH2CI2), ( EtOH ) 244,4 HaH0M6Tpa ( ε 28710 ), vmax ( CHBr3), 3530 ( OH ), 3455 ( NH ), 1720 (cno)KHbiii 3φΜρ ), 1720 + 1510 ( Kap6aMaT ) m 993 cm'1( C-0 ), δ ( CDCL3) BKniOMaeT 1,78 (CMHrneT, 3H ), 2,86 (Ay6neT,5 repiļ, 3H ), 3,29 (Ay6neT 14 rep«4, 1H ), 3,83 ( CMHrneT, 3H ), 4,80 ( κβμητθτ, 5 repiļ, 1H ) m 5,50 (MynbTnnneT, 2H). ΠΡΜΜΕΡ 12
123 / E /-MeTOKCHHMHHO OaKTOP A. 5 MeTnnKap6oHaT K pacTBopy / 23 / Ε /-μθτοκομμμμηο Oaiaop A, b KonunecTBe 150 μγ. β ΑΜχηορΜβτβΗΘ, β κοηΜΗΘΟΤΒΘ 15 Μη., μ γμρμαμηθ ( 0,3 Μη ) npn 44 nepeMemuBaHMM npn TeMnepaiype 0 °C npon3BO,qnnocb flo6aB/ieHne ΜθΤΜηχηορφορΜβτβ (0,7 mji. 1,0 M pacTBopa b αμχπορμθτθηθ). nonyMeHHan τθκμμ o6pa30M peaKLļMOHHaa CMecb noABeprajiacb nepeMeiiJMBaHmo npn TeMnepaType 0-3 °C b ιθηθημ© 20 μμη>γγ, a 3aieM Ao6aBJiRnncb κ flnx/iopM6TaHy, b κοπμηθοτβθ 70 μπ. m npoMbieajiacb AByXHOpMa/1bHOM ΧΠΟρΜΟΤΟΒΟΑΟρΟΑΗΟίί ΚΜΟΠΟΤΟΡί, B KOflMHeCTBe 70 MJl.M BOfloii b KOiiMsecTBe 50 mji. OpraHHMecKaa 4)a3a cyiunriacb cynbφaτoM MarHMfl, m pacTBopuTenb yflajinncn c o6pa30BaHneM neHbi, KOTopan noABepranacb ομμοτκθ nyTeM χροΜβτοφθφΜροΒΒΗΜΗ, npn cpeflHeM ΑΒΒΠΘΗΜΜ, Ha ΚΟ/ΙΟΗΚΘ, 38ΠΟΠΗβΗΗΟΜ flByOKMCbK) ΚρβΜΗΜΑ (40 Γ.,“Μβρθ< Kn3ejibre/ib 60”, cmto Na 230 - 400. B pe3ynbiaie 3JnonpoBaHMfl CMecu, cocTOflUļefi M3 ΑΜχηορΜβτ3Η3 m 3THJiaiļeTaTa, b cooTHOiueHmi 30:1, 6bi/io nonyHeHo coeAMHeHne, yKa3aHHoe b 3aronoBKe, b βμαθ ēenoPi neHbi, b KonusecTBe 127 μγ. /α/2^ + 145 °C ( C=0,41, CH2CI2), λ™* ( EtOH ) 244,4 HaH0M6Tpa ( ε 3121 ), δ ( CHBr3), 3460 + 3540 ( OH ), 1342 ( Kap6oHaT ) 1710 ( cno>KHbiM 3φκρ ) m 992 cm‘1( C-0 ), 5 ( CDCL3) BKniOMaeT 1,82 ( ομηγπθτ, 3H ), 329 (Ay6neT, 14 Γο, 1H ), 3,82 ( ομηγ/ιθτ, 3H ), 3,83 (CMHrneT, 3H ), 5,2-5,4 ( MynbTnnneT, 3H ). 5,56 (ομηγπθτ, 1H). ΠΡΜΜΕΡ 13
/ 23 / Ε /-ΜβτοκοΜΗΜΗΗο OaKTOP II. 5 aueTaT B COOTBeTCTBMM C 3TMM ΠρΜΜθρΟΜ paCTBOp, COAepjKaiiļUM 23-κβτο Φθκτορ fl, 5 aiļeTaT ( β κοπμμθοτβθ 251 μγ, nojiyHeHHbifi, κβκ yKa3aH0 b npuMepe 119, β ΠβτβΗΤΗΟΜ onncaHm BejiMK06pnTaHMM Na 2176182) aiļeTaT HaTpmi, b KonunecTse 250 μγ, β μθτθηοπθ, β κοπμμθοτβθ 40 mji., ripu TeMnepaiype 20 °C β τβΗβΗΜβ 24 nācos, Aanee KOHiļeTpupoBancfl ao οδ-beMa, paBHoro npMMepHO 10 mji, pa36aBJiajicfl 3Tmiai4eiaTOM, b KommecTBe 50 mji m 3aTeM TiAaienbHO npoMbieancfl 0,5 hopm. XJ10pMCTOBOAOpOAHOM KMCJIOTOM Μ ΒΟΑΟΜ. BblCyiUeHHafl OpraHMMeCKafl φ838 Bbinapneanacb c nonyHeHneM b pe3yjibTaie neHbi >κθπτογο iļBeia, KOTopaa OMnunanacb nyieM χροΜθτοφθφΜροΒθΗΜΗ, Ha “MepcK Kn3enbrejib 60", chto Na 230 - 400. B pe3y;ibTaTe ajiioMpoBaHMii kojiohkm reKcaHOM 6bino 45 LV 10781 ηοηγΜθΗΟ coeflMHeHMe, yKa3aHHoe b 3aronoBKe, b βμαθ naneeo - >κβ/ιτοΜ neHbi, b KO/iimecTBe 144 μγ. ( EtOH ) 244 HaHOMeipa ( ε 3121 ), vmax ( CHBr3),( cm*1) 3500 ( OH ), 1742 (OAc) 1710 (C=0), 6 ( CDCL3) βκπκ)Μ3/ι 5,54 ( ΜγπετΜπηβτ, 2H ). 4,92 (MyjibTMnneT, 1H ), 3,84 ( cviHmeT, 3H ), 3,32 (MyjibTnnneT, 1H) 3,30 (fly6/ieT, 14, 1H ), 2,17 ( CMHmeT, 3H ), 1,91 (fly6neT 14, 1H) 1,76 (CMHmeT, 3H ), 1,51 (CMHmeT, 3H ),1,01 (τρΜπηβτ 7, 3H ). 0,99 (fly6neT 6, 3H ), 0,92 (Ay6neT 6, 3H ). ΠΡΜΜΕΡ 14 / 23 / E /-MeTOKCMMMHHO Oaicrop il. B COOTBeTCTBMM C 3TMM ΠρΜΜΘρΟΜ paCTBOp, COflepMOLAMM npOflyKT yKa3aHHbiM b ilpMMepe 13, β κοπμηθοτβθ 140 μγ m OAHOHopManbHbiM pacTBop rMApooKMCM ΗβτρΜη, b KOJiMMecTBe 0,6 m/ι., b MeTaHO/ie ( 8mji ) noABeprancn nepeMewMBaHMK> β πθαβηομ 6aHe β τθμθημθ 1,5 Mača. nonyMeHHbiM pacTBop pa36aB/iHJica οτΜ/ίθμβτβτοΜ, m TinaTe/ibHo npOMblBa/lCP OAHOHOpMa/lbHOM XflOpMCTOBOAOpOAHOM KMCTIOTOM Μ BOAOM. BbicyujeHHan opraHMMecKafl cfea3a BbinapuBa/iacb c no/iyHeHMeM b pe3ynbTaTe neHbi >κθπτογο ι^βθτθ, KOTopaa OMMinajiacb nyTeM xpoMaTorpa0MpoBaHM«, Ha "MepcK KM3enbrenb 60”, cmto Na 230 - 400. B pe3yribTaTe 3.nioMpoBaHMfl οοαθρ>κμμογο κοποηκμ cMecbio, cocTomiļeM M3 reKcaHa μ STMJiaLļeTaTa β οοοτηοιαθημμ 2:1 6bmo nonyMeHO coeAMHeHMe, yKa3aHHoe β 3aronoBKe, β βμαθ πθηη 5enoBaToro LļBeTa, b KonMMecTBe 105 μγ. Ια?\ + 96 °C (^=1,38, CHCI3), Xmax{ EtOH ) 244 HaHOMeTpa (ε 26700 ), vmax ( CHBr3),( cm*1) 3550, 3500 ( OH ), 1710 ( C = O ), δ( CDCL3 ), BKJHOMan 4,93 (MynbTMnneT, 1H), 4,30 ( τρΜπηβτ 6, 1H ), 3,95 ( Ay6neT 6,1H), 3,84 (CMHmeT, 3H ), 3,30 (Ay6/ieT 14, 1H ), 3,27 ( My/ibTMn/ieT, 1H ), 1,88 ( CMHmeT, 3H ), 1,64 ( CMHmeT, 3H ), 1,52 ( CMHmeT, 3H ), 1,01 ( τρΜπηβτ 7, 3H ). 1,00 (Ay6neT 6, 3H ), 0,92 (Ay6neT 6, 3H ). ΠΡΜΜΕΡ 15
/ 23 / Ε /-μθτοκοηημηηο OaKTOD B
PacTBop, C0Aep>KamMM 23-κβτο Φβκτορ Β, ( β κοηΜΜβοτΒβ 1 r, nonyHeHHbiM, κβκ yxa3aHO β IlpMMepe 119, β ΠβτβΗΤΗΟΓΟ onMcaHMH 46
BejiMKo6pmaHMM Na 2176182) aLļeTaT ΗβτρΜΠ, b κοπμηθοτβθ 400 μγ, μ γμαροχπορμα MeTOKCnaMUHa, β κοπμηθοτβθ 400 r, noABepranca πθρθμθιιιμββημκ) npM TeMnepaType 20 °C β τθηθημθ 20 Hacoe, flanee noABepranca KOHLieTpMpoBaHMio ao oāteMa, πρΜΜβρκιο paBHoro 10 mji, a 3Θτθμ pa36aBJianca 3TMnaiļeTaT0M m npoMbieancn boaom. OpraHMHecKan 0a3a TiAaTenbHo npoMbieanacb 0,5 HopManbHoii χπορμοτοβοαοροαηομ κμοποτομ m boaom, h BbicyweHHafl opraHunecKaa 0a3a noABepranacb BbinapuBaHMK). riojiyMeHHbiPi nonynpoAyKT - cbipeiļ 6bin noABepmyT οημοτκθ nyTeM χρ0Μ3Τ0Γρ3φΜρ0Β3ΗΜΒ, Ha “Μβροκ Kn3e/ibrejib 60”, cmto Na 230 -400. B pe3y/ibTaTe 3nwnpoBaHMfl οοαθρ>κμμογο kojiohkm CMecbio, cocTOHLneM M3 STMnaiļeTaTa m AnxnopMeiaHa b οοοηοιιιθημμ 1:9, 6bmo nonyneHO οοθαμηθημθ, yKa3aHHoe b 3aronoBKe, β βμαθ πθην 6θπογο ABeTa, β κοπμηθοτβθ 500 μγ. /α/2^ + 128 °C ( c=1,09, CHCI3), Xmax ( EtOH ) 244 HaHOMBTpa ( ε 30100 ), vmax ( CHBr3),( cm'1) 3540, 3460 ( OH ), 1708 (C=0), δ ( CDCL3), βκπκϊηθπ 5,46 (κβμητθτ 6, 1H), 4,03 (Ay6neT 5, 1H ), 3,97 (Ay6neT 5, 1H), 3,83 ( ομηγπθτ, 3H ), 3,50 ( ομηγπθτ, 3H ), 3,32 (My/ibTnnneT, 1H), 3,29 (Ay6/ieT 145, 1H), 1,82 ( ομηγπθτ, 3H ), 1,68 (Ay6neT 6, 3H), 1,00 (Ay6neT 6, 3H ), 0,92 (Ay6neT 6, 3H ). flpuMep 16
/ 23 / Ε /-μθτοκομμμμηο OaKTOP C
B ΟΟΟΤΒΘΤΟΤΒΜΜ C 3TMM ΠρΜΜβρΟΜ 6e3BOAHblM θμβΤΘΤ Η3ΤρΜΗ, B κοπμηθοτβθ 0,54 r, μ γμαροχπορμα μθτοκομθμμηθ, b κοπμηθοτβθ 0,58 r, Ao6aBnanncb κ pacTBopy 23-κβτο Φβκτορ C (β κοπμηθοτβθ 1,97 r, nOJiyHeHHOrO Β ΟΟΟΤΒΘΤΟΤΒΜΜ C ΠρΜΜβρΟΜ 12 ΠβΤΘΗΤΗΟΓΟ OnMCaHMB BemiKo6pMTaHMM Na 2176182) β μθτθηοπθ, β κοπμηθοτβθ 300 μγ, C0Aep>«aiAMM βοαυ β κοπμηθοτβθ 5 μπ, μ ποπυηθηηθπ τβκμμ o6pa30M CMecb noABepranacb πθρθμθιιιμβθημκ) β τθηθημθ 30 MMHyT npn κομηθτηομ TeMnepaiype. ΘτΜΠβμΘΤ, β κοπμηθοτβθ 30 μπ, 0,5 xnopMCTOBOAopoAHan KMCHOTa, Β ΚΟΠΜΗΘΟΤΒΘ 30 ΜΠ, AOOaBHflnMCb K nonyneHHOM Bblllie CMeCM M 06pa30BaBUJMMCfl BOAHbIM CHOM nOBTOpHO SKCTparMpoeancn 3ΤΜΠ3Ι4ΘΤ3ΤΟΜ, Β ΚΟΠΜΗΘΟΤΒΘ 15 ΜΠ. CMeUUaHHbie OpraHMHeCKMe ΟΠΟΜ npOMbIBanMCb no 47 47LV 10781 OMepefln 0,5 M xnopncTOBOflopoflHoii kvicjiotom, 5% Hacbiu^eHHbiM bo^hum pacTBopoM xxiopi4Aa Haipnn, a 3θτθμ noflBepranncb κοΗμβΗτρΜροΒβΗΜΚ» b BaKyyMe c nonyMeHneM b pe3y/ibTaie neHbi >κβητοΓο μΒβτβ. 3tot npoflyior noflBepra/icfl οημοτκθ nyTeM χροΜβτοφθφΜροΒβΗΜΗ, Ha cenMKarene “MepcK 9385" c nepeoHaManbHOM οδρβδοτκοίί κοηοΗΚΜ ΑΜχηορΜβτβΗΟΜ, a 3aieM npon3BOflnnocb θακϊμροβθημθ c noMoiAbto flnx/iopMeTaHa coflepKauļero He3HaHHTe/ibHoe κο/nmecTBo ΘΤΜηβμθτβτβ ( ao 10% ), c nonyHeHneM οοθαμηθημη, yKa3aHHoro b 3aronoBKe, b KonMHecTBe 1,0 r. / α /2^ + 64 °C ( c =1,0, CH3OH3), 1H «a©Pho - MamMTHbiii pe30HaHc ( CDCL3) BīcniOMan b ce6n cneAyioiAMe CMmanbi: 4,95 (MynbTnn.neT, 1H), 4,29 (τρΜπηβτ, 1H, 7 Γμ), 3,96 (Ay6neT 1H, 7 Γμ) 3,85 ( CMHrneT, 3H [=NOCH3 ]), 3,66 ( Ay6feT 1H, 10 Γμ ), 1,51 ( CMHrneT, 3H ), 1,42 (τρΜπηβτ 1H, 12 Γμ), MHtfcpaKpacHbiii cneKTp (CHB3) 3620-3340 cm'1 (-OH), 1711 cm’1 (C=0). rīpMBOAHMbie AaTiee npMMepbi othochtch κ κθΜηο3ΜμΜΗΜ, npMrOTOBneHHbIM B COOTBeTCTBMM C HaCTOnLLļHM Μ3θδρβΤβΗΜβΜ. ΤβρΜΜΗ “AlCTMBHblM ΜΗΓρβΑΜΘΗΤ”, MCnOnb3yeMblM OTHOCMTCfl Κ COeAMHeHMHM, ηβηηιοίμΜΜοη πρθαμθτομ ΗβοτοηιμβΓΟ Μ3θ6ρβτβΗΜΗ μ μο>κθτ npeACTaennTb co6om, HanpHMep, coeflHHeHHe, yka3aHHoe b npuMepe 4. MHoropa3QBaa 1103a lina napeHTepajibHbix μηί>θκιιμη flpHMep 1 % Ββε/οδ^ΘΜΗ. flnana30H AKTMBHbIM ΜΗΓρβΑΜΘΗΤ 2,0 0,1-6,0% Bec./o6*beMH BeH3MHOBblM CflMPT 1,0 noiiMCop6aT 80 10 OopManb r/iMAepMHa 50 BoAa flnn ΜΗΐ>βκμΜΜ AO 100,0 B cooTBeTCTBMH c 3TMM npMMepoM npoM3BOAMnocb pacTBopeHMe aiaMBHoro MHrpeAMeHTa b (1onncop6aTe 80 μ φορΜβηβ ΓηΜμβροηβ. /ļanee npon3BOAnnocb AoOaBneHHe 6θη3μποβογο cnupTa h CMecb AOBOAHnacb ao Hy>KHoro o6bēMa nyTeM Ao6aBneHnn βοαη, πρμγοαηομ a-πα ΜΗΐ>βκμΜΜ. CTepnnn3aAnn npoAyicra npon3BOflHTca o6bNHbiMM μθτοαβμμ, HanpHMep, 48 CTepttnbHOM φΜ/ibTpaLļneii mjim πγτβΜ HarpeBaHun b aBTOKnaBe c nocneflyioineii ynaKOBKoii b cTepmibHbix ycjiOBMnx. % Bec/o6teMH. flMana30H AKTMBHbIM ΗΗΓΡβΑΜβΗΤ 4,0 0,1-7,5% Bec./o6i>ēMH. BeH3HJ10BblH CflMPT 2,0 TpMaueTaT r/iMuepM/ia 30,0 ΠροπΜ/ieHrjiHKOHb AO 100,0 Πρμμθρ 2 B cooTBeTCTBMM c 3tmm nptiMepoM npoM3BOflMTCfl pacTBopeHkie θκτμβηογο MHrpeflMeHTa b 6θη3μποβομ αίΜρτβ μ τρΜβμβτβτβ r/umepnHa. flanee npon3BOAMTCfl Ao6aBneHne προπΜ/ιβΗΓΠΜκοπ« ao η>οκηογο o6i»ēMa. CTepmiM3ai4M« no/iyHeHHoro npc>AyKTa npoM3BOAHTcn c noMouļbio ο6μηηηχ 0apMaiļeBTMMecKMx μθτοαοβ, HanpMMep, nyTeM cTepM/ibHOM φΜΠΒτρβμΜΜ, c nocneAyK)iiļeii ynaKOBKOM b cTepnnbHbix ycnoBnnx. Πρμμθρ 3 % βθρ/ο6ι>θμη. flMana30H AKTMBHbIM ΜΗφβΑΜβΗΤ 2,0 0,1-7,5% Bec7o6bēMH. ΘτβΗΟ/Ι 36,0 ΗβΜΟΗΟΓβΗΗΟβ ΠΟΒβρΧΗΟΟΤΗΟ 3κτΜΒΗθβ BeuiecTBO, TaKoe κβκ HanpMMep, Synperonic PEL44X 10,0 Π po Π Mil ΘΗΓΠ MKOJlb AO 1000 B COOTBeTCTBMM C 3TMM ΠρΜΜβρΟΜ aKTMBHbIM ΜΗφβΑΜΘΗΤ pacTBopneTcn b STaHone m noeepHOCTHo - 3κτμβηομ βθιαθοτβθ m cMecb Aoboamtca ao Tpe6yeMoro oāteMa nyTeM Ao6aBneHMn προπΜπβΗΓΠΜκο/ΐΗ. CTepnnn3aiļMfl nonyMeHHoro npoAyKTa ocyunecTBnneTCJi b οοοτβθτοτβμμ c OČbNHblMU φβρΜβμβΒΤΜΗβΟΚΜΜΜ ΜΘΤΟΑΘΜΜ, HanpMMep, nyTeM CTepMJlbHOM φΜΠΒτρβίΐΜΜ, c nocneAyiou4eM ynaKOBKOM b cTepn/ibHbix ycnoBnnx. 49 49LV 10781 npHMep 4 % βθο/ο6ϊ.θμη. flnana30H AKTHBHblii ΗΗΓρβΑΜβΗΤ 2,0 0,1-3,0% Bec^o6i>ēMH. HeMOHoreHHoe ποββρχΗοστΗο aKTMBHoe eeiuecTBO, τβκοβ κβκ HanpMMep, Synperonic PEF68X 2,0 5eH3M/IOBblM CilMpT 1,0 Myglyol 840xx) 16,0 BOfla ΑΠΒ ΜΗ1>βΚ1|ΜΜ AO 100,0 ΠρΜΜβΜΘΗΜΘ : X) - npOflyKT, npOM3BOAHMblM φΐφΜΟίί I.C.I. XX) - npoAyKT, npoM3BOAMMbiii φιιρΜΟΜ Dynamit nobel. B cooTBeTCTBMM c 3tmm πρΜΜβροΜ npoM3BOAMTCfl pacTBopeHue aKTMBHoro liHrpeAMeHTa b Myglyol 840. npon3BOAmca pacTBopeHne ΗΘΜΟΗΟΓΘΗΗΟΓΟ ΠΟΒβρΗΟΟΤΗΟ-ΘΚΤΜΒΗΟΓΟ ΒΘίμβΟΤΒΘ Μ 6βΗ3ΜΠΟΒΟΓΟ ΟΠΜρΤΘ Β čoJibiueM MacTM BOAbi. ΠροΜ3ΒθΑΜτοη πρΜΓοτοΒΠβΗΜΘ 3MynbCMM nyieM AoāaBJieHMfl μθοπηηογο pacTBopa κ βοαηομυ pacTBopy μ οαοβρθμθηηο ocyiAecTB/iaeTC« reMoreHM3a4M« c noMombio o6bNHbix μθτοαοβ. 06beM CMecH AOBOAMTcn ρ,ο Tpe6yeMoro h ocymecTBiifleTCfl ynaKOBKa b CTepmibHblX yCHOBM«X. A3P030Jib nrm pacnbmeHHfl % Bec/o6"beMH. flnana30H AKTMBHbIM ΜΗΓρβΑΜβΗΤ 0,1 0,01-2,0% eec./Becoe Tpnx/iop3TaH 29,9 T ΡΜΧ/1θρφΤΟΡΜβΤ3Η 35,0 ΑΜΧΠΟΡΑΜφΤΟΡΜβΤβΗ 35,0 B COOTBeTCTBMM C 3TMM ΠρΜΜβροΜ npOM3BOAMTCJļ CMemeHHe aKTMBHoro ΜΗΓρβΑΜβΗΤβ C TpMXJ10p3TaH0M, Μ ΠΟ^ΘΗΗβΛ CMeCb BBOAMTCfl B aapoaonbHbiM κοΗτβίίΗβρ. OcymecTBJiyieTcfl npoAyB«a βθρχηθμ Mac™ 6anoHa ra3006pa3HbiM προπβππβΗτοΜ m ocymecTBJiaeTca οβχοτιιβ «nanaHHoro y3na b wy>KHOM ποπομθημμ. OcyinecTBiiaeTcn 3anonHeHMe ao 50 rpe6yeMoro eeca >kmakmm nponenneHTOM ποα Α3βπθημθμ nepe3 KnanaH. npOM3BOAMTCfl yCTaHOBKa Η3>ΚΜΜΗθίί ΓΟΠΟΒΚΜ M KpblLUKM.
Ta6neTKn.
CnocoS npon3BoncTBa - Bna>KHoe rpaHvnuDOBaHue. AKTHBHblM ΗΗΓΡΘΑΜΘΗΤ 250,0 μγ. CTeapaT μ3γημλ 4,5 μγ. MaHCOBbm xpaxMaji 22,5 μγ. ΓnMKonaT KpaxMa/ia ηθτρμλ 9,0 μγ. Cynb*aT naypnna HaTpim 4,5 μγ. MHKpoKpMCTanHHecKaa L|e/i.moji03a aπλ noKpbiTMB Ta6neTOK, eecoM AO 450 μγ. B COOTBeTCTBMM C 3TMM ΠρΜΜβρΟΜ npOM3BOAMTCB Αθ63ΒΠΘΗΜβ AOCTaTOMHoro κο/umecTBa 10% KpaxMa/ibHotf nacTbi κ aianBHOMy MHrpeflneHTy c nonyMeHneM b pe3yjibīaTe Tpe6yeMofi Bna>KHOM Maccbi, npuroAHoii απ^ rpaHynnpoBaHMfl. ΠροΜ3ΒθΑΜτοη nony4eHne rpaHyn m mx cyniKa c ncnonb30BaHneM cymnnKn c κμπηιαμμ cnoeM μπμ jiotkobom cymnnKM, a A=Lnee npon3BOAMTCH npocenBHne Μβρβ3 cmto, Ao6aBJieHne ocTaBLUnxcn μηγρθαμθητοβ m Ta6/ie™poBaHne. B cnyMae ηθο6χοαμμοοτμ τβδ/ιβτκΜ MoryT 6biTb ποκρωτω πχιθηκομ c ncno/ib30BaHneM OKCMnponnnMeTM/iiļejinK)no3bi \λι\\λ Apyroro aHanornHHoro n/ieHKoo6pa3yioiAero MaTepnana, c Mcno/ib30BaHneM pacTBopmoLiļeū cncTeMbi Ha boahom mum 6θ3βοαηομ ocHoee. ΠηβοτΜφιιιοτορ min npuroAHbiii Kpacmerib Moryr 6biTb ββθαθηβι b pacTBop, o6pa3yiOLLļMM nneHOMHoe ποκρωτνιβ.
BeTePMHaPHbie Ta6/ieTKn nna πθμθημα ManeHbKHx HOMaLUHMX >KHBOTHblX.
Cnoco6 npon3BOflCTBa - 6e3BOflHoe rpaHynnpOBaHnei
AlCTMBHbIM ΗΗΓΡΘΑΜΘΗΤ 50 μγ. CTeapaT MarHMB 7,5 μγ. MMKpoKpMCTajiMHecKaa ueiuiiono3a απβ noKpbiTMB Ta6neTOK, eecoM okojio 75 μγ. 51 51 LV 10781 B ΟΟΟΤΒβΤ CTB Μ M C 3TMM ΠρΜΜθρΟΜ npOM3BOflmCfl ΟΜΘΐυβΗΜΘ aKTUBHoro MHrpeflueHTa co cieapaTOM Mamu m MMKpoKpMCTanMHecKoii Lļenruono3oii. flanee npon3BOflHTcn ynnoTHeHne atlecu m pa3MenbMeHMe komkob cMecu nyieM nponycKaHnn Μβρβ3 poTaLļMOHHbiū rpaHyn«Top c nonyMeHneM b pe3yjibTaie CBo6oAHOTexyHMx rpaHyn h nocneAyioiAeii nepepaSoTKoii stmx rpaHyn b τβδπβτκιι. Ta6neTKM MoryT 6biTb ποκρωτω ΠΠβΗΚΟίί ripu Heo5xOflMMOCTM, KBK 6blJ10 yKa3aHO BblLUe.
MH~beKUMH UTIS BBOHa B MOflOHHVK) >ΚΘΠΘ3ν >KMBOTHblX
Mr/fl03a flnana30H AKTHBHbIM ΜΗΓρβΑΜΘΗΤ 150 ΜΓ 0,05-1,0 r nomicop6aT 60 3,0% eec/eec Benbīii rmenMHbiti BOCK 6,0% eec/eec ao 3 r Ao 3 nnn 15 r ApaxMcoBoe Macno 91,0% eec/eec B COOTBeTCTBUM C 3ΤΙΊΜ ΓφΜΜβρΟΜ np0M3B0AMJ10Cb Η3φβΒ3ΗΜβ apaxncoBoro Macna, 6enoro πηθπμηογο Bocxa m nonncopāaia 60 ao TeMnepaTypbi 160 °C npn nepeMeujMBaHMM. nonyHeHHaa τθκμμ o6pa30M CMecb BbiAep>KMBanacb ripu TeMnepaType 160 °C β Tenemie 2-Macoe m 3aieM oxna>KAaiiacb ao κομηθτηομ TeMnepaiypbi ripu nepeMeLUMBaHMM. flanee npon3BOAnnocb AoāaeneHMe b CTepnnbHbix ycnoBtmx θκτμβηογο MHrpeAMeHTa κ Hocmenio m npon3BOAnnocb AncneprupoeaHHe θκτμβηογο MHrpeAHeHTa c ncnonb30BaHneM BbicoKOCKopocTHoro cMecmena. Οημοτκθ npon3BOAnnacb nyTeM nponycKaHnn nepe3 KonnonAHyro MenbHm4y. flanee npoAyicT BBOAuncn b CTepunbHbie mnpMLļbi M3 nnacTMKa.
BonbLUMe BeTepnHapHbie nmitonu c μθζιπθηηνμ βναθπθημθμ aKTUBHoro ΚΟΜΠΟΗΘΗΤΘ AKTHBHbIM ΜΗΓρβΑΜΘΗΤ 0,25-2 r. KonnoMAHan AeyoKMCb κρβΜΗπη 2,0 Heo6xoAMMoe κοπ-βο ao ποπηογο og^eMa MMKpoKpMCTa/iMHecKae qenniono3a AO 100,0 52
B COOTBeTCTBMM C 3TMM ΠρΜΜβρΟΜ aKTMBHbIM ΜΗφΘΑΜβΗΤ CMeLUMBa/lCn C ΚΟΠηΟΜΑΗΟίί AByOKMCbK) KpeMHMfl MMKpOKpMCTa/lMMeCKOM qe/into/i030ii nyTeM Mcnojib30BaHMH npuroflHoii anuKBOTHoii τθχηοπογμμ CMeiueHMn c τθμ, Μτοδω o6ecnemiTb Heo6xoflMMoe pacnpe,qeneHMe aKTMBHoro MHrpeflueHTa no eceMy o6beMy ηθποπημτθπα. flanee ocyuļecTBnneTcn bboa nonyHeHHOM κομπο3μι1ΜΜ b φθρΜβμθΒΤΜΗβοκοβ ycTpoMCTBO, o6ecneMMBaK>uļee ΜβΑπβΗΗΟβ BbiflejieHne 3κτμβηογο MHrpeflueHTa, κοτοροβ oāecneHMBaeT 1) ποοτοηηηοθ BbiAe/ieHne βκτμβηογο MHrpeAneHTa mjim 2)MMnyjibCHoe BbifleneHMe 3κτμβηογο MHrpeflMeHTaA
BeTepnHaPHoe cpeacTBO mia opa/ibHoro οροιιιθημα % Bec/o6-beMH. flnana30H AKTMBHbIM ΜΗφβΑΜβΗΤ 0,35 0,01-2,0% Bec/o6beMH. noiiMCOpēaT 85 5,0 5eH3M/10BblM enMPT 3,0 ΠρΟΠΜϋβΗ ttlMKOJlb 3,0 ΒγφβρΗωΑ φοοφθτ Ao Be/iMH. boaopoah. noi<a3.= 6,0 - 6,5 eA. pH BoAa AO 100 % nojiHoro o6i>eMa B COOTBeTCTBUH C 3TMM ΠρΜΜβρΟΜ npOM3BOflkinOCb paCTBOpeHMe θκτμβηογο MHrpeAMeHTa b ΠοπΜοορδβτβ 85, 6θη3μποβομ cnupie n nponuneH rnuKone. flanee npon3BOAmiocb Ao6aB/ieHne BOflbi m, b cnynae Heo6xoAHMOCTM, BenMMMHa βοαοροαηογο noKa3aTerm AOBOAMJiacb ao 6,0 -6,5 θα. pH nyTeM Ao6aBneHMn δγφβρΗΟΓΟ φοοφβτβ m 3aTeM Ao6aBneHMe BOflbi ao Hy>KHoro oO'beMa. nonyHeHHan KOMno3mļMfl 3arpy>Kanacb b ΚΟΗΤβΜΗβρ ΑΠ^ OpajībHOrO ΠρίΙΜβΗΘΗΜΑ flJin >KMBOTHblX.
BeTepMHaPHbie nacTbi una opanbHoro πρκμθηθημβ % Bec/BeCOBbIM. flnana30H AKTMBHbIM ΜΗΓρβΑΜβΗΤ 4,0 1-20% eec/sec. CaxapMH HaTpMH 2,5 no/iMCop6aT 85 3,0 /ļMCTeapaT amoMMHMH 5 ΦρβΚΜΜΟΗΜρΟΒβΗΗΟβ KOKOCOBOe Macno AO 100,0 53 53LV 10781 B COOTBeTCTBMH C 3TMM ΠρΜΜβρΟΜ npOH3BO,AmiOCb ΛΜΟΠθρΓΜρΟΒΘΗΜΘ AUCTeapaia aruoMMHMn bo φρβκμποΗΜροΒβΗΗΟΜ kokocobom Macne m nonncop6aTe 85 nyTeM HarpeeaHHfl. flanee nonyseHHaii cMecb OKnajKflanacb ao κομηθτηομ TeMnepaTypbi m npoM3BOAM/iocb AMcneprupoBaHHe caxapnHa HaTpun b μθοιηηομ HOCMTe/ie, a zaretA AncneprupoBaHue θκτμβηογο MHrpeAueHTa b nonyMeHHOM τθκμμ o6pa30M ocHOBe. Γοτοβημ MaTepnan ρθοφθοοΒωΒβηοη b nnacTMKOBbie LunpMLļbi. fpaHVJibi. npenHa3HaMeHHbie ajia npneMa βμθοτθ c numeti. b BeTepnHaPHH. % Bec/BeCOBbIM. flnana30H AKTMBHbIM ΗΗΓρβΑΜΘΗΤ 2,5 0,05-5% eec/BecoBbiM Cyxib0aT Ka/ibiļMfl noiiyrMApaT AO 100,0 B cooTBeTCTBMM c 3tmm npMMepoM npoM3BOAM/iocb CMemeHMe aicTMBHoro MHrpeAneHTa c cyr^aTOM Ka/ibiļMn. flna nonyHeHMii rpaHyn ncnonb30Bancjļ npoiļecc μοκρογο rpaHynnpoBaHMq. CyiUKa rpaHyn ocymecTBJifl/iacb c noMoiiļbio cyujnnKM b κμπαι^θμ cnoe mjim c πομοιαβιο jiotkobom cyiUM/iKM. no/ryHeHHbie rpaHynbi 3arpy>Ka/iMCb b npMroAHbiii ΚΟΗΤΘΜΗβρ.
BeTepnHapHas κομπο3μιιηα nna noriHBa % Bec/BeCOBbIM. flnana30H AKTMBHbIM ΜΗΓρβΑΗβΗΤ 2,0 ot 0,1 ao 30 % flMMeTMJlCyjlb0OKCMA 10,0 MeTMJiM3o6yTMJiKeTOH 30,0 ΠρθΠΜ/ieHniMKOJIb (m ΠΜΓΜβΗΤ) AO 100 B COOTBeTCTBMH C 3TMM ΠρΜΜΘρΟΜ npOM3BOAMTIOCb paCTBOpeHMe aicTMBHoro MHrpeAneHTa b AMMeTMricyr^OKCMAe m MeTM/iM3o6yTM/iKeTOHe. flanee npoM3BOAnnocb AoSaB/ieHMe πμγμθητθ μ προπΜπβΗΓΠΜκοηη b KOAMMecTBe, ηθο6χοαμμομ ao 3aAaHHoro oābeMa. nonyHeHHan κ0ΜΠ03ΜμΜΒ pa3nMBa/iacb no KOHTeMHepaM, npeAHa3HaHeHHbiM a-πα ποπμβκμ. 54
3MVJibrnpyeMb)ti KOHueHTpaT AKTMBHbIM ΜΗΓρβΑΜβΗΤ 50 r. AHMOHHbiii 3My/ibraTop 40 r MMKpoKpMCTammecicafl uemnono3a ( Τ3κοη, κβκ HanpuMep, φβΗΗ/ι cynb<J)OHaT CA LX) HeHOHoreHHbm 3MyxibraTop (τβκοϋ, κβκ HanpuMep, Synperonic NP-13X) ApoMaTtmecKMH pacTBopMTenb -ao 1n (τβκοκ, κβκ HanpHMep, Solvesso 100 ) npuMeMaHue: X) ripOflyKT, npOM3BOflMMblii φΜρΜΟΜ I.C.I. B COOTBeTCTBMM C 3TMM ΠρΜΜβρΟΜ npOH3BOflHJHOCb ΟΜΘΙΒΘΗΜΘ ΒΟβΧ μηγρθαμθητοβ ao τβχ nop, noxa He npon3ow/io μχ ποπηοθ pacTBopeHne. Γ paHvnbi lai AKTMBHblti ΜΗΓρβΑΜβΗΤ 50 r. BKCTpaKMHOHHaa KaHM<t>ojib 40 r fpaHynbi runča (chto Ns20-60) b κοπ-βθ ao 1κγ (ranne, κβκ HanpHMep, Agsorb 100 A) 1 B / AKTMBHbIM ΜΗΓρβΑΜβΗΤ - 50 r Synperonic NP -13* 40 r ΓpaHynbi rMnca ( chto Ns 20-60) b κοη-Ββ ao 1 κγ npuMeMaHue: X npon3BOflHTenb - φπρΜβ I.C.I.
MeTOflUKa McnbīTaHMM, npnHfuafl b οτηοιαθημμ 6onbuniHCTBa HaceKOMbix, BicriioMana b ce6n coaepKaHMe onpeAeneHHoro KonunecTBa HaceKOMbix b cpefle, KOTopaa o6biHHo npeACTaB/meT co6oti cpefly oāMTaHMfl ΜΠΜ ΠγτβΜ 06pa60TKM CpeAbl nOJiyMeHHblM ΠρΜΓΟΤΟΒΠβΗΜβΜ (OCTaTOHHbIM TecT) μπμ, b cnyHae τθκμχ HaceKOMbix κβκ Tetranychus urticae, Mususpersica, Nilaparvata lugens, Musca domestica xax HaceKOMbie, τθκ m cpeAa noABepranncb o6pa6oTKe πρμγοτοβπθημθμ (κοητθκτηημ τθοτ). B cnyMae Meliodogyne incognita pacTBop HaHOCunca Ha noMey, b KOTopyio 6binn Bbica>KeHbi caKeHijbi τομθτοβ, KOTopbie 3aTeM nopa>xajiiicb μθρβημμ, m onpeAe/m/iocb yMeHbiueHMe κοπμμθοτβθ HapocTOB Ha κορηηχ no CpaBHeHHtO C KOHTpOJlbHblMM ρβΟΤΘΗΜΗΜΜ.
Mcnonb3y« 3tm προμβΑΥρω, coeAHHeHMe, xapaKTepM3yeMoe φopMyJ^oίί ( I ), b κοτοροΜ R1 npeACTaBnneT co6oii vi3onponnn, R2 LV 10781 55 npeflCTaBrmeT co6oii μ©τμ.π m R npe,qcTaB/ineT co6oii BOflopofl, κθκ 6bmo yCTaHOBJieHO, HBJlfleTCH 3φφθΚΤΗΝΜ npM ΚΟΗΙ^ΘΗΤρβφΐηΧ, paBHblX 100 nacTeii eecoBbix Ha μμππμοη μπμ MeHee. 56 56 LV 10781
OoDMvna n3o6peTeHna 1. CoeflMHeHMH 4>opMy/ibi (I)
mjim ero conu, r^e R1 npeflCTaBn»eT co6oii Μβτιυ^Ηγιο, 3TwnbHyto μπμ M3onponnnbHyio rpynny, R2 npeflCTaBrmeT co6oii aTOM Boflopofla, Ci_e -anKnnbHyio rpynny nnn 2 C3.eanKeHmibHyK) rpynny m rpynny =NOR , κοτορβΗ ηθχοαμτοα b E - KOHCpMrypai4MM; 3 57 OR npeflciaBrmeT co6om rnflpoKcnnbHyK) rpynny, nnn 3aMeifleHHy»o rnflpoKcnnbHyK) rpynny, coflep>KamyK) ao 25 aTOMOB ymepofla, o6naflaioiflMe
3ΗΤΜ6Μ0ΤΜΗΘ0Κ0Μ M MHCeKTULļMflHOM aKTMBHOCTblO 2. CoeflMHeHMfl no nyHKTy 1, rfle OR3 npeflCTaB/iaeT co6oii
MeTOKCMKap6oHnr!OKCMrpynny, aLļeTOKCnrpynny, MeTo«cnrpynny min rnflpoKcnnbHyto rpynny. 3. CoeflMHeHnn no nyHKTy 1, rfle OR3 npeflCTaB/iaeT οοδοίί rnflpoKCnnbHyio rpynny. 4. CoeflMHeHne no n»o6oMy 113 yKa3aHHbix Bbiiue nyHKTOB, rfle R1 npeflCTaBJisieT οοδοίί M30-nponmibHyio rpynny. 5. CoeflMHeHne no nK>6oMy M3 yKa3aHHbix Bbiiue nyHKTOB, rfle R2 npeflCTaBnfleT οοδοίί MeTmibHyio rpynny. 6. CoeflMHeHnn no nyHKTy 1, rfle R1 npeflCTaBrmeT οοδοίί M30- 2 3
nponnnbHyto rpynny, R npeflCTaBJineT co6om MeTWibHyio rpynny m OR npeflCTaBnneT οοδοίί OKCnrpynny, aiļeT0Kcnrpynny min
MeTOKCMKap6oHnnoKcnrpynny. 7. CoeflMHeHMfl no nyHKTy 1, rfle R1 npeflCTaBrmeT οοδοίί H30-nponnnbHyro rpynny, R2 npeflCTaBnneT οοδοίί MemnbHy»o rpynny m OR3 npeflCTaBrmeT οοδοίί rnflpoKCnnbHyto rpynny. 8. CoeflMHeHnn no nyHKTy 1, rfle R1 npeflCTaBnneT οοδοίί MeTH/ibHyio
rpynny, R2 npeflCTaBrmeT οοδοίί MeTMnbHyio rpynny m OR3 npeflCTae/ifleT
1 2 οοδοίί MeTOKCnrpynny; μπμ R npeflCTaBnneT οοδοίί 3TnnbHyio rpynny, R npeflCTaBnfleT οοδοίί MeTHJibHyK) rpynny n OR npeflCTaBnneT οοδοίί mflpOKCnnbHyK) rpynny. 58 58LV 10781 9. KoMno3mļnn fljia ncnonb30BaHna b MeflmļMHe flnn πθηθημα ntofleii ommNaiomaHCfi meM, mto OHa οοββρ>κΜΤ οφφβκτκΒΗοβ KonuMecTBO no MeHbiueii Mepe οαηογο οοθαμηθημα b οοοτβθτοτβμμ c πυηκτομ 1, βμθοτθ c
OflHMM MflM HeCKOJlbKMMM ΗΟΟΜΤβΠΗΜΜ pa36aBMTe/lflMM (HanOJIHMTenflMM). 10. ΚθΜΠ03Μ14ΜΗ flJlfl MCn0nb30BaHMfl B BeiepMHapMM, omnuHatomafJca meM, mto OHa 00Αβρ>ΚΜΤ οφφβκηίΒΗοβ κοπμμθοτβο no ΜβΗΒΐυβίί Mepe οαηογο οοθαμηθημα no nyHKTy 1, ΒΜβοτβ c oahmm mjim HecKonbKMMM HocmennMM n/nnn v\ HanonHMTejinMM.
11. ΚθΜΠ03ΜμΜη fl/lfl 6opb6bl C CeJlbCK0X03HHCTB6HHblMH
BpeflMTennMM, omnu^afomaaca meM, mto OHa coflep>KMT οφφβκτΜΒΗΟβ κο/iMMecTBO no MeHbmeii Mepe οαηογο οοθαμηθημη no nyHKTy 1 ΒΜβοτβ c
OflHMM Unu HeCKOJlbKMMU ΗΟΟΜΤΘΠΜΜΜ H/WH4 Μ ΗΘΠΟ/ΙΗΜΤβΠΗΜΜ. 12. KoMno3MLļHfl no nio6oMy 0flH0My M3 yKa3aHHbix Bbiiue nymaOB 9-11, omnu^atouļaaca meM, mto OHa coflep>KMT 3φφβκτΜΒΗ0β κοπμμθοτβο coeflMHeHMH no nyHKTy 7, βμθοτθ c oahhm μπμ HecKonbKMMM HOCnTennMM n/nnn m HanonHMTennMM. 13. Cnoco6 yHMMTO>KeHMfl BpeflMTeneii b cenbCKOM χο3«ίίοτΒβ, caAOBOM χο3ηίίοτΒβ mjim necHOM xo33MCTBe, nnn Ha ctcnaAax, b xpaHminmax, b 3flaHnnx μπμ flpyrnx o6iAecTBeHHbix μθοτθχ hjim μθοτθχ nx o6nTaHnn, omnu^aiomuuca meM, mto πρμμθηαιοτ Ha pacTeHnnx Unu OBoinax, min HenocpeflCTBeHHO Ha caMnx βρθαμτθπηχ, min Ha MecTax nx oāHTaHHn oaho HilM HeCKOJlbKO COeflMHeHMM B COOTBeTCTBMH C nyHKTOM 1. 14. Cnocoā no nyH«Ty 13, omnu^aiomuūcfi meM , mto yi<a3aHHbie BpeflMTenM npeflCTaBnnioT οοδοίί pa3nnMHbie HaceKOMbie, MepBH m HeMaTOflbi. 59 LV 10781 ΡΕΦΕΡΑΤ
OnncaHbi coeflMHeHMii, xapaKrepM3yeMbie φοριν^Γίοιί (I)
3 CH. (I) Μ MX COflM, B KOTOpblX, R1 npeflCTaenneT co6oū μθτμπβηυκ), 3TnnbHyK) v\m M30-nponmibHy rpynny, R npeflCTaBrmeT co6om θτομ ranoreHa, Ci.8ajiKnnbHyto rpynny m/im C3-8anKeHnnbHyK> rpynny m rpynny, =NOR2 HaxoflMTCfl b E - KOK^nrypaLļMn; OR npeflCTaBJineT co6oii rnflpoKCnnbHyio rpynny, μπμ 3aMetiļeHHyio rMflpoKcmibHyio rpynny, coflep>Kainyto flo 25 btomob ymepofla. 3tm coeflMHeHMH MoryT 6biTb Mcno/ib30BaHbi b κθηθοτβθ 3ητμ6μοτμκοβ αγία niOAeii μ >κμβοτηνχ μ flna yHMHTO>KeHMfl cenbCK0X03fliicTBeHHbix Bpeflmeneii.

Claims (13)

  1. LV 10781 Izgudrojuma formula 1. Savienojumi ar formulu (I) NOR1
    vai to sālīs, kur: R1 ir metilgrupa, etilgrupa vai izopropilgrupa; R1 ir ūdeņraža atoms, Ci-salkilgrupa, Cs-salkenilgrupa vai grupa =NOR1, kas atrodas E-konfigurācijā; OR2 ir hidroksilgrupa vai aizvietota hidroksilgrupa, kurā aizvietotājs satur līdz 25 oglekļa atomiem, kam piemīt antibiotiskā un insekticīdā aktivitāte. 1 1 Savienojumi pēc 1. punkta, kuros OR2 ir metoksikarboniloksigrupa, 2 acetoksigrupa, metoksigrupa vai hidroksilgrupa.
  2. 3. Savienojumi pēc 1. punkta, kuros OR3 ir hidroksiigrupa.
  3. 4. Savienojums pēc jebkura no iepriekšējiem punktiem, kurā R1 ir izopropilgrupa.
  4. 5. Savienojums pēc jebkura no iepriekšējiem punktiem, kurā R2 ir metilgrupa.
  5. 6. Savienojums pēc 1. punkta, kurā R1 ir izopropilgrupa, R2 ir metilgrupa un OR3 ir metoksikarboniloksigrupa, acetoksigrupa vai hidroksiigrupa.
  6. 7. Savienojums pēc 1. punkta, kurā R1 ir izopropilgrupa, R2 ir metilgrupa un OR3 ir hidroksiigrupa.
  7. 8. Savienojums pēc 1. punkta, kurā R1 ir metilgrupa, R2 ir metilgrupa un OR3 ir metoksigrupa, vai arī R1 ir etilgrupa, R2 ir metilgrupa un OR3 ir hidroksiigrupa.
  8. 9. Kompozīcija, kas paredzēta cilvēku ārstēšanai, atšķiras ar to, ka tā satur efektīvu daudzumu vismaz viena savienojuma pēc 1. punkta, kopā ar vienu vai vairākiem nesējiem un/vai atšķaidītājiem (pildvielām).
  9. 10. Kompozīcija, kas paredzēta pielietojumam veterinārijā, atšķiras ar to, ka tā satur efektīvu daudzumu vismaz viena savienojuma pēc 1. punkta, kopā ar vienu vai vairākiem nesējiem un/vai pildvielām.
  10. 11. Kompozīcija, kas paredzēta lauksaimniecības kaitēkļu apkarošanai, atšķiras ar to, ka tā satur efektīvu daudzumu vismaz viena savienojuma pēc 1. punkta, kopā ar vienu vai vairākiem nesējiem un/vai pildvielām.
  11. 12. Kompozīcija pēc jebkura no 9. līdz 11. punktam, kas atšķiras ar to, ka tā satur efektīvu daudzumu savienojuma pēc 7. punkta, kopā ar vienu vai vairākiem nesējiem un/vai pildvielām.
  12. 13. Paņēmiens kaitēkļu apkarošanai lauksaimniecībā, dārzkopībā un mežkopībā, vai noliktavās, glabātuvēs, celtnēs un citās sabiedriskās vietās, vai kaitēkļu uzturēšanās vietās, kas atšķiras ar to, ka uz augiem vai dārzeņiem, vai tieši uz kaitēkļiem vai to uzturēšanās vietām pielieto vienu vai vairākus savienojumus pēc 1. punkta.
  13. 14. Paņēmiens pēc 13. punkta, kas atšķiras ar to, ka minētie kaitēkļi ir dažādi kukaiņi, tārpi un nematodes. 2
LVP-93-1233A 1986-06-06 1993-11-15 Macrolides LV10781B (en)

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GB868613790A GB8613790D0 (en) 1986-06-06 1986-06-06 Chemical compounds
GB868625854A GB8625854D0 (en) 1986-10-29 1986-10-29 Chemical process
GB878708423A GB8708423D0 (en) 1987-04-08 1987-04-08 Chemical compounds

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LV10781B true LV10781B (en) 1996-10-20

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GB8813150D0 (en) * 1988-06-03 1988-07-06 American Cyanamid Co Chemical compounds
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US4988824A (en) * 1989-09-11 1991-01-29 Maulding Donald R Process for the preparation of 23-(C1-C6 alkyloxime)-LL-F28249 compounds
JPH06505711A (ja) * 1990-12-07 1994-06-30 テンプル　ユニバーシティ−オブ　ザ　コモンウェルス　システム　オブ　ハイヤー　エデュケーション 安定化された昆虫寄生性線虫組成物
JP2855181B2 (ja) 1993-12-10 1999-02-10 敏雄 鈴木 松類の枯損防止用組成物及び防止方法
PT1197215E (pt) 2000-10-10 2006-07-31 Wyeth Corp Composicoes antelminticas
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JP4939025B2 (ja) * 2005-09-30 2012-05-23 三菱電線工業株式会社 電熱ヒータ付きハンドル用グリップ部材
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