LV10777B - A process for preparing of chemical compounds, composition thereof, a method of combatting infections or infestations - Google Patents

A process for preparing of chemical compounds, composition thereof, a method of combatting infections or infestations Download PDF

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Publication number
LV10777B
LV10777B LVP-93-372A LV930372A LV10777B LV 10777 B LV10777 B LV 10777B LV 930372 A LV930372 A LV 930372A LV 10777 B LV10777 B LV 10777B
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compound
hydroxy
hydrogen
group
ηλη
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LVP-93-372A
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English (en)
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LV10777A (lv
Inventor
John B Ward
Hazel M Noble
Porter Neil
Richard A Fletton
Noble David
Derek R Sutherland
Michael V J Ramsay
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American Cyanamid Co
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Priority claimed from GB858510943A external-priority patent/GB8510943D0/en
Priority claimed from GB858510942A external-priority patent/GB8510942D0/en
Priority claimed from GB858510944A external-priority patent/GB8510944D0/en
Priority claimed from GB868606103A external-priority patent/GB8606103D0/en
Application filed by American Cyanamid Co filed Critical American Cyanamid Co
Publication of LV10777A publication Critical patent/LV10777A/lv
Publication of LV10777B publication Critical patent/LV10777B/lv

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    • C—CHEMISTRY; METALLURGY
    • C07—ORGANIC CHEMISTRY
    • C07H—SUGARS; DERIVATIVES THEREOF; NUCLEOSIDES; NUCLEOTIDES; NUCLEIC ACIDS
    • C07H15/00—Compounds containing hydrocarbon or substituted hydrocarbon radicals directly attached to hetero atoms of saccharide radicals
    • C07H15/20—Carbocyclic rings
    • C07H15/22—Cyclohexane rings, substituted by nitrogen atoms
    • C07H15/238—Cyclohexane rings substituted by two guanidine radicals, e.g. streptomycins
    • 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
    • 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
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P33/00—Antiparasitic agents
    • A61P33/10—Anthelmintics
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12N—MICROORGANISMS OR ENZYMES; COMPOSITIONS THEREOF; PROPAGATING, PRESERVING, OR MAINTAINING MICROORGANISMS; MUTATION OR GENETIC ENGINEERING; CULTURE MEDIA
    • C12N1/00—Microorganisms, e.g. protozoa; Compositions thereof; Processes of propagating, maintaining or preserving microorganisms or compositions thereof; Processes of preparing or isolating a composition containing a microorganism; Culture media therefor
    • C12N1/20—Bacteria; Culture media therefor
    • C12N1/205—Bacterial isolates
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12P—FERMENTATION OR ENZYME-USING PROCESSES TO SYNTHESISE A DESIRED CHEMICAL COMPOUND OR COMPOSITION OR TO SEPARATE OPTICAL ISOMERS FROM A RACEMIC MIXTURE
    • C12P17/00—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms
    • C12P17/18—Preparation of heterocyclic carbon compounds with only O, N, S, Se or Te as ring hetero atoms containing at least two hetero rings condensed among themselves or condensed with a common carbocyclic ring system, e.g. rifamycin
    • C12P17/181—Heterocyclic compounds containing oxygen atoms as the only ring heteroatoms in the condensed system, e.g. Salinomycin, Septamycin
    • C—CHEMISTRY; METALLURGY
    • C12—BIOCHEMISTRY; BEER; SPIRITS; WINE; VINEGAR; MICROBIOLOGY; ENZYMOLOGY; MUTATION OR GENETIC ENGINEERING
    • C12R—INDEXING SCHEME ASSOCIATED WITH SUBCLASSES C12C - C12Q, RELATING TO MICROORGANISMS
    • C12R2001/00—Microorganisms ; Processes using microorganisms
    • C12R2001/01—Bacteria or Actinomycetales ; using bacteria or Actinomycetales
    • C12R2001/465—Streptomyces

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  • Chemical & Material Sciences (AREA)
  • Health & Medical Sciences (AREA)
  • Organic Chemistry (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Engineering & Computer Science (AREA)
  • General Health & Medical Sciences (AREA)
  • Biotechnology (AREA)
  • Genetics & Genomics (AREA)
  • Zoology (AREA)
  • Wood Science & Technology (AREA)
  • Biochemistry (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Veterinary Medicine (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Medicinal Chemistry (AREA)
  • General Chemical & Material Sciences (AREA)
  • Microbiology (AREA)
  • General Engineering & Computer Science (AREA)
  • Tropical Medicine & Parasitology (AREA)
  • Molecular Biology (AREA)
  • Public Health (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Animal Behavior & Ethology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • Virology (AREA)
  • Biomedical Technology (AREA)
  • Oncology (AREA)
  • Communicable Diseases (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Oxygen Or Sulfur (AREA)
  • Saccharide Compounds (AREA)
  • Agricultural Chemicals And Associated Chemicals (AREA)
  • Preparation Of Compounds By Using Micro-Organisms (AREA)
  • Nitrogen And Oxygen Or Sulfur-Condensed Heterocyclic Ring Systems (AREA)
  • Heterocyclic Carbon Compounds Containing A Hetero Ring Having Nitrogen And Oxygen As The Only Ring Hetero Atoms (AREA)

Description

2 npeflCTaBrtinoT co6oft rpynny ροαοτβθηηνχ οοθαμηθημη, HMeiomnx He-no/iHyio $opMy/iy (I)
(I) HTaK, Kax onncaHo b flaHHOM onHcaHHH, BtiflB/ieHa αοποληη-Te^ibHaii rpynna coeflHHeHMfi, o6jiaflapmnx aHTH6noTHHecKcm aKTMB-HOCTblO, KOTOpbie MŪ5KHO nOJiyMHTb noepeflCTBOM XHMHHeCKOft MOflHCfcH-KaLļMH aHTn6noTHKOB S541 ηλη nyTeM BbiAe^eHHH ηχ M3 Ky/ibTypbi MHKpoopraHMSMOB pofla Streptomyces. Hoebie coeflHHSHHfi npefl/iarae-ΜΟΓΟ Μ3θ6ρθΤΘΗΗΛ OČ/iaflaiOT aHTMāHOTHMeCKOii aKTHBHOCTblO h/hjw πρΜΜβΗΛίοτοίΐ ksk npoMe>KyTOHHbie npoflyKTbi npH noyiyMeHnn Apyrnx aKTHBHbIX COeflHHeHHH H/H/IH npH ΒΜΛβΛΘΗΜΜ H-ΠΜ OHHCTKe COeflMHeHMH aHTH6MOTHKOB S541.
CoeflHHeHHH HacTOKmero H3o6peTeHHH npeflCTaB/ΐίΐιοτ cočofi 23-ΚβΤΟΗ, 23-fleOKCH, H 23-rHflpOKCH/l HAH 3aMeiI(eHHbie rHflpOKCH/Ib-Hbie aHaJlOTH aHTH6nOTMKOB S541, KOTOpbie ΗΜβΙΟΤ rHApOKCH/lbHyiO ΗΛΗ 3aMemeHHyio rnflpoKCH./ibHy!0 rpynny b πο/ιο>κβΗΗΗ 5.
TaKHM o6pa30M, b oahom EapHaHTe HacTOflmero M3o6peTeHHfl - 3 - LV 10777 npeflJiaraioTCfl, b Hcicthocth, coeflHHeHHfl $opMy/ibi (II)
rfle R1 npeflCTaBJineT MeTR/ibHyio, 3TM.flbHyio hjik H3onponH/ibHyio rpynny; R2 npeflCTaBii^eT aTOM Boflopofla ηλη rpynny OR5 (r«e OR5 ΛΒΛΛβΤΟΗ rHflpOKCH/IbHOM rpynnoiĪ, 1ΛΛ1Λ 3aM€ll(6HHOH rMflpOKCHTIbHOH rpynnoH, coflep*auiefi ao 25 aTOMOB yr\nepofla) h R3 npeflCTaB/iiieT aTOM Boflopofla, ηλη R2 m R3 ΒΜβοτβ c aTOMOM yi\nepoaa, κ κοτορο-My ohh npMcoeflHH«ioTCii, npeflCTaB/iinoT >C=0 rpynny; m OR4 npenc-TaBMiieT rpynny OR5 , HMe»myio BbimeyKa3aHHbie oHaHeHHH, a co/ih yKa3aHHbix coeflHHeHHft, npw yc.noBHH, mto b c/tyMae, Kor^a R2 npeflCTaBJi^eT rHjapoKcn./ibHyio rpyrmy, to OR4 «βλκθτολ ποηηηο μθ-tokch rpynnw 3aMemeHHOfi rHflpoKCH/ibHofi rpynnoH. B c/iynae, Korfla coeflHHeHM« 4>opMy.nbi (1) npnxoflnrcji npMMe-H«Tb b KanecTBe npoMe*yTOHHbix npoflyKTOB, oflHa h/ih o6e H3 rpynn R2 H/1H “OR4 HaCTO CTaHOBflTCfl 3aiHHlLļeHHOH rMflpOKCM/lbHOH rpynnofi h npefl/iaraeMoe κ3οδρβτβΗΜβ, b nacTHocTH, coAep>KHT TaKHe aa^H- 4 meHHbie coeflHHeHHii.
Koma rpynnw R2 κλη OR4 b coeflHHeHH jix tļ)opMy.nbi (1) 3aMetiļe-Hbl rHflpOKCH/lbHbIMH rpynnaMH, OHH MOryT 6blTb OflHHaKOBblMH ΗΛΗ OT-jiHMaTbCii npyr ot flpyra h MoryT npeflCTaB./iflTb aiļHAOKcnrpynnbi [HanpHMep, rpynny $opMyAbj -OCOR6 , -OC02R6 hah -OCSOR6 (rfle R6 AB-me-rci? rpynnoft 3ΛΗφ3ΤΜΜβοκοΓθ, apoMoa.πHφaτH^ecκoΓO ηλη apo-MaTHMecKpro pana, HanpHMep, anKHAbHOH, a/iKeHHflbHOft, aflKHHHflb-HOfi, LļHKnoaAKHAbHOfl, apa/IKHflbHOfi H/IH apMJIbHOPi rpynnofi)], φορ-MHJioKCHrpynny, rpynny -OR7 (rfle R7 ΗΜββτ BbiineyKa3aHHbie rau R6 3HaHeHH^), rpynny -0S02R8 (rfle R8 HB/ineTCH Cļ_4 a/iKHflbHOH ηλη Cg -10 apHAbHOH rpynnoR), CHAHiIOKCHrpynny, LlHK/IHHeCKyiO ΗΛΗ ai4HKAHHecKyio aiļeTanbOKCH rpynny ηλη rpynny OCO (CH2)nC02R9 (rfle R9 HBAHeTCA aTOMOM Boflopofla hah rpynnofi, KOTopaa ημθθτ BwmeyKa3aHHbie rjih R6 3HaHeHH*, a n paBHo Ο , 1 ηλη 2). B cnynae, Koma R6 h R7 ηβλϊποτοη a/iKH/ibHbiMH rpynnaMH, ohh Moryr 6biTb, HanpHMep, Cj.g a/iKH/ibhoh rpynnofi, T.e. μθτηλομ, 3ΤΗΛΟΜ, Η-ηρΟΠΗΛΟΜ, Η30Πρ0ΠΗΛ0Μ, H-6yTHflOM, H306yTHfl0M, TpeT-6yTHAOM ηλη η-γθπτηλομ, ayiKH/ibHbte rpynnbi κοτορωχ MoryT 6biTb TaK>Ke 3aMemeHH. B anynae, Korfla R6 ΛΒΛΗβτοΗ 3aMemeHHofi aiiKHAbHOH rpynnoH, oHa μο*θτ 5biTb 3aMemeHa, HanpHMep, oflHofi ηλη HecKOJibKHMH, HanpHMep, flByMH hjih TpeMH aTOMaMH ranoreHa (aTOMaMH xAopa ηλη čpoMa), ηλη KapSoKCH, C!_4 anKOKCH (HanpHMep, ΜβΤΟΚΟΗ , 3TOKCH) , φβΗΟΚΟΗ ΗΛΗ ΟΗΛΗΛΟΚΟΗrpyΠΠΟΗ . ΕΟΛΗ R' npeflCTaBnHeT cočoH 3aMemeHHyio anKHiibHyx3 rpynny, OHa ηο*θτ 6biTb 3aMemeHae 03.7 ι4ηκλο3Λκηλομ, HanpHMep, LļHK/ionponH/ibHoPi rpyn-noH.
Korfla R6 ΗΛΗ R7 ΑΒΛίΠΟΤΟΗ a/IKeHHJlbHOH ΗΛΗ aflKHHHflbHOfl rpynnaMH, ohh MoryT 6biTb npeflCTaB/ieHbi, HanpHMep, C2_8 anKeHH- - 5 - LV 10777 λομ, HanpHMep, a/i/iM/ioM, ηλη C2-g a/iKHHHJībHbiMH rpynnaMH. B cnyMae, Korfla R6 ηλη R7 npeflCTaB/ΐΛΐοτ coSoii αηκλοβλκηλβ-Hwe rpynnu, ohh MoryT 6biTb, HanpHMep, Μηκλοαλκηλομ, Ta- KHM KaK C3_7 Ι4ΗΚΛ03ΛΚΗΛ0Μ. TaKHM o6pa30M, R6 ΜΟ)ΚβΤ npeflCTaB-JiHTb, HanpHMep, qnKJionponMJibHyio, !4HKJio6yTHJibHyio, iļHKJioneHTmīb-Hyio ηλη UHK/toreKCHJibHyio rpynny. R7 Μο>κβτ 6biTb ηηκλοπθητηλβηοη rpynnoii. ; Εολη R6 ηλη R7 npeflCTaB^iinoT apayiKHJibHbie rpynnu, ohh npefl-noHTHTejib-Ho HMeioT ot 1 flo 6 aTOMOB yrflepofla b anKHflbHofi HacTH, a apHJībHaH rpynna (rpynnw) μο>κθτ 6biTb Kap6ouHKflHwecKofi ηλη re-τβροΜΗΚΛΗΗβοκοίί h coflepacaTb npeflnoHTHTe/ibHO 4-15 aTOMOB yr/ie-pofla, HanpHMep, φβΗΗΛ. ΠρΗΜβρω TaKHX rpynn coflep*aT $eH-C!_6 βΛΚΗΛ, HanpHMep, 6eH3HΛbHble ΗΛΗ φβΗΟΤΗΛΒΗΜβ rpynnbl.
Korfla R6 ηλη R7 λβλλιοτολ apHnbHbiMH rpynnaMH, ohh MoryT 6blTb Kap50I4HKnHHeCKHMH ΗΛΗ ΓβΤβρομΗΚΛΗΗβΟΚΗΜΗ Η ΒΚΛΙ0Η3Τ b npefl" ποητητθληηο 4-15 aTOMOB y™epofla, η Μοτγτ πρβΑ0Τ3ΒΛΛ^, HanpHMep, φeHHΛbHyίo rpynny. Β τομ Gnynae, Korfla R2 ηλη -OR4 λβληιοτοη rpynnoii -0S02R8 ohh MoryT 6biTb, HanpHMep, MeτHΛcyΛbφoHHΛoκcH ηλη n-Tonyoncynb-Φοημλοκοη rpynny. Εολη R2 ηλη -OR4 npeflCTaBnaioT cočoh iļHKnHHecKyio aijeTanb-oKCHrpynny, ohh MoryT coflepjKaTb, HanpHMep, 5-7 ηλθηηηθ μπκΛω η MoryT 6biTb, HanpHMep, TeTparHflponHpaHHnoKCH rpynnofi.
Korfla R2 ηλη -OR4 npeflCTaBfl^ioT CHnHOKCHrpynny ηλη R6 co-flep»HT CHΛHΛOKCH-3aMeCTHTeΛb, ΟΗΛΗΛΒΗβΛ rpynna Μ03ΚΘΤ HeCTH τρπ rpynnbl, KOTOpbie MOryT 6blTb OflHHaKOBbIMH ΗΛΗ ΟΤΛΗΗβΙΟΤΟίΙ flpyr OT flpyra, BblČpaHHblMH H3 aΛKHΛbHOH, aΛKeHHΛbHOfļ, aflKOKCH, LļHKnoan-KHΛbHOH, 3ρ3ΛΚΗΛΒΗθίί, apHΛbHo^I η ΒρΗΛΟκοπ rpynn. TaKHe rpynm>i 6 C.
MoryT HMeTb BbiujeyKa3aHHbie rtir R 3Η3μθημλ m, b MacTHocTH, BK/iKJHaTb MeTH/ibHyio, TpeT-6yTH/ibHyio h $eHn/ibHyra . rpynnbi. Kohk-peTHblMH npHMSpaMH T3KHX CH/ĪH.nOKCHrpynn HB.niIIOTCi? ΤρΜΜΘΤΗΛΟΗΛΗ-/IOKCH H TpeT-6yTM/]flHMeTMyiCHJIM/10KCH . B c/iyMae, Korfla R2 hah OR4 npeACTaB/iflioT rpynny OCO(CH2 )nC02R9 ohh MoryT 6biTb, HanpHMep, rpynnoH OCOCOgR9 n/rn OCOCH2 CHjC02R9 rfle R9 npeflcraB/iHer aTOM Boflopo^a μλη Cj_4 a/i-KH/ibHyK3 (HanpHMep, MeTn/ibHyio h/ih 3TH/ibHyio) rpynny.
CoeflHHeHH^ 4)opMy/ibi (II), coflep>KamMe KncnoTHyio rpynny, mo-ryT o6pa30BbiBaTb coah c cooTBeTCTByiomHMn οοηοββηηαμη. ΠρΗΜβρω TaKHX conefi βκλιομθιοτ coah ιιιθλομηογο MeTa/ma, HanpHMep co/ih HaTpmt h Ka.nvin. K BaHHOM rpynne coeflHHeHHM <ļ)opMy/ibi (II) othochtca rpynna, b KOTopoft R1 npeflCTaB/iiieT co6ofi MeTUJibnyxi, 3THAbHyio ηλη H3on-ponH/ibHyio rpynny, R2 m OR4 , KOTopbie Moryr 6biTb οαηηβκοβημη h/ih pasHbiMH, Ka)Kflbifi npeflCTaB/ΐΛβτ rpynny OR5 (r^e OR5 HB/uieTCfl rHflpoKCHJībHofi rpynnoH h/ih aaMemeHHOH rHflpoKCH/tbHoii rpynnofi, BK/nowaioineii ao 25 aTOMOB yr/iepofla) h R3 npeACTaB/iAeT aroM boao-pofla h ee co/ih b tom c/iyHae, Korfla R2 npeflCTaBJineT γηαροκοηλβ-Hyio rpynny, OR4 «ΒΛΛβτσ« πομημο μθτοκοη/ιβηοΗ aaMemeHHOH γηα-pOKCH/IbHOH rpynno£i. K flpyrofi Ba*Hoft rpynne coeAHHeHHH 4>opMy/ibi (II) othochtch rpynna, b κοτοροή R1 npeACTaB/iHeT co6om MeTH/ibHyio, 3TH/ibHyio h/ih n3onponH/ibHyio rpynny, R2 h R3 BMecTe c aTOMOM yr/iepoAa, κ KoropoMy ohh npHcoeflHHnioTcs, o5pa3yioT rpynny >C=0 h OR4 npeflc-τββ/ιαθτ rpynny OR5 (r«e OR5 αβληθτοη rHflpoKCH/ibHoii rpynnon h/ih 3aMemeHHOft rHApoKCH/ibHofi rpynnofi, HMeiomeii ao 25 aroMOB yr/iepo-Aa) h ee co/ih . - 7 - LV 10777 K eiue BajKHoii rpynne οοθαμηθημη $opMyjibi (II) othocmtch rpynna, b κοτοροίί R1 npeflCTaBJi«eT co6ofi MeTHJibHyio/ 3THJibHyio, ΗΛΗ H3OnponH/lbHyi0 rpynny, R2 H R3 ΛΒΛΛΘΤΟΛ KaJKflblfi aTOM BOflopo-fla h OR4 npeflCTaBJiiteT rpynny OR5 (rfle OR5 npeflCTaB-niieT rHRpoK-CH/ibHyio μλμ 3aMemeHHyw rHflpoKcn/ibHyίο rpynny, . coflep>Kaiityio flo 25 aTOMOB yr\nepofla) h ee οολμ. B yKa3aHHbix coeflHHeHH*x φορΜγΛΜ (II), R1 «BiiiieTCH npefl-noHTMTe^ibHo Η3οηροπΗΛΒΗθΗ rpynnofi. R2 ΗΒΛΛβΤΟΗ npeAnOHTKTeilbHO aTOMOM BOflOpOfla ΗΛΗ TļHflpOK-CH/ibHOH rpynnoii, viAVi rpynnoH $opMyvibi -OCOR6 (rfle R5 κβλλβτοη ¢1.5 a/iKH^bHOii rpynnofi (npH «(eJiaHHH 3aMeuteHHyio Cļ_4 ajiKOKCHr-pynnofi), τΛΤίΐΛ φβΗ-^.β ajiKH/ibHOH rpynnoft), -0C02R6 (rfle R6 -Cļ _ 8 a/iKM/ibHas rpynna, 3aMeuieHHan npH «ejiaHHH οαηημ ηλη τρβΜΛ aTOMaMH ra/ioreHa, HanpHMep, τρπχΛοροτΗΛ), - 0C0C02H, -OR7 (r«e R7 ΛΒ-ΠΛβΤΟΛ Cļ _ 8 a/ΙΚΗΛ, C3 _ η LļHKJIOaJIKHil, a/lKH/IbΚ3Λ VIJIH Ι1ΗΚΛΟΠ- ponHJiMeTHJībHaK rpynna) μλμ R2 h r3 ΒΜβστβ c btomom ynnepofla, κ KOTOpOMy OHH npHCOeflHHBIOTCH, o6pa3y»T >C=0 rpynny. B HaCTHOC-TH, R2 npeflnOMTHTe/IbHO ΛΒΛΛβΤΟΗ aTOMOM BOflOpOfla ΗΛΗ 3TOKCM, H-nponOKCH, n-6yTOKCH Ι4ΗΚΛΟΠρθΠΗΛΜΘΤΟΚΟΗ, aiļeTOKCM , {fceHaiļeTOK-CM, npOIlHOHOKCH , H306yTHpH0H0KCH HJIH IļHKROnpOnaHKapČOHHJIOKCH rpynnofi hjih R2 h R3 βμθοτθ c aTOMOM y™epofla, κ KOTopoMy ohm πρΗοοβΑΗΗίΐιοτοΛ o6pa3yiOT >C=0 rpynny.
Tpynna -OR4 B COeflHHeHHHX (ļ)OpMyūbl (II) ΛΒΛΛβΤΟίΙ npeflnOH-THTe/IbHO rHflpOKCH-flbHOČI, MeTOKCH/tbHOft, aUeTOKCMJIbHOM ΗΛΗ ΜΘΤΗΛ-
Kap6oHwyioKCH rpyrinofi ·
Ba)KHbiMH aKTHBHbtMH coeflHHeHvtHMH npen.aaraeMoro H3o6peTeHna ΛΒΛΗΙΟΤΟΛ COeflHHeHHH φopMyΛbl (II), B KOTOpbIX R1 ΗΒΛΗΘΤΟΗ Μβ-TH/lbHOpi, 3TM/IbHOH H/IM, B HaCTHOCTH, H30nporiH.abHOW rpynnOH, R2 8 npeflCTaBJiiieT aTOM Boflopofla m/im otokch, H-nponoKCH, H-6yTOKCM aiļeroKcn, h/ih npormoHOKCM rpynny h R3 ABAiieTCA aTOMOM BOAopofla u/iH R2 m R3 ΒΜθοτβ c aTOMOM ymepona, κ KOTopoMy ohh npHcoeflH-haiotch, o6pa3yiOT rpynny >C=0, h OR4 npeACTaBAAeT co6ofi γηαροκ-cHAbHyro, aueTOKCHAbHyio hah ΜβτοκοΜκβρόοΗΜΛοκοΗ rpynny.
OcoēeHHO Ba^KHbiMH aKTHBHbiMH coeflHHeHHHMH npeflJiarae«oro H3o6peTeHH8 abahiotca coeflHHeHHfl (ļ>opMyAbi (II), b κοτορωχ: R1 ABAHercK H3onponnAbHOM rpynnoH, R2 ηβλλθτοη 3τομομ bo-flopofla, R3 ΛΒΛίτβτοΗ aTOMOM BOflopofla h OR4 npeflCTaBAAeT γηα~ poKCMAbHyio rpynny; R1 RBJlR&TCfi M30nponMAbHOH rpynnoR, R2 ΛΒΛΗβΤΟΗ ηρΟΠΗΟ-HOKCHrpynnoH, R3 ΑΒΛΑβτοΑ aTOMOM Boflopofla h OR4 npeflCTaBAaeT rnApoKCMAbHy» rpynny; R1 8ΒΛΑβΤΟΑ H30nponMAbHOW rpynnofl, R2 H R3 BMeCTe C aTOMOM yr/iepofla, κ KOTopoMy ohh πρηοοθαηηηιοτοα npeACTaBAAfOT rpyn-ny >C=0 h -OR4 ABAAeTCA rMApoKCHAbHOH rpynnoft; R1 ABAAeTCA H30nponHAbHOft rpynnOH, R2 ΑΒΛΑβΤΟΑ 3TOKCH-rpynnofi, R3 npeACTaBJineT aTOM BOAopoAa h -OR4 ΛΒΛΛβτοη γηα-poKCH/ib Hofi rpynnoft; h R1 ΗΒΠΗβΤΟΛ H30np0nM/IbH0H rpynnOH, R2 ΑΒΛΑβΤΟΑ Η-Προ-noKCHrpynnoft, R3 npeACTaB^i^eT aTOM BOAopoAa h OR4 abaastca rHApoKCHJībHOM rpynnoH. R1 «ΒΛΗβτοΛ MeTMAbHofi rpynnoH, R2 npeACTaBAAeT aqeTOKCn-rpynny, R3 αβλλθτολ aroMOM BOAopoAa h OR4 «βληθτοη rnApoKCH/ib-Hoiļ rpynnoft. R1 ABAAeTCA OTHAbHOH rpyrmoH, R2 npeACTaBAAeT aqeTOKCH-rpynny, R3 «βλαθτοα aTOMOM BOAopoAa h OR4 npeACTaBJiHeT co6oft rHApoKCH^bHyro rpynny. - 9 - LV 10777 R1 aB^eTCfl H3onponn/ibHOfi rpynnon, R2 npeflCTaB.nsT aqe-TOKCHrpynny, R3 «ΒΛΗβΤΟΛ 3TOMOM BOflOpOfla H OR4 ΛΒΛΛΘΤΟΛ ΓΗΑ-pOKCHJlbHOH rpynnOM. R1 ABASeTCB HBonponMAbHofl rpynnoft, R2 npeACTaB/iseT H-6y-TOKCH-rpynny, R3 ΑΒΛΚβτση aTOMOM Boflopona h OR4 sB-nseTcs γηα-poKCHAbHoft rpynnofi;
KaK':yKa3biBaAocb panee, coeflHHeHHH npeflAaraeMoro H3o6peTe-HHfl MOryT npMMeHflTbCfl B KaMeCTBe aHTMČHOTHKOB h/ksih ΚΆΚ npOMe-*yTOHHbie COeflHHeHHA ΑΛΗ nOAyweHHH flpyrHX aKTHBHblX COeflHHeHHfi H/HAH npH Bblfle/ieHHH H OHHCTK6 COeffHHeHHft aHTH6HOTHKOB 5541. B tom c/iynae, Korfla npefl/iaraeMbie οοθαμηθημα npHXOflHTC« Hcnoyib30-BaTb Kax noAynpoflyKTbi, R2 η/μλμ -OR4 MoryT 6biTb 3autnmeHHtiMH rHflpoKCHAbHbiMH rpynnaMH. Hcho, mto TaxaH rpynna flOA*Ha HMerb MHHHMa/IbHOG ΚΟΛΜΜβΟΤΒΟ βΟΠΟΛΗΜΤβΛΒHblX φyHK^HOHaΛbHblX rpynn, MToēbj M36e>KāTb «onoAHHTe/ibHbix peaKL(HOHHbix Liene# h AOA*Ha 6biTb TaKOBa, hto6w cTa.no βο3μο>κηι>ιμ M36MpaTeiibHo BoccTaHaB/tHBaTb H3 HeerHflpoKCHAbHyio rpynny. ΠρΗΜβρΗ 3auiHTHbix rHspoKCHAbHbix rpynn HSBecTHbi h onHcaHbi, HanpHMep, b MOHorpacļ)wn "3amnTHbie rpynna b opraHHHecKOM CHHTe3e" ("Protective Groupe in Organic Synthesis" by Theodora W. Greene. Wiley-Interscience, New York 1981) h "3aqHTHbie rpynnbi b opraHHHecKofi χημηη" ("Protective Groups in Organie Chemistry" by I.F.W VcOmie Plenum Press, London, 1973). ΠρΗΜβρυ R H OR* 3amHUteHHblX rHflpOKCHAbHbIX rpynn BK-flIOMaiOT φeHOKCHa^eτOKCH, CHAHUOKCHaiieTOKCH (HanpHMep, TpHMeTHJĪ-CH/ĪH-AOKCHaiļeTOKCH H TpeT-6yTHAAHMeTHACHAHAOKCHaL(eTOKCH) , H CH/IM-jiokch, HanpHMep, TpHMeTH/icHAHnoKCH h TpeT-6yTHnAHMeTMncHnn-jiokch . npennaraeMbie coeflHHeHHfl, coflep*amHe TaKHe rpynnbi 6yflyT, 10 r/iaBHbiM o6paaoM, ncno/ib30BaTbCfl b KanecTBe npoMewyTOHHbix coe-Αηηθηη&. flpyrne rpynnbi, HanpHMep, aqeroKCn, MoryT BbicTynaTb KaK 3amwmeHHbie rHflpoKCH/ibHbie rpynnbi, ho, κροΜβ τογο, MoryT npncyTCTBOBaTb b Lļe.neBbix aKTHBHbix coeflHHeHH«x.
HpyrHe aKTHBHbie coeflHHeHHfl HacTO«uļero H3o6peTeHHH, koto-pbie TaK*e npHroflHbi b KanecTBe no.nynpoflyKTOB, ηβ/ιλιοτοη coeflHHe-ηηλ 0opMy/ibi (II), b κοτοροή R2 npeflCTaB/iHeT rpynny -0C0C02Η. B nacTHOCTH, yKa3aHHbie οοθαμηθημα Haxoαητ Hcno/ibsoBaHHe npn Bbi-ββΛβΗΗΗ H OMHCTKe COeflHHeHHfl aHTHČHOTHKOB S541. OCoSeHHO 3Ha-MMTe/lb HbIM COeflHHeHHeM B 3TOM ΟΤΗΟΙΙΙΘΗΗΗ ΛΒΛΛβΤΟΛ COeflHHeHHe φopMyΛbl (II), b κοτοροΜ R1 npeflCTaB/iiieT H3onponn/ibHyio rpynny, R2 «BJiiieTCH rpynnofi -0C0C02H, R3 λβ/ιηθτολ btomom Boflopofla h OR4 npeflCTaBJiiieT rnflpoKCHJibHyo rpynny, KOTopaa μο*θτ b ochob-HOM HCn0yib30BaTbCH ΠρΗ BblflefleHHH H OMHCTKe COeflHHeHHfl aHTH6MO~ thkob S541, npHBOfluMoro HH)Ke b φopMy.πe (V), rfle Rla λβληθτοη H3onponnjibHOH rpynnofi, a R npeflCTaBJiHeT θτομ Boflopofla. CoeflH-HeHHe φορί^ΛΜ (V) b ΗβΟΜΗίμβΗΗΟΜ BHfle μο*θτ 6biTb npeBpaii{eHO B cooTBeTCTByiomee coeflHHeHHe φορΜγηυ (II), b κοτοροπ R2 «BJiiieTCH rpynnofi -0C0C02H h BbifleneHO, HanpHMep, b κρηοτβλλημθοκοη φορ-Me. CoeflHHeHHe φopMy.πbl (V) μο*θτ 6biTb aaTeM pereHepHpoBaHo b ΠΟΜΤΙ1 OMHUteHHOM BHfle H3 ΠΟΟΠβΑΗΘΓΟ COeflHHeHHil OnHCbIBaeMbIMH B flaHHOM onHCaHHH CnoCOČaMH, ΤΘΧΗΟΛΟΓΗΛ BblfleJieHHfl H OMHCTKH KO-Topbix o6pa3yeT flono/iHHTe^ibHbie npH3HaKH HacTOiimero HsoāpreKH*. 3a«B/ieHHble COeflHHeHHH OČ/iaflaiOT aHTH0HOTHMeCKOH aKTHB-HOCTblO, HanpHMep, aUTHrenbMHHTHOH aKTHBHOCTbiO, HanpHMep, npo-ΤΗΒ HeMSTOflOB, Η B MaCTHOCTH, aHTH_3HflOnapa3HTapHOH Η 3ΗΤΗ~3Κ_ TonapasHrapHOH aKTHBHocTbio. 3KTonapa3HTbi h 3Hflonapa3HTbt 3apaxcaioT fliOfleH h ije/itin p«fl - 11 - LV 10777 «ΗΒΟΤΗΜΧ, H OCOSeHHO ΗΜβΙΟΤ ΙΙΙΗρΟΚΟΘ paCnpOCTpaHeHHe CpeflM CeyibCK0X03«HCTBeHHbIX WHBOTHblX TaKMX KBK CBHHefi, ΟΒΘΙ4, ΚργΠΗΟΓΟ poraToro CKOTa, κο3 h AOMauiHeft πτΗίΐω, jiomaflefi η αομ3ιιιηηχ *h-bothux , HanpHMep, co6aK h KorneK. napa3HTapHafl ΗΗφβκμΗΛ «oMaui-ΗΘΓΟ CKOTa, npHBOflHmafl κ 3ΗΘΜΗΗ, HeflOCTaTOHHOCTH nHTaHHJI Η no-Tepe Beca, aB/ifleTCii ochobhoh πρημηηοη 3Kohomhh6ckhx noTepb bo BceM MHpe. K npeflCTaBMTeji^M 3Hflonapa3HTOB, sapa*aiomMx yKa3aHHbix >kh-βοτηβιχ H/miH jiKDfleii othoc^tch Ancvlostoma, Ascaridia, Ascaris. Aspicularis. Brugia . Bunostomum. Capi1laria. Chabertia. Coope-ria, Dictvocaulus , Dirofilaria. Dracunculus, Enterobius . Hae-monchus. Heterakis . Loa, Necator. Nematodirus, Nematospiroides (Heligomoroides). Nippostrongvlus. Oesophagostomum. Onchocer-ca, Ostertagia, Oxvuris. Parascaris. Strongvlus. Strongvloi-des, Svphacia . Toxascaris. Toxocara. Trichonema. Trichostron-gvlus. Trichinella. Trichuris. Uncinaria h Wuchareria. npHMepaMH 3KTonapa3HTOB, 3apa*aiomHX «ηβοτηηχ η/ηλη Jiiofleii HBJTHKDTCH ΜΛβΗΗΟΤΟΗΟΓΜβ 3KTOnapa3HTbI, HanpHMep, »a/IHIi;He HaceKO-Mbie, naflajībHan Myxa, 6λοχη, bihh , KJieuļH, cocyuiHe HaceKOMbie, HCKOflOBbie K/ieuiH h apyrHe flByKpbuibie HaceKOMbie - BpeflHTejiH. K npHMepaM TaKoro pofla 3KTonapa3HTOB, 3apaxcaiou{Hx >khbothwx η/ηλη Λΐοββίϊ othochtch Ambvlomma. Boophilus. Chorioptes. Culliphore, Demodex, Demallenia. Dermatobia. Gastrophi1us. Haematobia. Haematopinus. Haemophvsalis. Hvalomma. Hvperderma. Ixodes. Linognathus . Licilia. Melophagus. Oestrus. Otobius. Otodectes. Psorergates . Psoroptes. Rhipicephalus . Sarcoptes. Stomoxvs h Tabanus. 06Hapy*eHO, hto npe«naraeMbie οοθαηηθηηλ οΦΦθκτηβηο nefic- 12 ΤΒγιοτ KaK in vitro τθκ h in vivo προτΗΒ mnpoKoro pa^a OHfiona-pa3MTOB h DKTonapasHTOB. B MacTHocTH, o6HapyxceHO, mto coeflHHe-hhh HacTOKmero H3o6peTeHH« βκτηβηο fleHCTByioT προτΗΒ HeHaTOflOB, TaKnx KaK Haemonchus contortus. Ostertaaia circumcincta. Tric-hostrongvlus colubiformis. Dictvocaulus viviparis. Cooperia oncophera, Ostertagia ostertagi. Nematospiroides dubius h Ņjp-postrongvlus brāz i 1 iensis . h napa3HTapHbix ΚΛβιαβΗ, KaK HanpHMep, Sarboptes sp. m Psoroptes sp.
TaKHM o6pa30M, npefl/iaraeMbie οοθαμηθημη HaxoflflT npHMeHeHHe npH ΛβΗβΗΗΗ *HBOTHUX Η ΛΙΟββΜ C PHflOnapa3HTapHOH Η/ΗΛΗ OKTOnā-pa3HTapHOii ΗΗφβΚ11ΗΗΜΗ . BHflbI napa3HTOB ΜΘΗΛΙΟΤΟΛ B COOTBeTCTBHH C Χ03ΛΗΗΟΜ (JKHBOT-HblM) H flOMHHHpyiOmHM MeCTOHaXO)KfleHH6M ΗΗφθΚΗΗΗ . C/ieflOBaTeJIb HO, HanpHMep, B036y,!ļHTeyiM Haemonchus contortus. Ostertagia circumcincta h Trichostrongvlus colubiformis o6whho nopawaioT OBeq h npeHMymecTBeHHO Ji0Ka/iH3yi0TCH b x<e/iyflKe μ τοηκοη κηιιικθ, b to BpeMii KaK Dictvocaulus viviparus. Cooperia oncophora h Ostertagia ostertagi oSumho nopaa<aioT KpynHbiH poraTbiiī ckot h /i0Ka/iH30BaHbi, r/taBHbiM očpa30M b λθγκηχ, KHuieHHHKe hJivi «e/iyAKe, COOTBeTCTBeHHO. AHTHdHOTHHecKaH aKTHBHOCTb npeflyiaraeMbix coeflHHeHHH μοκθτ 6biTb npofleMOHCTpHpoBaHa, HanpHMep, CBoen aKTMBHOcTbio in vitro προτΗΒ cboSoaho x<HBymnx HeMaTOflOB, HanpHMep, Caenorhabiditis elegans.
KpoMe τογο, oaHBnenHbie coeflHHeHHH ημθιοτ ripHMeHeHHe b Ka-necTBe προτΗΒΟΓρΗδκοΒωχ 'BemecTB, HanpHMep, προτΗΒ ιπτβμμοβ Candida KaK HanpHMep, Candida albicans h Candida glabrata h προτΗΒ ηροχοκβΜ, τβκηχ KaK Saccharomvces carlsbergensis. - 13 - LV 10777
CoeflMHeHHH HacTOiimero Η3θ6ρετβΗΗη, κροΜβ τογο, ημθιοτ πρπ-ΜβΗΘΗΗβ Β 6opb6e C ΒρβΑΗΤβ,ΠΑΜΗ-HaceKOMblMH , KJiemaMH Η HeMaTOfla-ΜΗ B Ce/IbCKOM X03AHCTBe, CaflOBOflCTBe, ZieCOBOflCTBe, 3flpaBOOXpa-hshhh h xpaHeHHH npoflyKTOB. Hmh mo>kho ycneujHo o6pa6aTbiBaTb BpeflHTe/iefi noHBbi h ceAbCKoxo3AiļCTBeHHux KynbTyp, BK/iiOHafl xne6-Hbie sjiaKH (HanpHMep, niueHHny, HMMeHb, MaHc, pnc), oboujh (HanpHMep, όριο), φpyκτbI (HanpHMep, flēnoKH, BMHorpafl h UHTpycoBbie) , Hapiifly c KopHennoflaMH (HanpHMep, caxapHyio CBeKny, κβρτοφβΛΒ), xapaKTepHWMH npHMepaMH TaKHX BpeflHTejieH hbaaiotch φpyκτoBbIe KneuļH h tam, HanpHMep, Aphis fabae. Aulacorthum circumflexum. Mvzus persicae. Nephotettix cincticeps. Nilparvata lugens, Panonvchus ulmi, Phorodon humuli. Phvllocoptruta oleivora. Tetranvchus urticae h npencTaBHTeAH pona Trialeuroides HeMaTo-flbi, HanpHMep, npeflCTaBHTenH pofla Aphelencoides, Globodera. Heterodera. Meloidogvne h Panagrellus HeuiyftMaTbie, HanpHMep, Heliothis. Plutella h Spodoptera: «onroHocHK-KajiaHflpHHo , KaK HanpHMep, Anthonomus grandis h Sitophilus granarius: xpymaKH MyHHbie, HanpHMep, Tribolium castaneum; MyxH, HanpHMep, Musca domestica: MypaBbH PHXTepa; MonH-MHHepw/y3KOKpbnibie; Pear psvl-la; TpHncbi TadaHHue; TapaKaHOBbie, HanpHMep, Blatella germanica h Periplaneta americana; μοοκητημθ, KaK HanpHMep, Aedes aegvp-ti . Β οοοτΒβτοτΒΗΗ 9 HacTOHmHM H3o6pereHHeM npefl/io^eHbi coeflH-ΗβΗΗΗ φopMyΛb! (II), Kax yKa3biBanocb Bbirne, κοτορκβ MoryT 6biTb MCnonb30BaHbl Β Κ3ΗΘΟΤΒβ aHTHČHOTHKOB. B HaCTHOCTH, HX MOJKHO Hcnonb30BaTb πρπ ΛβΗβΗΗΗ >κηβοτημχ h JiiofleM, nopa>KeHHbix 3Hflona-paTH3apHOH, 3KTOnapa3HTapHOH Η/ΗΛΗ ΓρΜδΚΟΒΟΗ ΗΗφβΚΑΗίίΜΗ Η Β KanecTBe necTHLļHAOB αλα 6opb6bi c BpeAHTe/iimn - HaceKOMblMH, 14 κ/iemaMH η HeMāTOflaMH, b ce/ibCKOM xo3«iicTBe, caflOBOACTBe, h/ih /leCHOM X03flflCTBe. Hx M0*H0 npHMeHSTb , ΚρΟΜβ ΤΟΓΟ OČblMHO H B KanecTBe necTHLļHflOB b Apyrnx o6cTO*?Te/ibCTBax, HanpHMep, b xpa-Hnyinutax, 3flaHHHx hnu flpyrnx o6uiecTBeHHbix MecTax vuivi MecTax λο-Ka/iH3aiļHn ceJibCK0X03«HCTBeHHbix BpeflHTe/iefi. no-cymecTBy npeflna-raeMbie coeflHHeHHfl MoryT 6biTb πρημθηθηη λη6ο k xo3iīHHy (*hbot-HOMyjf^H-;HeiioBeKy, λμ6ο k Ky/ibTypHbiM pacTeHHHM ηλη flpyrofi pacTHTe/ibHOcth), jih6o k caMHM βρθαητθ/ιλμ nmi MecTy hx pacnojio-«eHHJi. 3aaB/ieHHbie coeflHHeHHfl MoryT 6biTb σφορι^ΛΜροΒ3ΗΜ npne-
Ma b /11060¾ yflo6HOfi φορΜβ ripu ncno/ib30BaHnn b BeTepHH'apHH h/im npaKTMMecKofi MennqnHe. TaxnM o6pa30M, HacTOKaļee H3o6peTeHHe coflep*HT b npefle/iax cBoero oēteMa φΒρΜΒίιβΒΤΜΜβοκΜβ κομπο3ηι1ηη, coflepjKa^He coeRHHenne cor/iacHO 3aiiBJieHHOMy Η3θ6ρβτβΗΗΐο, npn-ΓΟβΗΟβ fl/lfl ΠρΗΜβΗΘΗΗΗ B ΒβΤβρΗΗΒρΜΗ H/IH TepanHH. TaKHe ΚΟΜΠΟ-3HIJHH MOryT 6bITb npeflCTaB/ieHbl npH HCnO/Ib30BaHHH B TpaAHLļMOHHOH φορΜβ C nOMOIIļblO OflHOTO H/IH HeCKO/IbKHX ΠΟβ,ΧΟΡ,ΧΚΗΧ HOCHTe/ieiī H/IH HanonHHTeJiefi. npefl/iaraeMbie κομπο3ΗΙ4ΗΗ coAep*aT cocTaBbi b φορ-Me, ocoSeHHO πρηγοαηοη a/ih napeHTepa/ibHoro (b tom μηο/ιθ, ββθ-fleHHe BHyTpb mojiohhoh a<e/ie3bi) , opa/ibHoro, peKTa/ibHoro, μθοτηο-ΓΟ ΠρΗΜΘΗβΗΗΑ B BHfle HMnjiaHTaHTa, fl/IH ΠρΗΜΘΗβΗΗΛ npH r/ia3Hbix, yiUHblX H/IH 3a60/ieBaHHflX ΜΟΗβΠΟ/ΙΟΒΟίί CMCTeMbl, nOflXOflflmHMH cnoco-6aMH h areHTaMH fl/ΐίΐ πρηγοτοβ/ιθηηλ cocTaBa coeflHHeHHči HacTosme-ro HSoSpeTeHHH, npHroflHoro ρ,ηχ Hcno/ib30BaHHii b BeTepHHapnn h/ih TepanHH, KB/iiiiOTCfl cnoco6bi, KOTOpbie onncaHbi b naTeHTe IOjkhoh Αφ~ pHKH N 85/7049 Rflfl COeflHHeHHH aHTH6H0THK0B S541. 3a«B/ieHHbie coeflHHeHHfl mojkho npuMeHJtTb b KOM6HHai4HH c flpy-ΓΗΜΗ φ3ρΐ^Ι*ΘΒΤΗΗΘ<ΞΚΗ aKTHBHbIMH ΗΗΓρβΑΗΘΗΤ3ΜΗ . - 15 - LV 10777
CyMMapHaa cyTOMHaA flosa npeA-naraeMwx οοθαμηθημη, πρημθηα-eMaa naK b BeTepHHapHH, TaK h b TepanHH, 6yaeT οοοτβθτοτβθηηο b HHTepBa/ie 1-2000 μγ/κγ Beca Te/ia, npeflnoMTMTe^ibHo 50-1000 μγ/κγ, npviHeM yKasaHHbte AoanpoBKH mo>kho npHHHMaTb b αρο6ηνχ Aoaax, HanpHMep, 1-4 pa3a b A^Hb. 3a«BJieHHbie ΟΟβΑΗΗβΗΗΑ MO*HO COCTaBilflTb B Λ1θ6θΗ yA06HOH φορΜβ ,'ίΠρΗΓΟΑΗΟίί ΑΛΑ 3βΜΛβΑβΛΗΑ ΗΛΗ CaAOBOACTBa. TaKHM o6pa~ 3θΜ, HacTOAUiee Η3θ6ρβτβΗΗβ BKAioHaeT b npeAeAax CBoero oāteMa cocTaBbj, coAep^amne coeAHHeHHe, npeAHa3HaHeHHoe αλα πρΗΜβΗβΗΜΑ β 3θΜΛθΑβΛΗΜ ηλη caflOBOflCTBe. Taxne peMenTypbi BK/iranaraT cyxne ηλη, >KHAKHe φορΜΗ, HanpHMep, AycTbi, BKAionaA ΠΗΛβΒΗΑΗΜβ cy6cTpa-Tbl HJIH KOHlļeHTpaTbl, nopoilIKH, B TOM ΜΗΟΛβ paCTBOpHMbie ΗΛΗ CMa-HHBaeMbie nopouiKH, rpaHynbi, BKAicmaA MHKporpaHyAbi h AHcneprnpye-Mbie rpaHy./ibi, TaGjieTKH, TexyMHe BemecTBa, 3MyaibCHH, HanpHMep, pa36aBAeHHbie 3MyjibCHH ηλη 3MyAbrHpyeMbie KOHijeHTpaTbi, προηπτοΜ-Hbie COCTaBbl, HanpHMep, COCTaBbl ΑΛΑ ηρΟΠΗΤΚΗ KOpHefi H CeMAH, npoTpaBJiHBaTeAH οθμαη, ceMeHHbie rpaHyAU, MacnAHbie KOHLjeHTpaTbi, MaCJlAHbie paCTBOpbl, ΗΗΒΘΚΙΙΗΗ, HanpHMep, ΗΗί>βΚ11ΗΗ B CTBOA, paCT-BOpbl ΗΛΗ OnpblCKHBaHHA, AbIMbI H TyMaHbI. ΠοΑΧΟΑΑΐΑΗβ cnocočbi h areHTbi aλα cocTaBAeHHA peijenTypbi ΠpeAΛaΓaeMblX COeAHHeHHH .Λλα ΠρΗΜβΗβΗΗΑ B CaAOBOACTBe ΗΛΗ 3ΘΜ-ΛβΑΘΛΗΗ ΒΚΛ10Η3!0Τ Τβ, ΚΟΤΟρΗβ paCKpbITbl Β naTeHTe Ι0)ΚΗΟΗ ΑφρΗΚΗ Ν 85/7049 ΑΛΑ aHTHGHOTHKOB S541. ΠρΗ ΟΟΟΤΒΒΛβΗΗΗ peLļenTypbI, KOHLļeHTpailHA ΒΚΤΗΒΗΟΓΟ BemeCT-Ba oSblHHO ΟΟΟΤΒΒΛΑβΤ OT 0,01 AO 99 ΒβΟ . % Η 6θΛββ ΠρβΑΠΟΗΤΜ-TeAbHO στ 0,01-40 Macc.%. npoMbiuineHHbie (TOBapHbie) npoAyKTbi o6whho πρηγοτοβλθηη β
BHAe KOHUeHTpHpOBaHHblX ΚΟΜΠ03Η11ΗΗ, ΚΟΤΟρΝΘ ΠρΗ HCnOAb 30BaHHH 16 paačaB/iHiOT bo Tpe6yeMOH KOHLjeHTpaiļMM, HanpHMep, ot 0,001 bo 0,0001 Macc.%. ΠρΜ HCnO/Ib 30B81HHH B BeTepHHapHH ΜΛΗ B CaflCBOflCTBe Η 3ΘΜ“ jieaenhh, h b c.nyHae, Koma npeBnaraeMbie coeflHHeHHH bb/ihiotcb npoayKTaMn, o6pa3yeMbiMM nocpeflCTBOM cfcepMeHTauHH, «eBaTenbHo HCnOBbSOBaTb Becb SpOflMBbHblft 6yBbOH B KaneCTBe HCTOHHMKa aK-THBHblX COeflHHeHHfi. ΚρΟΜβ ΤΟΓΟ, ΜΟ)ΚβΤ 6blTb ΠρΗΓΟΒΗΗΜ MCnOJIb 30-BaHHe o6e3Bo>KeHHoro 6yBbOHa (coflepMcamero MHiiajiHfi) hjm Mmie/imi, oTfle/ieHHoro H3 6y./ibOHa h nacTepH30BaHHoro, h/ih 6oJiee npeflnon-THTe/ibho BbicyuieHHoro. ripu >KeyiaHHM, yKa3aHHbift 6ynbOH ηλκ mmus-ΛΗΗ MOryT 6bITb C(J)OpMy./IHpOBaHbI B K0Mn03MlļHH, KaK yKa3biBayi OCb Bbime, BKBlOHaiOmHe TpaBHlJHOHHbie HHepTHbie ηοοητθλη, HanOBHHTejIH ΗΒΗ pa36aBHTeBM. AHTHSHOTMHecKMe coeflHHeHHfl npefl/iaraeMoro H3o6peTeHHH mo-ryT BBOBHTbCH H npHMeHHTbCH B KOM6HHaqHH C flpyrHMH aKTHBHblMM HHrpeflH€HTaMH . B MacTHOCTH, npeBnaraeMbie coeflHHeHHfi aHTn6noTMKa MOryT HCnOJlb30BaTbCiI BMeCTe C COeflHHeHHHMH aHTH6nOTHKOB S541 ΗΛΗ C flpy ΓΜΜΗ aHTH6MOTHHeCKHMH COeflHHeHMSMH HacTOHinero Η3θ6ρβ- τθηηη. 3το Μθ*βτ B03HHKHyTb, HanpHMep, b cByHae, Koma ηβομμ-qeHHbie npoflyKTbi 6po*eHHH B3aHMOfleMCTByioT corjiacHO cnoco6y HacTOHqero Η3θ6ρθτβΗΗΛ 6ea npeBmecTByrouiero hjih nocjieflyiomero οτβθλθηηη; yKa3aHHoe μο*θτ 6biTb npeflnoHTHTeBbHbiM, HanpHMep, npn Hcnonb30BaHHH coejņHHeHHHi b aeMJieflejiHH, rfle EaHCHO očecne-MHTb (COXpaHHTb ) HH3KyiO CeSeCTOHMOCT b npOByKI4HH.
SaHB/ieHHbie οοθβηηθηηη mo>kho nonyMHTb cnocoSaMH, KOTopbie onHcaHbi HH)Ke. B ΗβκοτορΜΧ H3 yKa3aHHbix cnocočoB kojkct 6biTb ne-06X0flHMblM 3aUļHTHTb rHflpOKCM.nbHyiO rpynny B ΠΟΛΟΚΘΗΗΗ - 5 ΜΛΗ 23 b qeneBOM MaTepnane bo ocymecTB/ieHHH onncbiBaeMoro B3anno- - 17 - LV 10777 ΑβΗΟΤΒΗΛ. B Τ3ΚΗΧ C/iyMaflX MOJKST 6blTb Heo6xOflHMO BriOC/teHCTBHH pa3pymnTb 3amnTy tom »e caMofi rnApoKcn/ibhoA rpynnu, Kax το/ibKo Β03ΗΗΚΛ0 B3aHMOfleiiCTBHe, mto5w no/iywHTb Tpe6yeMoe coeAHHeHHe HacTOHinero H3o6peTeHHH. OāmenpHHHTbie cnocočbi 3amHTbi h οηλτηλ 3amHTbi mo)kho Hcno/ibsoBaTb, HanpHMep, KaK onncaHO b BbimeyKa3aH-ημχ MOHorpa$Hiix Greene h McOmie.
TaKHM oēpaaoM, HanpHMep, aiļH/ibHaii rpynna, TaKaA KaK aiļe-TH/ibHaA rpynna Μθ>κβτ 6biTb oTinen/iena b pe3y/ibTaTe rHApoAH3a ocHOBaHHeM, HanpHMep, Hcnoyib3y« rHflpooKHCb HarpnA ηλη κάληκ b βοαηομ pacTBope cnHpTa ηλη c noMouļbio rHAponH3a khcaotoh, HanpHMep, Mcno./ib3yfl KOHueHTpHpoBaHHyio cepHyio KHonoTy β MeTaHone. AiļeTaJībHbie rpynnbi, TaKHe KaK TeTparHflponHpaHH/i MoryT 6biTb ot-menjieHbi, HanpHMep, πρΗ γηαρολη3θ khcaotoh (HcnoAb3yH KKCJioTy KaK, HanpHMep, yKcycHyio ηλη τpHφτopyκcycHylo KHc/iOTy ηλη pa3-6aB/ieHHyio MHHepaAbHyio KHc/iOTy) . CH/iHJībHbte rpynnbi MoryT 6biTb OTIHen/ieHbl HOHaMH φτσρΗβΒ (HanpHMep, H3 ΤβΤρ33ΛΚΗΛ3ΜΜΟΗΗΗφΤθρΗ-fla, TaKOTO KaK Teτpa-H76yTHΛaMMOHHftφTOpHfl), φΤΟρΗΟΤΗΜ BOAOpO-flOM B BOflHOM pacTBope aiieTOHHTpH/ia ΗΛΗ KKOrtOTbl TaKOfi KaK π-το-ΛyoΛcyΛbφoκHCΛoτbl (HanpHMep, b MeīaHone) . ΑρΗΛΜβτΗ/ibHbie rpynnbi MoryT 6biTb oTUļenneHbi npn očpačoTKe κηολοτοΑ no JlbioHcy (HanpHMep, 3φΗρΒΤ3 φτσρΗΟΤΟΓΟ 6opa) B npHCyTCTBHH THO/ia (HanpHMep, OTaHTHOJia) b cooTBeTCTByiomeM pacTBopHTeAe, KaK HanpHMep, ahx-nopMeTaHe πρΗ κομηβτηοΛ TeMnepaType. M36HpaTeAbHoe οτιΐ{θΠΛβΗΗβ SamHTHOft rpynnbl Β ΠΟΛΟ)ΚβΗΗΜ-5 5,23-flHCHAHAbHblX COefiHHeHHfl HacTOHUļero Η3θ6ρβτεΗΗΑ Μθ>κβτ 6biTb ocyuļecTBJieHO c HcnoAbaoBaHH-θμ TeTpa-H-6yTHnaMMOHHi^TopHAa, β to βρθμα KaK H35npaTe.nbHoe οτ^βΠΛβΗΗβ 3amHTHOH rpynnw β ποΛθ>κεΗΗΗ-5, 5,23-AnaueTOKcncoe-ΑΗΗΘΗΗΑ MO*eT 6blTb ΒΜΠΟΛΗΘΗΟ ΠρΗ HCnOAb30BaHHH ΓΗΑΡΟΟΚΗΟΗ HBT- 18 pMfl b BOflHOM pacTBope MeTaHona.
ripeA-rtaraeMbie οοθαμηθημη, B KOTOpblX R2 Η/ΗΛΗ rpynna 1 0 50 rb/ihiotch 3aMemeHHoii rnApoKCH/ibHofi rpynnoii OČblHHO μο*θτ 6bJTb noyiyHeHa nyTeM B3aHMOAsftCTBHH coeAHHeHHii aHTHČHOTHKOB S541 (HanpHMep, coeAHHeHHii <ļjopMy.ribi (V), CM. Aa/iee) ΗΛΗ 5 H/IH 23-0-oflHO3aHemeHHbix npoH3BOflHbix c peareHTaMH, cj)yHKUHOHnpyioiiiHMH Αλη o6pa30BaHH8 3aMemeHHofi rHApoKCHJībHOH rpynribi. B o6meM, γηα- pOKCH/IbHafl rpynna B ΠΟΛΟΚβΗΗΗ 5 HB/lfleTCil 60/iee XHMHMeCKH aK-THBHa, ΜβΜ rHflpoKCHJībHaH rpynna b πολοκθηηη 23. rnflpoKcn/ibHbie rpynnbi b πολο>κθημη-5 6o/iee * λθγκο oTmeruiflioTCH, μθμ γηα~ poKCH^ibHbie rpynm>i b πο.πο>κβΗΗΗ 23. Boočuie, 5-oflH03aMemeHHbie coeflHHeHHii HacTOHiiļero H3o6peTeHHfl mojkho no/iyMHTb nyreM B3āHMo-flefiCTBHil 5,23-He3aMeu;eHHOrO OKCHCOeAHHeHHfl aHTHČHOTHKOB S541 c orpaHHHeHHbiM κο/iHMecTBOM peareHTa πρπ μηγκηχ ycJiOBHflx, b to BpeMH KaK 5,23-flH3aMemeHHbie coeflHHeHHfl o6pa3yfOTC* πρπ ncno/ib-30BaHHH 6o/ibiuero KO/iMMecTBa peareHTa η b MeHee μηγκηχ >ό.ποβηηχ h/hah b npHcyTCTBHn KaTayiH3aTopa. 23-0flH03aMemeHHbie coeflHHeHHJi npejĻnaraeMoro H3o6peTeHHH mo>kho no/iyMHTb, Bo-nepBbix, nocpeflCTBOM o6pa30BaHHii 5,23-3aMemeHHoro coeAHHeHMH η οθλθκ-THBHoro OTinen/ieHHH 3ainHTHofi rpynnbi b πο/ιο>κηηη-5 . 5,23-AH3aMe- uļeHHbie coeflHHeHHi? flaHHoro H3o6pereHH8, HMeiomHe pas/iMHHbie sa-MeCTHTe/IH B ΠΟ.ΠΟ>ΚβΗΗΗΧ-5 H 23 MOJKHO nO/iyHHTb nyTeM B3aHMO-AefiCTBHH coeflMHeHHH, κοτοροθ oAHOsaMeujeHO b λιο6ομ πολο>κθημη-5 Yum -23 c peareHTOM, npHroflHbiM αλη o6pa30BaHHH flpyroiļ 3aMemeH-hoh rnflpoKcnyibHOii rpynnbi B ApyrOK ΠΟΛΟ*ΘΗΗΚ.
CoryiacHO Aono/iHHTejibHOMy BapnaHTy HsoSpeTeHMH npefl/iara-eTCfl cnoco6 noJiyMeHHH coeflHHeHHH i>opnysibi (II), b κοτοροίί oflHa H3 rpynn R2 H OR4 ΗΒΛΗβΤΟΗ 3aMemeHH0fi rHApOKCH/IbHOH rpynnOH, a - 19 - LV 10777
Apyraji npeACTaB-fiAeT rnApoKCH.nbHyio ηλη 3aMemeHHyio rHflpoKcn/ibHyio rpynny, KaK yKa3biBa/iocb Bbiuie, BKAiOMatomuPI B3aHMoneitcTBHe coeflM-ΗβΗΜή (fopīiy.nM (III): OR5
(r^e R1 ημθθτ BbuueyKa3aHHbie 3Ηβμθηηη h oflHa H3 rpynn OR4 h -OR5 npeflCTaB/iBeT rnflpoKCH.nbHyio rpynny, b to BpeMJi KaK apy- ra« ΛΒΛΛβΤΟΛ rHflpOKCH/IbHOH ΗΛΗ 33Μβ1ήβΗΗθί1 rMflpOKCH/IbHOH rpyn~ noii), c peareHTOM, πρηγοαηημ αλη npeBpameHHH rHApoKCHAbHovi rpynnbi b 3aMeineHHyio γηAP°KCHAbHy 10 rpynny, a npw «eviaHHH c noc-AeAy«01HMM H36HpaTeAbHbJM ΟΤϋΙβΠΛβΗΗΘΜ 3ΑΙΙ(ΜΤΗΟΜ rpynnbl ΟΟΘΑΗΗβΗΗΗ <Ī>opMy.nbi (II), b κοτοροΑ R2 -OR4 o6e npeACTaBA^ioT 3aMeujeHHbie rHApOKCHAbHbie rpynnbl ΑΛΗ 06pa30BaHHfl ΟΟβΑΗΗΘΗΗ0OpMy/lbl (II), rfle OR4 ΗΒΛΑβΤΟΛ rHflpOKCHAbHOfl ΓργΠΠΟΗ, a R2 ΠρΘΑΟΤάΒΑΛβΤ 3a-MemeHHyio rHApoKcn/ibHyio rpynny.
I 20
Boo6iue γοβορλ, yKa3aHHas peaKUHfl BKiiiOMaeT auHAHpoBaHHe, φθρΜΗ/lMpOBaHHe, BBefleHMe CyJlb$OHHJIbHOM rpynnbl, 3TepH$HKaumO , ΒΒβββΗΗβ CH/iH/ibHOH rpynn« h o6pa30BaHHe aqeTajieM.
TaKHM o6pa30M, aiļHJiHpoBaHHe μο*θτ ocymecTB.aJiTbCfl c Hcno/ib30BaHH6M ai4HnHpyiomero areHTa, HanpHMep, khcjiotm φopMy/lbI R6COOH ηλη ero peaKHHOHHocnoco6Horo npoM3BOflHoro, HanpHMep, raiioHflaHpHflpHfla (Tanoro KaK xnopaHrHflpHfla), aHrHflpHfla hjih ax-THBHpoBaHHoro ολο*ηογο οφπρβ, hjih peaKijHOHHocnoco6Horo npOH3-ΒΟΑΗΟΓΟ yroyibHOiļ KHCJIOTbl R6OCOOH HJIH THOyrOJIbHOfil KMCJIOTbl r6ocsoh.
AqHJIHpOBaHHe C Hcno/Ib 30BaHHeM raJIOHflaHrHApHflOB H aHrHApH-ROB, ΠρΗ *e/iaHHH ΜΟ)ΚβΤ npOBOflHTbCil B npHCyTCTBHH KHCAOTHOrO cBii3yiomero areHTa TaKoro, KaK τρβτΗΜΗΜΗ bmhh (HanpHMep, τρΗ3-TH/iaMHH, flHMfiTHJiaHHJIHHa ΗΛΗ nHpHflHHa), HeopraHHKeCKHX OCHOBa-HHiļ (HanpHMep, KapSoHaTa KajībiļHii hjih 6HKap6oHaTa HaTpHS) h OKCHpeHbi TaKHe ksk HH3ume 1,2-aJiKHJieHOKCHflbi (HanpHMep, 3THJie-HOKCHfl hjih nponHneHOKCHfl), κοτορυε cBJi3biBaioT ranoreHBOAopofl, OTUļennHeMbifi npH aiļHJinpoBaHHH. Jļna ceneKTHBHoro 3aMemeHHii πολο>κθηηη-23, hto6w nojiyHHTb 2 ·ς
coeAHHeHHe φopMyJIbI (II), b κοτοροΗ R npeflCTaBnneT rpynny OR , Γ Re R5 ΛΒΛΛβΤΟΗ 33ΜβΙΙ1ΘΗΗΟΗ rHflpOKCHJlbHOH rpynnOH H OR4 HBJIfl-eTCfl rHflpoKCHnbHOM rpynnofi mo>kho npoBORMTb peaKLiHH aLļHJinpoBa-HHfl C HCnO/Ib 30BaHHeM BbICOKO 3JieKTpO($>HJIbHblX X/IOpaHrHflpHflOB (HanpHMep, OKce;iHJix^opnfla, MeTOKCHaneTH/ix;iopHfla, XJiopaqeTHJi-χ/iopnfla hjih 6poMaqeTHnxnopHfla) , npeflnoHTHTejibHO b npncytctbhh KHcnoTHoro ποΓΛοτΗτεΛΛ TaKoro KaK KapēoHaTa KajībUHs. ALļHAHpoBaHHe c HcnoflbsoBaHHeM khc/iot «enaTejibHO npoBOflHTb b npncytctbhh KOHfleHCHpyioiner o areHTa, HanpHMep, KapSoRHHMHRa - 21 - LV 10777
TaKoro KaK N, N 1 -flHUMK/ioreKCH/iKapSoflHHMHfla hah N-3tha-N'1( flHMe-TMJiaMMHonponn/iKap6oflHHMMfl; Kap6oHHAbHoro coeAHHeHHH, HanpHMep,
Kap6oHHAAHHMHAa3ona; hah H30Kca30AHeB0fi coah, TaKofi KaK N-3THA-5^eHHAH30Kca30AHftnepxAopaT. AKTHBHpOBaHHblft CAOJKHblfi 3φΗρ ΜΟ*ΘΤ 6bITb OČpaSOBaH Ha Μβοτβ, Hcnojib3y«, HanpHMep, l-oKCH6eH30TpHa3on b npHcyTCTBHH KOHfleHCHpyioinero areHTa, KaK yKa3WBanocb Bwme. ΠρΗ «eAaHHH, aK-THBHpOBaHHblH CAO)KHblft 3φΗρ ΜΟ*βΓ 6blTb 6pHKeTHpOBaH.
PeaKLļHro aLļHAHpOBaHHH MOJKHO npOBOAHTb B BOflHOH HAH 6e3BOfl-Hofi peaKiļHOHHofi cpefle, npeflnoHTHTenbHO npH TeMnepaType b hh-Tepeajie -20° - +100°C, HanpHMep, -10° - +50°C. ΦΟρΜΗΛΗρΟΒΒΗΗβ MOKHO npOBOflHTb C ΠρΗΜβΗβΗΗβΜ aKTHBHpOBaH-ΗΟΓΟ npOH3BOflHOrO MypaBbHHOH KHCAOTbl, HanpHMep, Ν-φορΜΗΛ-ΗΜΗ-flasona hah aHTHflpHfla MypaBbHHOfi KHCAOTbl πρκ CTaHAapTHbix ycAo-ΒΗΛΧ peaKlļHH. BBefleHHe cyΛbφoHHΛbHOH rpynm>i μο*θτ ocymecTBAATbCA c no-MOIIlbKD peaKIļH0HH0Cn0C06H0r0 npOH3BOflHOrO CyAbφOKHCΛOTbl R8so3H TaKoro Kax cyΛbφoHHΛΓaΛOHA, HanpHMep, ΧΛορΗΑ R8S02CL hah aH-γηαρηα cyΛbφoκHCΛoτbi. CyAbφypHΛOBaHHe npeflnoHTHTeAbHo npoBo-AHTb b npHcyTCTBHH ποαχοαη^θγο κηολοτηογο cBH3yiomero areHTa, KaK yKa3biBanocb Bbitue. ΘτβρΗφΗκβιΐΗΐο mo)kho ocymecTBA«Tb c ncnoAb3οββηηθμ peareHTa φopMyΛbI R7 Υ (ΓΑβ R7 vmeeT BbimeyKa3aHHbie 3HaHeKHiī, a Y npeAc-τβΒΛΗβτ yxoAAmyio rpynny TaKyio KaK aTOM XAopa, 6poMa hah fioAa HAH ΓHApoκap60HHΛCyΛbφOHHΛOKCHΓpyΠΠy, TaKyiO KaK MeTHΛCyΛbφOHH-aokch hah τoΛHΛcyΛbφoHHΛOκcH, hah raAOHAaAKaHOHAOKCH rpynny, HanpHMep, AHxnopai4eTc>KCH). PeaKLļHH MO*eT conpoBOJKAaTbca o6pa-30BaHHeM anKoroAHTa MarHHH npH ηοποαβ30Βαηηη peareHTa rpnHb- 22 apa, TaKoro KaK ra/ioHflMeTH.nMarHHH, HanpHMep, MOflMeTHnMarHHH HJ1H ra/lOHjUTpHa/lKH/ICM/IH/IMeTHJlMarHHfi, HanpHMep, Χ/ΙΟρΤρΗΜΘΤΗΛΟΗ-ΛΗ/ΐΜβΤΗΛΜ3ΓΗΗΗ c noc.neflyiomeiļ o6pa6oTKOH peareHTOM R7Y. Πρπ «e/iaHHH, peaKMHii MO*eT npoBOflHTbcn b npHcyTCTBHH conn cepeSpa, HanpHMep, okhch cepeSpa, nepxnopaTa cepeSpa, KapčOHa-Ta cepeSpa hjih ca.nHi4H.naTa cepeSpa h/ih hx CMecefi, npnneM yxa-3aHHaii CHCTeMa μο>κθτ 6biTb ocoSeHHO ποαχοααπιθη , Korfla οτερΗφπ-KaiļHio nppBOflHT b npHcyTCTBHH ra.noMfla.nKM.na (HOflMeTH.na) . 3τβρΗφΗΚβΙ4ΗΚ) MOJKHO, COOTBeTCTBeHHO, npOBOflHTb B paCTBOpH-Tefle TaKOM, KaK npocToii οφπρ, HanpHMep, αηοτηλοβομ npocTOM ΟφΗρβ. 06pa3OBaHHe aneTa/iePi MO*eT ocymecTB.nflTbCJt nocpeflCTBOM pe-aKlļHH c LļHKflHHeCKHM ΗΛΗ aiļHKflHHeCKHM npOCTbIM ΒΗΗΗΛΟΒΗΜ ΟφΗρΟΜ . yKa3aHHbiH cnoco6 ocoSeHHO npnrofleH fljin noflyMeHHii TeTparHflponH-paHH/ioBbix προοτωχ οφπροΒ c Hcnoflb30BaHHeM b KanecTBe peareHTa flHrHflponHpaHa, ηλη l-aflKOKCHanKHJibHbix npocTbix οφπροΒ, TaKoro xaK 1 -DTOKCHaflKHflbHbiH npocTOM οφπρ, πρΗΜβΗΛΚ b KanecTBe peareHTa BHHHflOBUft npocToii οφΗρ. yKa3aHHyio peaKLļHio «eflaTeflbHO npOBOflHTb b npncytctbhh cH/ibHo KHcnoTHoro KaTaflH3aTopa, HanpHMep, MHHepanbHofi KHcnoTbi, TaKoPi KaK cepHaa KHC/iOTa, hah opra-HHHecKofi cyΛbφoκHCJ^oτbI, τεκοϊί KaK π-τo.nyo.ncy.nbφoκHc.πoτa, ~b He-rHflpOKCHflbHOM, Se3BOflHOM pacTBopHTefle.
Ee3BOflHbie pacTBopHTenH, κοτορωε mo>kho Hcno/ib30BaTb b bh-BieyKa3aHHbix peaKLiH«x BK/iranaioT κθτοημ (HanpHMep, aueTOH), aMHflbi (HanpHMep, Ν,Ν-ΑΗΜβΤΗΛφορΜ3ΜΗΑ, N,N-flHMeTHAaqeTaMHfl h/ih reKca-ΜβΤΗΑφοεφορεΜΗΑ, npocTbie οφκρΗ (HanpHMep, iļHKAHHecKHe npocrbia οφΗρω, TaKHe KaK τeτpaΓHflpoφypaH hah flHOKcaH, h aiļHK/iHMecKHe npocTbie 3φΗρΜ, HanpHMep AHMeTOKCHDTaH ΗΛΗ flHOTHAOBblH npOCTOH - 23 - LV 10777 οφπρ), HHTpH/ibi (HanpHMep, aqeTOHHTpH/i) , yrfleBOflopoflbi TaKne KaK rayioMA3aMemeHHbie yrneBOflopoflbi (HanpHMep, μθτηλθηχλορηα) h CAO>KHUe 3φΗρυ, HanpHMep, οτκΛβμβτθΓ, a TāK*e cnecvi flByx h/ih 6onee yKasaHHbix pacTBopHTe/ieH. Ββθαθηηθ CHiiHJībHoft rpynnw Μοκετ ocymecTBflATbcfl nyTeM B3a-HMOfleHCTBHA C CHAHAraAOreHHflOM (HanpHMep, ΧΛΟρΗΑΟΜ), npeHMy-meCTBeHH'Ģ B npHCyTCTBHH OCHOBaHH«, TaKOrO KaK HMHfla30flTpH3TH-AaMHHa ηλη nwpHflHHa c Hcnonb30BaHHeM pacTBopHTenH, HanpHMep, HHMeTH^OpMaMHfla .
Bo μηογηχ cAynaHx, HanpHMep, Korfla 5,23-flHrHflpoKCHCoeflH-HeHHe φopMyΛbl (III) πρΗΜβΗΛίοτ b KanecTBe ueneBoro Marepnana o6pa3yeTCA cMecb 5-oflH03aMemeHHbix h 5,23-flBy3aMeii(eHHbix npoH3-BOflHblX. OflHaKO HX MOHCHO OTfleflHTb C ΗΟΠΟΛΒ30ΒΒΗΗβΜ ΟδΐΙΙβΠρΗΗίΙΤΜΧ MeTOflOB, HanpHMep, ΧρθΜ3ΤΟΓρ3φΗβΗ (ΧρθΜ3ΤΟΓρ3φΗβΚ Ha CHAHKare-Λβ ηλη npenapaTHBHOft τοηκοολοΛηοΑ xpoMaTorpa$Hefi) . B cooTBeTCTBHH c eme oahhm cnoco6oM HacTOflUļero H3o6peTe-ηηλ, coeflHHeHHe φopMyΛbt (II), b κοτοροΗ R2 h R3 npeflCTaBflflioT Ka*AbiH aTOM BOflopofla, Μθ>κβτ 6biTb nonyHeHO B3aMMOflewcTBHeK coe-Αηηθηηλ φopMyΛbI (III), rfle R1 ΗΜββτ BbimeyKa3aHHbie sHaneHHH h OR4 λβληθτολ 3aMemeHHofi[ rHflpoKCHAbHOft rpynnoft h OR5 ΛΒΛΛετca rHflpoKCHAbHOH rpynnoH nyTeM 3aMemeHHA 2 3-OKCHrpynnbi btomob bo-Aopofla c nocneflyiomHM οτιιιβΠΛβΗΗβΜ 3amHTHoft rpynnw OR4 , rfle He-o6xoahmo coeflHHeHHe, b κοτοροΜ rpynna OR4 λβλλθτcs ΓHflpoκcHΛb-Hoft rpynnofi, h npn «eflaHHH, c nocfleflyiomHM ποβτορηημ saMemeHHeM ΑΛΛ ΠΟΛ^ΜβΗΗΗ COeflHHeHHA φOpMyΛbl (II), rfle OR4 JIBJlSieTCS 3aMe-meHHofi rHflpoKCHnbHOH rpynnoft.
TaKHM o6pa30M, HCXOflHbie MaTepnanbi φopMynbI (III), rfle OR4 npeflcraBfl«eT 3aMeti(eHHyio rHflpoKCHflbHyio rpynny, a OR5 ηβλλθτοη 24 rMflpOKCM/lbHOM ΓργΠΠΟίί ΜΟ>ΚβΤ B3HMOfleŪCTBOBaTb c peareHTOM, cny->KaiiļHM fl/ΐΛ saMemeHHfl rHApoKCM/ibHoPi rpynnu yxoAmiļefi rpyrmoH α-πη nojiyMeHH« οοθαηηθημη φopMy/lbl (IV)
(IV) [rfle R1 h -0R4 ΗΜβιοτ BbiweyKa3aHHbie 3HaHeHHfl , a L αβακθτοη aTo-MOM HJIH rpynnOH, ΟΤ^βΠΛΛεΜΟϋ nOCpeflCTBOM peaKLļHH BOCCTaHOBJie-HHfl, HanpHMep, rOMO/IHTHMeCKOrO BOCCTaHOBAeHHil, TaKOTO KaK rpynna R11OCSO (rfle R11 αβλαθτολ Cļ_6 a/iKHAOM, apn/iOM, HanpHMep, φβΗΜϋΟΜ, ηλη (Cj _6 a/iKMJioM) apn/iOM, HanpHMep, Π-ΤΟΛΗΛΟΚ-CHTHOKap6oHHnoKCH rpynnon]]. ΠρΗΓΟβΗΗΜΗ peareHTaMH, κοτορωβ mojkho Hcno/ibsoBaTb aji« BBefleHHH φρεΓΜθΗτε L abahkjtch, HanpHMep, apH/ira-noTHC^opMaTbi, TaKne κβκ π-το/ΐΗΛΧΛοροτΗοφορΜετ. yKa3aHHyjo peaKLjHio mo>kho npo-BOflHTb b npHcyTCTBMM ocHOBaHHA, HanpHMep, aMHHa, Tanoro KaK rinpnflHH, b pacTBopHTejie, TaKoro KaK ra/ioreH3aMemeHHt>ie ymeBO-Aopoflbi, HanpHMep, flHX/iopMeTaHe. ΠρΜ >Ke/iaHHH, npoMe>KyTOMHbie coeflHHeHHA φορΜ>'ηω (IV) mo>kho - 25 - LV 10777
BblfleOlHTb . npoMe>KyTOHHbie coeflHHeHHfl φορΜγΛΜ (IV) mohcho 3areM BoccTa-HOBHTb c nojiyMeHHeM Tpe6yeMoro coennHeHHH 4>opMy./ibi (II) c no-Montbio pereHHpyiomero areHTa, TaKoro KaK onoBorHflpHfla.nKHn (HanpHMep, TpH-H-6yTHJioyioBorHflpnfla) b npncyTCTBHH HHHiļHaTopa paflH-Ka/ioB, HanpHMep, nepeKHCH, a3o6ncn3o6yTHpoHHTpH/ia h/ih πολ flefiCTBHeM* CBeTa.
PeaKiļHio mo)kho TaK*e npoBOflHTb b cooTBeTCTByiomeM pacTBopn-Tene, KOToptiH μοκθτ 6biTb BbičpaH H3 rpynnw KeTOHa, HanpHMep, aqeTOHa; npocToro 3$npa, HanpHMep, flHOKcaHa, yrneBOflopona, HanpHMep, reKcaHa ηλη To.nyo.na; ra/ioreHsaMemeHHoro yrneBOflopo-fla, HanpHMep, Tpnx.nop6eH30.na; ηλη c7io*Horo ocjmpa, HanpHMep, OTHnaLļeTaTa. Mojkho TaK>t<e Hcno/ib30BaTb κομ6ηηβι4ηη yKa3aHHbix pacTBopHTenefi λη6ο caMHX, λη6ο c Bonofi. yxa3aHHyio peaKUHio mohcho npoBOflHTb npH TeMnepaType ot 0° no 200° C, npennoMTHTejibHo b HHTepBa/ie 20-130°C. B cooTBeTCTBHH c eme oflHHM cnocoSoM HacTOHUļero Η3θ6ρβτβ-hhh, coeflHHeHHe $opMynbi (II), rne R2 h R3 ΒΜβοτβ c aTOMOM yr-nepofla, κ KOTopoMy ohh npHcoeflHHiiioTCii npencTaB.nnioT rpynny >C=0, Μο*βτ 6biTb nonyneHo nyTeM οκηοπθηηλ οοθαμηθηκη <fcopMy.nbi (III), me OR5 HBJiHeTCH rHflpoKCH/ibHOH rpynnoft, a OR4 λβληθτοη 3aMemeHHofi rHflpoKCHnbHofi rpynnoH c nocnenyiomHM oTuienneHHeM 3a-lUHTHOii rpynnbi OR4 , rne ΗβοδχοβΗΜο coeRHHeHHe, β κοτοροΜ OR4 ΗΒΛΗΛΟΗ THflpOKCH/IbHOH rpynnoft, Η ΠρΗ *ΘΛ3ΗΗΗ nOCneflyiOIIieM ΠΟΒ-τορΗΟΜ aaMemeHHH αλκ nonyHeHHH coeflHHeHHfl $opMynw (II), rfle OR4 jtBAfleTcs 3aMemeHHoft rHflpoKCH.nbHoft rpynnofi. yica3aHHyio peax-iļHio mojkho npoBOflHTb c noMOHļbio OKHCiiHTe^bHoro areHTa, BbiCTynaio-mero npeBpameHHH BTopHHHofi rHflpoKCHnbHoft rpynnofi b okcot- 26 pynny, no/iyMaii τβκΗΜ očpascm οοθληηθηηθ φopMy.αb^ (II). nOflXOflHUtHe OKHCTIHTeJlbHbie areHTbl BKJIlOHaiOT 6eH30XHH0Hbl B npHCyTCTBHH BOflbl, HanpHMep, 2,3-ΑΗΧΛΟΡ-5,6-flHI4HaH-l , 4-6eH30XH-HOH HJĪH 2,3,5,6-TeTpaX/IOp- 1,4-6eH30XHH0H ; ΧΡΟΜ (IV) -okhcjih-Teoib, HanpHMep, flHxpoMaT nHpHflHHa ηλη TpnoxHCb xpoMa b πηρηαη-He; MapraHLļeBbiiļ (IV) OKHC.nHTe.nb, HanpHMep, flByoKHCb MapraHua b flHxnopMeraHe; N-ra/iocynHHHMHfl, HanpHMep, N-xnopcyijHHHMHfl ηλη N-6poMcynHHHMHfl; flHa.riKH.ncy.nb<i>oKCHfl, HanpHMep, flHMeTH.ncy.nb-φΟΚΟΗβ, B npHCyTCTBHH aKTHBaTOpa TaKOTO KaK N, N ’ -flHlļHK/IO-reKCHnKap6oflHHMHfla ηλη aLļHnranonfla, HanpHMep, oKcanHnxnopH«a; ΗΛΗ KOMnneKCa-nHpHflHHCepHblH aHrHflpHfl. yxa3aHHyio peaKLļHio mo>kho Tax>Ke npoBOflHTb b noflxoflnmeM pacTBopHTene, κοτορΗΗ μοκθτ 6uTb BbiSpaH hs rpynnu κθτοηβ, HanpHMep, aiļeTOHa; npocToro acļjHpa, HanpHMep, αηοτηλοβογο 30npa, flHOKcaHa hjih TeTparHApo$ypaHa; yrneBOflopofla, HanpHMep, reKca-Ha, ranoreH3aMemeHHoro yrneBOflopofla, HanpHMep, x.nopo<i)opMa ηλη MeTH,neHxnopHfla; ηλη c-noacHoro 3$)Hpa, HanpHMep, oTHJiaueTaTa h/ih saMemeHHoro aMHfla, HanpHMep, flHMeTH/HķopMaMHfla. B peaKLļHH mojkho TaKJKe Hcnonb30BaTb KOMČHHaiļHH yKa3aHHbix pacTBopHTenefi λη6ο ofl- ΗΗΧ, ΛΗ6θ C BOflOH.
PeaKiļHio mo>kho npoBOflHTb npH TeMnepaType ot -80° C flo +50° C.
CorflacHO eme oflHOMy BapHaHTy HacTOiniiero H3o6peTeHH« npefl-AaraeTCH cnoco6 no.nyHeHH« οοθαηηηηη φopMyΛbl (II), rfle R2 w R3 BMecTe c aTOMOM yrnepofla, κ KOTopoMy ohh npHcoeflHHflioTCfl npeflc-TaBAniOT rpynny >C=0, a OR4 «B/iiieTCH rHflpoKCHAbHOH hah mctok-CHJlbHOH rpynnOH, BKAlOHaiOmHH CTaflHIO KyJIbTHBHpOBaHHH MHKpoopra-HH3Ma BHfla Streptomvces cnocoSHoro očpasoBbiBaTb xota 6h oflHO H3 npefl/iaraeMbix οοθαηηθηηη, h npn «enaHHH BbiAenHTb H3 Hero - 27 - LV 10777 yKa3aHHoe coeflHHeHHe, a κροΜβ roro, ecsia ηθο6χολημο μοαηΦημη-poBaTb rpynny OR4 cnocoGaMH, κοτορΜβ onncaHbi Bbiuie. npeflnoMTHTe/ibHbiMH MHKpoopraHH3MaMH, cnoco6HbiMH očpaaoBbi-BaTb BbimeyKa3aHHbie BeuiecTBa «βλλιοτολ ιιιτβμμμ ηοβογο BH^a posa Streptomvces. κοτορΜβ HasbiBaioTCfl Streptomvces thermoarcha-ensis. 06pa3eq yKa3aHHoro MHKpoopraHH3Ma, κοτορΜή «ΒΛΛβτο« noMBeHHoft'iKyxibTypoft, noMemeH Ha xpaHeHHe (10.09.84 r.) b nocTOflHHyto KOJi/ieKLļMio HaLļHOHa/ibHoro co6paHHii προμμπιλθηηηχ h MopcKHX 6aKTepnft Torry Research Station, Aberdeen, United Kingdom c npHCBoeHHeM eMy perHCTpaiļHOHHoro HOMepa NCIB 12015. MyTaHTbi uiTaMMa Streptomvces thermoarchaensis NCIB 12015 MoryT TaK)Ke 6biTb npeHMymecTBeHHo HcnojibsoBaHbi, h b nocTOKHHyio κολ-ΛβκυΗΡ KyvibTyp HaqnoHaJibHoro coāpaHHii npoMbim.neHHbix h mopckhx SaKTepHft esama b neno3HTapHoe xpaHeHHe (26.06.85 r.) 4 uiTaMMa MyTaHT0B, KOToptiM 6ηλη npucBoeHH perHCTpaiļHOHHbie HOMepa NCIB 12111, NCIB 12112, NCIB 12113 H NCIB 12114. no/iyMeHHe npefl/iaraeMbix coeflHHeHHfi nocpeflCTBOM φθρΜβΗΤΒΐ^ΗΗ noflxofliiinero BMfla Streptomvces μο*θτ 6biTb /;ocTnrHyTO o6menpnHH-
TblMH MeTOflaMH, HanpHMep nyTeM BbipaiHHBaHHH MHKpOOpraHH3Ma \
Streptomvces b npncyTCTBMn cnono6Hbix κ accviMM/iHLļHH hctomhhkob yrnepofla, aaoTa h MHHepa./ibHbix co/tefi.
CnocodHbie κ accMMHJi^LļHH hctohhhkh y r/iepofla, a30Ta η μηηθ-pa/ΙΟΒ MOryT 6blTb npH Ha/IHMHH ΛΗδΟ npOCTblX ΜΛΗ KOMīl./ieKCHbIX πη-TaTe/ibHbix BeuiecTB. Hctohhhkh yr\aepona οδωΗΗΟ BK/uowa©T rjii0KO3y, Ma/ibT03y, xpaXMan, r/tMLļepHH, KopMOByio naroKy, ββκστρΗΗ, /iaKTO-3y, caxapo3y, φpyκτo3y, Kap6oKCH/ibHbie κηοποτη, βμηηοκηο/ιοτη rflHLjepHfla, cnnpTbi, a/iKaHbt h pacTHTenbHbie Mac/ia. Hctomhhkh yr-nepofla očhmho conepacaT 0,5-10 nacč.% c6pa>KHBaeMoft cpeflti. 28
Hctomhhkh aaoTa očbiHHO BK^iioMaioT, 6o6oBOCoeByio Μγκγ, HacTOMKy nuieHHLļbi, pacTBopu neperoHKH, ApoaoKeBbte 3KCTpaKTbi, My-κγ H3 ceM«H xJionKa, πθπτοηη, Μγκγ M3 3ΘΜλαηογο opexa, cojioro-Bblfi 3KCTpaKT, ΜβρΗγίΟ naTOKy, KaSeHH, CM6CM aMHHOKHC-ΠΟΤ, aMMO-HHH (ra3006pa3Hbliļ H/IH paCTBOp), CO/1H aMMOHHJl H HHTpaTbl. ΚρΟΜβ ΤΟΓΟ MO/KHO HCnO/lb SOBāTb ΜΟΜΘΒΜΗγ H ΑργΓΜΘ aMHflbl. HCTOMHMKH a30Ta o6h,mho coflep»aT 0,1-10 Macc.% cāpajKHBaeMoii cpeflbi. * riHTaTe/lbHbie MHHepa.HbHbie CO/IH, KOTOpbie ΜΟΓγΤ 6bJTb ΒΚΛΙΟΜβΗΗ b Ky^bTypHyK3 cpeny, coflep>KaT 06UHH0 npHMeHjieMbie cojih, MMeioinne cnocoČHOCTb OTflaeaTb hohn HaTpHii, KaJiHH, βμμοημη, *eiie3a, Mar-hha, UHHKa, ηηκθλλ, Ko6a/ibTa, Mapramļa, BaHaflHH, xpoMa, Ka/ib-14ΗΛ, MeflH, MO/in6fleHa, 6opa, $oc$aTa, cy/ib$aTa, xjiopHAa h Kap-čoHaTa.
Ky/tbTHBnpoBaHne Streptomvces CTperiTOMHLļeTbi ο6μμηο npoBO-AHTCA npM TeMnepaType b HHTepBa/ie, 20-50°C, npeflnoHTWTeyibHo 25-40° C, 60.nee npeflnoHTMTe/ibHO οκολο 34° C, npnweM «e/iaīe^bHO conpoBO>KflaTb ee a3paL(Me8 h B36a/iTbiBaHMeM, HanpuMep, BCTpHXHBa-ηηθμ hjih HHTeHCMBHbiM nepeMeuiHBaHHeM. Cpefla Μθ*βτ 6biTb nepBOHa-MaAbHO HHOKy/lHpOBaHa Ηθδθ/IbUIHM KOAHMeCTBOM CnopyAMpOBaHHblX B3Becefi MHKpOOpraHMSMOB, HO fl/ΙΛ H36e*aHH5ī 3aflep)KKH pOCTa MOJKHO npHroTOBHTb pacTMTeAbHbifi noceBHofi MaTepnaA MHKpoopraHH3Ma ny-T6M ΗΗΟΚγΛΑμΗΜ HeSOAbllIOrO KOJIHHeCTBa KyyibTypa/IbHOfļ cpeflbl cno-poo6pa3Hofi φορΜοίϊ yKa3aHHoro opraKH3Ma, ripu stom pacTHTeAbHbiii ΗΗΟΚγΛΛΤ, KOTOpblŪ ΠΟ-ΠγΗβΗ , ΜΟ)ΚβΤ 6bITb ΠβρβΗΘΟΘΗ B c6pa»HBae-Myio cpefly, h/ih, 60/iee npeflnoMTHTe/ibHo b oahy wsm 6onec CTaflHH noceBa, rfle B03HHKaeT flono.nHHTe.abHbiM pocT nepefl nepeHocoM b OCHOBHyiO φβρΜβΗΤΒ14ΜΟΗΗγΚ3 Cpefly . npOLļeCC φβρΜΘΗΤβμΜΗ o6blMHO npOBOflAT npH pH B ΗΗΤβρΒΒΛΘ 5,5-8,5, npeflnoHTHTe/ib Hee 5,5-7,5. - 29 - LV 10777 tPepMeHTaUHlO MO)KHO npOBOAHTb B ΤβΗΘΗΗΘ 2-10 ΛΗΘΗ, HanpHMep OKO/IO 5 βΗβΗ.
I B tom cyiyMae, Korfla we.naTe.nbHO OTflenHTb MaTepHan, coflep->Kamnii οοθαηηθηηλ npe,qnaraeMoro H3o6peTeHHK H3 Bcero čpoflHnbHo-ro 6y/ibOHa hjih BNflenHTb nioāoe H3 oTflenbHbrx coeflHHeHHH, yKasaH-Hoe mojkho ocymecTB/iiiTb nocpeflCTBOM oSmenpHHnTOft μθτοαηκη Bbifle-neHHfi η oTfle^eHHS BemecTB. npeflnaraeMbie coeflHHeHHH b ochobhom coflepjKaTCH b ΜΗμβηΗκχ κλθτοκ, ho hx Tax>Ke mo*ho o6Hapy>KHTb b GpOflH/IbHOM 6y/lbOHe, H T3KHM o6pa30M, TeXHMKa Bblfie/ieHHJĪ ΜΟ*ΘΤ
TaK)Ke 6biTb npHMeHeHa κ 6poflH/ibHOMy 6ynbOHy nocne ohhctkh. Hcho, hto MeTOflHKa BbiflejieHHjļ BeuļecTB Μοχβτ ΗΜβτb umpoKoe pas-Hoo6pa3He. npefl/taraeMbie coeflHHeHHH MoryT 6biTb BbifleneHbi η oTfleneHbi nocpeflCTBOM pa3Hoo6pa3Hbix MeTOflOB φρΒκΐ4ΗθΗΜροΒΒΗΜΛ, HanpHMep, 3/IIOHpOBaHHeM, OCd)KA6HHSM, (fcpaKLJHOHHOH KpHCTannH3ai4HeH , 3KCTpaKI4Hefi paCTBOpHTe/ieM, KOTOpbie ΚΟΚΚΟ KOMČHHHpOBaTb pa3yiHH-HblMH CnOCOČaMH.
BbiiiB/ieHo, hto OKCTpaKUHH pacTBopHTe/ieM h xpoMaTorpa$HK HaH6onee noflxoflnu{H flnn BbifleneHHH h oTflejieHHa npeflnaraeMbix coeflHHeHHH . ΠΟΟΛΘ φβρΜΘΗΤ311ΗΗ, MHLļeAHH ΜΟ*βΤ 6bITb COČpaH TpaflHlļHOHHbl-mh MeTOflaMH, HanpHMep, 0HnbTpaqHeH hjih i4eHTpHiļ)yrHpoBaHHeM. tr nocne 3τογο, HanpHMep, coeflMHeHHn MoryT 6biTb DKCTparHpoBaHH H3 ΜΗΜΘΛΗΗ COOTBeTCTByK)UlHMH OpraHHHeCKHMH paCTBOpHTenKMH, TaKHMH KaK KeTOHbl, HanpHMep, aiļeTOHOM, ΜβΤΗηΟΤΗηΚβΤΟΗΟΜ HflH ΜΘ.ΤΗΠΗ30-6yTHnxeTOHOM; yrneBOflopoflOM, HanpHMep, reKcaHOM; ranoreHaaMe-ιιιθηηημ yrneBOflopoflOM, HanpHMep, χηοροφορΜΟΜ, Kap6oHTeTpaxnopH-flOM, ΗΛΗ ΜΘΤΗΛβΗΧΛΟρΗΑΟΜ; CnHpTaMH, HanpHMep, MeTaHOAOM ΗΛΗ 30 OTaHO/lOM; ΗΛΗ ΟΛΟΗίΗΝΜΗ ΟφΗρβΜΜ, Η3ΠρΗΜβρ, MeTH/iai^STaTOM , ΗΛΗ 3TH/iai4eTaTOM, λοηο, μτο eonn μηηθληΑ coflep>KHT 3HaHHTe/ibHoe κο-/IHHeCTBO BOflbI, npeflnOHTMTe/lb HO HCn0/Ib3OBaTb BOflOpaCTBOpHMbie pacTBopHTe/in. βΛΛ flOCTH*eHHfl onTHMailbHOrO Η3ΒΛβΜβΗΗΛ COeflHHeHHfi oSbIMHO *e/iaTejibHo npoBOflHTb 6ολθθ oahoh 3KCTpaKiļHH. FIpeflnoMTHTe/ibHo nepBy» DKCTpaKiļMio βμποληλτβ c Hcnonb30BaHMeM cMeuiMBaiomerocfl c BOflofļ pcČcTBopHTenn, HanpHMep, MeTaHo/ia ηλη aqeTOHa. Ahthčhoth-kh mo>kho H3BJieMb KaK HeoMHiiļeHHbiH oKCTpaKT πγτβΜ yfla/ieHHH paCT-ΒορΗΤθϋΛ. 3KCTpaKTbi pacTBopMTejiH MoryT flanee 6biTb OKCTparHpo-BaHbi, ecjin «ejiaTejibHO, nocne yMeHbuieHHii o6i>eMa pacTBopHTe^fl, HanpHMep, BbinapHBaHHeM. Ha btoh cTaflHH npeflnoHTHTenbHO ncnonb-soBāTb HecMeuiHBaioiiiHHC« c Boflofi pacTBopHTenb, HanpHMep, reKcaH, ΧΛΟροφορΜ, ΜβΤΗΛβΗΧΛΟρΗΑ ΗΛΗ ΟΤΗΛβμβΤβΤ, ΗΛΗ ΗΧ CMeCH, ΠρΗ 3ΤΟΜ ΑΛΛ ΑΟΟΤΗ>ΚΘΗΗΛ ΧΟρΟΙΙΙβΓΟ paSfleneHHfl COeflHHeHHft aHTHČHOTHKa BBOAHTCfl flOCTaTOMHOe ΚΟΛΗΜΘΟΤΒΟ BOflbI. ΠρΗ yflaΛeHHH BOflOHepaCT-ΒΟρΗΜΟΗ φ33Μ nonyHa!0T npOflyKT, COflep*amHH OflHO ΗΛΗ δΟΛΘβ COeflHHeHHfi npejEĻnaraeMoro Η3θ6ρβτβΗΗΛ, bo3mo*ho ΒΜβστβ c coeflHHe-HHHMH aHTHēHOTHKa S541. OHHcTKy η/ηλη οτλθλθηηθ npefl^araeMbix coeflHHeHHfi mojkho OCyifleCTBnflTb TpaflHIflHOHHblMH MeTOflaMH, HanpHMep, ΧρθΜ3ΤΟΓρ3φΗβΗ, (βκλιομ3λ BbIcoκo^φφeκτHBHy!o H<HAKocTHyio xpoMaτoΓpaφHio Ha COOT-BeTCTByiOmeH ΠΟΑΛΟ*Κθ) , TaKOH KaK flByOKHCb ΚρβΜΗΗΛ, HeφyHK^HO-HanbHan MaKpocernaTaH aflcopčiflHOHHafl CMona, HanpHMep, nonepen-HocuiHTbie nc^HCTHpc^bHbie ομολει, τ3κηθ KaK ομολν Amberlite XAD-2, XAD-4 ηλη XAD-1180 (Rohm & Haus Ltd) ΗΛΗ CMona S112 (Kastei 1 Ltd) ηλη nonepeHHOcuiHTbiH fleKCTpaH, cMeuiHBaiOiiiHHCH c opraHHMecKHM ρΒΟΤΒορΗΤθΛβΜ, HanpHMep, Sephadex LH20 (Pharmacia - 31 - LV 10777 UK Ltd) ΗΛΗ, B C/iyMae ΒΙ>10:θΚΟ3φφβΚΤΗΒΗθΛ >KHflKOCTHOft XpOMaTOr- ρ3φΗΜ TaKofi na noflno>KKax c očpaTHofi ^asofi, Taxnx xax yr\neBOflo- pofl, HaHeceHHbiū Ha flByoKHCb κρβΜΗΗΛ, HanpHMep, Cj 8 cuiHTafl ABy- OKHCb κρβΜΗΗΗ. noflnoacKa MOHceT 6btTb b BHfle cjioh c HacaHKoii paa-
ΜβΠΙΘΗΗΟΓΟ B ΚΟΛΟΗΗβ. B C/iyHae HCnonb30BaHHfl H6$yHKI4HOHā/IbHblX
MaKpoceTHaTbix ομολ, HanpHMep XAD-H80 ηλη S112, fl/ia onioHpoBa- ηηλ μο>κη*Φ Hcnonb30BaTb CMecH opraHHHecKHX pacTBopHTenefi, Han-♦ pHMep, aLļeTOHHTpHna c Bo^oft.
PacTBop yKa3aHHbix coeflHHeHHft b cooTBeTCTByioiiieM pacrBopn-Tejie OČblHHO 3arpy*aiOT B ΧρθΜ3ΤΟΓρΒφΜΜβΟΙψ!0 KOAOHKy H3 flByOKHCH κρβΜΗΗΛ ηλη Sephadex npņ «enaHHH noc/ie nepBoro yMeHbiu'eHH* o6b-eMa pacTBopHTen^. KonoHKy Moryr no Bbi6opy npoMNTb, a 3aTeM bh-MbiTb pacTBopHTeneM noflxon«mefii πολϊφηοοτη. B cnynae/ κολοηοκ Μα Sephadex h AByoKHCH κρβΜΗΗΛ, b KanecTBe pacTBopHrenefi mo>kho Hcno/ibsoBaTb cnHpTbi, HanpHMep μθτβηολ; yrneBOflopoflw, HanpHMep, reKcaH; βμβτοΗΗτρΗΛ; ranoreH3aMemeHHbie y ivieBOflopoflbt, HanpHMep, ΧΛΟρΟφΟρΜ ΗΛΗ ΜβΤΗΛβΗΧΛΟρΗΑ; ΗΛΗ ΟΛΟΚΗΝβ ΟφΗρΜ, ΗβΠρΗΜβρ, 3ΤΗ~ ΛΒμθΤΒΤΗ.
SnioHpoBaHHe η pa3fleneHHe /oHHCTKy 3aflBneHHbix οοθαπηθημη MOJKHO perynHpOBaTb ΟδίμβΠρΗΗΛΤΗΜΗ CnOCOČaMH, HanpHMep, TOH-KOCnofiHOfi XpOMaTOrpa$Hefi Η ΒΝΟΟΚΟΟφφβΚΤΗΒΗΟΛ JKHflKOCTHOfi xpoMa-ΤΟΓρΒφΗβίί ΗΛΗ HCnonb3yB CBOHCTBa COeflHHeHHH, OnHCblBaeMblX fla-nee.
IlpeflnaraeMMe coeflHHeHHa Moryr nepBOHaManbHO 6biTb οηηιι1θηη ΧρΟΜβΤΟΓρβφΗβή Ha flByOKHCH KpeMHHH, npeflnOHTHTejlbHO HCnonb3yH onioaT, TaKofi xax χηοροφορΜ: 3ΤΗΛ3μβΤ3τ, πρκ «enaHHH c nocneAy-
»meii ΒΗΟΟΚΟΟφφβΚΤΗΒΗΟίί MCHflKOCTHOH ΧρΟΜΒΤΟΓρΒφΗΘΗ . nonyHeHHblH
TaKHM o6pa3QM οηηιι1θηημη npoflyKT μοκθτ 6biTb 3aTeM noflBeprHyT 32 xpoMaTorpac£)nn Ha ce$aAeKCOBbix Ko/ioHKax, npeflnoMTHTe/ibHo c ncno/ib30BaHneM 3.moaTa , HanpHMep, aiļeTOHHTpH/ia, a 3aTeM 3anB-/leHHbie COeflHHeHHfl MOryT 6blTb BblAe/ieHbl )KHflKOCTHOH ΧρΟΜΒΤΟΓρΒφΗ-eft c BbJCOKofi xapaKTepncTHKofi.
Hcno.nb3y.fl noflxofliniļHe KOM6HHat4HH BbimeyKa3aHHbix μθτοηηκ, οοβΑΗΗβΗΗΛ $opMyjibi (II), KaK yTOMHeHo cefiMac, BHflejieHbi KaK TBepflbie -pemecTBa b ποητη hhctom BHfle. Hcho, mto noc/ieflOBaTe/ib-HocTb, npn κοτοροπ ocyuiecTB.nfliOT BbiuieyKa3aHHbie CTaflHH omhctkh, BbiSop τθχ, KOTopbie Hcno/ib3yiOT h cTeneHb flocTHraeMoft omhctkh MoryT OMeHb oT/mnaTbCA. YKa3aHHbie coeAUHeHHfl MoryT πρπΜβ-HflTbCfl, OflHaKO, KaK yKa3WBa/10Cb Bbliue, npH CTeneHH MHCTOTbl, cooTBeTCTByromefi nx npeflHa3HaMeHHio. Πρπ HcnoJib βοββηηη hx b Me-BHiļHHe, JKejiaTeAbHO HMeTb CTeneHb mhctotu xoth 6bi 90%, npeflnoH-THTeiibHo 60/iee, μθμ 95%. A/ia BeTepeHapnH h flpyroro πρΗΜβΗβΗΗΑ flocTaTOMHa 6ojiee HH3Ka« CTeneHb mhctoth, HanpHMep, 50% h/ih hh- npoMe*yTOMHbie οοθαμηθηηα 3Ητη6ηοτηκοβ S541 φopMyΛbl (III), rAe OR5 aBJīfieTCii rHApoKCH/ibHofii rpynnon h OR4 npeACTaB/tseT γηα-poKCHyibHyio ηλη MeTOKCHAbHyio rpynny MoryT TaK>Ke 6biTb noJiyMeHbi c Hcno/ib30BaHHeM cnoco6oB φβρΜθΗΤΒΑΜΜ h BbiASjieHHλ, HanpHMep, KaK onncaHo b naTeHTe 10>κΗθή ΑφρπκΗ N 85/7049. HpyrHe npoMe>KyTOHHbie coeflHHeHHfl φopMy/lbI (III) homho no.nywHTb H3 yKa3aHHbix coeAHHe-HHfi, Hcno/ib3yii onHcaHHbie Bbliue cnoco6bi jnuu no/iyMeHHfl coeAHHeHHft φopMyΛbl (II).
HacTOiimee H3o6peTeHHe A^iiee npeACTaB/ieHo c/ieAyiomHMH npe-napaxaMH h npHMepaMH. Bce TeMnepaTypu npHBeAeHbie °C. ΟοβΑΜΗΘΗΗΛ 0603HaMeHbl CO CCbl/lKOH Ha HCTOMHHK "φΒΚΤΟρΗ" , KOTopue npeACTaBBJivoT cočoh nepeMHC-neHHbie HM*e coeuHHeHHa φορ- - 33 - LV 10777
<PaKTop R R1 A -H -CH(CH3 )2 B -ch3 -ch3 C -H -ch3 D -H -ch2 ch3 E -ch3 -ch2 ch3 F -CH3 -CH(CH3 )2 «PaKTopbi A, B, C, D, E, F mojkho nojiyHHTb cnocofioM, KOTopbiii onHcaH b naTeHTe I0>khoh ΑφρΗΚΗ N 85/7049. 1 34 ΠΡΜΜΘΡ 1 5-d)6HOKCMaueTOKCM μ 5.23-ni^eHOK:cnaueTOKcn Φβκτορ Α Φβκτορ Α (2,0 γ.) β pacTBope flMx/iopMeTaHa (25 μλ) η πηρη-flHHa (0,35 ΜΛ) ΓφΗ 0° C o6pa6aTblBa»T paCTBOpOM φβΗΟΚσΗ311ΘΤΗΛΧ-
TiopnflOM (0,5 μλ) β ΑΜΧΛορΜβτβΗβ. 4epe3 18 nacoB πρκ TeMnepaTy- i pe 3° C noyiyMeHHbiii pacTBop o6pa6aTWBaioT πηρηαηηομ (1,0 μλ) η φβΗΟΚΟΗΒΙΙβΤΜ/ΙΧΛΟρΗΑΟΜ (1,0 Μ/Ι) Β ΑΗΧΛΟρΜΘΤβΗβ (5 ΜΛ) . PaCTBOp τιι{βτ€λ &ηο nepeMeuiHBaioT ripu TeMnepaType 0-5°C b τθηθηηθ 30 mh-HyT, npe*fle weM βμλητβ b BOfly co ^bflOM. ΠροστοΗ οφκρ (100 mji) ΒΒΟΑΛΤ Β pacTBop, H CMeCb- nepeMeuiHBaiOT Β ΤβΜβΗΗβ 20 MHH. Bofl-HblH CJIOii 3KCTparnpyiOT npOCTbIM ΡφΗρΟΜ. 3φΜρΗΗΗ ΟΠΟΗ θ6ϊ>βΑΗΗΗ»Τ, ΠΟΟΛβΑΟΒΒΤβΛΒ ΗΟ npOMblBaiOT BOflOH Η ΟΟΛΛΗΜΜ paCTBOpOM, BblCyUIHBa-ΙΟΤ Μ BbinapHBaroT . OCTaTOK OMHUļaiOT ΧρθΜ3ΤΟΓρΒφΗθΑ Ha ΚΟΛΟΗΚΘ H3 flByOKHCH ΚρβΜΗΜΛ CMeCb» ΑΜΧΛθρΜΘΤ£Η3 C atļeTOHOM (40:1) C ΒΜΧΟ-flOM ΗΒ3ΒΒΗΗΜΧ COeHHHeHHft B BHfle CMeCH (1,8 r μοηοβιιηλ: ΑΗΒΑΗΛ = 6:1), KOTopyio ρ33αθλλιοτ ββκξοκορΦΦθκτμβηοη npenapaTHBHcm kha-KOCTHOii ΧρΟΜΒΤΟΓρΒφΗΘΗ C o6paTHOft φ330Η, nCXnyMafl 5-d)eHOKCHaue-tokch Φβκτορ Α. δ (CDC13 ) coflepjKHT 6,8-7,4 (μ; 5H) h 4,66 (c; 2H) m/3 BioiioHaeT 746, 728, 710, 594 h 576, η 5,23-nH0eHOKCHa- ueTOKCH taKTOP A, 5(CDC13 ) coflep*HT 6,8-7,4 (μ, 10H), 4,60 (c, 2H) H 4,70 (c, 2H).
IlPHMep 2
5-aeHOKCMaueTOKCH-23- f 4~ΜβΤΗΛΦβΗΟΚΟΜΤΜΟΚΒΡ6θΗΗΛΟΚΟΗ ) cbaK-top A 5^eHOKCHai4eTOKCH φβκτορ Α(747 ΜΓ) Β ΑΗΧΛΟρΜΘΤΒΗβ (10 ΜΛ) πρκ 0° C β aTMoc$epe aaoTa o6pa6aTbiBaiOT πμρμαηηομ (0,81 μλ), a 3aTeM 4-ΜβΤΜΛφθΗΜΛΧΛθρΤΜθφθρΜΒΤΟ (0,75 Γ) Β ΑΜΧΛθρΜΘΤ3ΗΘ (2 ΜΛ) . r^y4eHHbIH ΤΘΜΗΗίί paCTBOp TUtaTeAbHO ΠθρβΜΘΙΙΙΜΒ8Ι0Τ Β ΤβΗβ- - 35 - LV 10777 HHe 15 MHHyT πρΗ TeMnepaType 0°C, η 3βτβΜ b TeneHHe eqe 22 wa-cob 6e3 oxiia)KfleHHfi'. nonyHeHHyio CMecb BbuiHBaioT b xonoflHyio Boay H COJ1HHOH paCTBOp (paCCOJI) H 3KCTparHpyiOT npOCTbIM ΒφΗρΟΜ. Coe-flHHHBUIHeCH C/tOH ΠρΟΟΤΟΓΟ ΟφΗρβ npOMblBaiOT BOflOH M ΟΟΛΗΗΜΜ paCT-BOpOM, BblCyUIMBaiOT H BbinapHBaiOT. OCTaTOK OMHllļaiOT ΧρθΜβΤΟΓρ3φΗεβ Ha ΚΟΛΟΗΚβ flByOKHCH KpeMH Hfl M npenapaTMBHOiī JKHflKOCTHOfi XpOMa-τοΓρβφΗθή c o6paTHofi φ&3θΡι c no^yweHHeM η33Ββηηογο coeziHHeHHfl (430 μλ), 5(CDC13) coflepjKHT 3,34 (m; 1H), 3,58 (m; 1H) , 3,97 (fl.10; 1H), 4,72 (c. 2H), 5,4 (Μ. 1H), 5,59 (fl 6; 1H) H 6,9 flo 7,4 (μ; 9H) , m/3 BK/iiOHaeT 728, 616, 576, 466, 464, 448, 354, 297, 247, 219 H 151. ΠΡΗΜβΡ 3
5-TpeT-6vTM.nnHMeTH.acH/iH.noKCHaueTOKCn Φβκτορ A Φβκτορ A (2,144 r) b 6θ3βοαηομ προστοΜ οφπρε (25 μλ) η nHpHflHHe (2,5 μλ) πρπ 0°C β βτΜοσφβρβ a30Ta o6pa6aTWBaraT c npHčaBneHHeM no Kaane TpeT-6yTHnflHMeTHncHnHnoKCHaueTHnxnopHfla (1,2 r) β προστοΜ οφκρβ (10 μλ). rionyMeHHyio CMecb nepeMeniHBaPT β τβΜβΗΗβ 90 MHHyT npH TeMnepaType 0°C npejKfle, μθμ o6pa6oTaTb no Kanne onnTb κηοποτηημ χλορηαομ (1,10 r) b npocTOM οφπρβ (10 μλ) . ΠoΛy^eHHy!o CMecb TI^aτeΛbHo nepeMeniHBaioT npH TeMnepaType 0° C Β ΤβΜβΗΗβ 60 MHHyT Η BbUlHBaiOT B XOΛOflHyO BOfly H npOCTOH ΟφΗρ. BOflHblfi ΟΛΟΗ npOMblBaiOT npOCTbIM ΟφΗρΟΜ. CoeflHHHBIUHecn op-raHHMecKHe cnoH npOMblBaiOT BOflOH η οοληηημ pacTBopoM, BucyuiMBa-iot h BbinapHBaoT. nonyMeHHbtfi OCTaTOK OMHmaioT nocpeflCTBOM xpoMa-τοτρβφΜΗ Ha flByoKHCH κρβΜΗΗΛ, Hcnojiīb3yn CMecb HHxnopMeTaHa c aqeTOHOM (25:1) b KanecTBe onioaTa c nonyMeHHeM HasBaHHoro coe-ΠΗΗβΗΗΗ. 6(CDC13 ) BKniOMaeT 0,09 (c; 6H), 0,78 (fl 6; 3H) , 0,90 (c. 9H), 0,93 (fl 6; 3H), 0,97 (fl 6; 3H), 1,03 (fl 6; 3H), 1,51 36 (c; 3H), 1,59 (c; 3H), 1,74 (c; 3H), 3,32 (m; 1H), 3,52 (a 10; 1H), 3,64 (m; 1H), 3,74 (A 10; 1H), 3,82 (m; 1H), 4,32 (c, 2H) H 5,57 (a5; 1H), M/3 COAepatHT 784, 766, 748, 595, 577, 484, 466, 354, 314, 297, 265, 247, 237, 219 H 151. ripHMep 4
5-TPeT-6VTHAAHMeTHACMAH.aOKCH <PaKTOP A ΦΒΚΤΟρ A (250 ΜΓ ) H HMHAa30A (163 ΜΓ ) B CyXOM ΑΜΜβΤΜ-Πφορ-MdMHfle (to ΜΛ) OČpaSaTbJBaiOT TpeT-6yTH/IAHMeTHnCHJIHAX/IOpHAOM (197 ΜΓ ) . riOAyMeHHblH paCTBOp TUtaTSAbHO nepeMeniHBaiOT B ΤΘΜβΗΜβ 2 MacoB h BbJAHBaiOT b xo.noAHyio BOAy yKa3aHHyio CMecb TmaTe/ibHO 3KCTparnpyi0T npOCTbtM 3φΜρθΜ, H COeAHHHBUIHeCil OKCTpaKTbl 3φΗρ3 BbicymnBaioT h BbinapuBaioT. OcTaTOK onmuaioT xpoMaτoΓpaφHef^ Ha AByoKHCH κρβΜΗΗΑ, HcnoAb3yA CMecb Anx/iopMeTaHa c aLļeroHOM (10:1) b KanecTBe OAioaTa c noAyMeHneM ηβ3Β3Ηηογο οοθαμηθημη (235 ΜΓ), 6(CDC13) coAepJKMT 0,13 (c,6H), 0,80 (fl6;3H), 0,92 (c; 9H), 0,96 (a6; 3H) , 1,00 (a6; 3H),1,03 (a6; 3H), 1,53 (c; 3H), 1,60 (c; 3H), 1,80 (c; 3H), 3,37 (m; 1H), 3,56(AlO; 1H), 3,64 (m; 1H), 3,75 (A-10; 1H) H 4,43 (a 5; 1H), M/3 coAep*HT 726, 708, 691, 651, 633, 466, 448, 354, 314, 297, 265, 247, 219 H 151. Πρημθρ 5
5-aueTOKCH h 5.23-AHaueTOK.cn Φβκτορ A
Φ3κτορ A (3,0 r) h nHpHAHHa (20 ma) ripu TeMnepaType -5°C ofipačaTbiBaioT κκο/ιοτημμ aHrnApnflOM (8μλ) h no/iyHSHHbiii pacTBop ocTaBAAioT πρκ TeMnepaType 3°C b τβΜθΗΗβ 20 nacoB. K pacTBopy AočaBAAioT 6βΗ3θΛ (100 μ η) η noAyHeHHyio CMecb crymaiOT b Baxyy-Me. OcTaTOMHoe mscjio xpoMaτoΓpaφ^^pyloτ Ha AByoKHCn κρβΜΗΗΗ, ncnoAb3yA b KanecTBe 3/iioaTa CMecb AHx/iopMeTaHa c aqeTOHOM - 37 - LV 10777 (40:1), no/iyHa« 5-aneTaT «PaKTopa A (2,06 r), coflepwamHH 5,23 -
flHaueTar (10¾). no/iyMeHHwe οοθαηηθηηλ οταθλλιοτ npenapaTHBHOH jKMflKOCTHOft xpoHaTorpa$HaH c o6paTHoū «fcaaoīi c noyiyweHHeM 5-aue- tokch tPaKTOPa A (79¾ Bbixofla), Xmax (EtOH) 244,5 hm (E^; 4,62),
6(CDC13) coflep)KMT 2,14 (c; 3H), m/3 coflep*HT 654, 594 H 576, H
5,23-flHaueTOKCH <PaKTopa A (6,5¾ Bbixofla) , 6(CDC13) coAep*HT 2,01 (c;\3H) H 2,13 (c; 3H), m/3 coflepjKHT 696 h 636. * ΠΡΜΜβΡ 6
5.23- nHaueTOKCH <PaKTOP A
PacTBop cpaKTopa A (600 μγ) b cyxoM πηρηαηηθ (1,0 μλ) o6-pačaTMBaiOT Η36μτομηι>ιμ koahmbctbom κηοποτηογο aHrHflpHfla (0,50 MJl) H HeCKOflbKHMH KpHCTaAAaMM 4~N,N “AHMeTHAaMHHOriHpHflHHa . Μβ“ pes 24 Mača npH κομηβτηοη reMnepaType pacreop BU/iMBaioT b npocTofi ο.φκρ h 3aTeM nooMepeflHo npoMbieaioT opraHHMecKy» $a3y c nOMOllļblO 2N COAflHOft KHCAOTOfi, HaCbUIteHHblM paCTBOpOM ČHKapČOHaTa HaTpHfl m, HaKOHeq, co/iahum pacTBopoM. BbinapHBaHHe npocymeHHoro opraHHMecKoro caoh očecneMHBaeT KaMeflb, κοτοργιο oMHmaiOT xpoMa-τοΓρ3φΗβΡί Ηβρβ3 Ko/ioHKy Merck Kieselgel 60 c AByoKHCbio κρβΜΗΗΛ (45 r) pa3MepoM 230-400 μθιπ. 3ΛΐοΗροΒ3ΗΗβ kojiohhw CMecbio ahx-AopMeTaHa c οφκροΜ (9:1) Aa.no HasBaHHoe coeflHHeHHe β BHfle čecuBeTHOfi πθημ (560 μγ), [CC]d26 +169° (c 0,48, CHC13 ) .
CoeflHHeHHe npnMepa 7 πο^μθηο aHaAorHMHbiM cnocofioM: ΠΡΗΜβΡ 7
5.23- nHaueTOKCH <PaKTop C
Τ.ΠΛ. 211-213°, [CC]D22 +200°(c, 0,40, CHC13),XmaxEt0H 238,5 (30,400) H 245 HM (Cmax 32,500); Vmax 3440 (OH) H 1718 cm* 1 (aLļeTOKCH h cflo>KHbifi 3φΗρ) ; δ (CDC13 ) coflep>KHT 4,90 (m, 1H), 4,04 (fl 6Γ14, 1H), 3,96 (fl 10Γμ, 1H), 3,58 (μ, 1H) , 3,32 38 (Μ, 1Η) , 2, ,14 (C, 3Η) , 1 ,75 (c , 3Η), 1,67 (β 6Γβ, 3Η), 1,60 (C, 3Η) , 1- ,52 (C, , 3Η), 0, 99 (β 6Γμ, 3Η), Η 0,71 (β 7Γμ, 3Η), Μ/3 = 668 (ΜΗ 0, Μ 3 <PaKTopa C (312 ΜΓ) .
PeaKqHOHHyio cMecb BbinuBaioT b οτηά, a ηθ b προοτοίί 3φκρ η b saK-nioMeHHH KpHCTaJi/iM3yioT Ha nopouiKOBaHue ffnnaonponunoBbiM ΟφΜρΟΜ. ΠΡΗΜβΡ 8
23-aueTOKcn Φβκτορ A K nepeMemaHHOMy h ox/ia>KfleHHOMy (0-5°) pacTBopy coeflHHeHHH npHMepa 6 (530 μγ) b MeTaHo/ie (10 m/i) ββοαατ no KannaM boahmh pacTBop (1 mji) rnflpooKncn Harpnsī (30 μγ) . 4epe3 1,3 Mača CMecb Bbi/iMBaraT b PTH/iaiļBTaT h opraHHHecKyio $a3y 3aTeM npoMbisaioT noo-MepeflHO c noMoiiļbio 2N οολληοΛ κηολοτοΛ ; ΒΟβοίί η β KOHiļe οολαημμ pacTBopoM. BbinapHBaHHe npocyuieHHOH opraHunecKOH φa3bI flaeT μθλ-Tyio CMo.ny, KOTopa* b flnx/iopMeTaHe bboahtcj? β χροΜβτοΓρβφΜΗβσ-Kyo KOJiOHKy Merck Kieselgel 60, c fločaBJieHHeM b tot *e caMbifi pacTBopHTejib flByoxncb KpeMHHa (50 r), pa3MepoM nacTHiļ 230-400 Mern. S^iOHpoBaHMe CMecbio flnx/iopMeTaHa c rrpocTMM οφκροΜ (9:1) flavio Ha3BaHHoe coeflHHeHHe, κοτοροβ ποΛγπβΗΟ b BHfle ποητη 6ec-iļBeTHoro TBepfloro BeņecTBa nyTeM BbmapHBaHHii pacTBopa H-neHTa-Ha. YKa3aHHoe BemecTBO (330 μγ) ημθθτ [Ct]D23 +166° (c 0,64, CHC13), XmaxEt0H 239 (26,500) m 245 hm (6max 29,300); Vmax (CHBr3 ) 3540, 3460 (OH) H 1712 cm'1 (c/io*Horo οφπρΒ); 5(CDC13) CO,qep)KHT 4,89 (Μ, 1H), 4,27 (t 6Γμ, 1H); 3,93 (β 6Γβ, 1H), 3,91 (fl ΙΟΓρ, 1H), 3,55 (μ, 1H), 3,25 (m 1H) 2,01 (c, 3H) , 1,85 (c, 3H), 1,59 (c, 3H), 1,51 (c, 3H), 1,03 (fl 6Γβ, 3H), 0,98 (β 6Γΐΐ, 3Η) , 0,94 (fl 6Γίΐ, 3Η) , Η 0,69 (β 7ΓΙ4, 3Η) . μ/3 = 654 (Μ+). - 39 - LV 10777
CoeflHHeHHe npHMepa 9 no/iyMeHO 3Η3λογμμηημ πγτβΜ: ΠΡΗΜβΡ 9
23-aueTOKcn <PaKTOp C
[0t]D23 +139° (C_ 0,52, CH2C12); XmaxEt0H 244,5 HM (£max 29,400); Vmax (CHBr3 ) 3550, 3480 (OH); 1716 (ολο>κηνη ρφκρ h aueTaT) h 1255 cm-1 (aqeTaT); δ (CDCL3) coflepacHT 4,91 (k, 3rq, 1H); 2,03 (c, 3H) H 1,64 (fl, 7Γμ, 3H) H 1,60 (c, 3H); M/a = 626 (M+), H3 coeflHHeHHH npHMepa 7 b BHfle 6θλογο βΜορφΗΟΓο TBepfloro BemecTBa. npHMep 10
5-aueTOKCH-23-KeTO <PaKTOP A
PacTBop OKcajTH/ixnopHfla (1,96 μλ) b cyxoM flHxyiopMeTaHe (25 μλ) npH TeMnepaType -70° β βΤΜΟοφβρβ a30Ta o6pa6oTaH no KannaM pacTBopoM flHMeτHΛcyΛbφoκcH,^a (3,19 μλ) b cyxoM «ΗΧΛορ-MeTaHe (15 μλ) h 3aīeM no Kanji^M pacTBopoM 5-aueTOKCH «PaKTopa A (4,91 Γ) B CyXOM βΜΧΛΟρΜβΤβΗΘ (30 ΜΛ) . ΠOΛy ΗβΗΗΜίί paCTBOp TmaTenbHo nepeMeuiHBaioT β τβΜβΗΗβ 1,5 naca npH TeMnepaType -70°C, npewfle HeM o5pa6oTaTb no Kao/iHM pacTBopoM TpnoTHnaMHHa (12,6 ΜΛ) B CyXOM ΑΗΧΛΟρΜΘΤβΗΘ (40 ΜΛ) . PeaKLiHOHHyiO CMeCb ne-peMeuiHBaioT β τβΜβΗΗβ 1,25 Mača 6e3 οχλ3*αθημλ η βηλμββιοτ b CMecb (1:1) χοΛΟΛΗΟϋ βολή h npocToro ρφπρ3. ΒοληηΛ anoii 3KCTparHpyiOT npOCTbIM ΟφΗρΟΜ. CoeflHHHBUIHeCM opraHHMeCKHe ΟΛΟΗ npoMbiBaioT BOfloft, οολληημ pacTBopoM, BbicyniHBaioT h BbinapHBaioT. OcTaTOMHyio neHy xpoMaτoΓpaφHpyloτ na flByoKHCn κρβΜΗΗΗ, ηοπολβ-3y« CMecb ΠΗΧΛορΜβτΒΗΒ c aiļeTOHOM (50:1) c πoΛy^eHneM HasBaH-ηογο coeaHHeHMa (3,4 r), 5(CDC13) coflepraT 3,33 (m, 1H), 3,49 (Μ, 1H), 3,70 (fl 10; 1H) H 5,52 (fl 5; 1H), m/3 co,qep>KHT 652, 634, 609, 591, 574, 482, 263, 235 H 151. 40 ΠΡΗΜΘΡ 11 23-κβτο Φβκτορ Α
CoeflHHeHHe npHMepa 10 (276 μγ) β ΜβτβΗΟ/ιβ (5 μ λ) πρκ τβΜ-nepaType 0°C oSpaSaTbieaioT no Kanne pacTBopoM 2Ņ-HaTpHH-rHfl-poKCHfla (0,42 μλ ) b HeTaHone (1,0 m/i) . riepefl τβΜ, KaK BbinHTb pacTBop b xojioflHyra Bony, ero BbiflepaoiBaioT npn TeMnepaType 5°C b τβΜβΗΗθ*:5 nacoB. CMecb 3KCTparHpyioT npocTbiM οφπροΜ h 3THnaqe-TaTOM. CoeflHHHBiiiHecfl opraHHMecKne c/ioh npoMbiBarar οολλημμ pacT-BopoM, BbicyuiHBaiOT h BbinapHBaioT c nonyMGHH6M TBepfloro BemecTBa, κοτοροβ onnuļaioT npenapaTHBHoft τοηκοολοηηοΛ xpoMaTorpa(ļmeft,
Hcnonb3yn β κβμθοτβθ pacTBopHTenii CMecb ΑΜχηορΜβτβΗβ c aueTo-hom (10:1) fl/in no/iyMeHHfl Ha3BaHHoro coenHHeHHH (140 μγ), 5(CDC13) conep>KHT 3,28 (m; 1H), 3,48 (m; 1H) , 3,70 (fl 10; 1H) H 4,28 (Tp 7; 1H) , M/3 BK/IlOHaeT 592, 549, 482, 370, 263, 235 H 151. Πρμμθρ 12
23-KeTO Φβκτορ A 0,4 μλ cnopoo6pa3Hofi cycneH3HM Streptomvces thermoarchaensis NCIB 12015 b 10% r/iHgepHHe Hcnonb3yioT αλλ HHOKyn«LiHH b 250 m/i KOJi6e Erlenmyer, coflep*autefi 50 m/i Ky/ibTyp-hoh cpeflbi, cocTOiiuiefi H3 D-rni0KO3bi 15,0 gL”1, r/nmepnHa 15,0 gL"1 , οοθβογο nenTOHa 15,0 gL-1, NaCl 3,0 gL"1 h CaC03 1,0 gL"1 , fločaB/ieHO ao HopMbi flncTnymnpoBaHHofi boaom. flepefl noMeme-ηηθμ b aBTOKJiaB, pH flOBefleHa no 7,0 βοαηημ pacTBopoM NaOH.
Kon6y MHKy6HpyraT npn TeMnepaType 28° β τβΜβΗΗβ 2 «Ηβη Ha KpyroBOfi Kana/iKe, paSoTaiomeH npw ckopocth 250 οόοροτοΒ b MMHy-Ty c 50 M/i b flHarieTpe αβμ>κθηηθμ no op6nTe. 4-x mji nopgnH ncnonb3yioT 3aTeM n/in nHOKyηηυ,νΐΗ KajKflofi H3 MeTbipex 2-x nnTpoBbix - 41 - - 41 - y LV 10777 (JuiaKOHOB c uiHpoKHM rop/ibiuiKOM, coAep*amafl Ka)Kflah no 200 m/i or-hoh m Toft «e cpeflbi nepefl HHKy6npoBaHKeM b τβχ >κβ caMbix yc.noBn-ΛΧ B ΤβΜβΗΗβ 2 flHeii .
CoflepacHMoe yKa3aHHbix 4 Φλ3κοηοβ fla/iee ncno.nb3yioT rjir hho-κγ/ίΛμΜΗ 70 λμτροβογο <ļ>epMeHTaTopa, coflepMcautero 40 ηκτροΒ τοή »e Ky/ibTypajibHoii cpeflbi c AočaB/ieHHeM προπηλθηγληκολη 2000 (0,06¾). ;noyiHnponHiieHr7iHKoyib 2000 bboahtch, xax Heo6xoflHMo, b TeneHHe Bcero npoiļecca φβρΜβΗΤ^ανίΜ αλλ peryAnpoBaHwa nenoo6pa-30BaHneM. <PepMeHTaqwo προβοαλτ ripu TeMnepaxype 28° c OHeprHM-HbiM nepeMeuiHBaHHeM h aopaijMeH, flocTaTOMHOiļ αλη noAAep*aHHK ypoBHH pacTBopeHHoro KHCAopoAa 6ojibiue 30¾ HacbiiqeHHH. Hepe3 24 waca npoiļecca 6pox<eHH« 800 μλ, h 9-ΛΗτροΒΗβ nopiļHH nepeHOCflT b 70 ΛΗτροΒΗή φβρΜβΗΤ3τορ, coAep>KaE{nfi 40 λητροβ KyyibTypajibHOH CpeAbl, H 700-yiHTpOBblH φβρΜβΗΤΒΤΟρ, COAep*amnfī 450 ΛΗΤΡΟΒ Kyilb-TypajibHofi cpeAfci, σοοτΒβτοτΒβΗΗο. 06a M3 yKa3aHHbix ĢepMeHTaTO-poB coAep«aT xy/tbTypajibHyio cpeAy, cocTonmyio H3 D-r.moK03bi 2,5 gL'1 Malt AeKCTpHHa (MD30E) 25,0 gL"1, Arkasoy 50 12,5 gL'1 , Beet Molasses 1,5 gL"1 , K2HP04 0,125 gL'1, CaC03 (Ar) 1,25 gL-1 h cH/iHKOHa 1520 (Dow Corning) 0,6 gL-1 πρΗΒβΑβΗΗγιο κ nop-Μβ AHCTM/I/IHpOBaHHOH BOAOft. ΠβρβΑ CTepHAH3aUHeft pH AOBOAHT AO 6,5 BOAHbIM paCTBOpOM H2 S04 . YKa3aHHbie npoqeccbi φβρΜβΗΤ3ΜΗΜ βηποληαιοτ npw TeMnepaType 34° C ΠρΗ ΟΗβρΓΗΗΗΟΜ paSMeUIHBaHHH H aopaLJHH, AOCTaTOHHOH R/1R coxpaHeHHH ypoBHA pacTBopeHHoro KHcnopoAa 6o.nbiiie, μθμ 3 0¾ HaCbimeHH«. ΠρΗ Heo6XOAHMOCTH AOSaBJliliOT aHTHBOCnAaMeHHTe/lH H3 ΠΟΛΜΠΡΟΠΗΛΘΗΓΛΗΚΟΛΛ 2000. 4βρβ3 24 Mača, pH B Ka»AOM H3 φβρ-ΜΘΗΤ3ΤθρθΒ A0B0A«T RO 7,2 nyTeM BBefleHHS ΒΟΑΗΟΓΟ paCTBOpa H2S04 . ΠρΟΑΥΚΤΗ φθρΜΘΗΤ3Ι4ΜΗ CO6npai0T H OČbeAHHitlOT Μβρβ3 4 AHfl . 42 MHLļe/IHH (10,4 ΚΓ) H 3 CoSpaHHOfl JKMflKOK cpeflbi (423 71.) Bbl- 6npatoT b ίίβΗτρΗφγΓθ Sharples PS16AY. Mmje/iHM ηητθηομβηο nepe-
MeuiHBaioT b MeTaHo/ie (50 λ) b TeneHHe 40 MHHyT h 3aTeM οτφΗnb-
TpoBbiBaraT. Οοτβτοκ ποετορΗο cycneHflnpyioT b MeTaHOTie (15 jī) h BHOBb φΗ/1ΒΤργΚ3Τ. CoeflMHHBUlHeCJĪ φΜ/ibTpaTbt (55 71) saTeM CMeuiHBa- K3T c BOflOH (27 jī) h 60-80 neTpoTieftHbiM 3φΗροΜ (npe^e/i KMneHHiī 60-80°) (30 jī ) h nepeMeuiHBaioT b TSMeHHe 20 ΜΗΗγτ. %
nojiyMeHHbie φβ3& οτβθ/ΐίϋοτ b ίίβΗτρκφγΓβ Westfalia MEM1256 a MeTaHoyibHyK5 φa3y (75 n) cMeuiHBaioT cHOBa c bobom (38 λ) h 60-80 ΠβΤρΟΛθίΪΗΗΜ 3φΜρ0Μ (30 71) . . Μθρβ3 20 MHHyT $3L3bl BHOBb OTfleTlfllOT Β μβΗΤρΗφγΓβ, ΠρΗΗΘΜ Β φΆ3y ΠβΤρΟΤΙΘΗΗΟΓΟ 3φΐφ3 , HTOSbl pa3py- uiMTb no7iyHeHHyio 3My7ibcwo bborht aiļeTOH (2,0 jī) . MeTaHOTib Hy.O φa3y (110 τι) CMeuiMBaioT c Boflofi (38 τι) h 60-80 neTpo/iefiHbiM οφπ-poM (30 λ) B TpeTHfi pa3, φa3bt OTfle/isioT KaK paHbuie. AqeroH (3 Jī) flo6aB7I7IIOT CHOBa K ΠΘΤροΤΙθΒΗΟή ΟφΜρΗΟίί φ33β RJĪK pa3pyilieHHfl nonyMeHHOfi 3MyjibCHn. ΤρΗ φβ3Μ reKcaHa oēbeflMHflioT (90 jī) η KOHi4eHTpnpyioT ripu HH3KOM flaB/ieHHH (TeMnepaTypa BbinapKH 25°)· KoHijeHTpaT (9,8 τι) BwcyuiiiBaioT cyΛbφaτoM HaTpHK (3 κγ) h BbinapHBaioT flo MacTia.
IlojiyHeHHoe Mac/io pacTBopaioT b nnx/iopMeTaHe (0,5 τι) h φHΛbτpyloτ Hepe3 Dicalite 478. PacTBop (0,9 τι) 3arpy>KaioT β xpo-ΜΒΤΟΓρβφΗΗβΟΪ^ΙΟ KOTIOHHy (150 X 10 CM) H3 flByOKMCH KpeMHHfl (Merck) ripu sarpy3Ke 6 τι/Mac, npoMbiBaioT βκχτιορΜβτβΗΟΜ (4 jī) h 37ifonpyioT CMecbio χ/ιοροφορΜβ c 3TMJiai4eTaTOM (3:1). «PpaKumi, otiio-HpyioiiiHe Me*fly 14,6 h 33,3 jī KOHqeHTpvtpyioT flo TBepfloro BemecrBa H paCTBOpKlOT B CMeCH χτιοροφορΜΒ c aiļeTOHOM (3:1). no/iyHeHHbifi pacTBop ποετορΗο xpoMaτoΓpaφHpyκDτ Ha κοΛΟΗΚβ flByoKHCM κρβΜΗΗΛ c τθμ we caMbiM pacTBopMTe/ieM. 9paKqnn, 3/non- - 43 - LV 10777 pyK>mne Me>Kfly 14,5 m 31,5 n, BbicyuinBaioT no TBepfloro BemecTBa m pacTBopaioT b CMecM xjiopo$opMa c BTHJiaiieTaTOM (3:1). noyiyMeHHbifi paCTBOp BHOBb XpOMaTOFpaφnpylOT Ha AByOKHCH ΚρβΜΗΜΛ npH xex Χθ yCAOBHHX, HTO H paHblIie, H 3aTeM $paKI!HH 3/nOHpOBaHHfl Me>KAy 14 H 31 λ BucyuiHBaioT ro TBepfloro BemecTBa. TBepfloe BemecTBO pacTBopnioT b 70%^μβτοΗπτρΗΛβ β βοαθ (1,23 Λ)*σ flocTaTOMHbiM KOJiHMecTBOM MeTaHo^a, flo6aBA«eMoro αλη nojiyHeHMii ceeT/ioro pacTBopa. Υκβββηημμ pacTBop xpoMaτoΓpaφHpy-k>t b 5 μλ nopuHHX Ha κοΛΟΗΚβ Spherisorb 0DS2. CoAep>KHMoe ko-ΛΟΗΚΗ 3/IK3HpyiOT C nOMOUļblO 70% aiļeTOHHTpH/ia npH CKOpOCTH Tene-hhh, KOTopan B03pacTaeT ot 20 μλ/μηη no 34 μλ/μηη nepes 21 mh-HyTy. Φρ3Κ11ΗΜ H3 KaJKflOft nopUHM, KOTOpbie OJlKDHpOBaHbl Me*fly 12,4 h 16 6ηλη coēpaHbi BMecTe h pa36aBJieHbi paBHbiM očteMOM BOflbi. Πο-/tyweHHbifi pacTBop aaīeM 3arpy«aioT b κολοηι^ Montedison S112 Ha ποΛΗΟΤΗροΛβ c ceTHaTOH CTpyKTypoft (2 λ). KcmoHKy npoMbiBaioT 35% pacTBopoM aiieTOHHTpH^a h 3/iraMpyioT aiļeTOHOM. ?paKLļHn, 3JHOHpyio-uļHe Me«fly 0,5 h 1,25 n, BbicyuiHBaioT flo TBepfloro BemecTBa. TBepfloe BeuļecTBo pacTBopfliOT b aiieTOHHTpmie (20 μλ) h xpo-MaτoΓpaφHpyκ3T Ha κολοηκθ H3 Sephadex LH20 b tom »<e pacTBopuTe-Λβ. ΦρΒκι^ΗΗ, ^ΛloHpyκ5I^He Me*Ay 1,08 Η 1,26 Λ, COČHpaiOT Η Bbicy-uiHBaioT flo TBepfloro BemecTBa. TBepfloe BemecTBO pacTBopflioT b 60% ΒμβτοΗΗτρκΛβ (10 μλ) c APCTaTOHHbIM ΚΟΛΗΗΘΟΤΒΟΜ ΜβΤ3ΗΟΛ3, Αθ6ΒΒΛΗβΜΟΓΟ RJIR ΠOΛy ΜβΗΗΛ MHCToro pacTBopa. PacTBop xpoMaτoΓpaφHpyιoτ b 2 μλ πορμΗίΐχ eme pa3 na κολοηκθ h3 Spherisorb ODS2 h 3Λ;oHpy!oτ c noMotīļt-ra 60% βμθΤΟΗΗΤρΜΛΒ ΠρΗ 25 ΜΛ/MHH. 9paKLJHH, ^ΛK3HpyI01^Me Me)Kfly 0,95 Λ M 1,08 λ, co6npaioT BMecTe η BbicymHBaioT ao TBepAoro BemecTBa. Πο-AyHeHHOe ΤΒβρΑΟΘ BeUteCTBO ΠΟΒΤΟρΗΟ paCTBOpflIOT β ΧΛοροφορΜθ (5 44 μλ) μ xpoMaTorpa$HpyioT Ha κολοηκθ Η3 cH/iHKare/in Merck 60. PaCTBOp 3JlKDHpyiOT ΧΛΟρΟφσρΜΟΜ npH 10 ΜΛ/ΜΜΗ · , H φρΒΚ11ΗΗ, 3ΛΙ0Η-pyiomHe Me*ny 400 μλ h 790 μλ, BbicyuiHBaioT c nojiyMeHHeM Ha3BaH-ηογο coeiiHHeHMn (33 μγ) b BHfle TBepfloro BemecTBa. ΗΜΡ-οπβκτρ cooTBeTCTByeT coflep)KameMycfl 23-κβτο <PaKTopy A. 3.M. Macc-cneKTpocKonHH flafla hoh ΜΟΛβκγΛΜ npH 610 h xapaKTepHCTH-neCKHe φρβΓΜβΗΤω ΓφΗ 592, 549, 498, 482, 370, 263 Η 151. 06pa-3ei4 npeflCTaB/ieH, hto6i>i cpaBHHTb 2 3-κβτο Φβκτορ A, no-
JiyMeHHblfi npH ΒΜΟΟΚΟΟφφβΚΤΗΒΗΟΗ JKHflKOCTHOfi χρΟΜβΤΟΓρβφΗβΗ C aHa/IorHMHbIM ΚβΤΟΗΟΜ, o6pa3yeMblM npH XHMHHeCKOM OKHCJieHHH 9aK-Topa A. ΠΡΗΜβΡ 13
5-(beHOKCnaueTOKCM-23-neoKCH <PaKTOP A
CoeflHHeHHe npHMepa 2 (350 μγ) h a3o5HCH3o5yTHpoHHTpHvia (25 μγ) b cyxoM TO/iyo/ie (20 μλ) η ΒΤΜοοφβρβ a30Ta npw TeMnepa-Type 120° očpaSoTaHO no KannaM pacTBopoM τpn-H-6yτHΛOΛOBo γηα-pHfla (0,5 μλ) b cyxoM τoΛyoΛe (10 μλ) . PaVeop HarpeBaioT c 06-paTHblM XOflOflHnbHHKOM B ΤΘΜβΗΜβ 90 MHH . , ΟΧΛ3*Α3!ΟΤ H BbinapHBa-iot. OcTaioK xpoMaτoΓpaφMpyloτ nepe3 flByoKncb κρβΜΗΗΛ, Hcnoflb3yn cMecb ΑΜΧΛορΜβτβΗδ c aiļeTOHOM (40:1) b KanecTBe pacτBopMτeΛί^ c βηχοαομ HasBaHHoro coenMHeHHa (280 μγ), δ (CDC13) coflep>KHT 3,32 (m; 1H), 3,42 (fl 10; 1H), 3,57 (m; 1H), 4,71 (c; 2H), 5,59 (6; 1H) h 6,8-7,4 (μ; 5H), m/3 coflep>KMT 730, 712, 578, 560, 468, 450, 356, 314, 299, 249, 248, 221 H 151. ΠΡΗΜβΡ 14
23-aeoKcn cpakTop A
CoeflHHeHHe npHMepa 13 (240 μγ) BBefleHO b HacbimeHHbiH pacT-Bop aMMOHHii b ΜβτβΗΟΛβ (10 μλ) npH TeMnepaType -5°. nonyMeHHbifi - 45 - LV 10777 pacTBop nepeMeuiHBaioT ripu TeMnepaType ot 0° ao 10° b τθηθημθ 2 MacoB nepefl ero BbinapHBaHHeM ao cyxoro coctoahhh. OcraTOK xpo-MaTorpa<ļ>HpyioT nepea AByoKMCb κρβΜΗΗΛ, ncno./ib3yfl CMecb αμχλορ-MeTaHa c aijeTOHOM (20:1) c noiiyweHHeM Ha3BaHHoro οοθαμηθηηα (180 μγ), δ (CDC13) coflep^HT 3,27 (m; 1H), 3,42 (a 9; 1H), 3,54 (m; 1H) H 4,29 (t6; 1H), m/3 coflep)KMT 596, 578, 560, 468, 450, 356; 314, 299, 249, 248, 221 H 151. ΠΡΗΜΘΡ 15
5-aueTOKCM-2 3-MeTHJICVJIb(tlOHHJIOKCH <PaKTOp A
PacTBop 5-aiļeTOKCH <PaKTop A (3,46 r) β πμρηαηηθ (30 mji) oxyiaa<flaioT b yieflsHoft 6aHe h o6pa6aTbiBaiOT MeτaHcy.πbφoHHeBblM aH-rnflpHflOM (2,2 r). Hepe3 30 MHHyT CMecb noAorpeBaioT flo TeMnepa-Typw oKpy>Kaiomeii cpeflbi h eqe Kepea 60 MHHyT pa3Ae/iflioT Me*Ay 3THAaqeTaTOM h 2N-coaaho& κηολοτοΛ. OpraHHHecKyio φ33>' οταθληιοτ H npOMMBaPT nOCAefldBaTeAbHO 2N-COAAHOfl KHC./IOTOft, HaCbiqeHHbIM BOflHbIM paCTBOpOM SHKapSOHaTa HaTpHil H B 3aKyiraweHHH HaCbimeHHblM coA^HbiM pacTBopoM. OpraHHHecKHfi pacTBop BbicyuiHBaioT (Na2S04) h pacTBopHTe/ib BbinapHBalOT c βηχοαομ πθηη, KOTopyra χροΜΑτοτρΑφΗ-pyioT nepea KOAOHKy Ha flByoKHCn κρβΜΗΗΛ (Merck Art 9385), ao-6aB/ieHHoro b CMecb reKcaHa (npefle^ibi κμπθημ« 60-80° )/c apeTH-na-peīaTOM (3:1) h 3/iranpyraT b tom xce pacTBopHTe/ie. CooTBeTCTByio-UļHe φρΒΚΑΜΗ OCHOBHOrO ΚΟΜΠΟΗΘΗΤά COeflHHAPT, H paCTBOpHTe/Ib Bbl-napHBaioT c nonyHeHHeM Ha3&aHHoro coenHHeHHfl b bha© πθημ (2,08 Γ). [Ct]D22 +154° (c=0,56; CHC13 ) , XmaxCHCl3 + 247 HM (Z 29070); Vmax (CHBr3 ) 3550, 3470 (OH) H 1735, 1715 (cyio>KHbifī 3φΗρ) ; 5(CDC13 ) coflepacHT 4,90 (m, 1H), 3,05 (C, 3H) h 2,16 (c, 3H) . 46 ΠΡΗΜβΡ 16 2 3 -T03M/I0KCH ĢaKTOP Β <PaKTop Β (250 μγ), το3Ηλοβι>ιη aHrHflpHfl (204 μγ) η HecKoyib-κο KpncTa/ι/ιθΒ 4-N,N-flHMeTHrtaMHHnHpHflHHa nepeMeuiHBaraT β cyxoM nupMflHHe (0,5 ΜΛ) β ΤβΜβΗΗβ 24 HaCOB. CMeCb BblJIHBaiOT Β npOCTOft οφΗρ, η opraHHwecKyra φa3y npoMbiBaioT nocjieflOBaTe/ibHo 2Μ co/ihhoh KMCJiOTOfί; HacbimeHHbiM BOflHbiM pacTBopoM 6HKap6oHaTa ΗβΤρΗΛ H, HaKOHeq, co/ihhwm pacTBopoM. BbinapHBaHHe BbicymeHHoro (Na2S04) οφΗρΗΟΓΟ c/ioii flaeT ηθομηιιιθηημη npoflyKT, β κοτορυΛ β αηχλορμθ-TaHe bboaht b χροΜΒΤΟΓρΒφΗΜβαι^ιο xo/ioHHy Ha cnyiHKareyie (50 r, Merck Kieselgel 60, 203-400 Mern), ΒΚΛΙΟΗβΗΗΟΓΟ b tot «e pacTBO-pMTe/ib. OcyqecTBJiHioT ojijoHpoBaHHe H3 oiecH Anx/iopMeTaHa c npOCTblM ΟφκρΟΜ (9:1) OCHOBHOrO KOMnOHeHTa, KOTOpbIH floSaBOHHO OMHmaiOT npenapaTHBHOfi ΒΜΟΟΚΟΟφφθΚΤΜΒΗΟή «HflKOCTHOf! XpOMaTOrpa-φΜβκ. HasBaHHoe coenHHeHne nonyHeHO b bma© cmo/ih [CC]D23 +173° (0,84, CHC13); Xmax (EtOH 235 (30,000) H 244,5 hm (£max 30,800); Vmax (Cand 1708 αΜ-1(3φΗρ); δ (CDC13) coAepa<HT 7,82 (A, 10 Γ14, 2H) , 7,29 (fl, 10 Γ14, 2H) , 4,83 (k, 3 Tu, 1H) , 3,50 (c, 3H) H 2,43 (c, 3H); m/3 = 752 (M+). ΠρΜΜβρ 17
5-aueTOKCn-23-H-6vTQKCH ?aKTop A
KapSoHaT cepečpa (λγ) AoSaBJiiiidT κ pacTBopy 5-aueTOKCH ?aKTopa A (325 μγ) b cyxoM npocTOM οφπρβ c nociieAy»mHM ββθαθ-ηηθμ uoAo6yTaHa (0,5 μλ) h nepx/iopaTa cepe6pa (550 μγ). riojiy-MeHHyū CMecb nepeMeuiHBaioT ripu κομηβτηομ TeMnepaType β τθηθηηθ 20 nacoB, KorAa ββοαλτ οολληαμη (0,5 μλ) . nocyie nepeMeuiHBaHHH - 47 - LV 10777 B ΤβΗβΗΜβ eme 20 MHHyT, CMeCb φΗΛΙ^ΤργίΟΤ H φΗ/IbTpaT npOMblBaiOT nooMepeflHO c noMombio 2N cojiHHOfi κηο/ιοτη, HacbiineHHoro βοαηογο pacTBopa 6nKap6oHaTa HaTpHH h BOflbi. BbJcyuieHHyio opraHHMecKyio $aay BbinapuBaioT ποητμ flocyxa h Mac/io oHHiiļaioT χροΜΒΤοΓρβφΗβκ Ha κολοηκθ H3 Merck Kieselgel 60 c pa3MepaMH nop 230-400 Mern. 3/iranpoBaHne H3 κολοηκη CMecbio reKcaHa c oTM/iaiļeTaTOM (3:1) fla-eī HasBaHHoe coenHHeHHe b BHfle SecuBeTHofi neHbi (276 μγ) [<X]D22 +160° (c 0,94, CHC13) \max (EtOH) 245 hm (8max ΠΡΜΜΘΡ 18
<PaKTQP Α-2 3-reMMOKca.naT Φaκτop A (λγ, j<a 70% ommctkh) h KapScmaT Ka^ibLļHii (1,5 r) nepeMeuiHBaraT αηχλορμθτβηομ (20 μλ) πρκ TeMnepaType 21°C h k noyiyHeHHoiļ cycneH3HH flo6aB/iinoT b Η3δωτκβ oflHOKpaTHO OKca./iH/ix-nopMfl (1,0 μλ) . Hepe3 4-5 MHHyT, yKa3aHHyio cMecb o6pa6aTbiBaioT BOflofi (15 mji) h eme qepe3 5 MHHyT 2M οολληομ kmcjiotoA (10 μλ) m 3Tnnai4eTaTOM (70 n/i) . OpraHHHecKyio φa3y οταθληιοτ, npoMbieaioT BOflOft H COJlHHblM paCTBOpOM H fl βΛθβ o5pa6aTblBaiOT o6eCI4BeMMBaiOmHM yryieM. Hepe3 5-10 MHHyT o6pa30BaHHbifi opraHHHecKHft pacTBop ot-φΗΛΒΤρθΒΜΒ310Τ Ηβρβ3 φ&3θρ&3 P,emiTem> HyiO 6yMary H $HilbTpaT fleCOp6HpyiOT H3 paCTBOpHTe/Iit. OCTaTOK B npOCTOM ΟφΗρβ (50 M/l) OMHmaraT nyTeM φΜ/ibTpoBaHHii Mepes "Hyflo" h, γιχ&ηηχ pacTBopH-τβ/ib, no/iyMaioT Č.nejļHo->KeyiTyio neHy. nopouiKOBaHue yKasaHHoro BcneHeHHoro MaTepnana ηηη3οπροπμλοβι>ιμ 3φκροΜ (Ka 7 mji) «aeT HasBaHHoe coejHHeHMe b BHfle KpHCTa.n.nj'iHecKoro TBepfloro EemecTBa (750 μγ ) noc/ie npoMbiBaHHfl TBepfloro BeuļecTBa αμη3οπροπμλοβμμ οφΗρΟΜ H H-neHTaHOM. Vmax (CHBr3) 3360-3600 (OH), 1805 (KHC/IOTHblM MOH'OMep) H 1720 CM~1(ΚΗΟΠΟΤΗΗΗ flMMep H C^lOKHbie 3φΗ~ 48 pbl): δ (CDCl3) coflep)KHT 4,30 (fl, 5Γιΐ, 1H) h 5,14 (Μ, 1H). ΠΡΗΜΘΡ 19
tPaKTOP A
PacTBop 23-reMnoKca.naT «PaKTopa A (500 μγ) b flnx.rcopMeTaHe (30 mn) 3HeprnMHO nepeMeuiHBaioT c boahum pacTBopoM γκαροοκκομ HaTpHH (1,54 r b 30 μλ H2Oļ b TeneHHe 2 wacoB npn TeMnepaType 21° . OprannMecKyio (J)a3y coSnpaioT, a BOflHyio $a3y npoMbiBaioT He-6o/lbIIIMM KO/IHHeCTBOM flHX/IOpMeTaHa . OpraHMHeCKHe $a3bl COeflMHSIOT, npoMtiBaiOT c noMouļbio 2M HC1, 3aTeM BbicymnBaioT (Na2S04) h flecop-6HpyroT H3 pacTBopHTe/iH c πο^μθηηθμ ηββββηηογο coenHHeHHfl (430 μγ) B BHfle BcneneHHoro BemecTBa. yKa3aHHoe coeflHHeHHe npofleHOHCTpHpoBaHo b KaMecTBe <PaKTopa A ripu cpaBHeHHH no/iyMe-
HHJĪ ΒΗΟΟΚΟΡφφβΚΤΗΒΗΟίΐ «HRKOCTHOŪ ΧρΟΪ^ΤΟΓρΒφΗβίί C aHaJIOrHMHbIM o6pa3LioM ĢaKTopa A. ΠρΗΜβΡ 20
<PaKTop A. 5-reMHcvKUHHaT
PacTBop «PaKTop A (306 μγ) h cyKiļHHOBoro aHrHflpHfla (60 μγ) b cyxoM nMpHAHHe (0,5 mji) nepeMeuiHBaioT npw TeMnepaType 22° C b ΤβΜβΗΗβ 24 MaCOB. CMeCb pa36aBAHK)T npOCTUM ΡφπρΟΜ H npOMblBaiOT opraHHHecKyio φa3y c noMoiiļbio 2N ρο,πληοη κηολοτβι η οολληογο pacTBopa. ΠρΗ BbinapMBaHHM BwcymeHHoro οφκρΗΟΓΟ caoji noyiyMaioT BcneHeHHoe BemecTBo, H3 κοτοροτο βηαθλλιοτ nocpeflCTBOM bmcoko-ΡφφθΚΤΗΒΗΟίί »MflKOCTHOH npenapaTHBHOH ΧρΟΜΒΤΟΓρΒφΜΜ C 06paTHOH φa30H Ha3BaHHoe coenHHeHHe. īlo.nyMeHHbiH npoAyKT b οφκρβ oca*na-eTcii b BH«e 6ejioro aMop$Horo TBepfloro BemecTBa (86 μγ) npw ββθαθημμ nonoAHHTeAbHO H-neHTaHa [Ct]D22 +125° (c. 0,44, CHC13 ) XmaxEt°H 245 HM (emax 30,700), Vmax (CHBr3) 3490 (OH), 3,300-2,200 (COgH), 1730 ( KHC/lOTHbifl KapSOHH/l) M 1710 cm'1 - 49 - LV 10777 (cJio>KHbiiļ cnupT); δ (CDC13) coflep*HT 2,74 (c, 4H) . m/3 = 712 (M+). rīDHMSP 21
5-aueTOKCH. 2 3-3THJioKca.nH.noKCH - Φβκτορ A
PacTBop 5-aqeTOKCH - «PaKTop A (320 μγ) m n36biTOHHbJii oth- /iOKca/iHJīXJiopMfl (0,5 μλ) b cyxoM flHX/iopMeTaHe (6 μλ) cMeiiiHBaioT * b npncyT<STBHH Kap6oHaTa Ka/ibUHii (300 μγ) b TeneHHe 1 Mača. 06-pa3OBaHHyi0 CMeCb, pa3ČaB/ieHHyiO npOCTHM ΟφΗρΟΜ, Bbl/lUBaiOT B HacbimeHHbifi 6m<ap6oHaT HaTpHfl-, v 3aTeM nepefl BbtfiHBaHHeM b otm-/laiļeTaT, nepeMeuiHBaioT b τβΗβΗΜβ 20 MHHyT.BbinapHBaHHSM BbicymeH-HOii (Na2S04) opraHHMecKofi <ļ>a3b\ no/iyHaioT CMO/iy (325 μγ), koto-paa b HMXJiopMeTaHe ββοαητολ b xpoMaTorpa4>nHecKyio Ko/ioHKy H3 Merck Kieselgel 60, πρμμθμ flByoKHCb κρβΜΗΜΛ (25 r) c pa3MepoM MacTHiļ 70-230 Mem, flo6aB/ieHa b tot xce pacTBopHTejib. 3.moHpoBa-HHe H3 ΚΟΛΟΗΚΗ βΗΧΛΟρΜβΤΒΗΟΜ H 3aTeM CMeCb» flHXHOpMeTaHa c npocTbiM οφπροΜ (95:5) flaeT HasBaHHoe coenMHeHHe (265 μγ) b bh-fle Se/ioro βοπθηθηηογο BeqecTBa [OCjp23 +157° (c 0,41, CHC13 ) ; XmaxEt0H 245HM (£max 32,800); Vmax (CHBr3) 3530, 3480, (OH), 1760 H 1735 CM-1 (ΟΠΟΚΗΗβ ΡφΗρω) ; 5 (CDCI3 ) COflep>KHT 5,4-5,6 (Μ, 2H); 5,05 (μ,1H), 4,32 (k, 7 Γμ, 2H), 2,13 (C, 3H) H 1,35 (t, 7 Γ14, 3H) . Πρμμθρ 22
2 3-MeTH.rcoKca.nn.noKCM - gaKTOP A
PacTBop'5-aqeTOKCn, 23-3THJioKca/iMJioKcn - VaKTopa A (50 μγ) b MeTaHO/ie (1 μλ), coflepjKamufi KOHi4eHTpHpoBaHHyio cepHyio KHC^oTy (0,01 μλ) BWflep>KHBaioT ripu TeMnepaType 21°C b τθηθηηθ 17 MacoB. 3aTeM CMecb βμλμββιοτ b DTH^aueTaT h opraHHHecKa« φa-sa fleficTByeT b KanecTBe HefiTpa^bHoro npoflyKTa. yKa3aHHbifi προ- 50 Αγκτ oHHmaioT χροΜΒΤΟΓρβφΜθίί Mepe3 κο/ιοΗκγ η3 Merck Kieselgel 60, flByOKHCM κρβΜΗΜΛ (15 Γ) C pa3MepOM MaCTHU .70-230 Mem. hc-nojib3yK)mHx b nanecTBe ολιοηρυιοιιιηχ pacTBopHTejieM nepBOHaMajībHO flnxjiopMeTaH, a aaTeM CMecw flHXAopMeTaHa c οφΜροΜ (9:1). Ha3-BaHHoe coeztHHeHHe ποΛγπβΗΟ b BHfle 6ecqBeTHOH cmo/iw (25 μγ), [CC]d23+ 147° (c, 0,28 CHCI3), XmaxEt0H 245 hm (8max 26,000);
Vmax (.CHBr3 ) 3550, 3480 (OH) , 1763, 1737 H 1710 CM-1 (cyio>KHbie οφπρΗ); δ (CDC13 ) coflep*HT 4,29 (br. t., 7 Γ14, 1H), 5,09 (Μ,1H) H 3,88 (c, 3H). ΠΡΗΜβΡ 23
5-aueTQKCM-23-UHK/IOnPOnHJIKap60HHJ10KCH - Φβκτορ A
PacTBop 5-atļeTOKCH - Φθκτορβ A (140 μγ) b πηρηαηηθ (1 mji) o6pa5aTbiBaiOT x/iopHflOM i4HKnonponaHKap6oKcn/ioBOH khc/iotw (0,08 M/i) . Mepe3 3 Mača peaKiļHOHHyio CMecb paafle/iiiioT Me«fly bth-/iaqeTaTOM η 2N cannHoii κηολοτμ. OpraHHMecKyio cj)a3y OTfle/iλκ»τ m npoMbiBaioT noc.neflOBaTe.abHO c noMoqbio 2N cojihhoh κηολοτμ h Hacbi-meHHbiM BoflHbiM pacTBopoM ČHKopboHaTa HaTpHH. OpraHHMecKHfi pacT-Bop BbicyuiHBaioT (Na2S04) h pacTBopHTeAb ynapHBa!0T c πολυμθηηθμ MaCJia, KOTOpoe ΧρθΜ3ΤΟΓρ3φΗργΐΟΤ B ΚΟΛΟΗΚΘ H3 flByOKHCH KpeMHHit (Merck Art 9385; 80 μλ), ββθαθηηογο b CMecb reKcaHa (npefleflbi κμπθη un 60-80° C) c 3TM/iaqeTaTOM (3:1) h 3/noMpyeMoro t3khm «e pacTBOpnTe/ieM. CooTBeTCTByioqHe φρΒκμππ ocHOBHoro KOMnoHeHTa oSTbeflMHHlOT H BbinapHBaiOT paCTBOpHTe/lb c ΠΟ/ίγΗΘΗΗβΜ Η33Β3ΗΗΟΓΟ coenHHeHHH b BHfle BcneHeHHoro BemecTBa (70 μγ) . COC]d22 +143° (C=0,54; CHC13); XmaxCHCl3 250,2 (Z = 20310); Vmax (CHBr3 ) 3550, 3470 (OH) h 1733, 1712 (c/io>KHbiM οφπρ); δ (CDC13 ) coflep-
>KHT 2,16 (C, 3H) , 3,33 (m, 1H), 3,88 (fl, D 10 Tlļ, 1H) , 5,01 (m, 1H) h 5,5 - 5,6 (μ, 2H) . CoeflHHeHHfl npHMepa 24 noflyMaioT - 51 - LV 10777 aHa/IOrH4HblM πγτβΜ. riPHMep 24 5-aueTQKCM-23-LiHKJioneHTH.nKap6oHH.noKCM - Φβκτορ A 5-aqeTOKCH - <PaKTopa A (0,28 r) h uwK.noneHTM.nKap6oHn.flx.rco-pHfla (0,2 μλ) flaioT HasBaHHoe coenHHeHHe b βηαθ BcneHeHHoro Be-mecTBa (0,17 r), [a]D22 + 149° (c = 0,475; CHC13); XmaxCHCl3 250,2HM 1ε = 19900); Vmax (CHBr3 ) 3480 (OH) . ņpHMep 25
2 3-uHK.aonponHJiKap6oHHJioKCH - <PaKTOP A nepeMeuiaHHbiH pacTBop 5-aueTOKCw-23-uwKAonponn.flKap6oHH.noK-ch - (PaKTopa A (230 μγ) b μθτ3ηολθ (15 mn) ox/ia*AaiOT b .neAflHOii 6aHe h o6pa6aTbiBaioT 3% BOflHbiM pacTBopoM γηαροοκηομ HarpMA (0,5 μλ) . Hepe3 5 nacoB, b τβΜβΗΜβ κοτορυχ peaKiļHOHHa^ CMecb Harpe-Banacb flo KOMHaTHOfi TeMnepaTypw, pacTBop pa3fle./iinoT Me*fly oth-JiaqeTaTOM η 2N cojihhoh khc/iotoh. OpraHHwecKyio 0a3y οταθλλιοτ, npoMHBarar 2N coahhoū KHC-ποτοή (x 2), BbicyuiHBaioT (Na2S04) w bh-napHBaioT pacTBopHTe/ib. Οοτβτοκ xpoMaTorpa<ļ)npyioT Ha κολοηκθ hs AByoKHCH κρβΜΗΗΗ (Merck Art 9385; 150 μλ) , BBeASHHoro b CMecb reKcana (ripeAe-flbi κηπθηηη 60-80° C) c 3Tw.naueTaTOM h 3/iiowpyeMoro τβΜ *e paCTBopMTe/ieM. CooTBercTByiomHe φρΒκμΜΗ οοηοβηογο κομπο-HeHTa ΟδΒβΑΗΗΛΙΟΤ H BbinapHBaiOT paCTBOpHTe/Ib C ΒΜΧΟΑΟΜ HaSBaHHO-ro cjio)KHoro 3<bHpa b bhab BcneHeHHoro BemecTBa (170 ΜΓ), [CC]D22 + 146° (C'= 0,46; CHC13); XmaxCHCl3 250,2hm (t = 20090); Vmax (CHBr3 ) 3550, 3480 (OH) n 1709 (c/lc»KHblfi 3φκρ) ; δ (CHC13 ) co-Aep*aT 3,26 (m; 1H), 3,88 (a, 0 10 Tq, 1H) , 4,29 (t, J 7 Γμ, 1H) h 5,01 (m; 1H) .
CoeAHHeHHH npuMepa 26 no.nyMaioT βηβλογμμηημ cnocoSoM. 52 ΠΡΗΜΘΡ 26 2 3-UMKJioneHTH.aKap6oHH.noKCH - Φβκτορ Α Οτιι{θπλθημθ sauļHTHofi rpynm>i 5-aueTOKCH-23-qnK.noneHTH.nKap-6ohh/iokch - «PaKTopa Α (0,25 r) flaiOT Ha3BaHHbiH c.no>KHbift οΦηρ b BHfle BcneHeHHoro BemecTBa (0,215 r) [CC]D2G + 141° (c = 0,63; CHCI3); XmaxCHCl3 250,2 HM (C = 19990); Vmax (CHBr3) 3550, 3480 (OHļ., 1710 (cJio*HWH 3φΗρ) ; δ (CDC13) coflepacHT 2,74 (kbhh-τβτ, J 1 Tq, 1H), 3,26 (μ, 1H), 3,91 (fl, D 10 rq;lH) 4,30 (t, D 7 Γμ, 1H), 4,95 (Μ; 1H). ΠρΗΜβρ 27
23-UHKJI0np0nHJlKap60HHJI0KCH-5-MeT0KCHKap60HHJI0KCH-yaKT0P A
PacTBop 23-qHKJionponHJiKap6oHH/ioKCH - cPaKTop A (0,1 r) b cyxoM flHX/iopMeTaHe (15 un) ox.na>KflaioT b neαηηοΛ 6aHe h o6pa6a-TbiBaioT nnpHflHHOM (0,2 Mii) c noc.neflyion(eH o6pa6oTKOH 1M pacTBO-poM MeTH/ix/iop$opMaTa b flHX.nopMeTaHe (0,3 μλ). 4epe3 20 MHHyT pacTBop pa36aB.nflioT αμχλορμθτθηομ h npoMbiBa«T 2N co/ihhoh khc/io-toA, saTeM BbicyuiHBaioT cy/ibcļ)aTOM ηβτρηη h BbinapHBaioT pacTBopn-Te/ib. OcaflOK xpoMaτoΓpaφHpyloτ b κολοηκθ H3 flByoKHCH κρθμηηη (Merck Art 9385; 100 mn) , BXOflflqero b cMecb reKcaHa (60-80°C) c 3THJiaqeTaTOM (3:1) m 3JiioHpoBaHHbiM τθμ x<e caMbiM pacTBopHTe-neM. CooTBeTCTByiomHe φρ3^ΗΗ ocHOBHoro κομποηθητβ οδΒβΑΗΗΗΐοτ, ,H pac~BOpHTe/lb BbinapMBaiOT C BblXOflOM Η33ΒΒΗΗ0Γ0 ΟΟβΠΗΗβΗΗΑ B BHfle BcneHeHHoro BeuļecTBa (0,106 r) [ CC ] D 2 0 + 149° (c=0,63; CHCL3) XmaxCHC 13 250,2 (8 = 20470); Vmax (CHBr3 ) 3470 (OH), 1745 (Kap6oHaT), 1710 (c.no>KHbiH οψπρ), 998 (C-O) ; δ (CDC13 ) coflep>KHT 5,56< (c; 1H), 5,01 (m; 1H), 3,88 (fl; 0 10 Tq, 1H), 3,83 (c; 3H), 0,67 (fl; J 7 Γμ; 3H). - 53 - LV 10777 Πρμμθρ 28
Φ3ΚΤΟΡ A, 5-aueTaT, 23-H3o6yTHpaT
PacTBop «PaKTopa A, 5-aqeTaT (131 ηγ) , H3o6yTHpH/ix/iopHfla (0,05 ΜΛ) , riHpHflHHa (0,1 M/l) H 4 -flHMeTM/iaMHHOnHpHflHHa (25 ΜΓ) b cyxoM flHX/iopMeTaHe (10 μ λ) nepeMeuiHBaioT ripu TeMnepaType 2 0°C B ΤβΜβΗΗΘ 16 MaCOB . PaCTBOp ρ3363ΒΛΛΙ0Τ ΑΗΧΛΟρΜβΤβΗΟΜ (30 MJ1) , npoMUBaioT; 2N co/ιληοη κηφλοτοΛ h BbicymnBaioT (cy/ib$aTOM MarHHfl), h ynapHBaioT flocyxa. Οστβτοκ OMHUjaioT xpoMaTorpa0Hefi Ha Kiesel-gel 60 (15 r). 3.moHpoBaHHe ,H3 κολοηκη cMecbto cBeivioH Ηβφτκ c 3TH/iaiļeTaTOM (4:1) flaioT Ha3BaHHoe coeziHHeHHe (57 μγ) b βηαθ 6ecqBeTHoro BcneHeHHoro npoflyKTa, [ Ot ] d 2 ° + 159° (c· 0,61, CHC13), Xmax (EtOH) 244 HM (i 30,400), Vmax (CHBr3) 3480 (OH), H 1713 cm-1 (c/iO)KHblfi 3φΗρ) , δ (CDCI3) coflepaa-iT 5,5-5,6 (M, 2H) , 4,95 (m, 1H), 3,93 (fl, 0 10 Γμ, 1H) , 2,55 (σβπτβτ 3 7 Γμ, 1H), 2,17 (c, 3H), 1,20 (fl, 3 7 Γμ, 6H) H 0,70 (fl, 3 7 Γμ, 3H) . ΠΡΗΜβΡ 29 <PaKTop A. 5.23-nH-H-6vTHpaTa
PacTBop ĢaKTopa A (306 μγ),H-6yTnpoBoro aHrHfipHfla (0,3 3ΜΛ) M 4-flMMeTH/iaMHHOnHpHAHHa (244 ΜΓ) B nHpHflHHe (5 MJl) nepeMeuiHBaioT npH TeMnepaType 20°C b τβπβΗΗβ 18 HacoB, a 3aTeM BbuiHBaioT b CMecb 3TH/iaueTaTa to 2Ņ coaahoh khc/ioth (50 μλ Kaxc-floro) . OpraHHHecKyio φa3y npoMbiBaioT 2Ņ cojihhom khc/īotoh, Hacbi-meHHbJM 6HKap60HaT0M HaTpHfl (25 M/l), H CO/IHHblM paCTBOpOM (25 μλ), h BbicyuiHBaioT (ο>'ΛΒφατοκ MarHHii) m ynapMBa!OT fiocyxa. Ocra-tok OMHmaKDT χροΜ3ΤθΓρ3φΗθΗ Ha Kieselgel 60 (40 r). 3/iionpoBaHHe Μ3 ΚΟΛΟΗΚΜ CMeCblO ΟΒβΤΛΟΗ ΗβφΤΗ C 3ΤΜΛ3μθΤ3ΤΟΜ (5:1) flaiOT Ha3~ BaHHoe coenHHeHHe (200 μγ) b BMfle όθομεετΗΟΓΟ βοπθηθηηογο βθ- 54 UļecTBa. [a]D20 + 144° (c 1,13, CHC13 ) , Xmax (EtOH) , 245 HM (Z 31,800), Vma x (CHBr3 ) 1720 cm"1 (c/ioatHbiH 3φΗρ) , δ (CDCI3 ) co-flep*HT 5,5-5,6 (Μ, 2H) , 4,94 (m, 1H) , 3,92 (fl, 3 10 Γμ, 1H) , 2,39 (T, 3 7 Γμ, 2H) , 2,28(t, 3 7 Γμ, 2H) H 0,70 (fl, 3 7 Γμ, 3H), M/3 = 752 (M+) .
CoeflMHeHMfl npMMepoB 30-32 nojiyMaioT aHa/iorMMHbiM cnocočOM: ΠρΜ-ΜβΡ 30 * tPaKTop A. 5-aueTaT, 23-nnBa/ioaT (70 μγ)
[CC]D20 + 159° (c. 0,69, CHCI3) Xmax (EtOH) 244 HM (C 29,900), Vma:[ (CHBr3 ) 3470 (OH) H 1730 H 1710 CM-1 (c/lo)KHblfi 3φκρ),. δ (CCC13) co,qep)KHT 5,5-5,6 (μ, 2H) , 4,95 (m, 1H) , 3,91 (fl, 3 10 Γμ, 1H), 2,16 (C, 3H), 1,22 (c, 9H), H 0,68 (R, 3 7 Γμ, 3H) , h3 <PaKTopa A, 5-3μβτΒΤ3 (131 μγ) h nnBa/ioH/ixiiopHfla (0,06 ΜΛ). Πρμμθρ 31 <PaKTOP A, 5-aueTaT. 23-6eH3oaT (180 μγ)
[€C]d2 0 + 153° (c, 0,59, CHC13 ) , Xmax (EtOH) 236 HM (Z 36,200), Vmax (CHBr3 ) 3460 (OH) H 1730 h 1707 cm"1 (c/iojkhmm 3φΗρ) , 5 (CDCI3) COflep>KHT 8,21 (fl, 3 7 Γμ, 2H) , 7,56 (T, 3 7 Γμ, 1H), 7,4'4 (τ, 3 7 Γμ, 2Η) , 5,5-5,6 (μ, 2Η) , 4,07 (fl, 3 10 Γμ, 1Η), 2,17 (c, 3Η) Μ 0,75 (fl, 3 7 Γμ, 3Η), Η3 ĢaKTopa Α, 5-aqeTar (327 μγ) η aHTHflpHfl 6eH3oyibHoii κμοποτν (339 μγ). ΓΙρημθρ 32
OaKTOP Α. 5,23-nn6eH3oaT {270 μγ) η 5- SeHsoaT ^200 μγ) Μ3 ĢaKTopa Α (613 μγ) η 6eH30HX/iopHfla (0,35 κλ) ; Hana/ib-Hbie φρακμΗΗ flaraT Ha3BaHHbifl nn6eH3oaT. [CX]D20 + 86° (c 0,65, CHCI3), Xmax (EtOH) 236 HM (8 46,200), 3>max (CHBr3) 3480 (OH), 1710 (cyio*Hbie οφΜρπ) H 1602 n 1585 cm”1 (φθΗΜ/ΐ) , 0(CDC13) co- - 55 - LV 10777 flep>KMT 8,2-8,0 (Μ, 4H) , 7,7-7,5 (Μ, 2H), 7,46 (T, 3 7 Γμ,4Η), 5,61 (c, 1H), 4,07 (fl, 0 10 Γμ, 1H) H 0,76 (fl, 3 7 Tu, 3H). riocyieflyiomHe φρβκμΗΗ flaior Ha3BaHHbiH 6βΗ3θβτ [CC]D20 + 80° (c, 0,61, CHC13), Xmax (EtOH) 237 HM (Z 39,200), Vmax (CHBr3) 3500 (OH), 1712 (c/io*Hbie οφκρω), h 1601 H 1585 CM-1 (φβΗΗΛ), 5(CDC13 ) cOflepiKHT 8,09 (fl, 3 7 Γμ, 2H), 7,58 (τ, 3 1 Γμ, 1H) , 7,45 (τ,’ϊ 3 7 Γμ, 2Η), 5,60 (C, 1Η) , 3,83 (Μ, 1Η) , 3,76 (fl, 3 10 Γμ, 1Η) Η 0,81 (λ, 3 7 Γμ, 3Η). ΠΡΜΜβΡ 33
tPaKTop Α6 5-x.nopaueTaT
PacTBop QaKTopa A (123 μγ) h nHpHflHHa (0,-1 μλ) b cyxoM AHX/iopMeTaHe (5 μλ) nepeMeuiHBaioT npw TeMnepaType 0°C h bboaht b ΧΛορ3μβΤΗΛΧΛορΗΗ (0,3 μλ 1M - pacreop b flHX/iopMeTaHe) . no/iy-ΜβΗΗΜίί pacTBop nepeMemHBaioT npH 0° C TeMnepaType b TeneHHe 15 MHHyT h 3aTeM ρ,ο6άβλμού eme χΛορ3μβΤΗΛΧΛορΗΗ (0,1 μλ ΙΜ-pacT-Bop) h npoflOrtKaioT nepeMeiuMBaHHe flono^HHTe^bHO b TeneHne 15 mh-HyT. PacTBop pa36aBrtHioT αηχλορμθτβηομ (50 μλ) , 3aTeM ripoMbiBaioT 2N ΟΟΛΛΗΟίϊ ΚΗΟΛΟΤΟΗ ( 2X 20 ΜΛ), H HaCbtlUeHHblM 6nKap6oHaTOM HaT-ΡΗΛ (20 ΜΛ) , H BbICyfflHBaiOT (CyΛbφatOM MarHHH), H ynapHBa!OT flO-cyxa. OcTaTOK (140 μγ) oHHiiļaraT χροΜΒτοΓρΒφΗβίί β κολοηκθ hs Ki-eselgel 60 (15 Γ). 3ΛΙ0ΜρθΒΒΗΜβ H3 ΚΟΛΟΗΚΗ CMeCblO ΟΒβΤΛΟΛ ΗβφΤΗ c 3ΤΜΛ3μβτΒΤθΜ (4:1) flaiOT HasBaHHoe coeflHHeHHe (90 μγ) b BHfle δβομΒθΤΗΟΓΟ BcneHeHHoro semecTBa, [ OC ] D 2 0 +143° (c, 1,11 CHC13), Xmax (EtOH) 245,5 HM (£ 30,400), Vmax (CHBr3) 3500 (OH) 1760 (ΧΛορ3μετΒΤ) h 1710 cm-1 (ολο*ημη οφΜρ), δ (CDC13) coflep>KHT 5,5-5,6 (Μ, 2H), 4,18 (c, 2Η), ca. 3,81 (m, ĪH), 3,74 (fl, 3 10 Γμ, 1H) Η 0,80 (fl, 3 7 Γμ, 3H), μ/3 = 688 (Μ+, 3 5 C1).
CoeflHHeHHe πρΜΜβροΒ 35, 45, 49 η 50 noflyHaioT aHaflornMHbiM 56 o6pa30M. Πρμμθρ 34 Φβκτορ A. 5-xJiopaueTaT > 23-κθτοη
PacTBop «PaKTopa A, 5-xTiopaueTaTa (276 μγ)ή flnxpoMaTa nw-pHflHHa (602 μγ) b cyxoM N,N- flHMeTH/i$opMaMHfla (10 M/i) nepeMe-uiHBaiOT npH TeMnepaType 20° C b τθμθηηθ 48 wacoB h 3aTeM B/lHBaiOT b CMecb OTH/iaLļeTaTa (50 mji) h 2Ņ -x/iopHCTOBOflopoflHoii kmc/iotu (25 m/i) OpraHHHecKyio φa3y npoMbieaioT 2Ņ -x.nopHCTOBojņopoflHOfi κμολοτομ h HacbimeHHbiM 6MKap6oHaroM HaTpmi, BbicyiiiMBaioT (cyΛbφaτ Μ3ΓΗΜΗ) H BbinapHBaiOT flOCyxa. .OCTaTOK OMHmaiOT ΧρθΜ3ΤΟΓρ8φΗΘΗ Ha κολοηκθ Kieselgel 60 (25 r). 3/noHpoBaHne kojiohkh CMecb» πβτρο-ziefiHbifi οφΜρ: sTHJiaiteTaT (4:1) naeT HasBaHHoe coeiiHHeHHe (85 μγ) b KanecTBe 6ecuBeTHofi neHbi, [Ct]D20 + 120° (c 1,05 CHC13), Xmax (EtOH) 245 HM (E 26,500), Vmax (CHBr3) 3480 (OH), 1760 (XAopaLļeTaT) n 1715 cm-1 (ολο*ηηη 3φκρ μ κθτοη), δ (CDC13) BKAlOMaeT 5,5-5,7 (Μ, 2Η) , 4,17 (c, 2Η) , 3,72 (fl, 3 10 Γΐ1, 1Η) , 2,50 (C, 2Η) H 0,85 (fl, 3 7 Γμ, 3H), M/3 = 686 (M+, 35C1). llPHMep 35 9axTop A, 5-6pcmaueTaT (447 μγ) [Ct]D20 + 132° (C 0,77, CHC13), Xmax (EtOH) 245,5 HM (6 31,500), Vmax (CHBr3) 3495 (OH) 1730 (6pOMaqeTaT) H 1712 cm-1 (c/lo>KHbiH 3φΗρ) , δ (CDC13) BK/iiOMaeT 5,5-5,6 (m, 2H) , 3,97 (r, 3 12 Tq, 1H), 3,90 (fl, 3 12 Tq, 1H), 3,81 (m, 1H), 3,75 (fl, 3 10 Γυ,, 1H) h 0,81 (fl, 3 7 Tīļ, 3H), H3 <PaKTopa A (613 r) H 6poMaH-rnflpHfla 6poMyKcycHOH khcjīotu (0,13 m/i). Πρμμθρ 36
Φθκτορ A, 5, 2 3-ziHx/iopaueTaT CMecb 9aKTopa A, 5-x/iopaqeTaTa ( 365 μγ), x/iopaHrn,qpH,qa - 57 - LV 10777 xyiopyKcycHOft KHc.noTbi (0,21 m/i) h Kap6oHaTa Ka/ibiļMii (265 μγ) b cyxoM flHX/iopMeTaHe (15 μλ) nepeMemuBaioT ripu TeMnepaType 20° b τβΜβΗΗβ 48 MacoB. nojiyHeHHyio cycneH3Mio pa36aBn«KDT ΒΗχηορΜβτβ-HOM (50 ΜΛ) , 3aTeM npOMbJBaiOT 2Ņ -XyiOpHCTOBOflOpOflHOfi KHC/IOTOH M HacbimeHHbiM 6HKap6oHaTOM HaTphk, BbicymnBaioT (cyΛbφaτ μβγηηη) h BbinapHBaioT flocyxa. OcraTOK OMHiiļaiOT χρομβτογρβΦηθη Ha κολοηκθ Kieselgql 60 (30 r) . 3.nionpoBaHne κολοηκη CMecbio neTpo/iefiHbiH 3φΗρ: OTHJiaiieTaT (4:1) flaeT Η33ββηηοθ coennHeHHe (167 μγ) b
KaMecTBe 6ecqBeTHOft πθημ, X0C]D20 + 151° (c 1,17, CHC13 ), Xmax (EtOH) 245,5 HM (£ 29,400), Vmax (CHBr3) 3470 (OH) H 1725 cm'1 (CJIO*Hbie 3φΗρυ), 5 (CDC13) ΒΚΛΙΟΜ3€Τ 5,5-5,6 (Μ, 2H), 5,00 (M, 1H), 4,17 (c, 2H) , 4,10 (fl, D 15 Γμ, 1H), 4,02 (fl, 3 15 Γμ, 1H) , 3,92 o r-i n Γμ, 1H) H 0,73 (A, J 7 Γ14, 3H) , M/3 = 764 (M+,35C1) .
CoeflHHeHHe npHMepoB 37, 38 h 46 noyiyHaioT βηβ/ιογηηημμ 06- pasoM. Πρημθρ 37 <PaKTop A, 23-MeTOKCnaueTaT (92 μγ) [a]D20+ 157° (C 0,75 CHCI3), ^max (EtOH) 244 HM (l 32300), Vmax (CHBr3) 3560 H 3480 (OH), 1740 (MeTOKCHaueTaT) H 1712 CM-1 (C/IOKHblfl 3φΗρ), δ (CDCl3) BK/lIOHaeT 5,01 (M, 1H),
4,28 (T, J 7 Γ14, 1H), 4,01 (c, 2H) , , 3,89 (A, 3 10 Γμ, 1H) , 3,46 (C, 3H) H 0,71 (fl, 0 7 Γμ, 3H) , H3 φΒΚΤΟρΒ A (184 ΜΓ) H
MeTOKCHaqeTH^xyiopHAa (0,3 mji). ΠΡΜΜβΡ 38 gaKTOP A. 2 3 —ΦβΗΟΚΟΜΒ11βΤ3Τ (112 ΜΓ ) 25900), Xmax [CC]D20 + 129° (C 0,75, CHC13 ) , Xmax (EtOH) 244 HM (Z (CHBr3) 3550 3470 (OH), H 1745 H 1708 CM-1 58 (CAOJKHbie 3(t>npbl) , δ (CDCI3 ) BKAlOMaeT 7,30 (T, J 8 Γμ, 2H) , 7,00 (T, 3 8 Γμ , 1H), 6,94 (A, 3 8 Γμ, 2H) , 5,02 (m, 1H) , 4,68 (fl, 0 16 Γμ, 1H), 4,58 (A, 3 16 Γμ, 1H), 4,30 (A> 3 7 Γμ, 1H), 3,92 (a, 3 10 Γμ, 1H) H 0,67 (a, 0 7 Γμ, 3H) , H3 φΒΚΤθρ3 A (184 ΜΓ) Η φβΗΟΚΟΗ3μθΤΗ/ΙΧ/ΙθρΗΑ3 (0,38 ma) . ΠΡΗΜβΡ 39 gaKļop A. 5,23-am-(2.2.2-tpmxaop3tha) KapčoHaT (362 μγ)
[a]D22 + 110° (c 0,94, CHCI3), Xmax (EtOH) 244 HM
(828000), Vmax (CHBr3) 3550.H 3460 (OH), 1750 (KapSoHaT), H 1710 cm-1 (cAOJKHbiii 3φκρ), δ (CDCI3 ) BK/iiOHaeT 5,60 (c, 1H) , 4,89 H 4,75 (ABq, 3 12 Γμ, 2H), 4,85 (m, 1H), 4,81 H 4,71 (ABq, 3 14 Γμ, 2H), h 0,79 (A, 3 7 Γμ, 3H), H3 φ3ΚΤθρΒ A (306 ΜΓ) H 2,2,2-TpHXΛOp^THΛXΛOpφOpMaTa (0,14 MA ) . ΠΡΜΜβΡ 40
<PaKTOP A. 23-(2,2,2-tphxaop3THA) KapčoHaT
PacTBop VaKTopa A, 5,23-ah-/2,2,2-TpnxAop3THA/Kap6oHaTa (200 μγ) b AHOKcaHe (10 ma) nepeMeuiHBaraT πρμ TeMnepaType ripuč-AH3HTeAbHO 20°C H AOSaBAfllOT lM-THApOOKHCb HarpHK (0,5 MA) . ΓΤΟ" AyMaeMbiH pacTBop nepeMeuiHBaioT b τθμθηηθ 30 MHHyT, 3aTeM npn-6aBAAfOT eqe ΙΜ-rnApooKHCb HāTpHH (1 ma) h nepeMeiuHBaHHe npo-AOA)Karc)T b τθμθηηθ 1 naca. PacTBop pa3čaBAHioT 3THAaqeTaTOM (50 MA), npOMblBaiOT 2Ņ-XAOpHCTOBOAOpOAHOH KHCAOTOft, BblCyiIIHBaK)T (cyAb$aT MarHHJi) w BbinapHBaioT Aocyxa. OcTaTOK xpoMaTorpa0HpyioT na KOAOHKe Kieselgel 60 (15 r). BAionpoBaHHe koaohkh cMecbio neTpoAefiHbiH 3φ«ρ: OTHiiaLļSTaT (2:1) rsct HasBaHHoe coenHHenHe (80 μγ) b KaMecTBe δβομΒθΤΗΟΗ neHbi, [CC]ļ 20 142° (C, 0,92, CHC13), Xmax (EtOH) 245 hm (829200), Vmax (CHBr3) 3560 H 3500 (OH), 1745 (Kap6oHaT) h 1710 cm-1 (cAO>KHbiH 3φΗρ), δ(0ϋ013) - 59 - LV 10777 BK/iionaeT 5,40 (c, 1H) , 4,80 H 4,70 (ABq, 3 14 Γμ, 2H) , 4,28 (Μ, 1H) H 0,79 («, 0 7 Γμ, 3H). Πρμμθρ 41 <PaKTOP A. 5-ΒμθΤΒΤ , 23-/2.2.2-TPHx.nop3TH.n/Kap6oHaT (385ηγ^
(CI]D20 + 140° (c, 1,07, CHC13), Xmax (EtOH) 245,5 HM, (C 29200), Vmax(CHBr3) 3300-3600 (OH), 1738 (Kap6oHaT), h 1720 CM-1 (c4o>KHbift ρφμρ) , δ (CDClļ ) BKJliOMaeT 5,53 (c, 1H) , 4,81 h 4,70 (ABq, 3 14 Γμ, 2H), 4,84 (M, 1H), 3,98 (a, 3 10 Γμ, 1H) ,
2,16 (c, 3H) H 0,79 (fl, 37 Γμ, 3H), H3 φ3ΚΤορ3 A, 5-aAeTaT (393 μγ) η 2,2,2-τρμχΛορ3ΤΗΛχ/ιορφορΜ3Τ3 (2 μ λ ΙΜ-pacTBopa Β ΑΗΧ/iopMeTaHe) . ΠΡΗΜβΡ 42
<PaKTOP Α. 5,23-nH-H-6vTHpaT
PacTBop «PaKTopa Α (306 μγ), H-MacjiHHoro aHrMflpHfla (0,33 ΜΛ) Η 4-flHMeTH/iaMHHOnHpHaHHa (244 ΜΓ) Β ΓΜρΗΑΗΗβ (5 ΜΛ) Πβρβ-MeuiHBaioT πρκ TeMnepaType 20°C β τβπβΗΗθ 18 nacoB η 3βτβΜ βλη-BaiOT Β CMeCb ΟΤΗ^μβΤΒΤβ Η 2Ņ -Χ/lOpHCTOBOAOpOAHOiĪ KHCJIOTbl (50 μλ Ka>KAoro KOMnoHeHTa) . OpraHHMecKyio φa3y npoMtiBaioT 2Ν-ΧΛορΜθ-ΤΟΒΟΑΟρΟΑΗΟΗ ΚΜΟΛΟΤΟΗ, HaCbllIieHHblM 6HKap60HaT0M HaTpHH (25 ΜΛ) h paccortOM (25 μλ), BwcyuiHBaioT (cyΛbφaτ μβγηηλ) m BunapviBaioT Aocyxa. OcTaTOK OMHujaioT χροΜ3τθΓρΒφΗβίϊ Ha κολοηκθ Kieselgel 60 (40 Γ) . ΟΛΙΟΗρΟΒΒΗΗβ ΚΟΛΟΗΚΗ CMeCblO ΠΘΤρΟΛβΛΗΗΜ 3φΜρ: 3ΤΗΛ3μβ~ TaT (5:1) flaeT HasBaHHoe cofijHHgHHe (200 μγ) b icanecTBe 6βομ-ΒβΤΗΟίΐ neHbt, [CC]D20 + 144° (c 1,13 CHCI3 ) , Xmax (EtOH) 245 HM (ε 31800), vmax (CHBr3 ) 1720 CM-1 (cflOKHbie οφΜρω) , δ (CDC13 ) βκλιομβθτ 5,5-5,6 (μ, 2H), 4,94 (Μ, 1Η), 3,92 (α, 3 10 Γμ, 1Η), 2,39 (τ, 3 7 Γμ, 2Η), 2,28 (τ, 3 7 Γμ, 2Η) Μ 0,70 (Α, 3 7 Γμ, 3Η), Μ/3 = 752 (Μ+). 60 ΠΡΗΜΘΡ 43
Φβκτορ Α. 23-H-6yTHpaT
PacTBop φΑκτορΑ Α, 5,23-flH-H-6yrHpaTa (160 μγ) β MeTaHo/ie (10 μα) nepeMeuiHBaoT πρκ 0°C η npučaBAinoT ΙΜ-rnApooKKCb HaTpHii (0,25 μα). rio/iyMaeMbift pacTBop nepeMeuiHBaiOT β τβΜβΗΜβ 90 MHHyT ripu TeMnepaType οτ 0 flo 5 °C, 3aTeM npw6aBAAioT eqe (0,25 μ a) lM-rnflpQOKHCb HaTpHii h nepeMeuiHBaHHe npoAOA*aioT β τθμθημθ 4 MacoB. PacTBop BAHBaioT b CMecb 3TH/iai4eTaTa (50 μα) η 2Ņ-xao-pHCTOBOAOpOflHOH KHCAOTbl (25 ΜΛ) , OpraHHHeCKyiO φa3y npOMblBaiOT BOflofi, paccoAOM, BbicymnBaioT (cyΛbφaτ μαγημα ) h BbtnapHBaioT ao-cyxa. OcTaTOK onmuaioT χροΜΑΤοτρΑφΜβΗ Ha KOAOHKe Kieselgel 60 (20 r) . 3/iiOMpoBaHHe koaohkh CMecbio neTpoAeiiHbifi οφκρ: 3THiiaiļe-TaT (2:1) AaeT HasBaHHoe coenHHeHHe (68 μγ) b KanecTBe 6ecq-ΒβΤΗΟίί ne'Hbl, [a]D20 + 164° (C 1,03, CHC13 ) , Xmax (EtOH) 244,5 HM (l 29600), Vmax (CHBr3) 3550 H 3470 (OH), H 1710 CM-1 (c.no>KHbie 3φΗρ«), δ (CDC13) βκαιοηαθτ 4,93 (m, 1H), 4,28 (t, 3 7 Γμ, 1H), 3,91 (fl, D 10 Γμ, 1H), 2,28 (t, 3 7 Γμ, 2H), 1,65 (m, 2H), 0,94 (T, 3 7 Γμ, 3H) h 0,69 (a, 3 7 Γμ, 3H), M/3 = 682 (M+) .
CoēAHHeHHe npHMepa 44 noAyMaioT aHaAorHMHbiM o6pa30M. Πρημθρ 44 Φακτορ A. 23-MeTHAKap6oHaT (155 μγ)
[a]D20 + 169° (c, 0,81, CHC13), Xmax (EtOH) 245 hm (Z 26600), Vmax (CHBr3) 3300-3610 (OH), 1735 (KapčOHaT), h 1710 CM-1 (c/lO)KHblM ρφκρ), δ (CDCi3) BKAlOMaeT 5,40 (c, 1H), 4,28 (M, 1H), 3,94 (A/ 3 10 Γμ, 1H) , 3,77 (c, 3H) M 0,76 (A/ 3 7 Γμ, 3H), M/3 = 670 (M+) , H3 φΑκτορΑ A, 5-aqeTaTa, 23-/2,2,2-τρΗΧ-AopoTMA/KapčoHara (300 μγ). - 61 - LV 10777 Πρμμθρ 45 23-neoKCH-0aKTOP A. 5-MeTH.nKap6oHaT (57 μγ)
[a]D20 + 152° (C 0,6, CHC13), Xmax (EtOH) 244,5 hm (C 28200), Vmax (CHBr3) 3530 M 3460 (OH), 1740 (Kap6oHar) M 1707CM-1 (CflOHCHblM ΊφΗρ), δ (CDClg) ΒΚΛΙΟΜΑΘΤ 5,55 (C, 1H), 3,82 (c, 3H) , 3,42 (fl, 0 10 Γμ, 1H) H 0,69 (fl, 3 4 Tu, 3H) H3 23-fleoKCk-<ļ)aKTopa A (90 μγ) m MeTHflXfloptj)opMaTa (0,3 m/i IM-pacTBopa b AHX.nopMeTaHe) . ΠΡΗΜβΡ 46 Φθκτορ A, 23-xnopaueTaT (193 μγ)
[a]D20 + 162° (c 1,04, CHCI3), Xmax (EtOH) 245 HM (Z
28900), Vmax (CHBr3 ) 3320-3620 (OH) , 1748 (x.nopafleTaT) , H 1710 cm-1 (cflOJKHbiii οφπρ), δ (CDC13 ) BKJīlOHaeT 5,42 (c, 1H), 4,28 (M, 1H), 4,09 M 4,01 (ABq, 3 15 Γμ, 2H), 3,91 (fl, 3 10 Γμ, 1H) H 0,73 (fl, 3 7 Γμ, 3H), m/3 = 688 (M+,35C1) M3 $aKTOpa A (306 μγ) xflopaHrHflpMfla xflopyKcycHoii khcaoth (0,2 μλ). Πρμμθρ 47 Φθκτορ A. 5,23-flMnponHOHaT (387 μγ) [ajD20 + 157° (c 0,96, CHC13), Xmax (EtOH) 244,5 HM (8 30200), Vmax (CHBr3 ) 3500 (OH) H 1720 cm-1 (CfloacHbie οφΗρυ) , δ (CDC13) BKJiiOHaeT 5,52 (c, 1H) , 3,93 (fl, 3 10 Γμ, 1H) , 2,43 (k, 3 7 Γμ, 2H), 2,32 (κ, 3 7 Γμ, 2H), 1,18 (Τ, 3 7 Γμ, 3Η), 1,16 (Τ, 3 7 Γμ, 3Η) Η 0,70 (fl, 3 7 Γμ, 3Η), μ/3 = 724 (Μ+), Η3 (ļiaKTopa Α (613 μγ> η προπηοηοβογο βηγμαρμαβ (0,5 mji) . Πρμμθρ 48 <PaKTop Α. 23-nponMOHaT (155 μγ)
[Ot]D20 + 168° (C 1,03, CHC13 ) > Xmax (EtOH) 244,5 HM
(8 30600), Vmax (CHBr3 ) 3550 H 3480 (OH) , M 1710 cm-1 (CflOttHbiM 62 3φΜρ), 0 (CDC13 ) BKTTioMaeT 5,39 (c, 1H) , 4,27 (m, ĪH), 3,91 (fl, 3 10 Γ14, 1H), 2,31 (K, 3 7 Γμ, 2H) , 1,14 (T, 3 7 Γ14, 3H) m 0,69 (fl, 0 7 Γ14, 3H) , M/3 = 668 (M+), H3 φΒΚΤΟρβ A, 5,23-flMn-ponHOHaTa (327 μγ), βηβλογμηημμ o6pa30M αλα coeflHHeHHH npMMepa 43. ΠΡΗΜβΡ 49 Φβκ-τορ A, 5-MeTH.aKap6oHaT, 23-κβτοΗ (830 μγ) [a]D20 + 132° (c 0,82, CHCI3), Xmax (EtOH) 245 HM (829800). HP H HMP cneKTpbi anaAorHMHbi τθμ, KOTopbie ημθιοτ coe-ΑΗΗβΗΜβ, onHCaHHoe B npHMepe 40, M3 φβκτορβ A, 23'KeTOHā (916 ΜΓ) H ΜΘΤΗΛΧΛθρφθρΜ3Τ3 (0,23 ΜΛ). Πρημθρ 50 Φβκτορ A. 5-6eH3HJiKap6oHaT, 23-κβτοΗ (57 μγ ) [CX]D20 + 99° (c 0,4, CHC13), Xmax (EtOH) 245,5 HM (829600), Vmax (CHBr3) 3600, 3550 M 3480 (OH), 1740 (KapSoHaT) H 1715 CM-1 ( CAOKHblft 3φ«ρ H ΚβΤΟΗ ) , 6 (CDCI3 ) ΒΚ/ΙΙΟΗΒβΤ 7,5-7,2 (Μ, 5H), 5,57 (c, 1Η), 5,21 (C,2H), 3,70 (A, 0 10 Γμ, 1H) , 2,49 (c, 2H) H 0,86 (A, 0 6 Γ14, 3H), H3 φΒΚΤΟρα A, 23-KeTOHa (92 μγ) h 6eH3HAxyiop0opMaTa (0,05 ma) . Πρμμθρ 51
5-aueTOKcn-23-H-6vTQKCn^aKTop A
Kap6oHaT cepeSpa (1 r) npn6aBAHioT κ pacTBopy 5-ai4eTOKcn-φΒΚΤΟρΒ A (325 ΜΓ ) B CyXOM 3φκρθ C ΠΟΟ/ΙβAyiOIiiHM KOA6yTaHOM (0,5 ma) h nepxAopaTOM cepe5pa (550 μγ) . CMecb nepeMeuiHBaroT ripu KOMHaTHOM TeMnepaType f. τθηθημθ 20 HacoB, nocAe Mēro npn-5aBA«KDT koaahahh (0,5 mji) . nocAe nepeMeuiHBaHMH b TeneHHe eme 20· MMHyT CMecb ΟΤφΜΛΒΤρθΒΗΒ3ΙΟΤ Μ φΜΑΒΤρΒΤ npOMbtBaiOT ΠΟΟΑβΑΟΒΒ-TeAbHO 2N XAOpMCTOBOAOpOAHOii KMCJIOTOH , HaCblUļeHHblM BOAHbIM paCT~ - 63 - LV 10777
BopoM 6MKap6oHaTa ΗβτρΗΛ η bojioh . BwcyiueHHyio opraHHMecKyio φa^y BbinapMBaioT ποητμ flocyxa h Macjio oMHmaioT χροΜ3τοΓρ3φΗθή Ha κο-λοηκθ Merck Kieselgel 60 c pa3MepoM 230-400 Meui (100 mji). 3jik>-MpoBaHHe kojiohkh cMecbio reKcaH: 3THJiaqeTaT (3:1) no3BOJifler no-/iyHHTb HasBaHHoe coenHHeHne b KanecTBe SeciļBeTHofi πθηη (276 μγ , 78%), [CC]D22 + 160° (c 0,94, CHC13 ) Xmax (EtOH) 245 hm (£max 28300); δ (CDC13) BKJifonaeT 3,16 (m, 1H) , 3,43 (m, 1H) , 3,59 (μ, 1H). Πρμμθρ 52 5-aueTQKcn-2 3-iiHK.nonponnjiMeTOKCn^aKTOp A [a]D21 + 174° (c 1,74, CHCI3) Xmax (EtOH) 244 HM (Cmax 28360) Vmax (CHBr3 ) 3470 (OH), 1732, 1710 (CJīOHCHbie 3φΗρω) h 998 cm-1 (C-O) δ (CDC13) BKJiioHaeT 5,5-5,6 (μ, 2H) , 3,96 (fl, 10; 1H), 3,49 (m, 1H), 3,37 (flfl. r 6, 10, 1H), 3,17 (flfl. fl 6, 10, 1H), 2,16 (c, 3H) , 0,76 (fl 7, 3H) , 0,44 (μ, 2H), 0,22 (M, 2H), H3 5-aiļeTOKCH-0aKTopa A h 6poMMeTHJiLļHKJionponaHa, aHa/10-γηηημμ o6pa30M nnfi coeflHHeHHfl npHMepa 17. Πρημθρ 53 5 —T-ČVTHJIHHMeTHJICHJIH/IOKCH- 2 3 -MeTOKCH ~Φ3ΚΤΟΡ A PaCTBOp MOflMeTHJIMarHHi! B npoCTOM 3φΗρβ (0,35 MJI 3M-paCT-Bopa) npH6aB/iiīK3T ripu KOMHaTHoft TeMnepaType non aaoTOM κ Mar-hmtho nepeMemaHHOMy pacTBopy 5-T-6yTHJiflHMeTHJicminjiOKCH^aKTopa A ( 239 ΜΓ) B CyXOM ΓβΚ03ΜβΤΗΛφ00φ0ρτρΗ3ΜΜΑΘ (18 MJI) C 6ypHblM BbiflejieHHeM rasa. Hepes 30 MHHyT npn6aBJiflioT MOflMeTaH (0,4 mji), h nojiyHeHHyK) cMecb nepeMeuiHBaioT b τθηθημθ 5 nacoB, paaSaBJia* npOCTbIM 3φΜρθΜ (100 MJI) H npOMblBail OČH/IbHO BOflOft . 3φΗρΗΗΗ pacTBop saTeM npoMbiBaioT paccojiOM (50 mji) h BbicyuieHHyio opranH-MecKyio φa3y BbinapMBaiOT. nojiyHeHHyio neHy (280 μγ) OHHUjaioT xpo- 64
MaTorpactmeft Ha κολοηκθ Merck Kieselgel 60 c pa3Mepcm 230-400 Meui (80 μλ) . 3jnonpoBaHMe cMecbio reKcaH: STH^auļeTaT (5:1) πο3βο-/IHKDT nO/iyMHTb Η33ΒΒΗΗΟβ COejtHHeHHe B KaHeCTB© ČeCLļBeTHOH neHbl (46¾), [d]D21 + 142° (c 1,13, CHC13) Xmax (EtOH) 244 hm (£max 27900), Vmax (CHBr3) 3460 (OH) , 1708 (uiHpoKHH, CAOHCHbiH ρφΗρ) n 995 CM-1 (C-O), δ (CDC13) BKJiKJMaeT 4,42 (μ, 1H), 3,92 (fl 10, 1H), 3,3.-3,4 (Μ, 2H) , 3,32 (c, 3H) , 0,92 (c, 9H) , 0,75 (fl 7, 3H), 0,12 (c, 6H).
CoeflHHeHMe npuMepa 54 noyiyMaioT aHa/iornHHbiM oēpasoM. ΠΡΗΜΘΡ 54
5-T-6yTH.riHMMeTH.nCH.nH.nOKCH-2 3-H-nponH-aOKCH-(PaKTOP A
[Ct]D21 + 153° (C 1,16, CHCI3), lmax (EtOH) 244 HM (Cmax 29950), Vmax (CHBr3 ) 3460 (OH), 1705 (CAOJKHbliļ 3φΗρ) H 995 CM-1 (C-O), δ (CDC13) BKJiiOHaeT 4,44 (m, 1H) , 3,96 (fl 10, 1H) , 3,56 (Μ, 1H), 3,45 (Μ, 1H), 3,14 (m, 1H), 0,93 (c, 9H), 0,75 (fl 7, 3H) , 0,13 (c, 6H) , H3 5-T-6yTH,nflHMeTH.ncH.nM.noKCM^aKTopa A m 1-ftoflnponaHa. npHMep 55 5-aueTOKCH-taKTOp D f923 μγ)
[Ct]D21 + 143,9° (c 0,9, CHC13), XmaxEt0H 239 (28700) H 245 hm (£max 31000), Vmax (CHBr3 ) 3490 (OH) 1730 H 1710 (c/IOK-Hbl& 3φΗρ), δ (CDC13) 0,81 (fl, 7 TU, 3H) , 0,99 (fl, 7 Tu, 3H), 1,00 (T, 7 Γμ, 3H), 1,53 (c, 3H), 1,59 (C, 3H), 1,75 (c, 3H), 2,16 (c, 3H) , 3,32 (m, 1H) , 3,65 (Μ, 1H), 4,04 (fl, 6 Γ14, 1H) H 5,53 (μ, 2H). m/3 = 640 (M+), H3 ļaKTopa D (2,5 r) h yKcycHoro aHTHflpHfla (0,47 ma) , aHa.norMMHbiM o6pa30M a/ih cooTBeTCTBypuļero coeflHHeHHfl npHMepa 5. - 65 - LV 10777 ΓίΡΜΜΘΡ 56 5.23-nnaueTOKCn-ti)aKTOP D (286 ηγ)
TeMnepaTypa n^aBJieHMJi 147-149° (poMČbi M3 neHTaHa b npoc-tom ΡφΗρβ [CC]D21 + 152,6° (c 0,9, CHC13), XmaxEt0H 232,5 (21500), 238 (26600), H 244,5 HM (tmax 28800), Vmax (CHBr3) 1720 CM-1 (c.no>KHbifi 3φπρ), δ (CHCI3 ) 0,72 (fl, 6 Γη, 3H) , 0,99 (A, 6 Γμ· 3H), 1,01 (τ, 7 Γη, 3Η), 1,53 (c, 3Η), 1,60 (c, 3Η) , 1,75 (C, 3Η), 2,02 (C, 3Η), 2,15 (c, 3Η), 3,31 (μ, 1Η), 4,04 (Α, 6 Γη, ΙΗ), 4,91 (Μ, 1Η) Η 5,5-5,6 (Μ, 2Η) . Μ/3 = 682 (Μ+), Η3 φβκτορ3 D (439 μγ) η yKcycHoro aHTHApnAa (0,25 μλ) ,- aHa.no-THHHblM OČpaaOM RJIX COeflHHeHHS npHMepa 6. Πρμμθρ 57 23-aneTOKCH^aKTOp D (127 μγ)
[Ct]D21 + 150° (C 0,5, CHCI3), XmaxEt0H 238 (29200) H 244,5 HM (£max 15600), Vmax (CHBr3) 3300, 3590 (OH) H 1710 cm"1 (α/ΐθ)ΚΗΝΗ 3φκρ), δ (CDCl3) 0,72 (A, 7 Γη, 3H) , 0,99 (R, 7 Γη, 3H), 1,01 (τ, 7 Tu, 3H), 1,53 (c, 3H), 1,60 (c, 3H), 1,86 (c, 3H) , 3,26 (Μ, 1H), 3,95 (A, 6 Tu, 1H) , 4,26 (τ, 6 Γη, 1H)
H 4,91 (Μ, 1H) . m/3 = 640 (M+) , H3 5,23-AHaneTOKCH^aKTopa D (207 ΜΓ), aHa/IOrHHHHM 06pa30M ΑΛΛ COeAHHeHHil npHMepa 8. ΠΡΗΜβΡ 58 5-aueTOKCH. 23-ΚθΤο-Φβκτορ D C152 μγ)
TeMnepaTypa π^βλθηηη 228-230° [(X]D21 + 84° (c 0,6, CHC13), XmaxEt0H 244,5 hm (8max 31100), Vņax (CHBr3 ) 3500 (OH), 1732 H 1714 cm” 1 (ono>KHblH 3φΗρ Η ΚΘΤΟΗ), δ (CDC13) 0,86 6 Γ14, 3H) , 0 ,98 (A, 6 Γ14, 3H) , 1,00 (T, 7 Γη, 3H), 1,49 3H) , 1,67 (c, 3H) , 1,74 (c, 3H) , 2, 14 (c, 3H) , > 3,33 (Μ, 4,03 (A, 6 Γ14, 1H) H 5,5-5,6 (M, 2H) . M/3 = 638 (M+). 66 Η3 5-aueTOKCM-cļ)aKTc>pa D (336 μγ), aHanoruMHbiM oēpasoM ρ,ηχ coeflHHeHHfl npHMepa 10. npHMep 59 23-κβτο-Φβκτορ D (59 μγ) [a]D21 + 84° (c 0,4, CHC13), XmaxEt0H 244,5 HM (imax 28000), Vmax (CHBr3 ) 3550 h 3500 (OH) H 1712 CM-1 (cAO>KHbiH 3φΗρ Η ΚΘΤΟΗ), δ (CDC13) 0,86 («, 6 Γμ, 3H) , 0,98 («, 7 Tlļ, 3H) , 1,00 (T, * 7 Γ14, 3H), 1,50 (c, 3H), 1,68 (c, 3H), 1,86 (c, 3H) , 3,27 (Μ, 1H), 3,73 (fl, 10 Tq, 1H), 3,95 (fl, 6 Γμ, 1H) H 4,27 (t, 6 Γ14, 1H), H3 5-ai4eTOKCM'-23-KeTO-<i)aKTopa D (96 μγ), aHano-γημημμ očpaaoM aaa οοθαμηθημα npHMepa 11. npHMep 60 gaKtop A, 2 3-ii)eHHJiaueTaT (240 μγ) [a]D20 + 140° (c 0,92, CHCI3), Vmax (CHBr3) 3550 h 3470 (OH) H 1730 cm-1 (cno>KHbie otjmpbi), 5(CDC13) BKAioMaeT 7,32 (c, 5H) , 5,0 (Μ, 1H), 4,29 (τ, 3 7 Γιι, 1H) , 3,88 (fl, J 10 Tq, 1H) , 3,62 (c, 2H) h 0,54 (fl, 3 1 Γ14, 3H), nonyMaioT cnoco6oM,aHano-γημημμ fl/iA coeflHHeHHH npHMepa 38 H3 φaκτopa A (306 μγ) η φβΗΜ-naqeTHnxnopMfla (0,33 ma) . Πρημθρ 61
23-3TOKCH-tfaaKTOP A
PacTBop 5-aqeTOKCH-23-3TOKCH φ3Κτορ3 A (806 μγ) b μθτβηο-iie (18 ma) oxna*AaioT b λθαηhoh 6aHe, 3aieM bboaht 1N boahuh paCTBOp rHAPOOKHCH HaTpHfl (1,3 ΜΑ) H nOAyHeHHbliļ paCTBOp CBeT-λο-*θλτογο qBeTa nepeMeuiHBaioT β αθααηοη 6aHe β τθμθηηθ 1,25 Mača. PacTBop pa36aBAnioT 3THAaqeTaTOM (80 ma), saTeM nocAeAo-BaTeAbHO npOMbIBa»T 1N XAOpHCTOBOAOpOAHOH KHCAOTOH, BOAOfi H CO~ AAHbiM pacTBopoM. BbicyiueHHyio opraHHwecKyio φa3y BbinapnBaioT h no- - 67 - LV 10777 .nyHeHHyio b pesyyibTaTe βτογο CMO/ty oHMiļaioT xpoMaTorpacl)Hefi Ha Merck Kieselgel 60 c paaMepoM HacTHiļ flByoKHCn KpeMHHH 230-400 Meui. (200 MJl) . 3/IlOHpOBaHHe H3 ΚΟΛΟΗΚΗ 15% 3TH-/iaLļeTaTC>M B flHX -jiopMeTaHe flaeT Ha3BaHHoe coenHHeHHe b BHfle 6ecqBeTHOH nenu (623 ΜΓ) [CC]D21 + 178° (C, 1,13, CHC13 ) Xmax (EtOH) 244 HM (£max 29400), § (CDCI3 ) BKJllOMaeT 4,29 (T, 7, 1H) , 3,65 (m, 1H) , 3,47 (Μ, 1H), 3,26 (Μ, 2H) , 1,15 (t, 7, 3H).
CoeflHHeHHH npHMepoB 12 3.-126 nojiy^eHbi aHa/iorHMHbiM odpaaoM. riPHMep 62
23-H-6vTOKCH-d>aKTOP A (61%) noviyvaioT b BHfle 6ecqBeTHOH neHbl [Ct]D21 + 161° (C 1,47, CHCI3 ) Xmax (EtOH) 244 hm (E 33100), 5 (CDC13 ) BKJlMMaeT 4,30 (τ, 7, 1H) , 3,60 (M, 1H) , 3,43 (Μ, 1H), 3,17 (Μ, 1H) H3 5-aqeTOKCH-23-H-6yTOKCH ĢaKTopa A. riPHMep 63 23-η-προποκομ-Φβκτορ A (83%) nonyHaioT b BHfle OeciļBeTHoft neHbl [<X]D21 + 165° (c, 1,01, CHC13), Xmax (EtOH) 2,45 HM {t 30 970), δ (CDC13 ) BKJHOHaeT 4,29 (τ, 7, H) , 3,55 (Μ, 1H), 3,44 (Μ, 1H), 3,13 (m, 1H) H3 5-aiļeTOKCH-23-H-nponoKCH «PaKTopa A. ΠΡΗΜβΡ 64 23-MeTOKCH Φβκτορ A (66%) noAyHa»T B BHfle 6eciļBeTHoii neHbi [(X]D21 + 175° (C 1,01 CHC13 ) Xmax (EtOH) 244 HM (£ 19, 100) δ (CDC13) BKAlOHaeT 4,29 (τ, 7, 1H), 3,40 (m, 1H) , 3,33 (c, 3H) H3 5-ai4eTOKCH-23-MeTOKCH - OaKTopa A. ΓίρΜΜΘΡ 65
23-UHKJioneHTHJioKcn OaKTOP A (75%)_noAynaiOT b BHfle 6ecq-ΒβΤΗΟίϊ neHbl [a]D21 + 160° (C 1,65, CHC13 ) , Xmax (EtOH) 244 HM (i 19,800), δ (CDC13) BKAioMaeT 4,29 (τ, 7, 1H), ca_3,96 (ηθβη- 68 AHMbiH Μ, 1H), 3,95 (fl, 5, 1H), 3,91 (fl, 10, 1H), 3,46 (m, 1H), 0,69 (Λ, 7, 3H) H3 5-aqeTOKCM-23-i4HK/ioneHTH/iOKCn <PaKTopa A. ΠΡΗΜβΡ 66
(a) 5-aueTOKcn-23-a/mnflOKCH-gaKTOP A
Ca/iHLiHJiaT cepečpa (872 μγ) no6aByiiiraT κ pacTBopy 5-aqeTOK- ch VaKTopa A (207 μγ) h aA/iHAfioflHfla (1,0 m/i) b cyxoM προοτοΜ ρφπρβ (25 m/i) , m noAyweHHyio cMecb nepeMeiuMBaior ripu κομηθτηομ \
TeMnepaT^pe b τθμθηηθ 4 flHefi, noc/ie wero φn.πbτpyιoτ. <Pn/ibTpaT BbmapuBaioT c no/iyMeHneM «θλτογο Mac/ia, κοτοροβ oMHinaioT xpoMa-τοτρΒφΜθΗ Ha κο/ιοΗΚβ Merck Keiselgel 60,fc pasMepoM nacTHLļ flBy-OKHCH ΚρβΜΗΜΛ 230-400 ΜβΙΙΙ . 3/IIOHpOBaHHe CMeCblO flMXJlo'pMeTaH c 3TMAaiļeTaTOM (19:1) flaeT HasBaHHoe coenHHeHHe β βη^θ čecLīBeT-ηοΛ neHbi (105 μγ) , [CC]D21 + 152° (c 1,00, CHC13 ) , Imax (EtOH) 245 HM (t, 28400), δ (CDC13) BK/IlOHaeT 3,54 (Μ, 1H), 4,14 (m, 1H) . Αηβλογηηηβιμ o6pa30M no/iyHaioT cneflyiouiHe coeflHHeHHii: (b) 5-aueTQKCH-23-H-nponmioKCH tPaicrop A no/iyHaioT H3 5-aiļeTOKCH - «PaKTopa A h H-nponM/īHOflHna. Πρπ ομηοτκθ xpoMaTor-ρΒφπβπ Ha κολοηκθ Merck Keiselgel 60, c pasMepoM MacTHLj flByo-khch KpeMHHH 230-400 Mem. , μ 3yiionpoBaHHH CMecbio reKcaHa c pth-AaueTaTOM (3:1) no/iyHaiOT Ha3BaHHoe coenHHeHHe b BHfle 6ecqBeT-Hoii neHbi [a]D22 + 160° (c 0,75, CHC13 ) , Xmax (EtOH) 245 hm, (C, 27600), δ (CDC13) BKAIOHaeT 3,33 (C, 3H), 3,39 (Μ, 1H) . (c) 5-aueTOKCH-23-MeTOKCH-gaKTOpa A no/iyHaiOT H3 5-aueTOK- ch ĪaKTopa A h MeTHnfioAHfla. Ha3BaHHoe coenHHeHHe no/iyMaioT b BHfle čeciiBeTHOH neHbi [CC]D22 + 159° (c 0,98, CHC13 ) , Xmax (EtOH) 245 HM (8, 27600), δ (CHC13) BKAtonaeT 3,33 (c, H) , 3,39 (Μ, 1H). - 69 - LV 10777 ΠρΗΗβρ 67 5-ai-teTOKcn-23-3TOKcn-(PaKTop A no-nvHaioT H3 5-aLļeTOKCH-<PaK-Topa A h OTH/ifioflHfla. HasBaHHoe coeiiHHeHHe βηχοπμτ b BHfle 6eciļ-ΒΘΤΗΟΜ neHbi [CC]D22 + 167° (c 1,02,CHC13 ) , Xmax (EtOH) 245 hm (i, 28070), δ (CDC13) BK/noMaeT 3,25 (m, 1H) , 3,46 (m, 1H) ,
3,64 (m, 1H), no/iyHaeMoe cnocoāOM, aHa/iorHHHbiM fl/iH coeflHHeHHH npmiepa J 7. LV 10777 <I>opMyjia H3o6peTeHHa 1. CoenHHeHne no <ļ)opMyjie (II)
R1 npencTaBJiaeT MerajībHjTO, 3THJibHyio hjih H3onponHJibHyio rpynny: R2 npejicTaBJiHeT aTOM Bojiopojia min rpynny OR5 (OR5 HBJiHeTca nmpoKCHJTbHOft hjih 3aMemeHHoft rmīpoKCHJībHoft rpynnoH, conepacamen mo 25 aTOMOB yrjiepo^a) R3 npencTaBJineT aTOM Bonopojia, hjih R2 hjih R3 BMecTe c aTOMOM yrjiepona, κ KOTopoMy ohh npHcoenHHHioTCH, npencTaBJiiiiOT >C=0 rpynny: h OR4 npe/icTaBJineT rpynny OR5 , KaK yKa3aHO Bbirne, omjumatomeecA mm, hto coe^HHeHHe, b κοτοροΜ oūhh hjih 06a H3 panHKajioB R2 h OR4 hbjihiotch 3aMemeHHofi[ rHzīpoKcmībHOH rpynnoH. 2. CoeiiMHeHHe no π. 1, onuuHarouļeeai mm, mo R1 «BJiaeTca Η30ΠρθΠΗΛί>ΗΟΗ Γρ>ΉΠΟΗ, 3. CoeflHHeHHe no π. 1, onviimaioineeai mm, mto R1 HBJiaeTCH Η3οπροπιυιι>Ηοίί rpynnoft, R2 npe^cTaBJineT aTOM Bojjopojia hjih stokch, Η-προποκοη, aueTOKCH HJIM npOIIHOHOKCH-rpynny H R3 HBJIHeTCH aTOMOM BOJIOpOfla HJIH R2 H R3 BMecTe c aTOMOM yrjiepo;ia, κ κοτοροMy ohh npHcoejiHHjnoTCH, o6pa3yioT rpynny >C=0 rpynna OR4 npejicTaBjmeT nmpoKCHJibHyio, apeTOKCH, hjih MeTHJiOKCHKap6oHHJioKCH rpynny. 4. CoejiHHeHHe no π. 1, onvumamufieca mm, hto R1 BBJiHeTCH H3onponHJibHoft rpynnon, R2 npe/icTaBJiaeT aTOM Bonopona, R3 «BJīBeTCH aTOMOM Bonopojia, OR4 npejicTaBJiaeT rHapoKauibHyio rpynny; R1 HBJiaeTca H3onponHJibHoft rpynnoH, R2 npeacTaBJiaeT nponHOHOKCHipynny, R3 HBJiaeTca btomom Bojiopojia, OR4 BBjiaeTca THUpOKCHJIbHOH TpļTinOH; R1 HBJiaeTca H3onponHJibHoft rpynnoH, R2 h R3 BMecTe c aTOMOM yrjiepojia, κ KOTopoMy ohh npHCoejiHHinoTca, o6pa3yiOT rpynny >C=0 h pajiHKaji -OR4 HBJiaeTca ranpoKCHJībHOH rpynnoft; R1 HBJiaeTca H3onponHJibHOH rpynnoH, R2 npejjcTaBJiaeT 3TOKCH-rpynny, R3 HBJiaeTca aTOMOM Boziopo/ia h -OR4 npe/iCTaBJiaeT rHapoKCHJibHyio rpynny; R1 HBJIHeTCH H30np0nHJIbH0H Γρ>ΊΙΠΟΗ, R2 npencraBJuieT H-nponoKCHrpynny, R3 BBJiaeTca aTOMOM Bonopona, OR4 HBJiaeTca rHjīpoKCHJībHOH rpynnoii; R1 HBJiaeTca MeTHjībHOH rpynnoft, R2 HBJiaeTca aneTOKCHrpynnoH, 2 LV 10777 R3 npeacTaBJiaeT aTOM Boaopoaa h OR4 HBJiaeTCH rnapoKcmībHOH rpynnoH; R1 HBJiHeTCH 3thjii>hoh rpynnoft, R2 npeacTaBJiaeT aiļeTOKCHipynny, R3 HRJiseTCH aTOMOM Boaopoaa h -OR4 npeacTaBJiaeT rHapoKCHabHyio rpynny; R1 ABJineTCH H3onponmibHOH rpynnoH, R2 npeflCTaBJIHeT aiieTOKCHipynny, R3 hr/mctch btomom Boaopoaa h paaHKaa OR4 npeacTaBJiaeT rHapoKCHabHyio rpynny; 5. ΚθΜΠ03ΗΙίΗΗ , IipeflHa3HalieHHaH ŪJIX ΠρΗΜβΗβΗΗΗ b ryMaHHoft ΜΛΗ BeTepHHapHOft MeflHIiHHe, COflepJKHT ΧΟΤΗ 6bl ΟΛΗΟ COeflHHeHHe no Π. 1 C ΟΛΗΗΜ HJIH HCCKOJIbKKMH HOCHTejIHMH H/ΜΛΗ ΗΒΠΟΛΗΗΤβΛΗΜΗ. 6. KoMno3HiiHH, npeaHa3HaqeHHaa aaa 6opb6bi c HaceKOMbiMH h, npHMeHHeMaa HanpnMep, b cejibCKOM xo3aftcTBe, caaoBoacTBe hjih jiecoBOjcTBe, coaepjKHT χοτη 6bi oaHO coeaHHeHHe no π. 1 c οληημ hjih HeCKOJĪbKHMH HOCHTeJIHMH H/HJIH HanOJIHHTejIHMH. 7. Cnoco6 nojiyHeHHH coeaHHeHHH ποπ. 1, npeaycMaipHBaioiiiHii: а) nojiyneHHe coenHHeHHH, rae οληη hjih o6a 3aMecTHTejw R2 h OR4 flBJunoTca 3aMeiueHHOH rimpoKCHJībHoft rpynnoft; juifl o6pa6oTKH peareHTOM 3aMemaiomHM rHapoKCHJibHyio rpynny, TaKoro coejiHHeHHH, rae οληη hjih o6a 3aMecTHTeji« hbjihiotch rHapoKCHJībHoii rpynnoH, πρΗΗβΜ OR4 bbjihctch 3aM6iii6HHOH rHJīpoKCHJībHoii rpynnoft Β TaKOH peaiaiHH, rae noayneHHO coejiHHeHHe, β κοτοροΜ OR4 HBJIHeTCH OH: б) nojiyMeHHe coeflHHeHHH, rae R2 h R3 -BoccTaHOBJieHHeM cooTBeTCTByiomero coeaHHeHHH, rae R2 roMoaHTH'iecKH BoccTaHaBaHBaeMbiH aTOM hjih rpynna: 3 b) nojiyaeHHe coeflHHeHHa, r^e R2 h R3 -06a o6pa3yiOT OKcorpynny-oKHCJieHHeM cooTBeTCTByiomero coenHHeHHH, rae R2 OH, a OR4 HBJiaeTca 3amHmeHHOH rniipoKCHJībHOH rpynnoft, juir nojiyMeHH« coejjHHeHHH, rae OR4 npejjcTaBaaeT rpynny OH: r) no;iyHeHHe coejiHHeHHH, me R2 h OR4 -npeacraBJiaeT ΓΗΛροκοΗΛΐ>Η>το rpynny-CHiiTHe 3amHTHoii rpynnw b cooTBeTCByioiueM coeaHHeHHH, rae R2 hjih OR4 HBJiaeTCH 3amMmeHHoii rmpoKCHJībHoii rpynnoft: λ) nojiyMeHHe cojih H3 khcjiotli (II)-o6pa6oTKofi κηοιοτμ ocHOBaHHeM hjih npeBpaiiieHHeM ohhoh cojih b zipyryio nyreM ηοηηογο o6MeHa; hjih e) nojiyqeHHe coeziHHeHH», me R2 h R3 -BMecTe o6pa3yioT OKCorpynny h OR4 r BJiaeTca OH hjih MeTOKCHrpynnoH-KyjibTHBHpoBaHHeM TaKoro opraHH3Ma pojia Streptomices, κοτορκβ cnocoēHbi npoayuHpoBaTb no KpaiiHefi Mepe οληο H3 yica3aHHbix COejIHHeHHHH, 8. Cnoco6 6opb6bi c Bpe/iHTejiflMH b cejibCKOM xo3HHCTBe, cajioBojicTBe hjih jiecoBoncTBe hjih hjih npyrHx nejieft (κροΜε jnoneft h xcHBOTHbix), npejiycMaTpHBaK)iHHe o6pa6oTKy KyjibTypHbix pacieHHH hjih jipyryK) pacTHTejibHOCTb hjih MecTa ο6ητβηηη HaceKOMbix 3φφεκτΗΒΗ0Η Λ03θϋ ΟΛΗΟΓΟ HJIH HeCKOJIbKHX COCflHHCHHH, yKa3aHHbix B n. 1 φopMyJIbI, HJIH Κ0ΜΠ03ΗΙΙΗΗ ΠΟ Π. 6. 4 LV 10777
AHHOTAUMR
OnHcaHbi coeflnneHM« $opMy/iw (II)
OR*>- M HX CO/IH , ΓΛβ R1 npeflCTaB/iiier MeTM/ibHyra, 3TM/ibHyio m/ih H3onponw/ibHyio rpynny; R2 npeflCTaB/iHeT aTOM BOAopoAa h/ih rpynny OR5 (rfle OR5 jib- /ifieTCfi rMApoKcmib Hofi rpynnoH h/ih 3a«einenHoii γμαροκοη/ιβηομ
rpynnoii[, coAepJKameii flo 2 5 aroMOB yr/iepoAa) h R3 npeACTaB-niieT aTOM BOflopoAa, asm R2 m R3 βμθοτθ c aTOMOM yrAepoAa, κ κοτο- poMy ohh npHcoeflMHJļioTCs npeACTaB/iHioT rpyririy >C=0; m OR4 npeflCTaBAAeT rpynny OR5 , Koropafl HMeer BbimeyKa3āHHbie 3na>ieHHa; o npH ycAOBMM/ MTo KorAa R npeACTaB/iAex rnApoKCM/ibHyio rpynny, OR4 npeACTaB/iiieT aaMeineHHyio rnApoKcn/ibnyio rpyrmy πομιινο ne- / TOKCM/ibHoii rpynnbi. YKa3aHHwe coeAvtHeHMA mojkho ripnMenflTb Rnn 6opb6u c uaceuo-MbiMM, K/iemeBHAHbiMH, HSMaTOAaMM h/ih Apyn-tMH napa3nxann.

Claims (8)

  1. LV 10777 IZGUDROJUMA FORMULA 1. Savienojums ar formulu (II)
    R1 ch3 (II) un ta salis, kur: 1 R ir metilgrupa, etilgrupa vai izopropilgrupa; 2 5 5 R ir ūdeņraža atoms vai grupa OR (kur OR ir hidroksilgrupa vai aizvietota hidroksilgrupa ar kopējo oglekļa atomu skaitu līdz 25) 3 2 3 R ir ūdeņraža atoms, vai arī R un R kopā ar oglekļa atomu, pie kura tie ir saistīti, veido grupu >C=0; 4 5 OR ir tāds pats kā jau definētais OR ; 2 4 ar noteikumu, ka tad, kad R ir hidroksilgrupa, OR ir aizvietota hidroksilgrupa, bet ne metoksigrupa.
  2. 2. Savienojums pēc punkta 1, kura R1 ir izopropilgrupa. - 1 2
  3. 3. Savienojums pēc punkta 1, kura R ir izopropilgrupa, R ir ūdeņraža atoms vai etoksigrupa, n-propoksigrupa, acetoksigrupa vai 3 2 3 propionoksigrupa un R ir ūdeņraža atoms vai ari R un R kopa ar 4 oglekļa atomu, pie kura tie ir saistīti, veido grupu >C=0; OR ir hidroksilgrupa, acetoksigrupa vai metoksikarboniloksigrupa.
  4. 4. Savienojums pēc punkta 1, kurā: 1 2 3 R ir izopropilgrupa, R ir ūdeņraža atoms, R ir ūdeņraža atoms 4 un OR ir hidroksilgrupa; 1 2 3 R ir izopropilgrupa, R ir propionoksigrupa, R ir ūdeņraža atoms 4 un OR ir hidroksilgrupa; 1 2 3 R ir izopropilgrupa, R un R kopa ar oglekļa atomu, pie kura tie 4 ir saistīti, veido grupu >C=0; un OR ir hidroksilgrupa; 1 2 3 R ir izopropilgrupa, R ir etoksigrupa, R ir ūdeņraža atoms un 4 OR ir hidroksilgrupa; 12 3 R ir izopropilgrupa, R ir n-propoksigrupa, R ir ūdeņraža atoms 4 un OR ir hidroksilgrupa; LV 10777 12 3 R ir metilgrupa, R ir acetoksigrupa, R ir ūdeņraža atoms un 4 0R ir hidroksilgrupa; 12 3 4 R ir etilgrupa, R ir acetoksigrupa, R ir ūdeņraža atoms un OR ir hidroksilgrupa; 1 2 3 R ir izopropilgrupa, R ir acetoksigrupa, R ir ūdeņraža atoms un 4 OR ir hidroksilgrupa.
  5. 5. Ķ2!£E25īEUa ar pielietojumu humānajā vai veterinārajā medicīnā, kas satur efektīvu daudzumu vismaz viena savienojuma pēc punkta 1 kopā ar vienu vai vairākiem nesējiem un/vai atšķaidītājiem.
  6. 6. Ķ25E2EĪEŪ2 kaitēkļu apkarošanai ar pielietojumu, piemēram, lauksaimniecībā, dārzkopībā vai mežkopībā, kas satur efektīvu daudzumu vismaz viena savienojuma pēc punkta 1 kopā ar vienu vai vairākiem nesējiem un/vai atšķaidītājiem.
  7. 7. ?a5§!Di5D§ savienojuma pēc punkta 1 iegūšanai, kas paredz: 2 4 (a) savienojuma, kurā viens vai abi aizvietotāji R un OR ir aizvietota hidroksilgrupa, iegūšanai - 2 4 tada savienojuma, kurā viens vai abi aizvietotāji R un OR ir hidroksilgrupa, apstrādi ar hidroksilgrupu aizvietojošu reaģentu, 4 pie kam OR ir aizsargāta hidroksilgrupa tādā reakcijā, kur tiek ie- 4 gūts savienojums, kur OR ir -0H; 2 3 (b) savienojuma, kura R un R ir ūdeņraža atomi, iegūšanai - 2 atbilstoša savienojuma, kura R ir homolltiski reducējams atoms vai grupa, reducēšanu; 2 3 (c) savienojuma, kura R un R abi kopa veido oksogrupu - 2 4 atbilstoša savienojuma, kurā R ir -0H, OR ir aizsargāta hid- 4 roksilgrupa, oksidēšanu, lai iegūtu savienojumu, kurā OR ir -0H; 2 4 (d) savienojuma, kura R vai OR ir hidroksilgrupa - 2 aizsarggrupas noņemšanu atbilstošam savienojumam, kura R vai 4 OR ir aizsargāta hidroksilgrupa; (e) skābes ar formulu (II) sāls iegūšanai - skābes apstrādi ar bāzi vai vienas sāls pārvēršanu otrā ar jonu apmaiņu; vai 2 3 4 (f) savienojuma, kurā R un R kopā veido oksogrupu un OR ir -0H vai metoksigrupa - tāda Streptomyces ģints organisma kultivēšanu, kas spēj producēt vismaz vienu no minētajiem savienojumiem.
  8. 8. kaitēkļu apkarošanai lauksaimniecībā, dārzkopībā vai mežkopībā, vai citām vajadzībām (izņemot cilvēka un dzīvnieku ārstēšanu), kas paredz augu vai citas veģetācijas, vai kaitēkļu atrašanās vietas apstrādi ar efektīvu daudzumu viena vai vairāku savienojumu pēc punkta 1 vai kompozīcijas pēc punkta 6. LV 10777 CnOCOE ΠΟ/ΙΥΗΕΗΜΗ XHMH4ECKHX COEflHHEHHH, Κ0ΜΠ03Η11ΗΗ HA HX OCHOBE H CnOCOE EOPbEbl C ΗΗΦΕΚ11Η4ΜΗ H HHBA3HHMH OnncaHHe HacTOiimee HaoSpeTeHHe oTHocnTCii κ hobuh coeflMHeHHflM buth-ČHOTHKa H CnOCoSaM ΗΧ ΠΟΛγΗΘΗΗjī . B 3aiiBKe na BbiAaMy naTeHTa Be.nnKo6pwTaHHM N 8522699 onncauo nO/iyMeHHe aHTH6nOTHK06S541, KOTOpbie MOJKHO Bblfle/lHTb H3 / προΑγκτοΒ φθρΜθΗΤΒΒΜΜ BHfla Streptomyces. Ahth6hothkh S541
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Families Citing this family (63)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
BE903232A (fr) * 1984-09-14 1986-03-13 Glaxo Group Ltd Composes antibiotiques et leur procede de preparation
ES8800986A1 (es) * 1985-07-27 1987-12-01 Pfizer Un procedimiento para la produccion de un nuevo derivado de avermectina
DE3650265T2 (de) * 1985-09-13 1995-07-27 American Cyanamid Co Makrolide Antibiotika und Verfahren zu deren Herstellung.
US5185456A (en) * 1986-03-12 1993-02-09 American Cyanamid Company Macrolide compounds
GB8606123D0 (en) * 1986-03-12 1986-04-16 Glaxo Group Ltd Chemical compounds
PH24180A (en) * 1986-03-12 1990-03-22 Glaxo Group Ltd Macrolide compounds,pharmaceutical composition containing said compound and method of use thereof
GB8606108D0 (en) * 1986-03-12 1986-04-16 Glaxo Group Ltd Chemical compounds
US5336789A (en) * 1986-03-12 1994-08-09 American Cyanamid Company Macrolide compounds
JP2577734B2 (ja) * 1986-03-12 1997-02-05 アメリカン・サイアナミツド・カンパニー マクロライド抗生物質
PH27415A (en) * 1986-03-12 1993-06-21 American Cyanamid Co Macrolide compounds
CA1296329C (en) * 1986-06-06 1992-02-25 Derek R. Sutherland Macrolide compounds
GB8613790D0 (en) * 1986-06-06 1986-07-09 Glaxo Group Ltd Chemical compounds
US5840704A (en) * 1986-07-16 1998-11-24 Pfizer Inc. Antiparasitic agents and process for their preparation
EP0254583B1 (en) * 1986-07-24 1994-09-07 Beecham Group Plc Parasiticidal milbemycin derivatives, a process for their production, and compositions containing the same
US4916154A (en) * 1986-09-12 1990-04-10 American Cyanamid Company 23-Imino derivatives of LL-F28249 compounds
EP0262384B1 (en) * 1986-09-12 1992-11-04 American Cyanamid Company 23-deoxy derivatives of ll-f28249 compounds
US5149832A (en) * 1986-09-12 1992-09-22 American Cyanamid Company Mono and diacyl derivatives of ll-f28249 compounds
EP0260537A1 (en) * 1986-09-12 1988-03-23 American Cyanamid Company 13-Deoxy-23-oxo(keto) and 23-imino derivatives of 13-deoxy C-076-aglycone compounds
EP0259779B1 (en) * 1986-09-12 1994-08-10 American Cyanamid Company 23-Oxo (Keto) and 23-imino Derivatives of LL-F28249 Compounds
US5525506A (en) * 1987-01-23 1996-06-11 Pfizer Inc. Process for production of avermectins and cultures therefor
US5234831A (en) * 1987-01-23 1993-08-10 Pfizer Inc Cultures for production of B avermectins
US5238848A (en) * 1987-01-23 1993-08-24 Pfizer Inc Cultures for production of avermectins
US4886830A (en) * 1987-03-06 1989-12-12 American Cyanamid Company Mono- and diepoxide derivatives of 23-deoxyl-LL-F28249 compounds
US4886829A (en) * 1987-03-06 1989-12-12 American Cyanamid Company 23-Oxo (keto) and 23-imino derivatives of mono- and diepoxy LL-F28249 compounds
US4956479A (en) * 1987-03-06 1990-09-11 American Cyanamid Company 23-deoxy-27-chloro derivatives of LL-F28249 compounds
US4806527A (en) * 1987-03-16 1989-02-21 Merck & Co., Inc. Avermectin derivatives
US4871719A (en) * 1987-03-24 1989-10-03 Ciba-Geigy Corporation Composition for controlling parasites in productive livestock
EP0285561A3 (de) * 1987-03-27 1989-10-25 Ciba-Geigy Ag Parasitizide und insektizide Milbemycin-Derivate
JPS6431776A (en) * 1987-07-28 1989-02-02 Sankyo Co Novel macrolide compound and production thereof
GB8721378D0 (en) * 1987-09-11 1987-10-21 Glaxo Group Ltd Chemical process
GB8721376D0 (en) * 1987-09-11 1987-10-21 Glaxo Group Ltd Chemical compounds
NZ226117A (en) * 1987-09-11 1990-01-29 American Cyanamid Co Preparation of 5-oh milbemycins from 5-keto milbemycins
GB8721377D0 (en) * 1987-09-11 1987-10-21 Glaxo Group Ltd Chemical compounds
GB8721373D0 (en) * 1987-09-11 1987-10-21 Glaxo Group Ltd Chemical process
GB8721375D0 (en) * 1987-09-11 1987-10-21 Glaxo Group Ltd Chemical process
GB8721647D0 (en) * 1987-09-15 1987-10-21 Pfizer Ltd Antiparasitic agents
US5240850A (en) * 1987-10-23 1993-08-31 Pfizer Inc. Cultures for production of avermectin aglycones
ATE87926T1 (de) * 1987-11-09 1993-04-15 Pfizer Ethylierte avermectine.
GB8726384D0 (en) * 1987-11-11 1987-12-16 Coopers Animal Health Veterinary treatment
GB8726730D0 (en) * 1987-11-14 1987-12-16 Pfizer Ltd Antiparasitic agents
GB8801908D0 (en) * 1988-01-28 1988-02-24 Glaxo Group Ltd Chemical compounds
GB8804440D0 (en) * 1988-02-25 1988-03-23 Pfizer Ltd Antiparasitic agents
AU628051B2 (en) * 1988-05-10 1992-09-10 American Cyanamid Company Macrolide compounds
GB8811036D0 (en) * 1988-05-10 1988-06-15 Glaxo Group Ltd Chemical compounds
GB8811037D0 (en) * 1988-05-10 1988-06-15 Glaxo Group Ltd Chemical compounds
GB8813150D0 (en) * 1988-06-03 1988-07-06 American Cyanamid Co Chemical compounds
GB8813760D0 (en) * 1988-06-10 1988-07-13 American Cyanamid Co Chemical process
US5428034A (en) * 1988-09-02 1995-06-27 Sankyo Co., Ltd. Milbemycin derivatives, their preparation and their use
ES2052173T3 (es) * 1989-04-11 1994-07-01 Pfizer Composiciones inyectables que contienen 25-cyclohexil-avermectina b1.
US6001822A (en) * 1989-04-11 1999-12-14 Pfizer Inc. Antiparasitic formulations
NZ234802A (en) * 1989-08-14 1992-11-25 Merck & Co Inc Long acting injectable formulations comprising an avermectin compound and triacetin. treatment for internal and external parasites of animals
US4988824A (en) * 1989-09-11 1991-01-29 Maulding Donald R Process for the preparation of 23-(C1-C6 alkyloxime)-LL-F28249 compounds
US5055486A (en) * 1989-12-22 1991-10-08 American Cyanamid Company 13-alkyl-23-imino derivative of LL-F28249 compounds and their use as endo- and ectoparasiticidal, insecticidal, acaricidal and nematocidal agents
JP2622197B2 (ja) * 1990-03-01 1997-06-18 三共株式会社 １３−エーテル置換ミルベマイシン誘導体
US5290804A (en) * 1991-05-01 1994-03-01 Merck & Co., Inc. Anthelmintic milbemycin analogs of novel microorganisms
ATE180671T1 (de) * 1991-09-30 1999-06-15 Merck & Co Inc Hydrierte rizinusöl-enthaltende injizierbare formulierungen mit verlängerter wirkstoffabgabe
US6103504A (en) * 1992-03-25 2000-08-15 Pfizer Inc. Process for production of avermectins and cultures therefor
DE19534366C2 (de) * 1995-09-15 2000-08-17 Asta Medica Ag Verfahren zur Herstellung von 2,3,4,6-Tetra-O-benzyl-D-glucopyranose und 2,3,4,6-Tetra-O-allyl-D-glucopyranose
CA2211949A1 (en) * 1997-07-21 1999-01-29 David Farley Johnson Nonaqueous compositions for parenteral administration
DE60118132T2 (de) 2000-10-10 2006-10-19 Wyeth Anthelmintika
NZ552040A (en) * 2006-12-13 2009-04-30 Bomac Research Ltd Veterinary formulation comprising an anthelmintic compound and glyceryl acetate
DE102010064245A1 (de) 2010-12-28 2012-06-28 Bayer Animal Health Gmbh Makrocylischen Lactone und deren Verwendung und deren Kombinationen mit anderen Wirkstoffen
WO2012028556A1 (en) 2010-08-31 2012-03-08 Bayer Animal Health Gmbh Macrocyclic lactones and their use and their combinations with other active substances

Family Cites Families (11)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
US4201861A (en) * 1977-10-03 1980-05-06 Merck & Co., Inc. Acyl derivatives of C-076 compounds
US4550160A (en) * 1979-08-13 1985-10-29 Merck & Co., Inc. Processes for the interconversion of C-076 compounds
JPS5632481A (en) * 1979-08-23 1981-04-01 Sankyo Co Ltd Antibiotic b-41d, its preparation, and acaricide and anthelminthic agent and repellent containing the same as active constituent
US4289760A (en) * 1980-05-02 1981-09-15 Merck & Co., Inc. 23-Keto derivatives of C-076 compounds
US4457920A (en) * 1981-09-03 1984-07-03 Merck & Co., Inc. 4a-Substituted avermectin compounds
US4423209A (en) * 1982-02-26 1983-12-27 Merck & Co., Inc. Processes for the interconversion of avermectin compounds
JPS59108785A (ja) * 1982-11-25 1984-06-23 Sankyo Co Ltd ミルベマイシン類の５−オキシム誘導体
JPS60126289A (ja) * 1983-11-14 1985-07-05 Sankyo Co Ltd ミルベマイシン類の５−カ−ボネ−ト誘導体
PT80577B (pt) * 1984-06-05 1987-09-18 American Cyanamid Co Processo para a producao de novos agentes macrolidos ll-f28249 uteis no tratamento de infeccoes helminticas por ectoparasitas artropodes e por acarideos
BE903232A (fr) * 1984-09-14 1986-03-13 Glaxo Group Ltd Composes antibiotiques et leur procede de preparation
ES8800986A1 (es) * 1985-07-27 1987-12-01 Pfizer Un procedimiento para la produccion de un nuevo derivado de avermectina

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