МСОС Лекции с поиском и закладками
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MeTOAbl aKTMBaU.MM Kap60KCMnbHOH rpynnbl 3. A3MAHbtM MeTOA (Kyp4Myca)
MeTOAbl nonyYeHHR a3HAOB
r |
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MeTOAbl aKTMBaU.MM Kap60KCMnbHOM rpynnbl
npHMeHeHHe a3HAHOro MeTOAa B CHHTe3e aMHAOB H nenTHAOB
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R,,,,,,,. |
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'R |
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1 )Ill |
-HN3
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R-1(_ |
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N-R |
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R2 |
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1/oMe
NHCbz Cbz-Val-OMe
1. NH2NH2 |
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NO2 ► |
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HCI/0 |
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1/ =®9=N |
H N |
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OBn |
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N N |
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H-Gly-OBn |
NHCbz |
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Cbz-Val-N3 |
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OBn |
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OH |
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NHCbz |
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Pd/C |
NH2 |
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H-Val-Gly- H |
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HeAOCT3TKM Cbz-Val-Gly-OBn |
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-HL-13KVIIII BblXOA <80%; cryneHYaTaR a1<TV1Ba41-1R; HeCTa6V1/lbHOCTb a3"1P,OB AoCTOHHCTea
-OTCyTCTBll1e pa4eM1-13aLJ. t1,1; AOCTynHOCTb peareHTOB
C00/1b3VIOT AJIR CMHTe3a t<OpOTKMX nenTMAOB M/1H CWHBKM nenTMAHblX 6110KOB
MeTOAbl aKTHBa4HM Kap60KCMnbHOM rpynnbl 3. A3MAHbtH MeTOA(Kypl.\Myca)
nplttMeHeHltte a3lt1AOB B ClttHTe3e aMlttHOB lt1 Kap6aMaTOB (neperpynnlttpOBKa Kypu. yca)
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0N
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_-_ """'" |
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---►►a |
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___N |
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N=C=O " |
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R'OH |
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isocyanate |
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R-+1z';".,,:
nitre •
II
R-HN/'-..OR'
R'=Me, Bn, t-Bu
neperpynn"1poeKa Kypu_"1yca crepeoce11eKn1aHa (c coxpaHeH"1eM cTepeox"1M"1"1)
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HN Ot-Bu |
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DPPA |
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t-BuOH |
t-BuOH |
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NEt3 |
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MeTOAbl aKTHB3U.MM Kap6oKCMnbHOM rpynnbl 3. A3MAHblM MeTOA (Kypu,Myca)
npv1MeHeHv1e a3v1AOB B Cv1HTe3e aMv1HOB v1 Kap6aMaTOB (neperpynnv1po0Ka Kyp4v1yca)
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◄ ► R Gi) T ► |
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R--{ (£) 0 |
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N-N |
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_____ / |
nitre |
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R-NH2
H2O
◄◄----- -CO2
r R-N=C=O
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isocyanate |
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- ►► |
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R'OH |
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R-N OR' |
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R'=Me, Bn, t-Bu |
neperpynnl
Ph_/JII
-1pOBK YP'-'l-1yca crepeoce11eKn1eHa (c coxpaHeHt.1eM crepeoxl-1M"1l-1) |
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0@ \._OEl |
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1.NaOH |
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DPPA/NEt3 |
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N=N |
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OH |
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Ph OEt |
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Jia |
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Cu or Rh |
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trans-O |
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H20/H+ |
Ph |
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Ph....._v-"' ,, |
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......V-'NH2 |
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N |
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Tranylcypromine |
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•......__ |
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nenTMAHblM CMHTe3
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upom OIITJeT MB&Kle. ffO OIRT88 n8IrrJDlOB |
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-Opt'8HJO(OB |
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"CpeJDI DNPJHJB |
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,_o1'BOM 00 CBOel oodoTBeHKOI |
OIIMBMJt- |
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11BJU18'!0I SOIJOCTBOII 11.D ..... |
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JC!O |
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1(()1, |
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ll3IIIOM |
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plTJ&IOII, |
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B81'TO |
OOB8p118KKO 1fY'U08 |
JIBT8pe08M |
Tex, |
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dOT&8T B A.PJX'&X 06JlaoT,at' |
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OcHOBHaA 4enb nenTHAH0ro Cll1HTe3a - o6pa30BaHHe nenTHAHOM CBR3"1 |
C-KOHe4 |
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:·o |
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-N,,,,n Jl |
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\Jl.\j__ a |
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y\__ |
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R a |
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OPG |
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( 'OPG |
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N1 |
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T 'LG |
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-HLG |
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NHPGN |
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R |
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PGNHN ··. .: 0 |
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PG - 3au,u,1THas:i rpynna |
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nenntAHaR |
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N-KOHeu, |
ca Jb |
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LG - YXOA a rpynna |
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CS>opMHPOBaHHe nenTHAHOM CBff3H BK/ltOl.faeT HeCKO/lbKOOCHOBHblX 3Tanos: |
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3aLLii&i1Ta N-KoH4eso1A AK no aM&i1Horpynne (PGN = Boe, Fmoc) |
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3aLLii&itTa C-KOH4eBOIA AK no Kap60KC"1 rpynne (PGC = Me, Bn, t-Bu) |
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KOHAeHca41-1R aM&itHO K&itC/lOT nyreM aKT&,1Ba41,11,1 N-KOH4eBOIA AK (BBeAeH&,1e LG) |
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-YAalleH1-1e 3aLLii&itTHblX rpynn
-KpoMe Toro, He06XOA&,1Ma 3al.Ui"1Ta Q>YHK4"10HaJlbHblX rpynn 60KOBblX 4ene1A
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nenTMAHblM CHHTe3
Pa38111Tll1e nenTll1AHOLII X"1Mil1"1 np111ee110 K nORB/leHiltK) 111 pa38"1T"1K) HOBblX nOAXOAOB l-1 MeTOAOB 3aw_111Tbl cpyHK4"10HallbHblX rpynn AK, aKTll1Ba41,11,1 Kap6oKC"1llbHOLII rpynnbl, KOTOpble CefOAHR Wl-1POKO "1CnO/lb3YK)T B pa3/1111'-1Hb1X 0611aCT.RX opraHl-1'-leCKOLII 1,1 MeAL-14"1HCKOi'.1 X"1Mil1"1.
1. 3aU4 1THble rpynnbt
Am t\.1HTe3a no11111nenn1AOB pa3pa6oraHa KOH4enu,111R «oproroHa/lbHOM 3aW.MTbl>> (P. Mep1,1cp1,111A): Ka>t<AaR 3aL1.1i111THaR rpynna MO>KeT 6b1Tb vAa11eHa He3ae111c1,1Mo or APvr111x
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I - TFA► |
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O N |
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OH |
)I, I |
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0 |
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Pip |
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,.N, |
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H |
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H-Lys-OH |
-9' |
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H2 |
Fmoc |
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Cbz-L I s-O-t-Bu |
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B npou,ecce nenr111AHOro Cl-1HTe3a y
5 Ha Ka>KAOM U,1-1Klle Hapaw_1-1aaHl-1R u,en1,1 npl-1XOAv1TCR vAamHb PG Ca -aMvtHorpynnbl («epeMeHHaA» 3aW.MTHaA rpynna"};
-pe>Ke YAallRK)T PG CL -Kap60KCLII rpynnbl (npLit CWLIIBKe 0/lLitronenTLIIAOB);
-PG 6oKOBbtX 4eneH YAa,rneTCR Ha 3aK11t01.11i1re11bHOM 3Tane cvtHTe3a («cra61rtnbHaA» 3aUJ.MTHaA rpynna)
nenTMAHblM C"1HTe3
Bb16op 3au.v1THblX rpynn onpeAem:ieTcR cxeM0111 c&.1HTe3a nenn1A.a.
B 3aev1C&.1MOCT&.1 OT l-1CnO/lb3yeMOi1 «epeMeHH0'1» 3a1.4&.1THO rpynnbl Hav16011ee pacnpocrpaHeHbl:
1.Boe- cTparerHR (Nci - Boe, c« 111 PG-60Koeb1x u_ene vAallRIOTCR a ocHoeaH111RM&.1)
2.Fmoc- CTparerHR (Nci - Fmoc, cci 1,1 PG-6oKOBblX 4enei1 vAaJ1RJOTCR e K"1CJ10TaMv1)
np1.1 n11aH1.1posaHl.1&.1 cxeMbl nenTIIIAHOro C"1HTe3a np"1MeHRIOT ABe TaKTv1K"'1 3at.4v1Tbl 60KOBblX u,ene (e 3a8"1Cl,1MOCTl,1 OT MeTOAOB aKn1eau,1,11,1 Kap60KCv1/lbHO rpynnbl}
-MaKCMManbHaR 3aU4MTa - 3al4&.1t.4a10T see <f>YHKU,1.10Ha/1bHble rpynnbl 60KOBblX u_enei:1
-(cMewaHHble aHrl.1AP111Ab1, Kap60A&.1&.1M&.1AHbl MeTOA}
-M.-tHMMa/lbHaR 33LL\MTa - 3aw,1-1l4at0T "10Hv13v1pyeMble rpynnbl (KOHAeHcv1pyt0l4v1e areHTbl}.
2. MeTOAbl 3KTMBal.\MH Kap6ot<CH/lbHOH rpynnbt
2.1. A3MAHblM MeTOA (npMMeHfleTCfl cpaBHMTeJlbHO peAKO)
■
nenTMAHblM cMHTe3
2.2. MeTOA cMewaHHblX aHrMAPHAOB
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CMewaHHbte aHntAPHAbt |
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Nu: |
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R 1Aa)lR2 |
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R1 )l0..,R2 |
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R1=Et. |
i-Bu |
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Kap60H08blX K-T |
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Kap60HOBO / |
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yronbHOt'.1 K-T |
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8: NMP |
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NMM |
DIEA |
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o |
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H2N |
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CiC02-iB\:, |
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OMe |
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OMe |
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JOH |
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H- |
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OMe |
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MPITHF |
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B |
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HBoci |
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NHBoc I-Bu |
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NHBoc |
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-20 |
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?, -i- |
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Boe-Ala-OH |
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OM |
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OMe |
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TFA |
-....... )lN |
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1.NaOH/MeOH |
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:: •• |
G |
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►TFA• NH2 |
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2· H |
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N 2 |
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TFA.. H-Ala-Gly-OMe |
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H-Ala-Gly-OH |
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-Hlt13Klt1 BblXOA <80%; cryneH4aTa.A at<Tl-1BaU.1t1.A; Hecra61-1J1bHOCTb aHflilAP"1AOB |
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AocTOMHCTBa |
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BblCOt<a.A CKOpOCTb peaKLJ."1"1, AOCrynHOCTb peareHTOB |
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-OTCYfCTB&iie pa4eM1it3aU."1"1; |
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WHpot<o Hcnonb3yior AnR CHHTela aMMAOS "' KopoTt<M>< nenntAOB |
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nenTMAHblM CHHTe3 2.3. Kap6oAMMMMAHblM MeTOA
npoH3B0.QHble
Kap6o.QHHMH.Qa
o+
R1 -N=C=N-R2 |
EDC (>t<HAKOQ)a3Hbl c1-1Hre3) |
Nu:/ |
DIC (TBepAo¢a3Hbl c1-1Hre3) |
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TFA •
Hf!AOCTaTK
Ph',,,-..... |
JL |
rs:: |
HF/PhOMe |
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NHBoc Bzh |
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H8oc-Phe•Cys-0Bn
H Phe•Cys-OH
- Pau,eM"13aU,"1fl <20%; Heycroi'.14"1BOCTb ype"1AOB, no604Hble peaKU,"1"1 o6pa3oBaH"1e A""l.J.""K11oreKc"111Mo4eB"1Hbl, a1111epreHHOCTb DCC AocroHHCTBa
- BblXOA >90%, BblCOKaR CKOPOCTb peaKU,"1"1, AOCTYnHOCTb peareHTOB
■ WHpOKO HCOO/lb3YtoT AJIR CJ,1HTe3a aMHAOB 111 nenTHAOB
npMMeHeHMe npOM3BOAHblX Kap60AMMMMAa B opraHM"leCKOM CMHTe3e
Kap60AHHMHAbt WHPOKO HCnOnb3YtoT A/1.R CHHTe3a aMHAOB, naKTaMOB, 34>Hpoe, aKTMBHpoeaHHbtX 34>Mpoe, aHrHAPHAOB, AerHApaTal,\HM, OKMCneHHff cnMpTOB
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1 EDC |
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DCC/RT |
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______ F |
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U |
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] H-Ser-OB; HO\ |
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H |
J°Bn |
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H H |
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OLO |
CH |
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0 |
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,--NH |
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N..,..OH H |
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3. Aen1Aparat..1i"1H |
R)lNH2 1-1m,R H |
DCC/RT• |
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_N |
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4.OK"1CJ1eH111e
(MeTOA Mocp4>a1a)
0
CyreHT
er-OBn |
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Y"l111TbJB8Tb s nenr111,t\HOM C111Hre3e |
An · |
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H2N 0 |
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H2N |
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O |
Gin |
|
|
Asn H2N |
|
||
OH |
H2N |
|
|
|
|
|
|
[ |
HO\ |
//O |
r,. |
||
Se H;iN |
OH |
|