1. 655
moc.revan@kamgnodd :liam-E
9219-278-2-28 :xaF ,2787-088-2-28 :leT
aeroK ,247-151 luoeS ,ytisrevinU lanoitaN luoeS
,ycamrahP fo egelloC ,gnoeJ noeS-gnoeyB :ot ecnednopserroC
gnisu retemortceps ])H ( zHM 004[ 004 XSG-MNJ LOEJ
1
)RAS( pihsnoitaler ytivitca erutcurts ,stnega gnilaeh dnuow
,retemortceps ])H ( zHM 003[ 003 AL-MNJ LOEJ no
1
wen fo tnempoleved eht drawot margorp ruo fo trap sA
derusaem erew artceps )RMN-H ( ecnanoser citengam
1
.)8791 ,tozioP ;7891 ,letnioP(
raelcuN .retemortceps TF 0171 remlE-nikreP dna E003 ®lossacedaM ,eman edart eht rednu noitcudortni laicrem
-RI/TF OCSAJ a no dedrocer erew artceps )RI( derarfnI -moc sti ot del sah tcartxe eht fo ytreporp gnilaeh
dnuow ehT .)b7691 ,a7691 ,ecnerwaL( ytivitca lacigol
SDOHTEM DNA SLAIRETAM -oib rof tneidergni laitnesse tsom eht si )2( dica citaisa
,senepretirt eerht eht gnomA .)5991 ,etnoB( simred niks eht
.detroper si tnega ni sisehtnys negalloc fo noitaludom eht htiw detaicossa si
gnilaeh dnuow tneiciffe na fo tnempoleved eht rof )2( dica ytivitca gnilaeh dnuow sti taht detroper neeb sah tI .)6991
citaisa fo yduts RAS dednetxe eht ,noitacinummoc siht nI ,radmanI( )3( dica cissacedam dna ,)2( dica citaisa ,)1(
.rehtruf yduts RAS eht eusrup ot su del gnidnif sihT .)6991 edisocitaisa :stneidergni dionepretirt tnereffid eerht sah
,mihS( ytivitca gnilaeh dnuow eht ecnahne ot tnatropmi tcartxe ehT .)2791 ,iksnajleB( tnega gnilaeh dnuow a sa
ylevitaler era ,)5 ,4( gnir D eht ni dica cilyxobrac )82(C desu neeb sah tcartxe eht ,yllacirotsiH .)1491 ,smetnoB(
eht htiw noitamrof retse dna gnir A eht ni spuorg yxordyh spuorg labirt dna serutluc tneicna esrevid yb stnenitnoc
eerht eht htiw noitamrof etateca sa hcus ,snoitamrofsnart tnereffid no desu tnalp labreh na si acitaisa alletneC
cilihpopil yllareneg taht detacidni yduts RAS tsrif ehT .)2(
dica citaisa gniyfidom yb demrofrep neeb evah seiduts NOITCUDORTNI
gnilaeh dnuoW ,RAS ,dica citaisA :sdrow yeK
.gnilaeh retfa racs tsellams eht tfel ti ,eromrehtruF .ytivitca gnilaeh dnuow
tsetsaf eht dna tsegnorts eht dewohs )21( etataisa-enedilyporposi-32,3-oxo-2 lyhtemyxohte
,meht gnomA .yassa aera dnuow a dna yassa htgnerts elisnet a gniyolpme yb detaulave erew
stceffe gnilaeh dnuow rieht dna deraperp erew dica citaisa fo sevitavired citehtnys-imes neT
)6002 ,71 lirpA devieceR(
aeroK ,247-151 luoeS ,ytisrevinU lanoitaN luoeS ,ycamrahP fo egelloC
gnoeJ noeS-gnoeyB
tnegA gnilaeH dnuoW weN rof
sevitavireD dicA citaisA fo ydutS pihsnoitaleR ytivitcA-erutcurtS
rk.ro.ksp.rpa//:ptth
6002 ,265-655 ,7 oN ,92 loV seR mrahP hcrA

2. J
3 ,s( 50.1 ,)H 1 ,zH 2.11 = ,d( 22.2 ,)H1 ,m( 55.3 ,)H 2 eht tpecxe b6 sa emas saw dohtem citehtnys ehT
J
,zH 0.01 = ,qBA( 30.3 ,96.3 ,)H 1 ,m( 77.3-48.3 ,)H 1 ,zH )c6( dica
J J
0.5 = ,q( 96.4 ,)H 2 ,zH 2.6 = ,tetrauq BA( 71.5 ,02.5 cio-82-ene-21-sruyxoidenedilyzneb-32,β3-yxordyH-α2
J 3
,)H 1 ,zH 2.3 = ,t( 22.5 δ ) lCDC ,zHM 003( RMN-H 1
.)dleiy %58( a6 fo daetsni b6 fo .] M[ 415 e/m +
)IE( ssaM . mc 5961 ,6292 )taen( RI .)H 3 ,zH 4.6 = ,d( J
1-
noitazitlu eht tpecxe a7 sa emas saw dohtem citehtnys ehT
)b7( etao-82-ene-21 J
57.0 ,)H 1 ,zH 05.5 = ,d( 58.0 ,)H 3 ,s( 56.0 ,)H 3 ,s( 59.0
-sruyxoidenedilyhte-32,â3-yxordyh-α2-lyhtemyxolytcO J
,)H 3 ,s( 89.0 ,)H 1 ,zH 4.01 = ,d( 71.3 ,)H 2 ,zH 1.01 = J
,qBA( 79.2 ,36.3 ,)H 1 ,m( 57.3 ,)H 1 ,zH 29.4 = ,q( 46.4 J
.] M[ 246 e/m )IE( ssaM . mc 4371 ,5743 )taen( J 3
,)H 1 ,zH 2.3 = ,t( 41.5 δ ) lCDC ,zHM 003( RMN-H
+ 1- 1
J
RI .)H 3 ,s( 67.0 ,)H 3 ,zH 6.5 = ,d( 88.0 ,)H 3 ,zH 4.6 = J .)%2.66 ,g 87.1( dilos etihw a dleiy ot )1 : 02 = HOeM
,d( 59.0 ,)H 3 ,s( 50.1 ,)H 3 ,s( 90.1 ,)H 3 ,s( 31.1 ,)H 1 ,zH 3
: lCHC( yhpargotamorhc nmuloc leg acilis yb deifirup saw
J J
8.01 = ,d( 52.2 ,)H 2 ,zH 0.01 = ,qBA( 67.3 ,40.3 ,)H 3 hcihw ,dilos wolley thgil a evag erusserp decuder ta tnevlos
J
,s( 35.3 ,)H 1 ,zH 8.01 = ,d( 22.3 ,)H 2 ,m( 85.3 ,)H 2 ,zH fo noitaropave dna noitartliF .etaflus muisengam suordyh
J J
0.9 = ,d( 49.4 ,)H 2 ,zH 9.5 = ,tetrauq BA( 42.5 ,12.5 -na revo deird saw reyal cinagro ehT .)Lm 08( noitulos
J 3
,)H 1 ,zH 2.3 = ,t( 62.5 δ ) lCDC ,zHM 004( RMN-H lCaN detarutas dna )3 × Lm 001( retaw htiw dehsaw dna
1
.)%24 ,gm 831( dilos )Lm 052( etateca lyhte htiw detulid saw erutxim noitcaer
3
etihw a dleiy ot )1 : 03 = HOeM : lCHC( yhpargotamorhc eht ,8-7 Hp ot HOaN .qa %5 htiw noitazilartuen retfA .h 2
nmuloc leg acilis yb deifirup saw hcihw ,dilos wolley rof erutarepmet moor ta derrits saw erutxim noitcaer ehT
thgil a evag erusserp decuder ta tnevlos fo noitaropave .)lomm 0.31 ,Lm 5.1( enahteyxohtemid-1,1 dedda saw
dna noitartliF .etaflus muisengam suordyhna revo deird )Lm 05( edimamrof lyhtemid yrd ni )gm 05( dica cinoflus
saw reyal cinagro ehT .)Lm 05( noitulos lCaN detarutas p
-eneulot- dna )lomm 81.5 ,g 55.2( 1 fo noitulos a oT
dna )2 × Lm 05( retaw htiw dehsaw dna )Lm 001( )b6( dica
etateca lyhte htiw detulid saw erutxim ehT .nim 03 rof C 0 o
cio-82-ene-21-sruyxoidenedilyhte-32,β3-yxordyH-α2
ta derrits saw erutxim noitcaer eht dna )lomm 35.0 ,Lm
1.0( rehte lytcolyhtemorolhc dedda saw )Lm 5( edimamrof .] M[ 005 e/m )IE( ssaM . mc
+ 1-
lyhtemid yrd ni )lomm 40.1 ,Lm 681( enimalyhtelyp 8961 ,2392 )taen( RI .)H 3 ,s( 57.0 ,)H 3 ,s( 50.1 ,)H 3 ,s(
-orposiid-N dna )lomm 25.0 ,gm 062( a6 fo noitulos a oT J
80.1 ,)H 3 ,s( 21.1 ,)H 3 ,zH 2.6 = ,d( 58.0 ,)H 3 ,zH 8.5
)a7( etao-82-ene-21 J J
= ,d( 59.0 ,)H 1 ,zH 1.01 = ,d( 91.2 ,)H 2 ,zH 1.01 = J
-sruyxoidenedilyhtem-32,β3-yxordyh-α2-lyhtemyxolytcO J
,qbA( 67.3 ,40.3 ,)H 1 ,zH 0.01 = ,d( 32.3 ,)H 1 ,zH 0.01
J J
,3.4 = ,td( 78.3 ,)H 2 ,zH 9.5 = ,dd( 59.4 ,)H 1 ,td( 46.3
.] M[ 825 e/m J 3
,)H 1 ,zH 2.3 = ,t( 42.5 δ ) lCDC ,zHM 003( RMN-H
+ 1
)IE( ssaM . mc 0021 ,8961 ,0443 )taen( RI .)H 3 ,s( 57.0
1-
.)%08 ,g 0.2( dilos
,)H 3 ,s( 40.1 ,)H 3 ,s( 60.1 ,)H 3 ,s( 90.1 ,)H 3 ,s( 54.1 ,)H 3
etihw a dleiy ot )1 : 02 = HOeM : lCHC( yhpargotamorhc
J
3 ,s( 64.1 ,)H 3 ,zH 4.6 = ,d( 58.0 ,)H 3 ,zH 4.6 = ,d( J nmuloc leg acilis yb deifirup saw eudiser eht dna erusserp
J
59.0 ,)H 1 ,zH 2.11 = ,d( 81.2 ,)H 1 ,zH 6.9 = ,d( 23.3 J decuder rednu detartnecnoc saw erutxim noitcaer
J
,)H 2 ,zH 8.01 = ,tetrauq BA( 15.3 ,64.3 ,)H 1 ,m( 87.3 eht ,noitcaer eht fo noitelpmoc retfA .syad 3 rof dexulfer
J 3
,)H 1 ,zH 2.3 = ,t( 42.5 δ ) lCDC ,zHM 052( RMN-H saw erutxim noitcaer ehT .)lomm 0.31 ,Lm 7.1( lCSMT
1
.)dleiy %78( enahteyxo dna )lomm 0.31 ,Lm 6.2( OSMD dedda erew )Lm 001(
-htemid-1,1 fo daetsni enaporpyxohtemid-2,2 fo noitazitlu FHT ni )lomm 81.5 ,g 35.2( dica citaisa fo noitulos a oT
eht tpecxe b6 sa emas saw dohtem citehtnys ehT )a6( dica
)d6( dica cio cio-82-ene-21-sruyxoidenedilyhtem-32,β3-yxordyH-α2
-82-ene-21-sruyxoidenedilyporposi-32,β3-yxordyH-α2
.noitacifirup lanoitidda tuohtiw desu erew
.] M[ 675 +
slacimehc elbaliava yllaicremmoc dna stnevlos llA .desu
e/m )IE( ssaM . mc 6961 ,7343 )taen( RI .)H 3 ,s( 77.0
1-
saw )hsem 032~07( 06 legleseiK kcreM .E ,yhpargot
J J
,)H 3 ,zH 4.6 = ,d( 58.0 ,)H 3 ,zH 1.6 = ,d(39.0 ,)H 3 ,s( -amorhc nmuloc hsalf roF .desu erew )mm 52.0 , FG 452
70.1 ,)H 3 ,s( 90.1 ,)H 3 ,s( 91.1 ,)H 1 ,zH 5.11 = ,d( 81.2 J 06 leg acilis( etalp CLT detaocerp kcreM ,sisylana )CLT(
J
,)H 1 ,zH 4.01 = ,d( 74.3 ,)H 2 ,zH 1.01 = ,qBA( 03.3 J yhpargotamorhc reyal-niht roF .retemortceps SM-CG 2
J
,09.3 ,)H 1 ,zH 2.3 = ,t( 42.5 ,)H1 ,s( 35.5 ,)H3 ,m( 53.7 -oirT GV a no dedrocer erew )SM( artceps ssam noituloser
3
-73.7 ,)H2 ,m( 94.7-25.7 δ ) lCDC ,zHM 003( RMN-H J
-woL .zH ni era RMN-H ni ) ( stnatsnoc gnilpuoC .RMN
1 1
.)dleiy %23( enahteyxohtemid 3
-H rof )62.7 δ( lCHC ro )05.2 δ( OSMD ot evitaler mpp
1
-1,1 fo daetsni eneznebllyhtemyxohtemid-1,1 fo noitazitlu ni detroper erew dna ,stnevlos sa - lCHC ro -OSMD d 3 6
d
755 tnegA gnilaeH dnuoW weN rof sevitavireD dicA citaisA fo ydutS pihsnoitaleR ytivitcA-erutcurtS

3. .] M[ 685 e/m )IE( ssaM . mc
+ 1-
5571 ,1292 ,0443 )taen( RI .)H 3 ,s( 47.0 ,)H 3 ,zH 3.6 = J .] M[ 046 e/m )IE( ssaM . mc 5371 ,8643
+ 1-
J
,d( 48.0 ,)H 3 ,zH 3.5 = ,d( 29.0 ,)H 3 ,zH 1.7 = ,t( 00.1 J J
)taen( RI .)H 3 ,s( 87.0 ,)H 3 ,zH 6.5 = ,d( 98.0 ,)H 3 ,zH
,)H 3 ,s( 50.1 ,)H 3 ,s( 80.1 ,)H3 ,s( 24.1 ,)H 3 ,s( 34.1 ,)H J
4.6 = ,d( 79.0 ,)H 3 ,s( 70.1 ,)H 3 ,s( 11.1 ,)H 3 ,s( 71.1
J J
1 ,zH 8.9 = ,d( 03.3 ,)H 2 ,zH 5.01 = ,qBA( 44.3 ,94.3 J J
,)H 1 ,zH 8.01 = ,d( 72.2 ,)H 2 ,zH 0.01 = ,qBA( 69.3
J
,)H 2 ,zH 1.7 = ,q( 46.3 ,)H1 ,m( 27.3-18.3 ,)H2 ,s( 12.5 J
,42.3 ,)H 1 ,zH 8.01 = ,d( 22.3 ,)H 1 ,s( 54.4 ,)H 2 ,zH
J 3
,)H 1 ,zH 2.3 = ,t( 52.5 δ ) lCDC ,zHM 003( RMN-H J J
0.9 = ,d( 49.4 ,)H 2 ,zH 0.6 = ,tetrauq BA( 82.5 ,22.5
1
.)dleiy %58( rehte J 3
,)H 1 ,zH 2.3 = ,t( 52.5 δ ) lCDC ,zHM 004( RMN-H 1
lytcolyhtemorolhc fo daetsni rehte lyhtelyhtemorolhc fo .)%1.42
noitazitlu eht tpecxe d7 sa emas saw dohtem citehtnys ehT ,g 54.1( dilos etihw a dleiy ot )1 : 03 = HOeM : lCHC( 3
)11( etao-82-ene-21-sruyxo yhpargotamorhc nmuloc leg acilis yb deifirup saw hcihw
-idenedilyporposi-32,β3-yxordyh-α2-lyhtemyxolyhtE ,dilos wolley thgil a evag erusserp decuder ta tnevlos fo
noitaropave dna noitartliF .etaflus muisengam suordyhna
.] M[ 045 e/m )IE(
+
revo deird saw esahp cinagro ehT .)Lm 06( noitulos
ssaM . mc 1021 ,2271 ,8543 )taen( RI .)H 3 ,zH 5.2 = J lCaN detarutas dna )3 × Lm 08( retaw htiw dehsaw saw
1-
J
,d( 17.0 ,)H 3 ,zH 4.6 = ,d( 97.0 ,)H 3 ,zH 0.6 = ,d( 88.0 J noitulos ehT .etatipicerp evomer ot deretlif saw erutxim
,)H 3 ,s( 89.0 ,)H 3 ,s( 30.1 ,)H 3 ,s( 60.1 ,)H3 ,s( 04.1 eht dna ,)Lm 003( etateca lyhte htiw detulid saw noitulos
J
,)H 3 ,s( 34.1 ,)H 1 ,zH 1.11 = ,d( 71.2 ,)H 1 ,zH 6.9 = ehT .h 2 rof dexulfer dna esiwpord )Lm 01( lC HC 2 2
J J
,d( 72.3 ,)H 2 ,zH 0.01 = ,qBA( 36.3 ,16.3 ,)H1 ,s( 24.4 suordyhna ni )lomm 64.9 ,g 80.6( a7 dedda saw erutxim
J 3
,)H 1 ,zH 2.3 = ,t( 91.5 δ ) lCDC ,zHM 004( RMN-H eht oT .erutarepmet moor ta nim 03 derrits saw )Lm
1
2 2
.)dleiy %56( d7 fo daetsni 9 fo 05( lC HC suordyhna ni )Lm 86.2( edirdyhna citeca dna
noitazitlu eht tpecxe d8 sa emas saw dohtem citehtnys ehT )lomm 65.7 ,g 36.1( etamorhcid muinidiryp fo noitulos A
)01( etao-82-ene-21-oxo )a8( etao-82-ene-21-oxo-2
-2-sruyxoidenedilyporposi-32,β3-yxordyh-α2-lyhteM -sruyxoidenedilyhtem-32,â3-yxordyh-α2-lyhtemyxolytcO
.] M[ 245 e/m )IE( ssaM . mc 1021
+ 1-
.] M[ 076 e/m )IE( ssaM . mc 3371
+ 1-
,4271 ,6643 )taen( RI .)H 3 ,zH 55.2 = ,d( 66.0 ,)H 3 J ,9643 )taen( RI .)H 3 ,s( 67.0 ,)H 3 ,zH 2.2 = ,d( 28.0J
J J
,zH 4.6 = ,d( 97.0 ,)H 3 ,zH 0.6 = ,d( 78.0 ,)H 3 ,s( 79.0 J
,)H 3 ,zH 55.2 = ,d( 58.0 ,)H 3 ,s( 40.1 ,)H 3 ,s( 70.1 ,)H
,)H 3 ,s( 00.1 ,)H 3 ,s( 20.1 ,)H3 ,s( 93.1 ,)H 3 ,s( 04.1 3 ,s( 01.1 ,)H3 ,s( 54.1 ,)H 3 ,s( 64.1 ,)H 1 ,zH 2.11 = ,d( J
J
,)H 1 ,zH 1.11 = ,d( 51.2 ,)H 1 ,zH 6.9 = ,d( 52.3 ,)H J J
52.2 ,)H1 ,m( 65.3 ,)H 2 ,zH 0.01 = ,qBA( 10.3 ,76.3 ,)H
J
2 ,zH 0.01 = ,qBA( 34.3 ,14.3 ,)H3 ,s( 35.3 ,)H1 ,m( 27.3 J
1 ,m( 28.3-37.3 ,)H 2 ,zH 2.6 = ,tetrauq BA( 61.5 ,91.5
J 3
,)H 1 ,zH 2.3 = ,t( 81.5 δ ) lCDC ,zHM 004( RMN-H J 3
,)H 1 ,zH 2.3 = ,t( 62.5 δ ) lCDC ,zHM 003( RMN-H
1 1
.)%58 .)dleiy %29( a6 fo daetsni d6 fo
,g 84.3( dilos etihw a dleiy ot )1 : 02 = HOeM : lCHC( 3 noitazitlu eht tpecxe a7 sa emas saw dohtem citehtnys ehT
yhpargotamorhc nmuloc leg acilis yb deifirup saw hcihw )d7( etao-82-ene-21 -sruyxo
,dilos wolley thgil a evag erusserp decuder ta tnevlos -idenedilyporposi-32,β3-yxordyh-α2-lyhtemyxolytcO
fo noitaropavE .h 2 rof derrits saw noitulos noitcaer
eht dna C 0 ta enahtemozaid fo ssecxe dedda saw )Lm
o
.]1+ M[ 817
+
05( rehte lyhteid ni )lomm 65.7 ,g 0.4( d6 fo noitulos a oT e/m )IE( ssaM . mc 0371 ,7963 )taen( RI .)H 3 ,s( 37.0
1-
)9( etao-82-ene J J
,)H 3 ,zH 2.2 = ,d( 28.0 ,)H 3 ,zH 06.2 = ,d( 48.0 ,)H
-21-sruyxoidenedilyporposi-32,β3-yxordyh-α2-lyhteM 3 ,s( 69.0 ,)H 3 ,s( 50.1 ,)H 3 ,s( 01.1 ,)H 1 ,zH 2.11 = ,d( J
J
23.2 ,)H1 ,m( 56.3 ,)H 2 ,zH 0.01 = ,qBA( 32.3 ,97.3 ,)H
.] M[ 866 e/m )IE( ssaM . mc 2371 J
1 ,m( 78.3-89.3 ,)H 1 ,zH 0.5 = ,q( 58.4 ,)H 2 ,zH 3.6 =
+ 1-
,3743 )taen( RI .)H 3 ,s( 77.0 ,)H 3 ,zH 2.2 = ,d( 28.0 J J J
,qBA( 73.5 ,54.5 ,)H 1 ,zH 2.3 = ,t( 25.5 ,)H3 ,m( 33.7
J
,)H 3 ,zH 5.2 = ,d( 58.0 ,)H 3 ,s( 60.1 ,)H 3 ,s( 80.1 ,)H 3
-53.7 ,)H2 ,m( 84.7-05.7 δ ) lCDC ,zHM 003( RMN-H 1
3 ,s( 21.1 ,)H3 ,s( 74.1 ,)H 3 ,s( 84.1 ,)H 1 ,zH 1.11 = ,d( J .)dleiy %29( a6 fo daetsni c6 fo
J
52.2 ,)H1 ,s( 14.4 ,)H 2 ,zH 0.01 = ,qBA( 10.3 ,76.3 ,)H noitazitlu eht tpecxe a7 sa emas saw dohtem citehtnys ehT
J
1 ,m( 28.3-37.3 ,)H 2 ,zH 2.6 = ,tetrauq BA( 61.5 ,91.5 )c7( etao-82-ene-21
J 3
,)H 1 ,zH 2.3 = ,t( 62.5 δ ) lCDC ,zHM 003( RMN-H 1
-sruyxoidenedilyzneb-32,β3-yxordyh-α2-lyhtemyxolytcO
.)dleiy %56( a7 fo daetsni d7 fo
noitazitlu eht tpecxe a8 sa emas saw dohtem citehtnys ehT .] M[ 656 e/m )IE( ssaM . mc 2371 ,7292
+ 1-
)d8( etao-82-ene-21-oxo-2-sruyxo ,1843 )taen( RI .)H 3 ,s( 27.0 ,)H 3 ,zH 2.2 = ,d( 28.0 J
J
-idenedilyporposi-32,β3-yxordyh-α2-lyhtemyxolytcO ,)H 3 ,zH 65.2 = ,d( 48.0 ,)H 3 ,s( 59.0 ,)H 3 ,s( 00.1 ,)H
gnoeJ .S-.B 855

4. fo puorg lykla eht nopu tnedneped saw tceffe gnilaeh
dnuow fo noitairav eht ,yteiom enotek a ot detrevnoc
si HO-)2(C eht nehW .tluser suoiverp ruo htiw tnetsisnoc .)etis/gm 05 yletamixorppa(
2 2 2
si hcihw ,) mc/g 563 :9 ; mc/g 563 :11 ; mc/g 733 :d7( baws nottoc a htiw tnemtnio sa deilppa erew selpmas
ytivitca gnilaeh-dnuow eht decuder retse yklub ehT .puorg ehT .delaeh yletelpmoc saw dnuow eht litnu yliad
2
R OC-)82(C eht ni puorg lykla eht yb detceffa ylraelc osla 001
sevitavired edisocitasa htiw detaert saw tar hcaE .) TH(
si tceffe gnilaeh dnuow ehT .) mc/g 503( lortnoc eht naht
2
emit gnilaeh si dnuow eht fo gnilaeh etelpmoc rof emit
ytivitca rehgih %01 dewohs ) mc/g 733 ;d7( evitavired 05
eht dna ) TH( emit gnilaeh %05 si delaeh eb ot puorg
2
lateklyhtemid eht ,yllaicepsE .lortnoc eht naht htgnerts tnemtaert hcae ni dnuow eht fo %05 rof emit ehT .delaeh
elisnet rehgih ylthgils ro elbarapmoc dewohs )d-a7( yletelpmoc saw dnuow eht litnu slavretni syad 2 ta repilac
sevitavired latek eht ,yllareneG .lortnoc eht revo ytivitca htiw derusaem saw dnuow fo aera ecafrus ehT .gnidnuow
gnilaeh dnuow decnahne wohs ton did flesti )2( dica gniwollof segac etarapes ni deniatniam erew star ehT
citaisa ,yldetcepxenu ,I elbaT ni nwohs sA .)7691 ,etluhcS ,I .lonahte %07 htiw denaelc yltneg erew yeht ,skcab rieht
elbaT( dohtem dehsilbup eht ot gnidrocca tnemges dnuow no edam erew sdnuow eht retfA .edam erew mc 8.0×8.0
eht morf spirts niks fo htgnerts elisnet eht gnirusaem yb fo sdnuow nepo erauqs owt dna ,denaelc dna devahs
detaulave saw )2( dica citaisa htiw gnola )21-9 ,d,a8 ,d-a7( erew )g 02 ± 002( star yelwaD-eugarpS elamef fo skcaB
sevitavired deraperp eht fo ytivitca gnilaeh dnuow ehT sdnuow nepO
.ylevitcepser ,noitalyhtemyxolyhte
dna enahtemozaid fo ssecxe na gnisu noitalyhtem yb .)etis/gm 05 yletamixorppa(
d6 morf deniatbo ylevitcepser ,11 dna 9 ,slohocla gnidnop baws nottoc a htiw tnemtnio sa deilppa erew selpmas
-serroc eht fo noitadixo CDP yb deraperp osla erew 21 ehT .noitarepo fo yad eht morf gnitrats syad evitucesnoc
dna 01 sdnuopmoC .)CDP( etamorhcid muinidiryp gnisu 6 rof noisicni eht fo setis ta yllacipot deretsinimda erew
noitadixo eht yb ,ylevitcepser ,d7 dna a7 morf deraperp sevitavired edisocitaisA .ecrof marg ni tuodaer latigid htiw
erew d8 dna a8 sdnuopmoC .d-a7 evag ,H OC-)82(C 2 retemoehR a yb derusaem saw htgnerts elisneT .dnuow
fo noitalyhtemyxolytco yb dewollof ,dica cinofluseneulot eht dnuora aera eht morf desicxe saw htiw 3 dna htgnel
p
- fo ecneserp eht ni slatekyxohtemid gnidnopserroc ni mc 1 gnirusaem niks lasrod fo pirts a dna devomer
eht gnisu yb ,2 fo HO-)32(C dna HO-)3(C fo noitamrof saw kcab eht fo niks eht ,syad 6 retfa dellik erew slamina
latek ehT .)0002 ,weJ( 21 ,11 ,d7 fo sisehtnys eht rof ehT .noitarepo eht retfa syad 4 devomer saw erutus
serudecorp nwonk eht detpada eW .)1 emehcS( acitaisa ehT .gnidnuow gniwollof segac etarapes ni deniatniam
alletneC fo tcartxe detartit eht morf deniatbo ylisae erew star ehT .desu erew seldeen devruc dna daerht
eb dluoc hcihw ,2 morf deraperp erew sdnuopmoc neT lacigrus enelyhteylop kcalB .trapa mc5.0 sehctits htiw
.yteiom retse na ot detrevnoc saw dica cilyxobrac-)82(C serutus suounitnoc htiw desolc erew sdnuow ehT .edam
eht ,oslA .enotek a ot demrofsnart saw HO-)2(C eht dna saw noisicni niks raenil lasrod mc 2 a ,aisehtsena rehte
spuorg latek ot deifidom erew HO-)32(C dna HO-)3(C eht rednu yad noitarepo nO .lonahte %07 htiw denaelc dna
,spuorg lanoitcnuf eseht gnomA .yticilihpopil eht dnetxe sreppilc lamina htiw devahs erew skcab rieht dna rehte
ot dennalp erew snoitacifidom lacimehc ehT .)82(C htiw dezitehtsena erew slamina ehT .derised sa retaw pat
ta puorg dica cilyxobrac a dna ;)21(C ta puorg nifelo dna doof kcots dilos nevig erew dna snoitidnoc dellortnoc
na ;)32(C dna ,)3(C ,)2(C ta spuorg yxordyh eerht :spuorg rednu tpek erew slamina ehT .seiduts eseht ni desu erew
lanoitcnuf fo sdnik eerht sah )2( dica citaisa ,yllarutcurtS g 02 ± 002 gnithgiew star yelwaD-eugarpS elameF
sdnuow lanoisicnI
NOISSUCSID DNA STLUSER noitaulave ytivitca lacigoloiB
t
.tset s'tnedutS gnisu ecnacifingis rof dezylana erew atad .] M[ 485 e/m )IE( ssaM
+
ehT .sdnuow retfa syad xis no nekat erew shpargotohp . mc 557 ,7271 ,4292 )taen( RI .)H 3 ,s( 77.0 ,)H 3 ,zH 6.6
1-
,sdnuow lanoisicni nI .ecnatsid dradnats a ta nekat erew J J
= ,d( 78.0 ,)H 3 ,zH 1.6 = ,d( 59.0 ,)H 3 ,zH 1.7 = ,t( J
shpargotohp ,gnidnuow retfa syad neetfif dna neves ,eno no J
72.1 ,)H 3 ,zH 1.7 = ,t( 10.1 ,)H 3 ,s( 50.1 ,)H 3 ,s( 51.1
,sdnuow nepo nI .sisylana rof degareva dna srotagitsevni J
,)H3 ,s( 34.1 ,)H 3 ,s( 25.1 ,)H 1 ,zH 1.7 = ,q( 66.3 ,)H
eht fo owt yb yletarapes dengissa erew serocs ehT .racs J
2 ,zH 7.01 = ,qBA( 96.3 ,95.3 ,)H 1 ,s( 04.4 ,)H2 ,s( 32.5
egral ot gnidnopserroc 0 dna racs on tsomla ot gnidnop J 3
,)H 1 ,zH 2.3 = ,t( 62.5 δ ) lCDC ,zHM 003( RMN-H 1
-serroc 3 htiw ,3 ot 0 morf gnignar erocs a nevig saw .)dleiy %58( d7 fo daetsni 11 fo
dnuow hcaE .dnuow delaeh yletelpmoc hcae rof edam noitazitlu eht tpecxe d8 sa emas saw dohtem citehtnys ehT
saw yrevocer fo ytilauq eht fo tnemssessa lausiv A )21( etao-82-ene-21-oxo-2-sruyxo
-idenedilyporposi-32,β3-yxordyh-α2-lyhtemyxolyhtE
tnemssessa lausiV
955 tnegA gnilaeH dnuoW weN rof sevitavireD dicA citaisA fo ydutS pihsnoitaleR ytivitcA-erutcurtS

5. tsehgih eht detibihxe 21 ,ylgnitseretnI .II dna I selbaT ni 05
gnilaeh dnuow laicremmoc ehT .)syad 81.6 : TH( lortnoc
nwohs era syassa htob ni sevitavired eht fo stnemssessa eht naht retsaf %8 laeh dluoc hcihw ,)syad 76.5 : TH( 05
lausiv ehT .)8991 ,lokkavaT( etadidnac eht fo noitceles eht 21 rof tpecxe semit gnilaeh eht ni secnereffid tnacifingis
rof tset tnemssessa lausiv a deyolpme osla ew ,stcepsa on erew ereht ,2 elbaT ni nwohs sA .)9691 ,tnuH( dohtem
citemsoc ot tcepser htiw tnatropmi etiuq si gnilaeh aera dnuow eht yb demrifnoc erew 11-9 fo esoht htiw
retfa gnirracs ssel osla tub ytivitca gnilaeh dnuow gnorts gnola 21 fo stceffe gnilaeh dnuow decnahne ehT .%3 yb
dna tsaf eht ylno ton ecniS .ssecorp gnilaeh dnuow eht desaercni )21( evitavired retse lyhtemyxolyhte fo taht tub
ni negalloc fo noitcudorp ssecxe eht yb desuac gnirracs fo ,ylevitcepser ,ytivitca ssel %9 dna %7 dah )9( sevitavired
noitneverp eht rof desu ylralupop si ,®lossacedaM ,tnega retse lyhtem dna )d7( lytemyxolytco ehT .R OC-)82(C 2
2 2 2
.%58 ,h 2 ,xulfer , lC HC ,CDP )iiv ,%58 ,h 5.0 ,C°0 ,FMD ,tEN rP
i 2 5 2 2 2 2 2 2 2
- ,lC HCO H C )iv ,%56 ,h 2 ,xulfer , lC HC ,CDP )v ,%58 ,h 1 ,C°0 , N HC ssecxe )vi ,%56-42 ,h 2 ,xulfer , lC HC ,CDP )iii ,%29-24 ,h 5.0 ,C°0
2 i 2 71 8 2 3
,FMD ,tEN rP- ,lC HCO H C )ii ,%78-23 ,h27-h2 ,FMD ,)tac(ASTP , ) HCO(C’RR ro FHT ,OSMD ,lCSMT )i :snoitidnoc dna stnegaeR .1 emehcS
gnoeJ .S-.B 065

6. ,.M .J ,tahevedeL dna ,.M ,ceraolC ,.H ,nolaccoB ,.P .J ,letnioP
.)b7691( 424-414 ,.locamrahP
.J .ruE .oviv ni dna ortiv ni niks nopu edisocitaisa fo stceffe .10.0<P** ,50.0<P* .E.S ± naem eht stneserper eulav
lacigolocamrahp dna lacigolohprom ehT ,.C .J ,ecnerwaL hcaE .sisylana rof degareva erew dna srotagitsevni eht fo owt yb
yletarapes dengissa erew serocs ehT .racs egral a ot gnidnopserroc
.)a7691( 69-59 ,94 ,.lotamreD .tsevnI 0 dna racs on tsomla ot gnidnopserroc 3 htiw ,3 ot 0 morf gnignar
.J .niks gip aeniug no edisocitaisa fo tceffe ehT ,.C .J ,ecnerwaL serocs nevig erew dnuow delaeh yletelpmoc hcae fo shpargotohPc
.)0002( 121-911 ,01 ,.tteL .10.0<P**
.mehC .deM & .grooiB .yticixotoruen decudni-)βA( diolyma ‚β ,50.0<P* .E.S ± naem eht stneserper eulav hcaE .)05TH( emit gnilaeh
tsniaga sevitavired edica citaisA fo yduts pihsnoitaler ytivitca % 05 eht si delaeh eb ot puorg tnemtaert hcae ni dnuow eht fo
-erutcurtS ,.G-.H ,kraP dna ,.H ,miK ,.h-.Y ,gnuJ ,.H ,iohC ,.M %05 eht rof emit ehT .delaeh yletelpmoc saw dnuow eht litnu slavretni
,gnuJ ,.I ,gnuJ-kooM ,.H ,miK ,.Y .D ,miL ,.H .J ,ooY ,.S .S ,weJ yliad ta srepilac htiw derusaem saw dnuow eht fo aera ecafrus ehTb
.)6991( 031-721 ,247 ,yhpargotamorhC .J .acitaisa .doirep latnemirepxe
eht gnirud yad a ecno sdnuopmoc detset eht fo tnemtnio %1 a fo
alletneC ni stneutitsnoc evitca yllacigoloib fo noitanimreteD gm 05 htiw yllacipot detaert saw dna ,tar hcae ni edam saw mc 8.0 ×
,.J .N ,azuoS ed dna ,.B .A ,eragohG ,.D .R ,eloeY ,.K .P ,radmanI 8.0 fo dnuow nepo ,erauqs A .star erom ro 02 deniatnoc puorg hcaEa
.)9691( 146-336 ,071
,.gruS .nnA .nam dna slamina ni sdnuow nepo fo gnilaeh **01.0 ± 76.2 51.0 ± 76.5 21
no enositroc fo tceffe yrotibihni eht gnisrever no A nimativ fo **11.0 ± 40.2 80.0 ± 70.6 11
tceffE ,.E .J ,yhpnuD dna ,.A .J ,aicraG ,.P .H ,hcilrhE ,.K .T ,tnuH **01.0 ± 33.2 90.0 ± 10.6 01
.)1491( 191-681 ,94 **11.0 ± 26.2 02.0 ± 11.6 9
,.locamrahP .icS .lluB )earefillebmU( .L acitaisa elytocordyH *80.0 ± 77.1 21.0 ± 99.5 2
morf detalosi ,edisocitaisa ,edisoreteh wen A ,.E .J ,smetnoB 80.0 ± 05.1 42.0 ± 81.6 lortnoc
)5991( 24-83 ,35 ,.rF .mrahP tnemssessa lausiV )yad( TH 05 dnuopmoC
c b a
.nnA .noiterces negalloc III dna I epyt tsalborbif namuh
no seitivitca evitarapmoc edisossacedam dna edisocitaisA star ni dnuow denepo yllatnemirepxe
fo gnilaeh eht no sevitavired dica citaisa fo tceffE .II elbaT
,.A ,kcebyeM dna ,.C ,engaduahC ,.M ,samuD ,.F ,etnoB
.)1791( 509-798 ,61 .10.0<P** ,50.0<P* .E.S± naem eht stneserper eulav
,.loiB .nilC .dutE .ruE .veR .ANR etalpmet yb sdica onima-L fo hcaE .sisylana rof degareva erew dna srotagitsevni eht fo owt yb
gnidnib eht ni senepretirt fo eloR ,.N ,elliapaV dna .M ,iksnajleB yletarapes dengissa erew serocs ehT .racs egral a ot gnidnopserroc
0 dna racs on tsomla ot gnidnopserroc 3 htiw ,3 ot 0 morf gnignar
SECNEREFER serocs nevig erew dnuow delaeh yletelpmoc hcae fo shpargotohPc
.10.0<P** ,50.0<P*
.yassa .E.S ± naem eht stneserper eulav hcaE .tuodaer latigid a htiw
lacigoloib eht rof kraP eeH nuE .forP knaht yllaiceps )napaJ ,oygoK hoduF( retemoehR a yb derusaem saw htgnerts elisneTb
ot ekil dluow I .ytisrevinU lanoitaN luoeS ,ycamrahP .doirep latnemirepxe eht gnirud yad a ecno sdnuopmoc detset eht
fo tnemtnio %1 a fo gm 05 htiw yllacipot detaert saw dna ,tar hcae
fo egelloC eht ni secneicS lacituecamrahP fo etutitsnI ni edam saw noisicni niks enO .star erom ro 02 deniatnoc puorg hcaEa
hcraeseR eht dna ,.dtL .oC lacituecamrahP kooK gnoD
,ytisrevinU lanoitaN luoeS fo tnempoleveD gurD weN fo **
41.0 ± 28.2 421 23 ± 773
*
22 21
retneC hcraeseR eht yb detroppus saw hcraeser sihT *31.0 ± 00.2 021 51 ± 563
*
12 11
*
41.0 ± 03.2 901 81 ± 333 32 01
STNEMEGDELWONKCA **
51.0 ± 14.2 021 72 ± 563 91 9
11.0 ± 77.1 201 72 ± 013 12 d8
.yawrednu yltnerruc era seiduts lacinilcerp dna **
21.0 ± 32.2 021 32 ± 763
*
81 a8
sisehtnysoib negalloc htiw detaicossa yduts citsinahcem 41.0 ± 82.1 011 02 ± 733 22 d7
A .tnega gnilaeh dnuow wen a rof etadidnac a sa 41.0 ± 38.1 601 81 ± 323 12 c7
21 poleved ot su segaruocne gnidnif sihT .racs tsellams 41.0 ± 60.2 201 42 ± 113 91 b7
*
eht sevael ti eromrehtruF .ytivitca gnilaeh dnuow tsetsaf
eht dna htgnerts elisnet tsehgih eht dewohs 21 ,meht *
02.0 ± 24.2 601 91 ± 223 32 a7
gnomA .)2( dica citaisa fo sevitavired citehtnys-imes htiw *
21.0 ± 69.1 691 12 ± 392 12 2
demrofrep saw yduts RAS dnoces eht ,noisulcnoc nI 80.0 ± 33.1 001 91 ± 503 52 lortnoc
.sisehtnysoib negalloc fo lortnoc eht ot eud c
tnemssessa eulav ) mc/g(2 N dnuopmoC
lausiV evitaleR htgnerts elisneT a
b
eb thgim tnemssessa lausiv eht ni 21 fo noitaulave hgih eht
,racs a sevael ssecorp gnilaeh eht ni negalloc fo noitcud yad evitarepotsop ht5 eht no sdnuow fo ecnaraeppa gnilaeh
-orp ssecxe eht taht gniredisnoC .syassa htob ni erocs dna htgnerts elisnet no sevitavired dica citaisa fo stceffE .I elbaT
165 tnegA gnilaeH dnuoW weN rof sevitavireD dicA citaisA fo ydutS pihsnoitaleR ytivitcA-erutcurtS

7. .)8991( 932-132 ,93 ,sititamreD .deM .nettaR ieb nednuwtuaH rednelieh tiekgitsefieR
tcatnoC .ecim sselriah desopxe-otohp dna lamron red ynummitseB ruz edohteM ,.R ,zojnemoD dna .R ,etluhcS
fo niks eht no stnatcafrus fo esu degnolorp fo stceffe ehT ,.G .)8791( 297-987 ,682 ,]D[ .icS .dacA
.T ,akfeloP dna ,.rJ ,.M .B ,nosirroM ,.L ,namgnilK ,.A ,lokkavaT .gnilaeh fo noitarud eht no sevitavired sti dna dionepretirt
.)6991( 0492-7392 ,6 ,.tteL .mehC a fo noitcA .tar eht ni siserexe evitareti retfa gnilaeh
.deM .grooiB .tnega gnilaeh dnuow sa scitemim edisocitaisA fo scitenik eht fo noitacifidoM ,.R .C .D ,zemuD ,.A ,tozioP
,.D-.H ,miK dna ,.H-.E ,kraP ,.s-.S ,weJ ,.H-.Y ,gnuJ .)7891( 05
,.H-.D ,miK ,.J-.M ,miL ,.S-.M ,gnahC ,.H-.J ,kraP ,.J-.P ,mihS -64 ,83 ,ygoloignA .sbmil rewol eht fo ycneiciffusni suonev fo
.)7691( 354 ,61 ,.pxE .locamrahP tnemtaert eht ni )ACET( acitaisa alletneC fo tcartxe detartiT
gnoeJ .S-.B 265