Hpi thdo khoa hgc ftjJ nigm 40 ndm th&nh ldp Vifn Hdn ldm KH&CN Vift Nam
SARCOPHITOLIDE I, SARCOPHITOLIDE J VA SARCOPHITOLIDE L,
BA Hgfp C H A T B I S C E M B R A N O I T P H A N L ^ DlTgfC Ttr LOAISAN HO MEM SARCOPHYTON PAUCIPLICATUM
Ninh Thj Ngpc', Ph?m Thi Tiing'^, Trin Thi HSng Hjnh', Ngay?n VSn Thanh', NguySn XuSn Cuing*, Nguyen Hoai Nam'', Tran Thn Hmmg', Do Cong Thung^, Chau VSn Minh'
'Vipn H6a sinh bien, Vi?n Hin lim Khoa hpc va C^ng nghp Vipt Nam (VAST)
^ i § n K? thuit Hda hpc, Dgi hpc Bich khoa Hi Npi
^ i ^ Tii nguygn vi Moi trudng biln, VAST Abstract
Three biscembranoids namely sarcophytolide I (1), sarcophytolide J (2), and sarcophytolide L (3) were isolated [bom the soft coral Sarcophyton pauciplicatum by repeated chromatographic experiments. Their structures were [elucidated by spectroscopic methods including one dimensional nuclear magnetic resonance (ID-NMR), two [dimensional nuclear magnetic resonance (2D-NMR), and electrospray ionization mass spectrometry (ESI-MS).
Keywords. Sarcophyton pauciplicatum, Alcyoniidae, soft coral, biscembranoid.
.M6DAU
San hd mim li d$ng vgt khdng xuong s6ng bupc b$ Alcyonacea, Idp Anthozoa vi nginh iiiidaria. Cic loii d^ng v§t khSng xuong song niy k ngudn cung cip ddi dio cic hgp chit tiao doi th^
ip nhu diterpenoid v i hydroxy sterol [1]. Cic loii lan hd mdm thuQc cic gidng Lobophytum, tarcophyton v i Sinularia l i pho bien nhit [2]. Cic o&i san hd mim thuOc gidng Sarcophyton d i dugc ighien cuu khi nhidu [2-4], tuy nhiSn hi^n chua cd
" og tiinh nao cong bd vd thinh phan h6a hpc ctia li S. pauciplicatum.
Trong Idiuon kho cic nghien cum ciia nhom tic i vd thioh phin hoa hpc v i hogt tinh sinh hpc cua
; loii san ho mdm sinh sdng tgi cic vung bien cua
^ Nam, chdng toi d i cdng bd mu£ri hpp chit icembranoit tii lo^i san hd mdm S. pauciplicatum
dinh gii ho^it tinh giy d^c td bio cua chii^ [5].
ong cdng trhih niy, chung toi cdng bo chi tiet qui A xic dinh cau trie ciia ba hgp chit icembranoidoit phin I§p ti^ loii 5". paudplicatitm.
rHUCNGHI$M 1. Thidt b t v i h 6 a chit
Phd 'H NMR (500 MHz) vi "C NMR (125 Hz) BC do tren miy Bruker AM500 FT-NMR vdi S dugc sii dyng lim chit chuin n^i. Phd khdi ig phun mil dipn tft (ESI-MS) dugc do tr6n may
Agilent 1260 series single cpiadmpole LCVMS. Sic k^ long trung &p (MPLC) dupc tiin hanh tren miy Biotage -Isolera One system (SE-7S1 03 Uppsala, Thvy Didn). SSc k^ c§t (CC) s^ dyng silica gel (Kieselgel 60, 70-230 mesh and 230-400 mesh, Merck) vi YMC RP-18 (30-50 gxn, Fuji Silysia Chemical Ltd). Sac ky ldp mdng (TLC) su dyng bin tring sin sihca gel 60 Fz54 (1.05554.0001, Merck) vi RP-18 Fz54s pUtM (1.15685.0001, Merck). V$t chit dugc phit bi$n bing cich phun ddu thudc thiic axit H!S04 10% vi ha ndng tvc ti^ ddn khi hi^nmiu.
2.2. MSU san hd mdm
MIU loai san hd mdm i^. pauciplicatum Verseveldt & Benayahu dugc thu tgi H4i Phdng, vio thing 11 nim 2013 vi dugc PGS TS DS Cdng Thung giim djnh. MIU tiSu bin dugc luu tgi Vi§n Hda sinh bidn va Vi$n Tii nguyen v i Mdi trudng bidn.
2 3 . Phin lip cic hpp chat
Miu Idid san hd mdm S. pauciplicatum (1,0 kg) xay nhd va chidt 03 lin vdi MeOH d nhi^t dO phdng (mSi Ian 7 ngiy) thu dugc cjln chiet MeOH tdng (70,0g, A). C§n niy dugc hda vao nude (1,5 L) vi chidt phin Idp lan lugt vdi n-hexane (3x0,8 L) vi CH2CI2 (SJ'O.S L ) thu du(;K; cac c^n chidt n-hexane (20,1 g, B) v i CH2CI2 (35,0 g, C). O n chiet CH2CI2
Ba dgng sinh hgc vd cdc ckdt cd hogt tinh sinh hgc
dugc tidn hinh phan tich thd bing hp thdng sic I^
Idng tnmg ip vdi cpt nhdi silica gel pha thudng rija giii gradient ndng dg ediyl acetate trong n-hexane (tCt 0 i ^ 100%) thu dupc biy phan dogn (C-l^C- 7). Phin dogn O^ (7,5 g) dugc phin tach tidp bing h§ thdng s5c k^ long trung ip vdi c^t pha dao YMC RP-18 sic dyng pha dOng li methanol-IfcO (4:1) thu dugc biy phin dogn k^ hi^u C6A-C6G. Phan dogn C6C (1,2 g) dugc phin tich tidp bing sic 1^ c$t sihca gel pha thudi^ rua glii vdi n-hexane-acetone (2:1) thu dugc biy phin dogn nhd hon ky hi|u C6CI-C6C7. Phin dogn nhd C6C5 (200 mg) dugc tinh chd bing sic ky c$t silica gel pha thudng nJca giii bingn-hexane-ethyl acetate (5:1), ket hpp vdi sic ky cdt silica gel pha dio YMC KP-18 nia giii bSug methanol-HzO (5:1) thu dugc cac hpp chit 1 (7,1 mg) vi 2 (4,8 mg). Phin dogn C-7 (15,5 g^ dugc phSn tich thinh 6 phSu dogn, C7A-C7F, bSng hp thdng sic k^ ldng tmng ip vdi c$t nhdi silica gel pha dio RP-18 sii dyn^ pha dpng liacetone-HzO(tu 1:2 ddn 3:1). Tioh che phin dogn C7E (0,75 g) bSng sic k^ c$t silica gel pha thudng sit dyng hp dung mdi nia ^ i i n-hexane-ethyl acetate (1:2), CHiCIi-MeOH (8,5:1), kdt hgp vdi sic 1^ cpt silica gel pha dio YMC RP-18 nia giii bing MeOH-IfcO (2:1) thu dugc hgp chit 3 (6,6mg).
SarcophytoUde 1 (1): Chit bpt mau tring; [ajo"
+ 48' (c=0,10, CHCh); 'H-NMR (500 MHz, CDCU) and '*C-NMR (125 MHz, CDCb). xem bing 1; ESI- MS: m/z 719 [M+Na]* (C42H«Og, M= 696).
Sarcophytohde J (2): Chit bijt miu tring; [ajo"
+ 60" (c=0,10, CHCb): 'H-NMR (500 MHz, CDCb) and "C-NMR (125 MHz, CDCU), xem bing 1; ESI- MS: m/z 237 [M-H]- (C15H26O2, M = 238).
SarcophytoUde L (3): Oiit b^t miu tring; [ajo"
+ 25" (c=0,10, CHCb); 'H-NMR (500 MHz, CD3OD) and "C-NMR (125 MHz, CD3OD), xem bing 1; ESI-MS: m/z 723 [M+Na]* (C11HS4O9, M=
700).
3. K 6 T Q U A VA THAO LUAN
Hgp chit 1 ciing dugc phan Igp dudi dgng chat bpt miu trine. Cic phd NMR cua nd ^ trung cho mpt hgp ch^ biscembranoit. So sinh so Upu ph^
NMR cda 1 vdi cic so U ^ tuong ung cua cic hpp chit biscembranoit di dugc cdng bd [6, 7] cho ph^p xic djnh cic hgp chit niy cd ciing cau trdc vong A sd Ufu phd cua vdng B-D cho thiy sy tdn tgi ciia hai USn kdt ddi hi thd ba v\ tri, m^t hen kdt doi bj tiie hoin toin, ba nhdm oximetin, mpt cacbon b$c hdn mang dxi vi bon nhdm metyl bic ba. Ngoai 40 tin hi$u cacbon cua phin khung biscembranoit, tren cac phd NMR ciia 1 cdn xuit hi§n cic tfn hipu ciia m^t nhdm metoxi tgi 5c 55,57 vi 5H 3,14 (3H, s). Tren phd ESI-MS xuit hifn pic ion phin tii tgi nt^ 719 [M+Na]* (phi hgp vdi cdng thiic C^zHwOg, M=
696). Tirong tac HMBC giiiB proton metoxi (5K 3,14) vdi C-33 (6c 80,26) khing djnh vi tri USn ket ciia nhdm metoxi t^i C-33. PhSn tich chl tiet cic tuong tic HMBC khac (hhih 2) cho phdp khing dinh chlnh xic ciu trie phing ciia hgp chit 1. So sinh s6 Ufu phd '^C-NMR cua 1 do hong CDCb vdi cic s6 lifu tuong ling cda hgp chit sarcophytoUde I [8] do trong DMSO-f/s nhgn dugc sy phii hpp. Tay nliien, 6 mOt sd vi tri vin cd s^ chSoh Ifch khi ldn, (£eu n^y Ii do inh sy Idiic nhau vd dung mdi sii d;mg d^ do phd.
c i u tnic hda I|p did ciia hgp chit 1 dugc xic djnh bing kdt qui phd ROESY. Tuong tic ROESY nh§n dugc giiia H-38 (5H 1.92) vi H-21 (5H 3,90)ffl- 26 (5M 4,04) chiing minh cho ciu hlnh a ciia H-26, Proton H-33 (5H 4,44) cd tuong tic ROESY vdi H- 22 (5H 5,24) vi H-30 (6H 3,58) xic djnh cho c3u Wnh p cua H-33 vi H-30. Khdng cd tuong tic ROESY nio dupc ghi nh§n gifta H-30 (5H 3,58) vi ^ H-40 (5H 1,03) cho phdp xdc djnh ciu hinh cia' nhdm OH tgi C-31. Nhu v§y, hgp chat 1 dupc xac dinh li sarxxiphytoUde I.
2 / V." 3 Hinh 1: Ciu tnic hda hgc cita cic hgp chit 1-3
152
H^i thdo khoa hgc 1^ ni^m 40 n&m th&nh lap Vi$nHan l&m KH&CN Vi$tNam
Bang 1: S6 li§u ph6 'H-NMR (500 MHz) vi '^C-NMR (125 MHz) ciia cac hgrp chSt 1-3 va cic chit fiiamkhao
Q 1 2 3 4 5 6 7 8 9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31 32 33 34 35 36 37 38 39 40 41 DMe
1' 6c 48,40 46,29 212,21 49,71 26,26 36,19 23,74 32,34 47,05 213,75 37,21 51,11 213,66 48,26 29,42 19,04 20,67 16,70 21,73 174,37
39,85 123,38 141,28 38,95 24,80 79,66 134,44 120,43 32,79 68,45 73,88 42,04 80,26 128,40 128,26 34,14 18,77 19,59 20,36 22,67 51,35 55,57
aH(y=Hz)
-
4,04 m 2,26 dd (4,5,18,5) 2,44 dd (7,5,18,5) 2,01m 0,90/1,20 m 0,97 m 1,39/1,61 2,37 m 2,20/2,88 m 2,88 m-
3,14 d (19,5) 3,28 d (19,5) 1,86 m 0,83 d (7,0) 0,92 d (7,0) 1,15 d (7,0) 0,88 d (7,0)-
3,90 dd (2,0,11,5) 5,24 d (11,5) 1,90/2,62 m 2,11m 4,04 m-
5,57 brs 1,82 m 3,58 m-
1,58 d (3,5) 1,76 d (2,5) 4,44 d (10,5)_
1,90 m/2,75 m 1,80 s 1,92 s 1,66 s 1,03 s 3,56 s 3,14 s2"
8c 49,93 48,38 213,64 53,77 27,44 37,63 25,68 34,19 47,89 213,41 31,29 51,09 209,40
46,20 28,89 17,86 21,31 17,63 22,03 174,54 46,76 122,13 138,46 37,41 33,57 79,93 135,06 118,95 24,81 67,19 77,57 37,68 122,91 131,17 136,64 123,44 19,86 19,82 20,42 23,87 51,32
8 H ( / = H Z )
-
4,06 m-
2,47/3,17 m 1,79 m l,62«,66m 1,04/1,29 m 1,48 m 2,47 m 1,89/2,94 m 2,99 m-
2,67 d (19,0) 3,10 d (19,0) 2,26 m 0,71 d (7,0) 0,98 d (7,0) 1,09 d (7,0) 0,85 d (7,0)-
3,37 m 4,79 d (10,5)-
1,04 m 1,69 m 3,88 d (5,5)-
5,46 brs 1,79/2,03 3 J 7 m-
2,12/2,40 m 5,76 d (9,0)-
5,17 brs 1,86 s 1,83 s 1,59 s 1,20 s 3,58 s3"
6c 51,45 45,10 213,83 55,20 28,55 38,64 26,79 34,99 48,49 216,83 32,50 53,26 211,24 46,82 29,96 17,83 21,66 17,85 22,65 176,71 44,94 126,36 139,61 41,19 26,72 80,82 71,74 38,32 18,76 81,76 75,68 42.87 66,52 133,61 129,34 33,88 18,83 15,70 22,78 19,88 51,65
6H(y=Hz)
-
3,641(8,5)-
2,43/3,221(10,5) 1,78 m 1,07 m 1,59/1,66 m 1,50 m 2,50 m-
1,97/2,94 m 3,02 m-
2,97 m 2,34 m 0,74 d (7,0) 1,03 d (7,0) 1,15 d (7,0) 0,88 d (7,0)-
3,39 m 4,99 d (11,0)-
2,04/2,36 m 1,15/1,29 m 3,29 m-
1,55/1.78 m 1,59/1,97 m 3,27 m-
1,38 dd (1,5,14,5) 2,57 dd (6,0,14,5) 4,93 dd (2,0,10,5)-
2,15 dd (8,5,19,0) 2,37 m 1,83 s 1,69 s 1,10 s 1,07 s 3,52 s Mo irong CDClj, 'do Irong CDjOD.Ba d^itg sink hgc va cdc chSt c6 hoot tinh sink hgc
Hinh 2: Cac tirong tdc HMBC chinh cila 1-3 H Q P chat 2 cQng dugrc phan l^p du6i d^ng chat
bQt m i u t r ^ g . C&c s6 li^u pho N M R cia DO tuong tif n h u cdc sd t i ^ phd b i o i ^ iJcng cua 1. S\f khac bift d§ nh$ii thSy nhat H s\i init di c ^ tin hi$u c ^ nhdm metoxi vS s\i xu^t hi^n cdc tin hi^u cia bai lien ket ddi bi the hai vi tii tr£n cdc phS cik 2 tbay cho m$t liSn k i t ddi bj th^ hoan toan v i m$t iih6ni oximetin tren cdc ph6 ciia 1. Tuong tac H M B C gjOa H-37 ( 5 H 1.86) vd C-34 (6c 131,17)/C-35 (6c 136,64)/C-36 (6c 123,44) vk gitta H-33 ( 5 H 5,76) vk C-21 (5c 46,74)/C-34 (5c 131,17) cho p h i p xdc dinh vj tri ciia hai USn Ut d6i t?! C-33/C-34 v i C-35/C-36 (Mnh 2).
Cdu hlnh tuong ddi c t k hqp c h i t 2 du^c xdc djnh tren CO scr k i t qua p h 6 ROESY tuong tvt nhu hqp chit 1, cho ph£p xdc dinh 2 Id sarcophytoUde J [8].
Cdc s6 l i ^ phd N M R cua hqp c h i t 3 cune d$c t n m g cho m$t hop c h i t biscembranoit. Cdc so li^u ph6 N M R ciia no tuong t^ nhu cdc sd li^u pho ciia h ^ c h i t 1. Sv kbdc bi^t d l nh§n t h i y n h i t la s\i m i t di cdc tin hi$u ciia nhdm metoxi vd s\i x u i t hi$n cdc thi hi$u ciia ni$t nhdm metUen va m$t cachon b^c b6n mang 6xi (5c 71,74) t r a i cdc p h 6 ciia 3 thay cho mpt li€n ket ddi b) till ba v) tri tren cdc ph6 ciia 1.
Tin hi^u proton ciia hhfim metyl b^c ba C-39 trSn p h 6 ciia 3 hi dich chuyen m^nh v^ phia vikig traJmg fliip t ^ 6H 1,10 (H-39) so voi tin hi?u tucmg iing ciia 1 t^i 5H 1,59 (H-39) cho p h ^ xdc ^\nh s\f m i t di USn ket ddi 6 C-27/C-28. Tirong tdc H M B C n h | a dm?c giOa H-39 ( 5 H 1,10) vd C-26 (6c 80,82)/C-27 (5c 71,74)/C-28 (6c 38.32) xdc djnh vj tri ciia cacbon bgc b6n mang 6xi t^i C-27. PhSn tich chi tiet cdc tuong tdc HMBC khdc (Unh 2) ciing v<3i phan tich ph6 ROESY cho ph6p xdc dinh hpp chit 3 chlnh Id sarcophytoUde L [8].
L M cdm ffn. Cdng trinh n^ dugc hoan thanh v&i stf tai trff kinh phi cm Vi^ Han Idm hhoa hgc va Cdng
ngh$ mtNam. de tai ma so: VAST.W.DAB.02/i3.
15.
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Lien he: NguySn Ho&l N a m
Vi§n H6a sinh b i ^ Vi§n Hdn l§m Khoa h p c vd Cdng ngfag Vi?t N a m 18 Hodng Qu6c Vi?t, C i u G i i y , H a NOi, Vi?t N a m
E-mail: [email protected].
