Hgi thdo khoa hgc ky ni^m 40 n&m thdnh lap Vi$n Hdn lam KH&CN Vi^t Nam
NGHIEN CLfU PHU'QNG PHAP M a i T O N G HQ^P D A N C H A T O X I N D O L E
T O YOHIMBINE
Nguyin Le Anh, Ngd QuIc Anh*
Vi$n Hda hgc, Vi0n Hdn Idm Khoa hgc vd Cdng ngh$ Vi^t Nam, 18 Hodng Quoc Vi^t. Cau Gidy. Hd Ngi;
A new method to synthesize oxindole derivative 9 from the indole alkaloid yohimbine was reported. The structures of obtained compound 9 was determined by MS and NMR spectroscopic methods.
I.M(3DAU
Yohimbine Id m$t ancaloit nhdn indol dugc tim thiy trong mOt lo^t cdc nguin thvrc v|t nhu rl cdy Ra\twolfia, ho$c td vd cua cay Yohimbe [1].
1
Hinh 1: Ciu tnic cua Yohimbine Vigc ting hgp cdc oxmdol td cdc ancaloit indol ) cau hinh dgng trans ho§c cty~DE-indol dd dugc
. H
cdng bd [2.3] . Nhtbig ancaloit oxindol vdi vdng trans- DE dugc ting hgp nhu mitraphylUne (2), rhyncophyllme (3) vd corynoxeine (4). MOt s l ancaloit oxindol khdc dgng ci5-DE cung dugc bilt din nhu imcarine B (5) fonnosanme [4], corynoxine (6) [5] vd carapanaubine (7). phdn l|,p td Aspidosperma carapanauba [6]. Yohimbinoid phdn dng vdi tdc nhdn electrophin nhu chi tetraacetate thu dugc din xuit acetoxyindolenine.
Acetoxyindolenine trong dung djch methanol cda axit axetic lodng chuyin v\ dl tgo thdnh cdc hgp chit oxmdol [7].
Trong bdi bdo ndy, chiing tfli cdng bl m^t phuong phdp mdi dl ting hgp cdc din xuat oxindol td yohimbine.
mitraphylline corynoxeine
uncarlne B
177
Ba tlgng sinh hgc va cac chat co hogt tinh sinh hgc
n.THVCNGHlBM
ciu triic Ciia cac hpp chat tong hpp dirpc xic dinh bing s\r kit hpp cic phuong pMp pho nhin phd h6ng ngoiii (FT-IR); ph6 khli (ESI-MS); pho khIi phin giii cao (HR-MS); vi pho cpng hudng tir hat nhin mptchieuvihaichilu(lD-vi2DNMR).
TdnghppdSnxuitS
H6a tan yohimbine (SOmg, 0,14mmol) trong aceton (2ml), th6m tu tu 6 0°C NBS (28mg, 0,16mmol) dupe hoa tan trong aceton (1ml), khuay dlu phin ting cr 0°C trong 15 phiit. Tien trinh phin iing dupe theo ddi bing TLC vdi hp dimg moi trien Idiai (Dichlorometban: MeOH = 95:5). Sau khi phin irng kit thuc, trung h6a phin ling bin^ NaHCOs bio h6a, quay khd aceton. Sau do, chilt bang CH2CIZ thu dupe sin phim 8.
" ' ' • H
Hpp chit 8
HijTi chit 8: Hi§u suit 95%; 'H-NMR (CDClj, 500 MHz); S 7.63 (d, / = 7,6 Hz, IH); 7,51 (d, y - 7,6 Hz, IH); 7,39-7.36 (m, IH); 7,28-7.27 (m, IH);
4,21 (s, IH); 3,78 (s, 3H); 3.70 (dd, J - 2,6 Hz, 11 Hz, IH); 3,00 (-0H); 2.93 (dd, y = 2,6 Hz, 11 Hz, IH); 2,87- 2,85 (m, 2H); 2,61- 2,57 (m, IH); 2,38 (dd, y = 2,0 Hz, 11,7 Hz, IH); 2,29 (t, / = 10,8Hz, IH), 2,17 (m, IH); 2,00 (m, 2H); 1,79-1,69 (m, 3H);
1,61-1,53 (m, 2H); 1,42-1,37 (m, 2H); 1,26 (s, IH).
ESI-MS m/z 432,1 [M+l]*
XSng hpp dSn xuit mjl 9
Hdn hpp 8 (20 mg, 0,05 mmol) vi AgBF4 (9 9 mg, 0,05mmol) trong THF/H2O (1:1) (2ml), anily dlu phin 6ng d SO^C trong 2 gi&. Tiln trinh phin ung dupe theo dOi bing TLC vdi h§ dung m5i trien khai (Diehloromethan: MeOH = 95:5). Sau khi phin ling kit thiic, quay khd CHzCh. Sau dd, chay c$t sic ky vdi he dung mdi triln khai (Diehloromethan : MeOH = 95:5) thu dupe hpp chit 9.
Hpp chat 9
Hpp chit 9: Hi?u suit 70%; 'H-NMR (CDCIj, 500 MHz): S 8,15 (s, -NH); 7,39 (i,J= 7,5 Hz, IH);
7,21 (t, y = 7,5 Hz, IH); 7,04 (t,J= 7,5 Hz, IH);
6,87 (i,J= 7,5 Hz, IH); 4,09 (s, IH); 3,57 (s, 3H);
3,29 (m, IH); 3,11 (dd, / = 3,8 Hz, 10,9 Hz, IH);
3,05 (s, -OH); 2,53 (m, 2H); 2,39 (m, IH); 2,12 (dd, J- 1,6 Hz, 11,8 Hz, IH); 2,01 (m, IH); 1,94 (m, 2H); 1,74 (dd, / = 3,0 Hz, 11,6 Hz, IH); 1,50 (dd, J
= 3,2 Hz, 9,0 Hz, IH); 1,46 (m, 3H); 1,08 (m, IH);
0,71(ni, IH). '=C NMR (125 Hz, CDClj): S 181,4;
175,4; 140,1; 133,8; 127,5; 127,5; 125,1; 122,4;
109,4; 109,3; 71,44; 66,7; 58,8; 56,7; 40,4; 36,2;
35,3; 31,3; 30,4; 23,4. ESI-MS m/z 371,1 [M+l]*.
m . K £ T QUA V A T H A O LUAN
yohimbine
Sa ah 1: So d6 ting hpp chit 8'
Yohunbine 1 dupe phan ling vdi NBS trong MS cho thiy tta hifu 432,1 [M+lf phii hpp viii aceton d O'C trong 2h thu dupe din ch5 phan tii lupng chit 8 vi mang d}c tnmg cua bW bromomdolenm 8 vdi hieu suit 95%. Phd 'H NMR chit chia brom Nhu vjy chit 8 di dupe ting bW ciia hpp chit 8 cho thiy tm hi|u die trung cho thinh cdng.
proton d vi tri C-l (-NH) khdng thiy xuat hifn; pho
H$i thdo khoa hgc kp niem 40 ndm thdnh ldp Vi$n Hdn lam KH&CN Vi^t Nam
Sa do 2: So d l tong hgp c h i t 9 , Thvc hi§n phdn d n g c h u y i n vj hgp c h i t 8 nhd m^t
• tdc nhdn axit Lewis AgBF4 thu dugc hgp c h i t oxindol 9 (so d o 2). Pho ' H N M R ciia hgp chat 9 chi ra tin higu Sa (ppm) 8,12 {s, -NH) d§c Irung cho proton cua nhdm N H trong nhan mdol; tin bi$u ^H (ppm) 3,29 (m, I H ) ; 3,11 (dd, J = 3,8 Hz, 10,9 Hz, IH) dugc %in cho proton cda C-6 vd C-7; trSn p h i
"C chi ra hai tin hi§u d^c t n m g cho nhdm C O t?i d (ppm) 181,4 v a 175,4. P h i H M B C x u i t hign tuong tdc cua proton trSn C-6 v d i C cua nhdm CO. Cdc proton trSn C-10 vd C-13 cdng cho tin hi§u tuong tdc vdi C cda n h d m C O . P h i M S m/z 371,1 [ M + l f phd hgp vdi cdng thdrc phdn t d ciia 9 khdng dfnh c i u
triic 9.
I V . K £ T L U J ^
Chdng tdi dd t i n g hgp d u g c m$t d i n x u i t mdi oxlndole 9 cda yohimbin qua trung gian h g p c h i t bromoindolenine 8 bdng p h u o n g phdp m d i sd dyng tdc nhdn eletrophin N B S vd gdy c h u y i n vi bdng axit Lewis AgBF4. C i u hlnh I$p t h i cua hgp c h i t 9 se dugc cdng b l trong nghiSn c d u t i l p theo.
Ldi cdm m\: Cdc tdc gid cdm an Vi^n HLKHCN n4t Nam dd tdi trg Idnh phi tu di tdi VAST 04.04/15-16 dithifc hi$n cdng trinh ndy.
TAl L I $ U T H A M K H A O
[1] Edwards, S. E., Rocha, I. d. C , Williamson, E. M.
and Heinrich, M. Yohimbe, in Phytopharaiacy; An ' Evidence-Based Guide to Herbal Medical Products,
2Q15, John Wiley & Sons, Ltd, Chichester, UK.
[2] Chiisdane Marti and ErickM. Carreira.
I ConstractioB of Spiro[pyrrolidine-3,3'-oxindole8] - ' Recent Applications to the Synthesis of Oxindole j Alkaloids. European Journal of Organic Chemistry.
' 2003, 72. pp 2209-2219.
[3] Neville. Finch, W. I. Taylor. Oxidative Transformations of Indole Alkaloids. I. The
Urn h4: Ng6 QuIc Anh
. Vi^n Hoa hgc, Vi^n Hdn lam Khoa hgc va Cong n ^ ? Vigt Nam E-mail: [email protected]
Pieparation of Oxindoles from Yohimbine; the Structures and Partial Syntheses of Mitraphylline, RhyncophyUine and Corynoxeine. J. Am. Chem.
Soc, 1962, 84 (20), pp 3871-3877.
[4] Y. Ban,N. Taga,T. Oishi, The Synthesis Of 3- Spirooxindole Derivatives. ViiL Total Syntheses Of (±)-Formosanine, (±)-Isoft)rmosanine, (±)- Mitraphylline And (±)>Isoniitraphylline. Chemical and Pharmaceutical Bulletin (1976), 4, pp 736-751.
[5] Martin J. Wanner, Steen Ingcmann, Jan H. van Maarseveen and Henk Hiemstra. Total Synthesis of the Spirocyclic Oxindole Alkaloids Corynoxine, Corynoxine B, Corynoxeine, and Rhynchopfaylline.
European Journal of Organic Chemistry. 2013, 6, pp 1100-1106
[6] B. Gilbert, J. A . Brissolese, S.Finch, W. I . Taylor, H. Budzikiewicz, J.M.Wilson and CDjerassi, Mass Spectrometry in Structural and Stereochemical Problems. XX.Carapanaubine, a New Alkaloid icom. Aspidosperma carapanauba and Some Observations on Mass Spectra of Oxindole Alkaloids. J. Am. Chem. 5 o c , 1 9 6 3 , S J ( I 0 ) , pp 1523-1528
[7] Neville. Finch, C. W. Gemenden, Iva Hsiu-Chu.
Hsu,W. I. Taylor. Oxidative Tnuisform^ons of Indole Alkaloids. IL The Preparation of Oxindoles fromcir-DE-Yohimbinoid Alkaloids. The Partial Synthesis of Carap anaubine. /. Am. Chem.
Soc, 196Z, 85 {iQ), pp 1520-1523
