Oxi hóa mạch nhánh isopropenyl của 3
-hydroxy-lup-20(29)-en-23,28-dioic axit

T¹p chÝ Hãa häc, T. 45 (6A), Tr. 171 - 175, 2007<br /> <br /> <br /> <br /> Oxi hãa m¹CH nh¸nh isopropenyl cña<br /> 3 -hydroxy-lup-20(29)-en-23,28-dioic axit<br /> §Õn Tßa so¹n 15-11-2007<br /> TrÇn V¨n Léc, TrÇn V¨n Sung<br /> ViÖn Ho¸ häc, ViÖn Khoa häc v& C«ng nghÖ ViÖt Nam<br /> <br /> <br /> Summary<br /> It is well-known that many lupane triterpenes possess anticancer and anti-HIV activity.<br /> During our phytochemical investigation on Vietnamese medicinal plants we isolated the<br /> triterpene -hydroxy-lup-20(29)-ene-23,28-dioic acid with high yield from Schefflera octophylla<br /> (Lour.) Harms (Araliaceae). From this compound a series of derivatives with modification of<br /> different functional groups have been synthetised. In this paper we report the synthesis of<br /> derivatives with changes in the isopropenyl moieties. All received derivatives are new compounds.<br /> Their structures were determined by IR, MS and NMR spectroscopic methods.<br /> <br /> <br /> I - Më ®Çu 8/2), khuÊy ë nhiÖt ®é phßng trong 48 giê. Sau<br /> ®ã 10 mg (0,1 mmol) NaHSO3 v 15 ml H2O<br /> Trong qu¸ tr×nh nghiªn cøu s ng läc c¸c hîp ®?îc thªm v o. Dung dÞch ®?îc läc v trung ho<br /> chÊt thiªn nhiªn cã ho¹t tÝnh sinh häc tõ thùc víi dung dich H2SO4 1N. Sau khi cÊt lo¹i dung<br /> vËt ViÖt Nam chóng t«i ®) ph©n lËp chÊt 3 - m«i h÷u c¬ d?íi ¸p suÊt gi¶m, pha n?íc ®?îc<br /> hydroxy-lup-20(29)-en-23,28-dioic axit (1) tõ chiÕt víi EtOAc, l m khan víi Na2SO4 v cÊt<br /> c©y ch©n chim [Schefflera octophylla (Lour.) lo¹i dung m«i. S¶n phÈm th« ®?îc tinh chÕ b»ng<br /> s¾c ký cét trªn silicagel, gi¶i hÊp víi<br /> Harms] víi hiÖu suÊt cao [1]. Trong hai b i b¸o CHCl3/EtOAc (95:5) thu ®?îc c¸c ®ång ph©n 2a<br /> tr?íc ®©y chóng t«i ®) c«ng bè vÒ viÖc tæng hîp<br /> (27%) v 2b (48%).<br /> v x¸c ®Þnh cÊu tróc cña mét sè dÉn xuÊt ester<br /> v amit cña chÊt 1 [2, 3]. Trong bài bào này, 3 -Acetoxy-20 , 29-dihydroxylupan-23,28-<br /> chóng t«i th«ng b¸o vi�c t�ng h�p c¸c d�n xu�t dioic axit (2a)<br /> c�a ch�t 1 v�i s� oxi ho¸ m�ch nh¸nh<br /> m.p. 206 - 208oC (Me2CO/CHCl3). [ ]D<br /> 24<br /> isopropenyl, �i�u ch� c¸c mono- và dieste, m�t<br /> s� d�n xu�t �ư�c chuy�n hãa ti�p thành c¸c +36.50 (MeOH, c = 2.0). IR: /cm-1(KBr): 3446<br /> amino axit cña chÊt 1. (m, br), 2947 (s), 2872 (w), 1718 (s), 1457 (m),<br /> 1378 (m), 1260 (s), 1025 (m), 988 (w). 1H-<br /> II - thùc nghiÖm NMR (CD3OD): /ppm = 4,92 (br s, H-3), 3,45<br /> (d, J = 11,0 Hz, H-29B), 3,36 (d, J = 11,0 Hz, H-<br /> 1. Ph¶n øng oxi ho¸ chÊt 1a 29A), 1,04 (s, H3-30). 13C-NMR (CD3OD):<br /> /ppm = 180,4(C-28), 179,0 (C-23), 77,0 (C-3),<br /> 259 mg (1 mmol) 3 -axetoxy-20(29)- en -<br /> 76,1 (C-20), 71,1 (C-29), 59,5 (C-17), 45,6 (C-<br /> 23,28-dioic axit (1a), 176 mg (1,5 mmol) N- 19), 22,3 (C-2), 19,5 (C- 30). ESI-MS (ion ©m);<br /> methylmorpholine-N-oxit v 20 mg (0,08 m/z (%) = 561,6 (100) [M - H]-.<br /> mmol) OsO4 ho trong 20 ml axeton/H2O (tû lÖ<br /> 171<br /> DÉn xuÊt C-20 Epimer (2b) - 1,60 (CHCl3, c = 1,0).1H-NMR (CDCl3): /ppm<br /> m.p. 197 - 198oC (Me2CO/CHCl3). [ ]D :<br /> 24 = 3,75(br s, H-3), 3,70 (s, OMe), 1,16 (s, H3-<br /> 24). 13C- NMR (CD3OD): /ppm = 180,1 (C-28),<br /> 7,10 (MeOH, c = 2,0). IR: /cm-1 (KBr): 3446 178,7 (C-23), 74,2 (C-3), 57,5 (C-17), 52,0<br /> (m, br), 2947 (s), 2878 (w), 1718 (s), 1457 (m), (OMe), 48,5 (C-19), 45,2 (C-5), 22,5 (C-6). EI-<br /> 1378 (m), 1259 (s), 1027 (m), 989 (w). 1H- MS: m/z (%) = 500 [M]+ (22), 482 (8), 468 (8),<br /> NMR (CD3OD): /ppm = 3,41 (s, H2- 29), 1,15 454 (14), 248 (37), 233 (79), 201 (55), 187 (80),<br /> (s, H3-30).(H- 3 Èn d?íi HDO ë 4.92). 13C- 173 (99), 119 (100), 107 (81), 95 (77).<br /> NMR (CD3OD): /ppm = 180,6 (C-28), 179,0 3 -Hydroxy-lup-20(29)-en-23,28-dioic axit<br /> (C-23), 76,1 (C-20), 69,5 (C-29), 60,1 (C-17), dimetyl este (6b)<br /> 46,6 (C-19), 24,8 (C-30), 23,3 (C-2). ESI-<br /> m.p. 83 - 84oC (Me2CO/n-hexan). [ ]D -<br /> 24<br /> MS(ion ©m): m/z (%): 561,5 (100) [M - H]-.<br /> 2. Oxi ho¸ chÊt 2a, 2b b»ng KIO4 4,00 (CHCl3, c = 1,0). 1H-NMR (CDCl3): /ppm<br /> = 4,70 (m, J = 2,2 Hz, H- 29B), 4,60 (q, J = 1,3<br /> 1mmol chÊt 2a hoÆc 2b v 690 mg (3mmol) Hz, H-29A), 3,73 (br s, H- 3), 3,70, 3,66 (s,<br /> KIO4 ho trong 20 ml MeOH/H2O (8:2), khuÊy OMe), 3,00 (m, H-19), 1,16 (s, H3- 24). 13C-<br /> ë nhiÖt ®é phßng trong 20 giê. Hçn hîp ®?îc NMR (CDCl3): /ppm = 178,1(C-23), 176,6 (C-<br /> quay cÊt d?íi ¸p suÊt gi¶m, s¶n phÈm th« ®?îc 28), 72,4 (C-3), 56,6 (C-17), 51,8, 51.1 (OMe),<br /> tinh chÕ b»ng s¾c ký cét (silicagel, 24,9 (C-2). EI-MS: m/z (%) = 514 [M]+ (56),<br /> CHCl3/MeOH = 95:5) thu ®?îc chÊt 3 (96%). 496 (10), 482 (11), 454 (26), 264 (75), 249 (77),<br /> 3 -Acetoxy-20-oxo-29-norlupan-23,28-dioic 233 (59), 203 (57), 189 (100), 175 (66), 107<br /> axit (3) (53), 93 (51), 81 (49).<br /> <br /> m.p. 155-157oC (EtOAC). [ ]D : + 61.80<br /> 24 4. Oxi ho¸ chÊt 6a, 6b b»ng<br /> m-cloroperbenzoic axit<br /> (MeOH, c = 1,0). IR: /cm-1 (CHCl3): 3674 (w),<br /> 3511 (w), 2950 (s), 2869 (m), 1733 (s), 1700 487 mg (1 mmol) chÊt 6a hoÆc 6b ®?îc ho<br /> (s), 1602 (w), 1452 (m), 1375 (m), 1357 (m), tan trong Et2O, nhá 432 mg (2,5 mmol) m-<br /> 1248 (s), 1172 (m), 1130 (w), 1027 (m), 990 chloroperbenzoic axit trong 10 ml CH2Cl2 v<br /> (w). 1H-NMR (CDCl3): /ppm) = 4,95 (br s, H- khuÊy ë 25oC trong 24 giê. Hçn hîp ph¶n øng<br /> 3), 3,23 (td, J = 10,7 and 4,4 Hz, H-19), 2,19 (s, ®?îc röa 2 lÇn víi n?íc, l m khan víi Na2SO4<br /> H3-30). 13C-NMR (CDCl3): /ppm = 212,2 (C- v c« ®Æc d?íi ¸p suÊt gi¶m. S¶n phÈm ®?îc<br /> 20), 182,7 (C-28), 181,7 (C-23), 75,3 (C-3), tinh chÕ b»ng s¾c ký cét (silicagel, n-<br /> 56,3 (C-17), 30,0 (C-30). EI-MS: m/z (%) = hexan/EtOAc = 75 : 25) thu ®?îc chÊt 7a, 7b v<br /> 530 [M]+ (35), 512 (16), 484 (20), 470 (46), 452 8a, 8b.<br /> (84), 426 (100), 383 (54), 261 (53), 219 (88), 3 -Hydroxy-29-oxolupan-23,28-dioic axit 23-<br /> 189 (69), 175 (74). metyl este (C-20 epimer 7a)<br /> 3. §iÒu chÕ c¸c chÊt metyl este 6a, 6b<br /> [ ]24D - 13,40 (CHCl3, c = 0,65). 1H-NMR<br /> 1 mmol chÊt 1 ho trong MeOH (20 ml) v (CDCl3): /ppm = 9,85 (d, J = 1,7 Hz, H-<br /> khuÊy 1 giê ë 25oC cïng víi 1 (hoÆc 2) mmol 29)/9,64 (s, H-29), 3,76 (br s, H-3), 3,71 (s,<br /> CH2N2 trong Et2O. Sau ®ã lo¹i bá dung m«i d?íi OMe), 1,12 (d, J = 6,9 Hz, H3-30)/1,02 (d, J =<br /> ¸p suÊt gi¶m v s¶n phÈm ®?îc tinh chÕ b»ng 6,9 Hz, H3-30). 13C-NMR (CDCl3): /ppm =<br /> s¾c ký cét (n-hexan/EtOAc= 8 :2) thu ®?îc chÊt 206,7/204,7 (C-29), 181,6/181,5 (C-28), 178,2<br /> 6a v 6b. (C-23), 72,5 (C-3), 24,9 (C-2), 56,6/56,3 (C-17),<br /> 3 -Hydroxy-lup-20(29)-en-23,28-dioic axit 23- 52,0 (OMe), 49,2/48,1 (C-19), 42,6/42,7 (C-14),<br /> metyl este (6a) 42,4/36,9 (C-20), 27,3/24,3 (C-21), 14,4/6,8 (C-<br /> 30). EI-MS: m/z (%) = 516 [M]+ (11), 498 (6),<br /> m.p. 125 - 126oC (Me2CO/n-hexan). [ ]24D 386 (14), 459 (14), 436 (16), 414 (27), 233<br /> 172<br /> (100), 173 (88), 147 (64), 133 (64), 121 (84), 5. Tæng hîp 3 -axetoxy-lup-20(29)-en-23, 28-<br /> 107 (81), 81 (82). diamit este<br /> 3 ,20 -Dihydroxy-29-oxolupan-23,28-dioic LÊy (1 mmol) chÊt 2a hoÆc 3 ho tan trong<br /> axit 23-metyl este (7b) 20 ml C6H6 khan, cho v o 0,53 ml (6,0 mmol)<br /> m.p. 230 - 232oC (Me2CO/n-hexan). [ ]D - oxalylclorit. Hçn hîp ®?îc khuÊy ë nhiÖt ®é<br /> 24<br /> phßng 18 giê. Sau ®ã cÊt lo¹i C6H6 v<br /> 3,80 (CHCl3, c = 1,0). 1H-NMR (CDCl3): /ppm oxalylchlorit d? d?íi ¸p suÊt gi¶m. ChÊt r¾n cßn<br /> = 9,53 (s, H-29), 3,75 (br s, H-3), 3,71 (s, l¹i ®?îc ho tan trong 40 ml CH2Cl2, thªm v o 6<br /> OMe), 3,45 (t, J = 9,2 Hz, H-19), 1,27 (s, H3- mmol trietyl amin v 3mmol axit amin metyl<br /> 30), 1,16 (s, H3-24). 13C-NMR (CDCl3): /ppm = hoÆc etyleste hydroclorit t?¬ng øng. TiÕp tôc<br /> 204,3 (C-29), 182,0 (C-28), 178,1 (C-23), 80,0 khuÊy 20 giê ë nhiÖt ®é phßng. Hçn hîp ph¶n<br /> (C-20), 72,5 (C-3), 58,8 (C-17), 45,0 (C-19), øng ®?îc röa víi H2O, HCl lo)ng v cuèi cïng<br /> 24,9 (C-2), 22,5 (C-30). EI-MS: m/z (%) = 532 víi H2O. L m khan b»ng Na2SO4, cÊt lo¹i dung<br /> [M]+ (17), 514 (6), 503 (18), 487 (100), 460 m«i d?íi ¸p suÊt gi¶m thu ®?îc chÊt r¾n, t¸ch<br /> (16), 409 (16), 381 (19), 233 (63), 173 (55), 147 trªn cét silicagel víi hÖ dung m«i n-<br /> (75), 121 (68), 95 (64), 81 (68). HR-MS: hexan/EtOAc. KÕt tinh l¹i ta thu ®?îc c¸c chÊt<br /> 532,3382 [M]+ (C31H48O7 requires 532,3400). 4(a-c), 5(a-b) s¹ch.<br /> 3 -Hydroxy-29-oxolupan-23,28-dioic axit 3 -Acetoxy-20-oxo-29-norlupan-23,28-dioic<br /> dimetyl este (C-20 epimer 8a) axit 23,28-di(serin metyl este) amit (4b)<br /> [ ]24D - 10,70 (CHCl3, c = 0,85). 1H-NMR m.p. 138 - 139oC (Me2CO/n-hexan). [ ]D -<br /> 24<br /> <br /> (CDCl3): /ppm = 9,85 (d, J = 1,7 Hz, H- 77,40(MeOH, c = 2,0). IR: /cm-1(CHCl3) =<br /> 29)/9,64 (s, H-29), 3,75 (br s, H-3), 3,704/3,665 3691 (w), 3442 (w), 2955 (m), 2870 (w), 1735<br /> (s, OMe), 3,689/3,669 ( s, OMe), 2,98 (m, H- (s), 1706 (w), 1659 (m), 1602 (w), 1501 (m),<br /> 19), 1,00/1,11 ( d, J = 6,8 Hz, H3-30), 1,17 (s, 1438 (m), 1375 (m), 1356 (m), 1240 (s). 1H-<br /> H3-24). 13C-NMR (CDCl3): /ppm = 206,8/204,7 NMR (CDCl3): /ppm = 4,86 (br s, H-3), 3,37<br /> (C-29), 178,12/178,08 (C-23), 176,47/176,42 (td, J = 11,0 v 3,9 Hz, H- 19), 2,17 (s, H3-30),<br /> (C-28), 72,4 (C-3), 56,75/56,53(C-17), 51,9 2,08 (s, CO-CH3). 13C-NMR (CDCl3): /ppm =<br /> (OMe), 51,32/51,27 (OMe), 42,46/36,87 (C-20), 213,0 (C-20), 176,6, 175,3 (C- 23, C-28), 74,8<br /> 49,96/49,89 (C-18), 49,2/48,2 (C-19), 14,9 (C- (C-3), 55,6 (C-17), 49,7 (C-19), 30,1 (C-30). EI-<br /> 2), 14,4/6,7 (C-30). EI-MS: m/z (%) = 530 [M]+ MS: m/z (%) =732 [M]+ (7), 714 (10), 672 (61),<br /> (8), 500 (37), 473 (16), 440 (14), 264 (42), 251 654 (20), 526 (40), 201 (39), 120 (32), 57 (100).<br /> (32), 233 (100), 189 (52), 175 (61), 161 (68),<br /> 119 (79), 105 (61), 81 (63). DÉn xuÊt dioxolan (5b)<br /> 3 ,20 -Dihydroxy-29-oxolupan-23,28-dioic m.p. 110-112oC (Me2CO/n-hexan).<br /> axit dimetyl este (8b) [ ]24<br /> D +76,9 (MeOH, c = 2,0). IR: /cm-1<br /> 0<br /> <br /> <br /> m.p. 116 - 117oC (Me2CO/n-hexan). [ ]D +<br /> 24 (CHCl3) = 3447 (m), 2868 (w), 1795 (s), 1733<br /> (s), 1662 (s), 1497 (s), 1374 (m), 1246 (m),<br /> 62,60 (CHCl3, c = 0,3). 1H-NMR (CDCl3): /ppm 1109 (m), 1069 (m), 1024 (w). 1H-NMR<br /> = 9,53 (s, H-29), 3,75 (t, J = 2,8 Hz, H-3), 3,70, (CDCl3): /ppm = 4,79 (br s, H-3), 4,26 (d, J =<br /> 3,66 ( s, OMe), 2,47 (t, J = 8,5 Hz, H-19), 1,27 8,6 Hz, H-29B), 4,10 (d, J = 8,8 Hz, H-29A ),<br /> (s, H3-30), 1,17 (s, H3-24). 13C- NMR (CDCl3): 2,72 (t, J = 8,8 Hz, H-19), 1,88 (s, CO-CH3),<br /> /ppm = 204,4 (C-29), 178,1 (C-23), 176,7 (C- 1,50 (s, H3-30), 1,13, 0,94, 0,86, 0,69 ( s 3H,<br /> 28), 80,0 (C-20), 72,5 (C-3), 51,9, 51,4 (OMe), CH3). 13C-NMR (CDCl3): /ppm = 175,3, 174,5<br /> 24,9 (C-2), 22,4 (C-30). EI-MS: m/z (%) = 546 (C-23, C-28 ), 154,6 (O-CO-O), 86,0(C-20),<br /> [M]+ (9), 528 (6), 517 (24), 501 (91), 473 (34), 75,3 (C-3), 72,1 (C-29), 57,5 (C-17), 46,0 (C-<br /> 423 (16), 329 (15), 233 (40), 175 (32), 161 (48), 19), 29,0, 27,9 ( C-21, C-15), 26,8 (C-30). ESI-<br /> 147 (56), 119 (38), 83 (100).<br /> 173<br /> MS (ion d?¬ng): m/z (%): 961,8 [M + Na]+ (70), nhËn ®?îc hçn hîp ®ång ph©n 20,29-dihydroxy.<br /> 941,0 (55), 880,6 (100). T¸ch hçn hîp n y qua s¾c ký cét silicagel thu<br /> ®?îc hai ®ång ph©n s¹ch 2a v 2b. TiÕp tôc oxi<br /> 6. Tæng hîp c¸c dÉn xuÊt 3 -hydroxy-lup-<br /> ho¸ 2a v 2b b�ng KIO4 sÏ cho ch�t 29-nor-<br /> 20(29)-en-23,28-diamit<br /> keton 3. Oxi hãa m¹ch nh¸nh isopropenyl b�ng<br /> Thñy ph©n c¸c chÊt 4(a-c), 5(a-b) b»ng axit m-cloroperbenzoic tõ 6a v 6b sÏ thu ®?îc<br /> NaOH 4N trong tetrahydrofuran/MeOH (1:1) ë c¸c ch�t andehit 7a, 7b v 8a, 8b sau khi t¸ch<br /> nhiÖt ®é phßng 24 giê. CÊt lo¹i dung m«i d?íi b�ng s�c ký c�t trªn SiO2(xem s¬ ®å 1).<br /> ¸p suÊt gi¶m, cÆn cßn l¹i ®?îc ho tan trong 15<br /> ml n?íc cÊt v trung ho b»ng HCl (5%) ®Õn pH 2. Tæng hîp c¸c dÉn xuÊt mono-và dieste<br /> = 6, chiÕt b»ng CH2Cl2 ba lÇn, dÞch chiÕt ®?îc Ch�t monometyleste 6a và dimetyleste 6b<br /> röa víi n?íc, l m khan b»ng Na2SO4, läc dÞch �) �ư�c �i�u ch� b�ng ph�n �ng c�a ch�t 1 v�i<br /> chiÕt. CÊt lo¹i dung m«i v kÕt tinh l¹i trong CH2N2 theo tØ lÖ mol kh¸c nhau. V� trÝ c�a nhãm<br /> axeton ta thu ®?îc c¸c chÊt 9 (a-b), 10 (a-c). este trong ch�t 6a v 6b �ư�c x¸c ��nh b�ng s�<br /> 3 ,20 ,29-Trihydroxylupan-23,28-dioic axit so s¸nh phæ 13C-NMR cña chóng víi phæ cña<br /> 23,28-di(phenylalanin)amit (9b) chÊt 1. Sù thay ®æi ®é dÞch chuyÓn ho¸ häc cña<br /> m.p. 168 - 169oC (EtOAc/n-hexan). nh÷ng nguyªn tö cacbon gÇn c¸c nhãm este<br /> [ ]24 ®?îc t¹o th nh (C-23 hoÆc C-28) l c¬ së ®Ó x¸c<br /> D +169,5 (MeOH, c = 1,0). IR: /cm-1<br /> 0<br /> ®Þnh vÞ trÝ cña c¸c gèc ester.<br /> (KBr) = 3434 (s), 1636 (s), 1507 (s), 1456 (m),<br /> 1387 (m), 1207 (m, br), 1032 (m), 919 (w), 737 3. Tæng hîp c¸c dÉn xuÊt amino axit<br /> (w), 701 (m). 1H-NMR (CD3OD): /ppm = 3,65 C¸c h�p ch�t diaxit 2 và 3 �ư�c chuy�n ho¸<br /> (br s, H-3), 3,35 (s, H2 -29), 2,28 (t, H-19), 1,10, thành c¸c este c�a c¸c axit diamino 4a, 4b, 4c<br /> 1,05, 0,91, 0,81, 0,41 ( s, CH3). 13C-NMR và 5a, 5b, th«ng qua b?íc ho�t hãa nhãm<br /> (CD3OD): /ppm = 175,5, 174,2 (C-23, C-28), cacboxyl v�i oxalylchlorit, sau ®ã ph�n �ng v�i<br /> 76,1(C-20), 73,5 (C-3), 69,5 (C-29), 59,4 (C- c¸c amino axit trong triethylamin [4]. B�ng c¸ch<br /> 17), 46,3 (C-19), 24,6 (C-30). ESI-MS: m/z (%) này, c¸c nhãm ch�c 20,29-dihydroxi c�a c¸c<br /> = 854 [M + K]+ (20), 815 [M + H]+ (100). ch�t 2 �ư�c chuy�n hãa thành oxo-1,3-dioxolan<br /> 3 -Hydroxy-20-oxo-29-norlupan-23,28-dioic 5a, 5b. Thñy ph©n c¸c amino axit 4(a-c) v 5a,b<br /> axit 23,28-dialanin amit (10b) trong NaOH thu ®?îc c¸c s¶n phÈm t?¬ng øng<br /> 10a, 10b, 10c v 9a, 9b.<br /> m.p. 210 - 212oC (EtOAc/n-hexan).<br /> [ ]24<br /> D +21,8 (MeOH, c = 2,0). IR: /cm-1 (KBr)<br /> 0 ViÖc x¸c ®Þnh chÝnh x¸c cÊu tróc hãa häc<br /> cña c¸c s¶n phÈm t¹o th nh dùa v o c¸c ph?¬ng<br /> = 3420 (m, br), 2944 (s), 2869 (w), 1734 (s), ph¸p phæ nh? phæ khèi EI-MS, ESI-MS, phæ<br /> 1636 (s), 1521 (s), 1457 (m), 1379 (w), 1201 hång ngo¹i IR v phæ céng h?ëng tõ h¹t nh©n<br /> (m), 1066 (w). 1H-NMR (CD3OD): /ppm = 1<br /> H-,13C-NMR mét chiÒu v 2 chiÒu.<br /> 3,75 (br s, H-3), 2,16 (s, H3-30). 13C-NMR<br /> (CD3OD): /ppm = 215,9 (C-20), 179,6, 178,8 t!i liÖu tham kh¶o<br /> (C-23, C-28 ), 73,7 (C-3), 56,7 (C-17), 49,2 (C-<br /> 19), 29,8 (C-30). ESI-MS: m/z (%) = 653 [M + 1. G. Adam, M. Lischewski, H. V. Phiet, A.<br /> Na]+ (12), 631 [M + H]+ (100). Preiss, J. Schmidt, Tran Van Sung.<br /> IR: (m: trung b×nh, s: m¹nh, w: yÕu). Phytochemistry, Vol. 21, P. 1388 (1982).<br /> 2. TrÇn V¨n Léc, TrÇn V¨n Sung. T¹p chÝ Ho¸<br /> III - KÕt qu¶ v! th¶o luËn häc, T. 45(1), Tr. 33 - 36 (2007).<br /> 3. TrÇn V¨n Léc, TrÇn V¨n Sung. T¹p chÝ Ho¸<br /> 1. Oxi ho¸ m¹ch nh¸nh isopropenyl häc ®) nhËn ®¨ng.<br /> Oxi hãa dÉn xuÊt 3 -acetyl 1a víi OsO4 ta 4. Y. Kashiwada, F. Hashimoto, L. M.<br /> 174<br />  Cosentino, Chin-Ho Chen, P. E. Garett, 1016 (1996).<br /> Kuo-Hsiung Lee. J. Med. Chem, Vol. 39, P.<br /> <br /> <br /> OH<br /> 29<br /> O<br /> 30 20 OH<br /> 19 21<br /> <br /> 22<br /> 12 18 17<br /> 11 13<br /> 25<br /> COOH<br /> 26<br /> 14 16 COOH<br /> 28<br /> COOH<br /> 1 9 15<br /> 2 10 8<br /> 27<br /> KIO4<br /> 3 5 7<br /> <br /> <br /> RO<br /> 4 6<br /> OsO4 AcO AcO<br /> 24 COOH COOH COOH<br /> 3<br /> 23<br /> <br /> <br /> <br /> 1. R= H 2a,2b (20-epimer) 1. Oxalylchlorid; C6H6<br /> 1a. R= Ac 1. Oxalylchlorid; C6H6 18h;25oC<br /> CH2N2 2. Amino acid ankylester<br /> 2. Amino acid ankylester<br /> O O<br /> O<br /> O<br /> <br /> <br /> COR2 COR2 COR2<br /> <br /> <br /> HO AcO AcO<br /> COR1 COR1 COR1<br /> 6a,b 5a,b 4(a-c)<br /> m-Chlorperbenzoic axit NaOH/ MeOH NaOH/ MeOH<br /> CHO O<br /> OH<br /> R3 OH<br /> <br /> <br /> COR2 COR2 COR2<br /> <br /> <br /> HO HO HO<br /> COR1 COR1 COR1<br /> <br /> 7a,b- 8a,b 9a,b 10(a-c)<br /> (20-epimer)<br /> <br /> <br /> S¬ ®å 1: Ph¶n øng t�ng h�p các d�n xu�t t� ch�t 1<br /> <br /> ChÊt R1 R2 R3 ChÊt R1 R2 R3<br /> 4a L-Ala-OMe L-Ala-OMe - 7b OMe OH OH<br /> 4b L-Ser-OMe L-Ser-OMe - 8a OMe OMe H<br /> 4c L-Glu(OMe)2 L-Glu(OMe)2 - 8b OMe OMe OH<br /> 5a L-Met-OMe L-Met-OMe - 9a L-Met-OH L-Met-OH -<br /> 5b L-Phe-OEt L-Phe-OEt - 9b L-Phe-OH L-Phe-OH -<br /> 6a OMe OH - 10a L-Ala-OMe L-Ala-OMe -<br /> 6b OMe OMe - 10b L-Ser-OMe L-Ser-OMe -<br /> 7a OMe OH H 10c L-Glu(OH)2 L-Glu(OH)2 -<br /> <br /> <br /> 175<br />