A Model Study toward the Synthesis of Xestoquinone Xestoquinone

전체 글

(1)Journal of the Korean Chemical Society 2003, Vol. 47, No. 4 Printed in the Republic of Korea. . Xestoquinone. *.

(2) (2003. 4. 28 ) A Model Study toward the Synthesis of Xestoquinone Chan Mug Ahn * and Ho Bum Woo Department of Basic Sciences, Institute of Basic Medical Science, Yonsei University Wonju College of Medicine (Received April 28, 2003). . Xestoquinone - 4 !"# $%"&'. ()*+ , 3-butyn-1-ol -."#, 5-iodo-1-methoxymethoxypentyne(5)- 5/ 01 2$34'. Ethyl 2-phenylpropanoate5 5 678+9: ethyl 7-methoxymethoxy-2-methyl-2-phenyl-5-heptynoate(6); 88% <=+ >?@8A, 68+9 : BC BDEF methyl 9-oxo-4-methyl-4-phenyl-2,7-nonadiynoate(13); 6/ 01 34'. 13 GHI J K67L 5% <=+ isobenzofuran 14 M"&8A, Lewis acid NO ", 4JK $+ 34'. : 2PQRS, GHI JK67 ABSTRACT. A strategy for synthesis of the furan-fused tetracyclic system of xestoquinone was explored through a model study. Using 3-butyn-1-ol as a starting material, 5-iodo-1-methoxymethoxy pentyne (5) was prepared in 5 steps. Reaction of ethyl 2-phenylpropanoate with 5 gave ethyl 7-methoxymethoxy-2-methyl-2-phenyl-5-heptynoate (6) in 88% yield, and then methyl 9-oxo-4-methyl-4-phenyl-2,7-nonadiynoate (13), the key intermediate, was synthesized in 6 steps from the ester 6. Intramolecular cycloaddition reaction of 13 afforded isobenzofuran 14 in 5% yield, which was converted to the tetracyclic structure 15 in the presence of Lewis acid. Keywords: Xestoguinone, Intramolecular, Cycloaddition. . 2. BC MT U VW 'X RS Y Z[+ RS\- ] ^X ^_`+9: GK34'. \ B xestoquinone halenaquinoneL JK a b"W 'c d JK; polyketide $T ef VJ g8A(Fig. 1), halenaquinone halenaquinol L hij. k ;, lKJ xestoquinoneL am n Y opq r /s* t-+o uvw2 (PTK) U x2"W k ; gy- zJ 34 '. 1985{ KitagawaW Y KT m0\ |0+ "# halenaquinone -}TF ~] 1-3. 4-6. 7-8. 8A, 1988{ HaradaL U VW (8aR)-(-) Wieland-Miescher ketone ()*+ Diels-Alder6 7 ^ (+)-halenaquinol (+)-halenaquinone "+,

(3) T8+ l ~]\ F"&'. HaradaL 1990{ (+)-xestoquinone (+)-xestoquinol "# - \ ~]

(4) T8+ F"&'. 1991{W Kanematsu; J K -67 "W (+)-xestoquinone 6 7 zJ"&'. - k ! asymmetric Heck reaction Y Suzuki cross-coupling 67 -." # (+)-halenaquinone (+)-xestoquinone "W \-zJ34'. XestoquinoneL halenaquinone 9. 10. 11. 12,13. 354.

(5) . 355. Xestoquinone. 4-(t-Butyldimethylsilyloxy)-1-butyne (1) 3-Butyn-1-ol(3.50 g, 50.0 mmol), triethylamine(10.45 mL, 75.0 mmol), 4-dimethylaminopyridine (DMAP, 0.61 g,. CH Cl (84 mL) ½.¾ t-butyldimethyl¿;'. - ½. ¾

(6) À, 40D`Á 6 , diethyl ether(250 mL) 9?¸'. ÂL a NH Cl.¾8+ B uJ, a NaCl .¾8+ ÃL , MgSO + Ä $'. ¨© ", ÅÆ"# >L 0Ç M r «+¬Ql®(silica gel, ethyl acetate/hexane, 10%)" # ¤2 , ÈÉ ¼ ÊL ¾E 8.19 g(89%) > 4'. IR(neat) 2864, 2208 cm ; H NMR(CDCl ) δ 3.75 5.0 mmol). 2. 2. chlorosilane(7.45 g, 50.0 mmol). Fig. 1. Xestoquinone. halenaquinone .. 4. 4. \L 'X MT U V - \ k=T8+ "J, l E\ ". - | # \ ^ 3J g'. ,W GHI JK67 -."# xestoquinone " + 2" JH '. 14-17. 3. (t, 2H, J=7.1 Hz), 2.41(tt, 2H, J=7.1 Hz, J=2.7 Hz), 1.97 (t, 1H, J=2.7 Hz), 0.91(s, 9H), 0.10(s, 6H); 13C NMR (75 MHz, CDCl3) δ 81.7, 69.5, 62.0, 26.1, 23.1, 18.6, -5.1. 4-(t-Butyldimethylsilyloxy)-2-pentyn-1-ol (2). 67 %. \ B 3-butyn-ol, 4-dimethylaminopyridine(DMAP), t-butyldimethylchlorosilane, chloromethyl methyl ether, tetramethylammonium fluoride, n-BuLi, diisobutylaluminum hydride, LiAlH4, carbon tetrabromide, pyridinium p-toluenesulfonate(PPTS), pyridium chlorochromate. paraformaldehydeW Aldrich% 2 %."&'. Dess-Martin L gW ¡¢ 2$"# %."&'. %. .\L 'y £- ¤2"# %."&'. Dichloromethane, toluene, triethylamine diisopropylamineL w¥¦ G " , CaH +9: m§"&'. THF5 diethyl etherW w ¥¦ G ", sodium benzophnone8+9: m §"&'. Methyl chloroformate5 γ-terpineneL w¥¦ G ", ¨© " /ª m§"# ¤2"&'. r «+¬Ql®W Merck% silica gel 60-F-254(70-230 mesh) %."&'. *\ F" "# IR P¯°±L Perkin Elmer 1320 grating spectrophotometer %."# ²¤34'. ³ ´H µ¶ P¯°±L Mercury-300(300 MHz) L Unity-300(300 MHz) spectrophotometer %."# ²¤348A, TMS I9· ¸*+ -."&8A, J ¹L Hz+ vtº'. C NMR P¯°±L Mercury-300(75 MHz) L Unity-300 (75 MHz) spectrophotometer %."# ²¤34'. » W¼L Fisher melting point apparatus %."&'. (PCC), imidazole. 16. 2. 13. 2003, Vol. 47, No. 4. −1 1. w¥¦ ;P G ", 4-(t-butyldimethylsilyloxy)1-butyne(1, 1.84 g, 10.0 mmol) Ä$ THF(30 mL) »F , −23 C+ ËÌÍ'. - À Î"_ , n-BuLi(2.50 M solution in hexanes, 4.37 mL, 10.4 mmol) % %."# ÏÏZ T; , 0 C+ À ÐÑ 2D `Á 6'. ' À -23 C+ ËÌÍ , Ä$ paraformaldehyde(0.45 g, 15.0 mmol) 'c Ò vÓ? ¿;'. - 67 £L À, 1D Ô 6"J ,,Z 0 C+ À ÐÑ ,

(7) À, 12D 6'. 67 Õ Öy ×J, diethyl ether(100 mLØ2)+ Ù( '. ÂL a NaCl .¾8+ BÚ ÛÎ Ã ?J, MgSO + Ä$ , ¨© " . ÜÑ , GÝ m§"# ¼ ÊL ÈÉ ¾E 2.08 g (97%) >4'. b.p. 116-118 C/2 mmHg. IR(neat) 3385, o. o. o. o. 4. o. 2903, 2123 cm ; H NMR(CDCl3) δ 4.29(d, J=5.50 −1. 1. Hz), 3.71(t, 2H, J=7.3 Hz), 2.44(brs, 1H), 2.42(t, 2H, J=7.3 Hz), 0.89(s, 9H), 0.070(s, 6H); 13C NMR(75 MHz, CDCl3) δ 83.3, 79.9, 62.1, 62.0, 51.4, 26.2, 26.0, 23.4, -3.2, -4.9. 4-(t-Butyldimethylsilyloxy)-1-methoxymethoxy-2pentyne (3).

(8) À, CH Cl (35 mL)Þ 4-(t-butyldimethylsilyloxy)2. 2. 2-pentyn-1-ol(2, 4.28 g, 20.0 mmol), diisopropylethylamine. chloromethyl methyl ßà+ »F 10D . (18.1 g, 24.4 mL, 140.0 mmol) ether(4.84 g, 60.0 mmol).

(9) . 356. 6'. 67 diethyl ether(150 mL) ;"J, a NaHCO .¾8+ BuJ, a NaCl . ¾8+ ÃJ, MgSO + Ä$ 'y, ¨© " . ÜÑ , r «+¬Ql®(silica gel, diethyl ether/ hexane, 20%á35%)"# âÉ ¼ ÊL ¾E 4.80 g(93%) >4'. IR(neat) 2892, 2213, 1257cm ; H 3. 4. −1. 1. NMR(CDCl3) δ 4.69(s, 2H), 4.18(t, 2H, J=4.19 Hz), 3.72(t, 2H, J=7.3 Hz), 3.37(s, 3H), 2.44(m, 2H), 0.89 (s, 9H), 0.070(s, 6H);. 13. C NMR(75 MHz, CDCl3) δ. 94.8, 84.0, 76.8, 62.1, 55.8, 54.9, 26.0, 23.5, 18.7, -4.9. 5-Methoxymethoxy-3-pentyn-1-ol (4). 4-(t-butyldimethylsilyloxy)-1-methoxymethoxy-2-pentyne(3, 3.57 g, 13.8 mmol) »F .¾ -20 C+ ËÌÍ , - .¾ tetrabutylammonium THF(20 mL) o. fluoride(TBAF, 1.0 M solution in THF, 29.0 mL, 29.0. mmol) ,,Z T;'. - À Î"_, 67 ½ 1D`Á 6'. a NH Cl.¾(40 mL) ;"J diethyl ether(150 mLØ3)+ Ù('. 1 ã Â\L MgSO + Ä$"J, ¨© ", . ÜÑ'. väÎ r «+¬Ql®(silica gel, ethyl acetate/hexane, 20%á50%)"# ¼ ÊL ¾E 1.61 g (81%) >4'. IR(neat) 3403, 2918, 2211 cm ; H 4. 4. −1. 1. 2H, J=7.66 Hz), 2.83(t, 2H, J=7.2 Hz);. 13. C NMR(75. MHz, CDCl3) δ 94.9, 85.4, 55.8, 54.7, 24.3, 1.5, -3.0. Ethyl 7-methoxymethoxy-2-methyl-2-phenyl-5heptynoate (6). w¥¦ ;P G ", Ä$ THF(100 mL) diisopropylamine(1.32 mL, 9.45 mmol) ;"J 0 C , n-BuLi(2.59 M solution in hexanes, 3.19 mL, 8.27 mmol) T; 'y 20GD Ô 6"#¸'(LDA. ¾). THF(10 mL) ethyl 2-phenylpropanoate(1.05 g, 5.90 mmol) »F .¾ -78 C, LDA.¾ Ï ÏZ T;"J 1D Ô 6'. - 67 ½ THF(10 mL)Þ 5-iodo-1-methoxymethoxy-2-pentyne (5, 1.50 g, 5.90 mmol) »F .¾ 15G `Á ç 1 T;'.

(10) À, 24D 6^¸ , a NH Cl .¾(150 mL) ;"J, diethyl ether(200 mLØ2)+ Ù('. 1ã Â\L a NaCl .¾8+ Ã J, MgSO + Ä$ , ¨© " . ÜÑ 'y, r «+¬Ql®(silica gel, ethyl acetate/hexane, 20%) "# ¼ ÊL ¾E 1.58 g(88%) >4'. IR(neat) o. o. 4. 4. 3005, 2971, 2212, 1735 cm−1; 1H NMR(CDCl3) δ 7.32-. 7.23(m, 5H), 4.68(s, 2H), 4.17(t, 2H, J=7.3 Hz), 4.13 (q, 2H, J=0.024 Hz), 3.37(s, 3H), 2.23 and 2.11(2 m,. NMR(CDCl3) δ 4.64(s, 2H), 4.15(t, 2H, J=2.3 Hz), 3.64. 4H), 1.56(s, 3H), 1.19(t, 3H, J=0.024 Hz);. (t, 2H, J=6.2 Hz), 3.32(s, 3H), 2.90(brs, 1H), 2.42(m,. (75 MHz, CDCl3) δ 175.6, 142.9, 128.6, 127.1, 126.1, 94.9,. 2H); C NMR(75 MHz, CDCl3) δ 94.9, 83.9, 77.3, 61.1,. 86.7, 75.9, 61.2, 55.8, 54.9, 50.1, 38.7, 22.8, 15.1, 14.4.. 13. 13. C NMR. 7-Methoxymethoxy-2-methyl-2-phenyl-5-heptynal (7). 55.8, 55.0, 23.4. 5-Iodo-1-methoxymethoxy-2-pentyne (5). 5 CH CN ½.(3:1) 30 mL triphenylphosphine(2.73 g, 10.4 mmol) imidazole(0.71 g, 10.4 mmol) ;"# »F'. - .¾ diethyl ether 5 CH CN ½.(3:1) 30 mL iodine(1.76 g, 6.94 mmol) »F .¾ 0 C, åæ T;'. 67 ½ 0 C, 30G 6uJ,

(11) À, 30 G 6Í , ' 0 C+ ËÌÍ'. - 67½ diethyl ether5 CH CN ½.(3:1) 20 mL Diethyl ether. 3. 3. o. o. o. 3. 5-methoxymethoxy-3-pentyn-1-ol(4, 0.50 g, 3.47 mmol). »F .¾ ¿;"J, 0 C, 1D`Á 6 '. .W ¨© " ÜKJ diethyl ether(100 mLØ2) + Ù( , r «+¬Ql®(silica gel, diethyl ether/ hexane, 40%)"# âÉ ¼ ÊL ¾E 0.71 g (81%) >4'. IR(neat) 2945, 2209, 1230 cm ; H NMR o. −1 1. (CDCl3) δ 4.72(s, 2H), 4.20(s, 2H), 3.39(s, 3H), 3.22(t,. Method A:. Þ. (2 mL). w¥¦ ;P G ", Ä$ toluene. ethyl 7-methoxymethoxy-2-methyl-2-phenyl-. 5-heptynoate(6, 0.50 g, 1.64 mmol). »F .¾. + ËÌÍ, # diisobutylaluminum hydride (1.0 M solution in hexanes, 1.97 mL, DIBAH) 10G ç1 ,,Z T;'. - 67½ -78 C, 2D 6"#¸ , diethyl ether(0.5 mL)Þ potassium fluoride(0.11 g) ; ½ ,,Z ¿;'. 6 7½ # "J, diethyl ether(50 mLØ3)+ Ã? ¸'. 1ã Â\ MgSO + Ä$ , ¨© " . ÜÑ 'y, r «+¬Ql®(silica gel, ethyl acetate/hexane, 30%)"# ¼ ÊL ¾E 0.21 g(49%) >4'. IR(neat) 3002, 2928, 2212, 1722 cm ; H o. -78 C. o. 4. −1. 1. NMR(CDCl3) δ 9.47(s, 1H), 7.33-7.22(m, 5H), 4.67(s,. 2H), 4.15(s, 2H), 3.35(s, 3H), 2.29-2.07 (2 m, 4H), 1.47(s, 3H); 13C NMR(75 MHz, CDCl3) δ 175.7, 143.0, Journal of the Korean Chemical Society.

(12) . 357. Xestoquinone. á. "# ÈÉ õ 2.03 g(76%) >4'.. 128.7, 127.1, 126.2, 94.8, 86.6, 75.8, 55.7, 54.8, 50.0,. 15% 25%). 38.6, 22.6, 14.3.. IR(neat) 3003, 2940, 2205 cm−1; 1H NMR(CDCl3) δ 7.34-. w¥¦ ;P G ", Ä$ diethyl LiAlH (LAH, 0.88 g, 23.08 mmol) èJ é 6"#¸ 'y diethyl ether(10 mL) ethyl. Hz), 3.36(s, 3H), 2.08-2.01(2m, 4H), 1.56(s, 3H);. 7-methoxymethoxy-2-methyl-2-phenyl-5-heptynoate (6,. 94.9, 89.9, 86.5, 76.1, 55.7, 54.8, 46.6, 43.0, 24.1, 14.6.. Method B:. ether(100 mL). 4. »F .¾ -78 C, ÏÏZ T;'. 67½ 3D 6Í , sodium sulfate hydrate(Na SO ·10H O) 4.96 g ;"J 1D Ô 6'. # "# #¾ 8J, ¨© " . ÜÑ , r «+¬Ql®(silica gel, ethyl acetate/ hexane, 20%á40%)"# 7-methoxymethoxy-2-methyl2-phenyl-5-heptyn-1-ol(8, 3.47 g, 86%) >4'. IR o. 4.68 g, 15.38 mmol). 2. 4. 2. (neat) 3408, 3002, 2965, 2201 cm−1; 1H NMR(CDCl3) 7.36-7.21(m, 5H), 4.66(s, 2H), 4.14(s, 2H), 3.68(dd, 2H, J=10.7 Hz, J=26.1 Hz), 3.35(s, 3H), 1.91-1.82(2 m and brs, 5H), 1.35(s, 3H);. 13. C NMR(75 MHz, CDCl3) δ. 143.8, 128.8, 126.8, 126.6, 94.8, 87.3, 75.6, 72.3, 55.8, 55.0, 43.6, 37.9, 21.7, 14.2.. Ä$ CH Cl (80. Þ. 7.21(m, 5H), 6.92(s, 1H), 4.67(s, 2H), 4.16(t, 2H, J=1.9 13. C. NMR(75 MHz, CDCl3) δ 145.4, 144.7, 128.6, 127.0, 126.5, 8-Methoxymethoxy-3-methyl-3-phenyl-1,6-octadiyne (10). w¥¦ ;P G ", Ä$ THF(18 mL)Þ 1,1-dibromo-8-methoxymethoxy-3-methyl-3-phenyl-1-. »-J -78 C+ o. octen-6-yne(9, 0.50 g, 1.20 mmol). ËÌÍ'. n-BuLi(2.54 M solution in hexanes, 0.95 mL, 2.40 mmol) 5G ç1 T;"J, - À Î" _, 1D `Á 6'.

(13) À, 1D`Á Ô 6"#¸ , m§(15 mL) ;"# 67 B/ Í'. THFÂL GK3J, ÂL diethyl ether(15 mL Ø3)+ Ù("J, 1ã Â a NaCl .¾ 8+ ÃJ, MgSO + Ä$ 'y r «+¬Ql® (silica gel, ethyl acetate/hexane, 15%)"# ÈÉ ¼ ÊL ¾E 0.30 g(97%) >4'. IR(neat) 3010, 2951, 4. 7-methoxymethoxy-2-. 2212, 2205 cm−1; 1H NMR(CDCl3) δ 7.49-7.22(m, 5H),. methyl-2-phenyl-5-heptyn-1-ol(8, 3.46 g, 13.20 mmol),. 4.68(s, 2H), 4.15(s, 2H), 3.36(s, 3H), 2.44(s, 1H), 2.46-. sodium acetate(0.27 g, 3.29 mmol). 2.05(2m, 4H), 1.61(s, 3H); 13C NMR(75 MHz, CDCl3). 2. 2. mL). 5 PCC (5.90 g, 27.36 mmol) »F'. 67½

(14) À, 2D 6 ` Á 6"#¸ , Ä$ diethyl ether(200 mL) ; '. - .¾ Florisil(50 g)- êëã r !"# ì J Ä$ diethyl ether d¾8+ %.'. .. íwgW JE diethyl ether+ îïZ ÃL , ' Florisil- êëã r ! Í'. 1ã # L MgSO + Ä$uJ, ¨© " . ÜÑ , r «+¬Ql®(silica gel, ethyl acetate/hexane, 20%) "# ðñ"-[(7, 3.36 g, 98%) >4'. 4. 1,1-Dibromo-8-methoxymethoxy-3-methyl-3-phenyl-1octen-6-yne (9). carbon tetrabromide(4.26 g, 12.85 mmol) ½, CH Cl (80 mL)Þ 7-methoxymethoxy-2-methyl-2-phenyl-5heptynal(7, 1.67 g, 6.43 mmol) »F .¾ 0 C , åæ T;'. £L À Î"_, 67½ 3D`Á 6 , 67½ Õ npentene(400 mL) 9?J, - ò óÉô¤ # "# 20'. #¾ ¨© ", . ÜÑ 'y, r «+¬Ql®(silica gel, ethyl acetate/hexane, Triphenylphosphine(6.74 g, 25.70 mmol). 2. o. 2003, Vol. 47, No. 4. 2. δ 143.8, 128.6, 127.0, 126.1, 94.8, 88.3, 86.8, 75.7, 72.7, 55.7, 54.9, 43.0, 40.5, 30.5, 15.5. Methyl 9-methoxymethoxy-4-methyl-4-phenyl-2,7nonadiynoate (11). w¥¦ ;P G ", Ä$ THF(10 mL)Þ. 8-methoxymethoxy-3-methyl-3-phenyl-1,6-octadiyne (10, 0.32 g, 1.25 mmol). »F .¾ -78 C+ ËÌ o. Í , - .¾ n-BuLi(2.56 M solution in hexanes, 0.54 mL, 1.37 mmol) % -."# åæ T;'. - 67½ -78 C, 1D6 6 "#¸ 'y, methyl chloroformate(0.12 mL, 1.50 mmol) T;'(.¾). - 67½ -20 C, 20 G 6"#¸ , ' 90G ç1 22 C+ ,,Z À ÐÑ'. 67L a NH Cl ;"# B/uJ, diethyl ether(30 mLØ3)+ Ù( 'y, a NaCl .¾8+ Ã?J, MgSO + Ä$ , ¨© " . ÜÑ'. väÎ r «+¬Ql®(silica gel, ethyl acetate/hexane, 20%)"# ¼ ÊL ¾E 0.32 g (80%) >4'. IR(neat) 3002, 2977, 2214, 2201, 1675 o. o. o. 4. 4. cm−1; 1H NMR(CDCl3) δ 7.45-7.22(m, 5H), 4.66 (s,2H),.

(15) . 358. 4.13(t, 2H, J=2.06 Hz), 3.79(s, 3H), 3.35(s, 3H), 2.362.00(2m, 4H), 1.64(s, 3H); 13C NMR(75 MHz, CDCl3) δ 154.2, 142.2, 128.8, 127.4, 125.9, 94.8, 92.2, 86.1, 76.7, 76.1, 55.8, 54.9, 53.0, 42.5, 40.8, 29.7, 15.8. Methyl 9-hydoxyl-4-methyl-4-phenyl-2,7-nonadiynoate (12). Þ methyl 9-methoxymethoxy-4methyl-4-phenyl-2,7-nonadiynoate(11, 0.32 g, 1.00 mmol)5 t-Butyl alcohol(15 mL). pyridinium p-toluenesulfonate(PPTS, 2.52 g, 10.00 mmol). »F §Í'. - 67½ 7D §Í ,

(16) À8+ ËÌuJ, # m§(15 mL) ; 'y diethyl ether(50 mLØ3)+ Ù('. 1ã etherÂ\L m§+ Ã? 9G t-butyl alcohol 20"J, MgSO + Ä$ 'y, ¨© " . Ü Ñ'. väÎ r «+¬Ql®(silica gel, ethyl acetate/ hexane, 30%)"# ðöÐ 0.21 g(76%) >4'. IR(neat) 4. 3445, 3003, 2988, 2220, 2201, 1675 cm−1; 1H NMR(CDCl3). δ 7.45-7.24(m, 5H), 4.15(s, 2H), 3.78(s, 3H), 2.29-2.08 (2m and brs, 5H), 1.63(s, 3H); 13C NMR(75 MHz, CDCl3) δ 154.4, 142.2, 128.8, 127.4, 126.0, 92.5, 85.3, 79.3, 76.8, 53.1, 51.4, 42.4, 40.8, 29.8, 15.7.. Þ. CH2Cl2(10 mL). methyl 9-hydoxyl-4-. methyl-4-phenyl-2,7-nonadiynoate(12, 0.18 g, 0.67 mmol). (0.31 g, 0.73 mmol) ;"J 0 C , 2D`Á é 6'. 67½ 1 M Na S O (7 mL)5 1 M a NaHCO (7 mL).¾ ½.¾ 9?J, é ÷\?¸'. CH Cl ÂL 8J, Â L CH Cl + Ù('. 1ã CH Cl ÂL a NaHCO + B"J, a NaCl .¾8+ ÃJ, MgSO + Ä $ , ¨© " . ÜÑ'. väÎ r «+¬ Ql®(silica gel, ethyl acetate/hexane, 30%)"# ð ñ"-[ 0.15 g(81%) >4'. IR(neat) 3011, 2945, Dess-Martin. 18. o. 2 2. 3. 3. 2. 2. 2. 2. 2. 2. 3. 4. 2221, 2214, 1672, 1645 m−1; 1H NMR(CDCl3) δ 9.08(s,. 1H), 7.47-7.25(m, 5H), 3.81(s, 3H), 2.51-2.16(2m, 4H), 1.68(s, 3H); 13C NMR(75 MHz, CDCl3) δ 177.1, 154.1, 141.5, 129.0, 127.7, 126.0, 97.9, 91.4, 82.1, 77.2, 53.1, 41.3, 40.9, 29.8, 16.2. 5-Hydro-4-methyl-4-phenyl-2-methoxycarbonyl isobenzofuran (14). Þ methyl 9-oxo-4-methyl-4-phenyl-2,7nonadiynoate(13, 0.10 g, 0.37 mmol), Ä$ toluene(8 mL) 10 mL tube. o. −1 1. NMR(CDCl3) δ 7.46-7.35(m, 5H), 6.50(s, 1H), 6.58(dt,. 1H), 5.93(dt, 1H), 3.82(s, 3H), 2.72(d, 2H), 2.01(s, 3H); C NMR(75 MHz, CDCl3) δ 152.2, 149.8, 133.0, 132.0,. 13. 128.4, 126.7, 125.1, 124.9, 120.1, 116.3, 23.9, 19.8. 10b-Methyl-phenanthro-[9,1-bc]furan-6-(10bH)-one (15) 0.39 mmol). Þ boron tribromide(99 mg, 0.037 mL, ;"J é 6"#¸ , - .¾ CH Cl. (1 mL). 5-hydro-4-methyl-4-phenyl-2-methoxycar-. CH2Cl2(1 mL). Þ. 2. 2. »F . ¾ -10 C, T;'.

(17) À8+ À ÐÑ 24 D 6"#¸ 'y, `ú 9® 0 C+ ËÌ 1 M H PO 9?¸'. CH Cl (20 mLØ2)+ Ù(" J, 1ã Â\L a NaCl .¾8+ ÃJ, Na SO + Ä$"J, ¨© " . ÜÑ , r « +¬Ql®(silica gel, ethyl acetate/hexane, 50%)"# É JE 4.8 mg (42%) >4'. IR(KBr) 3002, bonylisobenzofuran(14, 10 mg, 0.039 mmol) o. o. 3. 2. Methyl 9-oxo-4-methyl-4-phenyl-2,7-nonadiynoate (13). Ä$. γ -terpinene(0.066 mL, 0.41 mmol) èJ 15GD w¥¦ ;P ì? 67Þ øùC E 20'. Sealed tubeÞ, - 67½ 110 C , 30D`Á ;]'.

(18) À8+ ËÌuJ, ¨© ", . ÜÑ , r «+¬Ql®(silica gel, ethylacetate/hexane, 50%)"# âÉ õ 5 mg (5%) >4'. IR(neat) 3018, 3001, 2962, 1672 cm ; H. 4. 2. 2. 4. 2940, 2830, 1653, 1592 cm−1; 1H NMR(CDCl3) δ 7.467.35(m, 4H, ArHs), 7.57(s, 1H, C-4), 6.62(dd, 1H, C3, J=2.6, 7.4 Hz), 6.11(ddd, 1H, C-2, J=4.2, 10, 14 Hz), 3.13 2.56(dd ddd, 2H, C-1), 1.56(s, 3H, 10b-CH3); 13C NMR(75 MHz, CDCl3) δ 172.7, 148.5, 144.2, 143.1, 141.5, 132.4, 128.8, 121.0, 117.5, 35.4, 35.2, 32.2..

(19) Xestoquinone ab"J gW - 4 $ L Fig. 2 û z #ã'. 5-Iodo-1-methoxymethoxypentyne 2$". ^,(Scheme 1), üï + A ¡¢ propargyl alcohol ý NO " MOMCl5 67þ'. TLC ÿ, 67L é ã"&8v, 67 GÝm§ ^ 3-methoxymethoxypropyne GK"W ¤, azeotrope ÿ8+ .5 b m§348A Kugelrohr -."&8v .5 67 *+9: GK ; Î '. 'y /, ethylene oxide Journal of the Korean Chemical Society.

(20) . 359. Xestoquinone. Fig. 2. Retrosynthesis of a furan-fused tetracyclic system.. Scheme 1.. '. ; Î 8A, - # ;Î ? ®" "# # /-Î

(21) ÌÌ L <= G K; /\+ + B "&'. 3-Butyn-1-ol ý 5 F DMAP NO" TBDMSCl 67 "-[ zp"&'. > ?ã M n-BuLi K"J -23 C, aõð ñ"-[ 67 ðöÐ 2 97% <=+ 2 $"&'. IR P¯°±ÿ, "-[ oÆ ; 3385 cm 9|, vt'. 2 "-[. zpW dÚ ý $Ä", Á ¤" MOMCl"#%."&8A diisopropylethyl amine"

(22) À, 10D 67 93% <=+ 3 >4'. , zp + -.34 TBDMS. W 1.0 M TBAF

(23) À, 1D K"# 20" &8A, H NMR P¯°±ÿ, 0.89 ppm 0.07 ppm o. −1. 1. 2003, Vol. 47, No. 4. , vt TBDMS efTF oÆ \%¢ÎJ 2.90 ppm, "-[ oÆ F"&'. ¬Î8+ "-[ C[ + u "# ethyl acetate5 acetonitrile 3:1½ ., iodine, triphenylphosphine, imidazole b 0 C, K"&8A, 5-iodo-1-methoxypentyne (5) 81% <=+ >4'. Diyne > W 'y 7/ ^, 34'(Scheme 2). üï 2-phenylpropanoate5 5 6 7L # ;Î $Ä", 348A, LDA ."W $Ä, ; ÊL <=(88%)+ ã34'. P: 6 ðñ"-[ 7+ "W 67L TF 2+, DIBAH -."&8A, tolueneÞ, 2 D 67 45-49% <=+ ã34'. H NMR P¯°±ÿ, 9.47 ppm, ðñ"-[ efT o. 1.

(24) . 360. Scheme 2.. F oÆ F"&'. lv - 67L # Ò 67 ø"J 9+, ðöÐ M(4047%)- 34'. l, h 2F LiAlH -."# ðöÐ+ þ8A(86%), >?ã ðöÐ 8 TF 2F PCC K"# ðñ"-[ 7 98% <=+ >48A, /-Î

(25) y , L <= GK ? J"_ Ô k=TF -¢ MÌ34'. ðñ"-[ 7 w 108+ u "# Corey-Fuchs 67 ."&8A, 7 2!Õ CBr 5 4!Õ PPh 67 76% <=+ dibromoalkene(9) > g48A, H NMR P¯°±ÿ, 6.92 ppm, vinyl proton efTF oÆ F"&'. 9 2!Õ n-BuLi K"# 97% <=+ 10 >4'. 2$ w 10 THF »-J -78 C 4. 19. 4. 3. 1. o. , n-BuLi K , chloromethyl formate 67 P: 11 80% <"+ >4'. zp + -. MOM 20" "# t-BuOHÞ, 10.0 !Õ PPTS ; 5D § ðöÐ 12 76% <"+ >48A, sodium acetate " T 2F Dess-Martin 0 C, 67 ðñ"-[ 13 81% <"+ >4'. H NMR P ¯°±ÿ, 2.29-2.08 ppm, vt ðöÐ singlet efTF oÆ ; %¢ÎJ, 9.08 ppm , ðñ"-[ singlet efTF oÆ F "&'. Scheme 3 ¡¢ diyne 13 JK ¿;67 ^, Ä$ tolueneÞ 13 »-J 67 ^3W ;P 20(degas) , H¢#$ ò "# γ-terpinene ;"&'. 67 ÀW y 80 C o. 1. o. Scheme 3. Journal of the Korean Chemical Society.

(26) . 361. Xestoquinone. Scheme 4.. , 15D 67þ8v TLCÿ, 0 67L ã 3Î 8A, 110 C+ À Ð 30D 67 Í JK ¿;67 MF isobenzofuran 14 5% <=+, > g4'. γ-Terpinene o "# BHT5 phenol -. 6%

(27) , Ô ÿ ÊL <=L >?ÎÎ 8A, À 180 C + Ð& 67 ú9; ,,Z G^34'. 67 ô W 1998{ Danheiser - zJ 67. ú"A, Scheme 4 z#ã'. ¬Î8+, 14 $Ä", 24D 67 4 $ 15 42% <=+ > g4'. H NMR P¯°±ÿ, 3.82 ppm, vt methoxy methyl oÆ ; %¢' F"&'. !"# (KW JK ¿;67 -."# xestoquinone " + ; ) 2"&'. lv ø"* ] JK ¿;67 /, ( L <=+ ã"& 8A, - / "# + Ô ÊL <= + 67$Ä , ^ B g'. o. o. 20. 1. W 2001{ -+ - ?@y. 2003, Vol. 47, No. 4. 1. Deborah, M. R.; Scheuer, P. J. J. Am. Chem. Soc. 1983, 105, 6177. 2. Kobayashi, M.; Shimizu, N.; Kyogoku, Y.; Kitagawa, I. Chem. Pharm. Bull. 1985, 33(3), 1305. 3. Nakamura, H.; Kobayashi, J.; Kobayashi, M.; Ohizumi, Y.; Hirata, Y. Chem. Lett., 1985, 713. 4. Kobayashi, M.; Nakamura, H.; Kobayashi, J.; Ohizumi, Y. J. Pharmacol. Exp. Ther. 1990, 257, 82. 5. Kobayashi, M.; Muroyama, A.; Nakamura, H.; Kobayashi, J.; Ohizumi, Y. J. Pharmacol. Exp. Ther. 1990, 257, 90. 6. Sakamoto, H.; Furukawa, K.; Matsunaga, K.; Nakamura, H.; Ohizumi, Y. Biochemistry, 1995, 34, 12570. 7. Lee, R. H.; Slate, D. L.; Moretti, R.; Alvi, K. A.; Crews P. Biochem. Biophys.Res. Commun. 1992, 184(2), 765. 8. Alvi, K.; Rodriguez, J.; Diaz, M. C.; Moretti, R.; William, R. S.; Lee, R. H.; Slate, D. L.; Crews, P. J. Org. Chem. 1993, 58, 4871. 9. Harada, N.; Sugioka, T.; Ando, Y.; Uda, H.; Kuriki, T. J. Am. Chem. Soc. 1988, 110, 8483. 10. Harada, N.; Sugioka T.; Uda, H.; Kuriki, T. J. Org. Chem. 1990, 55, 3158. 11. Kanematsu, K.; Soejima, S.; Wang, G., Tetrahedron Lett. 1991, 32, 4761..

(28) 362. . 12. Kojima, A.; Takemoto, T.; Sodeoka, M.; Shibasaki, M. J. Org. Chem. 1996, 61, 4876. 13. Miyazaki, F.; Uotsu, K.; Shibasaki, M.; Tetrahedron 1998, 54, 13073. 14. Carlini, R.; Higgs, K.; Older, C.; Randhawa, S. J. Org. Chem. 1997, 62, 2330. 15. Sutherland, H. S.; Souza, F. E. S.; Rodrigo, R. G. A. J. Org. Chem. 2001, 66, 3639. 16. Sutherland, H. S.; Higgs, K. C.; Taylor, N. J.; Rodrigo,. R. Tetrahedron, 2001, 57, 309. 17. Toyooka, N.; Nagaoka, M.; Sasaki, E.; Qin, H.; Kakuda, H.; Nemoto, H. Tetrahedron, 2002, 58, 6097. 18. Dess, D. B.; Martin, J. C. J. Am. Chem. Soc. 1991, 113, 7277. 19. Corey, E. J.; Fuchs, P. L. Tetrahedron Lett. 1972, 36, 3769. 20. Wills, M. S. B.; Danheiser, R. L. J. Am. Chem. Soc. 1998, 120, 9378.. Journal of the Korean Chemical Society.

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A Model Study toward the Synthesis of Xestoquinone Xestoquinone  

A Model Study toward the Synthesis of Xestoquinone Xestoquinone