Synthetic Studies toward Neopeltolide:A Potent Anti-cancer Natural Product
- Corresponding author: Yang Zhen, yangzhen09@usx.edu.cn
Citation:
Yu Jiangfan, Feng Ruokun, Yang Zhen. Synthetic Studies toward Neopeltolide:A Potent Anti-cancer Natural Product[J]. Chinese Journal of Organic Chemistry,
;2017, 37(10): 2526-2543.
doi:
10.6023/cjoc201703017
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Ji-Quan Liu , Huilin Guo , Ying Yang , Xiaohui Guo . Calculation and Discussion of Electrode Potentials in Redox Reactions of Water. University Chemistry, 2024, 39(8): 351-358. doi: 10.3866/PKU.DXHX202401031
Reagents and conditions: (a) (ⅰ) BH3•SMe2, THF; (ⅱ) TBDPSCl, DMF; (ⅲ) DIBAL-H, Et2O, -78oC; (ⅳ) 1, 3-propanedithiol, I2, CHCl3, 68% (over 4 steps). (b) (ⅰ) t-BuLi, THF, 5, -78oC; (ⅱ) CaCO3, MeI, MeCN/H2O, 50% (over 2 steps). (c) (ⅰ) Zr(Ot-Bu)4, i-PrCHO, -78oC. (ⅱ) Me3OBF4, Proton Sponge, CH2Cl2, 90%. (ⅲ) 49% HF in H2O, MeCN, r.t., 91%. (ⅳ) (COCl)2, DMSO, CH2Cl2, Et3N, -78oC to r.t., 73% (over 4 steps). (d) 8, TfOH, CH2Cl2, benzene, -78oC, 75% (dr 10:1). (e) (ⅰ) NaCN, DMF, 60oC, 84%; (ⅱ) DIBAL-H, Et2O, -78 oC, 96%; (ⅲ) DIBAL-H, CH2Cl2, -78oC, 60%; (f) (ⅰ) NaClO2, NaH2PO4•H2O, t-BuOH, H2O, 85%. (ⅱ) 2, 4, 6-trichlorobenzoyl chloride, toluene, DMAP, Et3N, 44%; (g) (ⅰ) Hg(O2CCF3)2, then NaBH4, 63% (d.r. > 20:1); (ⅱ) 12, EDCI, HOBT•H2O, CH2Cl2, 99%; (ⅲ) 18-crown-6, KHMDS, -78oC, then 13, 85oC, 62%
Reagents and conditions: (a) (ⅰ) CF3CO2H, 0 ℃, aq. NH4OH; (ⅱ) BnOC(NH)CCl3, TfOH (cat.); (ⅲ) PdCl2, CuCl2, DMF, H2O, O2 (64% for 3 steps). (b) (ⅰ) 16, Cy2BCl, Et3N; (ⅱ) PPh3MeBr, KHMDS, then HCl quench (75% for 2 steps). (c) (ⅰ) Et2BOMe, NaBH4; (ⅱ) TMSOK, Et2O; (ⅲ) 2, 4, 6-trichlorobenzoyl chloride, toluene, DMAP, Et3N (55% for 3 steps). (d) (ⅰ) H2, Pd/C; (ⅱ) p-NO2C6H4CO2H, PPh3, DEAD; (ⅲ) K2CO3, MeOH; (ⅳ) Me3OBF4; (ⅴ) H2, Pd(OH)2 (41% for 5 steps). (e) 20, PPh3, DIAD, 83%
Reagents and conditions: (a) (ⅰ) (S)-BINAP, Ru(Ⅱ), H2; (ⅱ) TBDPSCl, Imidazole; (ⅲ) DIBAL-H, -78 oC (90% for 3 steps). (b) (ⅰ) 22, CH2Cl2; (ⅱ) Me3OBF4; (c) (ⅰ) OsO4, NMO; (ⅱ) NaIO4, MeOH (70% for 4 steps). (d) Ph3P=CHCOSEt, CH2Cl2; (ⅱ) MeMgBr, CuBr•SMe2, (S, R)-Josiphos (86% for 2 steps). (e) (ⅰ) Et3SiH, Pd/C; (ⅱ) 27, TFA, -5oC; (ⅲ) K2CO3, MeOH (62% for 3 steps). (f) (ⅰ) MOMCl, DIPEA; (ⅱ) H2, Pd/C; (ⅲ) DMP, NaHCO3; (ⅳ) NaClO2, NaH2PO4(86% for 4 steps); (g) (ⅰ) TBAF, THF; (ⅱ) Yamaguchi lactonization; (ⅲ) HCl (80% for 3 steps); (h) 20, PPh3, DIAD, 80%
Reagents and conditions: (a) (ⅰ) NaH, Cl3CCN, Et2O, 0 ℃, 100%; (ⅱ) 31, TfOH, cyclohexane, 77%; (b) 33, CuI, i-Pr2NH, [(Ph3P)2PdCl2], 89%; (c) [Pt(DVDS)], THF, then H2O2, KF, Bu4NF, KHCO3, DMF, 40 ℃, 57% (67% based on starting-material purity); (d) (ⅰ) EtCHO, SmI2, THF, -10℃, 77%; (ⅱ) Me3OBF4, proton sponge, CH2Cl2, 0 ℃, 93%; (e) (ⅰ) LiOH, H2O, MeOH, 45 ℃; (ⅱ) Et3N, 2, 4, 6-Cl3BzCl, THF, then DMAP, toluene, 65 ℃, 72% (two steps). (f) HOAc, Na2CO3, [{Ru(p-cymene)Cl2}2], 1-decyne, (2-furyl)3P, toluene, 80 ℃, 82%. (g) DDQ, 2, 6-Cl2Py, LiClO4, DCE, 65%. (h) H2, Pd/C, EtOH, 74%. (ⅰ) NaBH4, MeOH, 95%. (ⅱ) 20, PPh3, DIAD, 93%
Reagents and conditions: (a) (ⅰ) (+)-Ipc2BOMe, allylMgBr; (ⅱ) MPMOC(=NH)CCl3, La(OTf)3. (b) (ⅰ) Grubbs' Ⅱ, methyl acrylate; (ⅱ) DIBALH, -78 ℃ (45% for 4 steps). (c) (ⅰ) (-)-DET, Ti(Oi-Pr)4, t-BuO2H; (ⅱ) PPh3, I2; (ⅲ) Zn, AcOH (73% for 3 steps). (d) (ⅰ) BOMCl, DIPEA; (ⅱ) DDQ, pH 7 buffer (72% for 2 steps). (e) (ⅰ) Ac2O, Et3N, DMAP; (ⅱ) KHDMS, (PhO)2P(O)Cl, -78 ℃; (f) (ⅰ) B-MeO-9-BBN, t-BuLi, then 47, Pd(PPh3)4; (ⅱ) Grubbs Ⅱ, 70 ℃; (ⅲ) H2, Pd/C, EtOAc (63% for 3 steps); (g) (ⅰ) TBAF, THF; (ⅱ) SO3•Pyr., Et3N, DMSO; (h) (ⅰ) NaClO2, NaH2PO4, t-BuOH; (ⅱ) TMSCHN2, MeOH (86% for 4 steps). (ⅰ) (ⅰ) DDQ, pH=7 buffer; (ⅱ) TMSOK, Et2O; (ⅲ) Yamaguchi lactonization (92% for 3 steps). (j) H2, Pd(OH)2/C; (k) 20, PPh3, DIAD, 61%
Reagents and conditions: (a) (ⅰ) (R)-(+)-Synphos-Ru(Ⅱ), H2; (ⅱ) MeNH(OMe)•HCl, AlMe3(87% for 2 steps). (b) (ⅰ) (2-methylallyl)magnesium chloride; (ⅱ) PhCHO, SmI2 (68% for 2 steps). (c) (ⅰ) acryloyl chloride, DIPEA; (ⅱ) Grubbs Ⅱ, reflux (83% for 2 steps). (d) H2, Pd/C, then, PPTS, n-PrOH; (ⅱ) MeO3BF4; (ⅲ) DIBALH, -78 ℃ (69% for 3 steps). (e) InBr3, 56%, 77%. (f) [CpRu(MeCN)3]PF6, but-3-enal, AcOH, 28%~58%. (g) (ⅰ) OsO4, NaIO4; (ⅱ) NaClO2, KH2PO4; (ⅲ) Yamaguchi lactonization; (ⅳ) NaBH4, MeOH (73% for 4 steps). (h) 20, PPh3, DIAD, 75%
Reagents and conditions: (a) (ⅰ) (S)-BINAP-Ru(Ⅱ), H2; (ⅱ) TBSCl, DMF; (ⅲ) DIBALH, -78 ℃ (76% for 3 steps). (b) (ⅰ) (-)-Ipc2B(2-methylallyl); (ⅱ) NaH, MeI (77% for 2 steps). (c) (ⅰ) O3, DMS; (ⅱ) (OMe)2POCH2CO2Me, NaH (68% for 2 steps). (d) (ⅰ) DIBALH, -78 ℃; (ⅱ) DMP, NaHCO3; (ⅲ) 62, Hantzch ester, dr=3:1 (86% for 3 steps). (e) 65, 4 Å MS, 8 d, CHCl3, 78%. (f) (ⅰ) DDQ, pH 7 buffer; (ⅱ) DMP, NaHCO3; (ⅲ) NaClO2, NaH2PO4; (ⅳ) TBAF, THF (88% for 4 steps). (g) (ⅰ) Yamaguchi lactonization; (ⅱ) NaBH4, MeOH (79% for 2 steps). (h) 20, PPh3, DIAD, 53%
Reagents and conditions: (a) (ⅰ) Lipase PS-30, n-PrOH; (ⅱ) BH3•Me2S, THF (98% for 2 steps). (b) (ⅰ) Swern oxidation; (ⅱ) (CH2OH)2, PPTS (89% for 2 steps). (c) (ⅰ) LiAlH4, Et2O; (ⅱ) OsO4, NaIO4; (ⅲ) (+)-Ipc2BOMe, allylMgBr (58% for 3 steps). (d) (ⅰ) NaH, MeI; (ⅱ) OsO4, NaIO4; (ⅲ) (-)-Ipc2BOMe AllylMgBr (64% for 3 steps). (e) (ⅰ) PPTS, AcOH; (ⅱ) LiCl, DIPEA; MeCOCH2P(O)(OMe)2; (ⅲ) TESOTf, Et3N (81% for 3 steps). (f) 74, TFA, 4 Å MS, 75, 83%; (g) (ⅰ) (CH2OH)2, PTSA; (ⅱ) NaCN, DMF (48% for 2 steps). (h) (ⅰ) 10% NaOH, EtOH; (ⅱ) PTSA, acetone (74% for 2 steps). (ⅰ) Yamaguchi esterification, 40%; (j) (ⅰ) Pd/C, H2; (ⅱ) NaBH4, EtOH (71% for 2 steps). (k) 20, PPh3, DIAD, 78%
Reagents and conditions: (a) (ⅰ) (OMe)MeNH2Cl, THF, i-PrMgBr; (ⅱ) PMB-OC(NH)CCl3, PPTS (68% for 2 steps). (b) (ⅰ) 82, t-BuLi; (ⅱ) DDQ, buffer. (c) (ⅰ) SmI2, PhCHO; (ⅱ) MeOTf, DTBMP; (ⅲ) K2CO3, MeOH (29% from 81). (d) (ⅰ) 85, Yamaguchi condition; (ⅱ) HF•pyridine; (ⅲ) TEMPO, H5C6I(OAc)2 (76% for 3 steps). (e) (ⅰ) Sc(OTf)3, CaSO4; (ⅱ) DMSO, H2O (21% for 2 steps). (f) (ⅰ) NaBH4, MeOH; (ⅱ) 20, DIAD, Ph3P (76% for 2 steps).
Reagents and conditions: (a) (ⅰ) 87, CSA, CH2Cl2; (ⅱ) NaH, BnBr, TBAI, THF/DMF (5:1); (ⅲ) O3, CH2Cl2, -78 ℃, Ph3P (49% for 3 steps). (b) (ⅰ) CH2C(CH3)CH2TMS, TiCl4, -78 ℃; (ⅱ) 89, DCC, DMAP, CH2Cl2 (78% for 2 steps). (c) (ⅰ) Rh(CO)2(acac), H2/CO; (ⅱ) H2SO4, HC(OMe)3; (ⅲ) KOH, EtOH; (ⅳ) NaH, MeI (40% for 4 steps). (d) (ⅰ) H2, Pd/C, MeOH; (ⅱ) 92, DCC, DMAP; (ⅲ) DDQ, pH 7 buffer (81% for 3 steps). (e) (ⅰ) TESOTf, TMSOAc; (ⅱ) K2CO3, MeOH (68% for 2 steps). (f) 20, DIAD, Ph3P, 79%
Reagents and conditions: (a) (ⅰ) TBSCl, imidazole; (ⅱ) OsO4, NaIO4 (58% for 2 steps). (b) (ⅰ) (+)-Ipc2BOMe, allylMgBr; (ⅱ) Grubbs' Ⅱ, methyl acrylate (78% for 2 steps). (c) (ⅰ) BOMCl, DIPEA; (ⅱ) TBAF, THF (90% for 2 steps). (d) (ⅰ) DBU, toluene; (ⅱ) TMSOK, Et2O; (ⅲ)98, Yamaguchi esterification (38% for 3 steps). (e) (ⅰ) Grubbs' Ⅱ, toluene, 1, 4-benzoquinone; (ⅱ) H2, Pd/C, Pd(OH)2/C (79% for 2 steps)
Reagents and conditions: (a) 101 (7.5 mol%), B2(pin)2, NaBO3, MeOH, THF, 86% (er=95:5). (b) (ⅰ) (2-methylallyl)magnesium chloride, PPTS, CH2Cl2; (ⅱ) SmI2, PhCHO; (ⅱ) Me3OBF4, proton sponge; (ⅲ) KOH, MeOH (53% from 52). (c) 1-(vinyloxy)butane, 103 (0.6 mol%), benzene, 88%, (er=99:1). (d) (ⅰ) 1.0 mol/L HCl, THF; (ⅱ) NaClO2, NaH2PO4 (86% for 2 steps). (e) EDC, DMAP, Et3N, 88%. (f) (ⅰ) 107 (8.0 mol%), toluene, 89%, (Z/E > 98:2). (g) (ⅰ) Pd/C, H2, EtOH; (ⅱ) 20, DIAD, Ph3P (68% for 2 steps)
Reagents and conditions: (a) 110 (3.0 mol%), vinyl-B(pin), 86% (Z:E > 98:2). (b) Pd(dppf)Cl2 (10 mol%), 112, 82%. (c) (ⅰ) PPh3, CBr4, 2, 6-lutidine, 81%; (ⅱ) CuCN (50 mol%), allylMgBr, 70%. (d) Z-2-butene-1, 4-diol, 115 (10 mol%), 70%. (e) (ⅰ) Dess-Martin, NaHCO3; (ⅱ) NaClO2, NaH2PO4•H2O, t-BuOH, H2O, 85% (75% for 2 steps)
Reagents and conditions: (a) (ⅰ) n-BuLi, THF, 1 h, then (R)-5-iodo-4-methylpenten; (ⅱ) n-BuLi, THF, then (R)-epichlorohydrin (66% for 2 steps). (b) (ⅰ) EtMgBr, CuI; (ⅱ) MeI, CaCO3 (84% for 2 steps). (c) (ⅰ) PhCHO, SmI2; (ⅱ) MeO3BF4 (81% for 2 steps). (d) (ⅰ) AD mix-β; (ⅱ) NaH, N-p-toluene sulfonylimidazole (85% for 2 steps). (e) (ⅰ) n-BuLi, HMPA, THF, 122, 75%; (f) MnO2, 3 h, then dimethyltriazolium iodide, MnO2, DBU, MeOH; (ⅱ) 0.1 mol/L LiOH, MeOH/THF (V:V=1:3) (77% for 2 steps). (g) (ⅰ) MNBA, CH2Cl2; (ⅱ) MeI, CaCO3; (ⅲ) NaBH4, MeOH (57% for 3 steps)
Reagents and conditions: (a) (ⅰ) TBDPSCl, DMF, imidazole; (ⅱ) mCPBA, CH2Cl2; (ⅲ) (S, S)-(Salen)Co(Ⅲ)(OAc), H2O; (b) (ⅰ) AcCl, -78 ℃; (ⅱ) MsCl, Et3N; (ⅲ) K2CO3, MeOH (71% from 125); (c) (ⅰ) vinylmagnesium bromide, CuI, THF, -40~0 ℃; (ⅱ) KH, MeI (81% for 2 steps); (ⅲ) (R, R)-(Salen)Co(Ⅲ)(OAc), H2O (60% from 126A). (d) (ⅰ) EtMgBr, CuI; (ⅱ) BnO(NH)CCl3, CF3SO3H; (ⅲ) TBAF, THF (77% for 3 steps). (e) (ⅰ) TsCl, Et3N; (ⅱ) NaCN, NaI; (ⅲ) DIBAL-H, -78 ℃ (75% for 3 steps). (f) 130, LiCl, DIPEA, 77%. (g) (ⅰ) HF-Py, CH3CN; (ⅱ) Pd(CH3CN)4BF4, CH2Cl2, r.t. (38% for 2 steps). (h) (ⅰ) Pd/C, H2; (ⅱ) TEMPO, BAIB; (ⅲ) NaClO2, KH2PO4; (ⅳ) Yamaguchi lactonization (61% for 4 steps)
Reagents and conditions: (a) (ⅰ) BH3•SMe2, THF; (ⅱ) (OMe)MeNH2Cl, i-PrMgCl; (ⅲ) DMP, NaHCO3 (86% for 3 steps). (b) (ⅰ) 134, BF3•Et2O; (ⅱ) BOMCl, DIPEA (55% for 2 steps). (c) 136, n-BuLi, LiDBB, 92%. (d) (ⅰ) SmI2, PhCHO; (ⅱ) Me3OBF4, Proton sponge (79% for 2 steps). (e) ICl, Na2S2O3, 71%. (f) (ⅰ) ethyl propiolate, Bu3P; (ⅱ) AIBN, n-Bu3SnH (93% for 2 steps). (g) (ⅰ) KOH, MeOH; (ⅱ) TCBCl, Et3N, DMAP; (ⅲ) H2, Pd/C (83% for 3 steps)
Reagents and conditions: (a) (ⅰ) 143, Hantzch ester; (ⅱ) TBME, TFA, 144, (S, S)-(Salen) (56% for 2 steps). (b) (ⅰ) NaBH4, CeCl3; (ⅱ) Ac2O, TEA (91% for 2 steps). (c) (ⅰ) LDA, TMSCl; (ⅱ) etheral CH2N2 (90% for 2 steps). (d) (ⅰ) LAH, THF; (ⅱ) TBSCl; (ⅲ) LDBB, THF, -78 ℃, then 148 (51% for 3 steps). (e) (ⅰ) IBX, DMSO; (ⅱ) TBAF, THF (81% for 2 steps). (f) (ⅰ) isobutanal, -50 ℃, Zr(Oi-Bu)4; (ⅱ) NaH, MeI (75% for 2 steps). (g) (ⅰ) K2CO3, MeOH; (ⅱ) PhI(OAc)2, TEMPO; (ⅲ) NaClO2, NaH2PO4; (ⅳ) Yamaguchi lactonization (39% for 4 steps). (h) Hg(OTFA)2, THF, 24 h, then NaBH4, aq. NaOH, 24 h, 60%
Reagents and conditions: (a) (ⅰ) NaH, BnBr, TBAI; (ⅱ) H2O2, (PhSe)2, t-BuO2H, CH2Cl2 (74% for 2 steps). (b) O3, -78 ℃, Me2S, 88%. (c) (S)-pent-4-ene-1, 2-diol, TFA, CH2Cl2then K2CO3, CH3OH, 56%. (d) (ⅰ) TsCl, Et3N, CH2Cl2; (ⅱ) TBDPSCl, DMAP, imidazole; (ⅲ) NaI, reflux (84% for 3 steps). (e) Zn, EtOH, reflux, 96%. (f) (ⅰ) Me3OBF4, CH2Cl2; (ⅱ) H2, Raney nickel, EtOH; (ⅲ) DMP, NaHCO3, CH2Cl2; (ⅳ) PTSA, CH(OMe)3, CH3OH (56% for 5 steps)
Reagents and conditions: (a) [Ir(cod)Cl]2, (R)-Cl, OMe-BIPHEP, allyl acetate, 70%. (b) PdCl2, CuCl2, CO, CH3CN, MeOH, r.t., 4 h, 83%. (c) (ⅰ) BnO(NH=C)CCl3, CF3SO3H; (ⅱ) Grubbs' Ⅱ, MeOH, 60 ℃ (73% for 2 steps). (d) (ⅰ) LiOH, MeOH; (ⅱ) 98, MNBA, DMAP (87% for 2 steps). (e) (ⅰ) Hoveyda-Grubbs' Ⅱ, toluene, 80 ℃; (ⅱ) Pd/C, H2, EtOH (53% for 2 steps)
Reagents and conditions: (a) (ⅰ) n-propyl bromide, Mg, -40 ℃; (ⅱ) (COCl)2, DMSO, Et3N, -78 ℃; (ⅲ) LiAlH4, LiI; (ⅳ) TBDPSCl, imidazole (46% for 4 steps). (b) (ⅰ) CuCl2, CH3CN; (ⅱ) BzCl, Bu2SnO; (ⅲ) TsCl, Et3N; (ⅳ) K2CO3, MeOH (58% for 4 steps). (c) (ⅰ) n-BuLi, BF3•Et2O; (ⅱ) MeI, NaH; (ⅲ) PPTS, MeOH (41% for 3 steps). (d) (ⅰ) Red-Al, Et2O; (ⅱ) (-)DIPT, Ti(Oi-Pr)4; (ⅲ) Me3Al, hexane (60% for 3 steps). (e) PPh3, imidazole, I2, 70%. (f) TBAF, THF, 84%
Reagents and conditions: (a) (ⅰ) (-)-DIPT, Ti(OiPr)4, C6H5C(CH3)2OOH, 4 Å MS; (ⅱ) Red-Al, THF, 0 ℃~r.t. (68% for 2 steps). (b) (ⅰ) p-anisaldehyde dimethyl acetal, PPTS, CH2Cl2; (ⅱ) DIBALH, CH2Cl2; (ⅲ) TBDPSCl, imidazole, CH2Cl2 (63% for 3 steps). (c) (ⅰ) CuCl2·2H2O, CH3CN; (ⅱ) p-TsCl, Bu2SnO, Et3N, CH2Cl2; (ⅲ) K2CO3, MeOH (62% for 3 steps). (d) (ⅰ) vinyl magnesium bromide, CuI, THF, -20 ℃; (ⅱ) MOMCl, DIPEA, DMAP (75% for 2 steps). (e) (ⅰ) TBAF, THF; (ⅱ) TEMPO, BAIB (60% for 2 steps). (f) (ⅰ) 152, DCC, DMAP, CH2Cl2; (ⅱ) Grubb's Ⅱ, CH2Cl2 (44% for 2 steps). (g) (ⅰ) DDQ, CH2Cl2; (ⅱ) Hg(CF3COO)2, CH2Cl2, KBr (76% for 2 steps). (h) (ⅰ) n-Bu3SnH, AIBN, toluene, reflux; (ⅱ) conc. HCl, MeOH (80% for 2 steps)
Reagents and conditions: (a) Pd(OAc)2, CuCl2, CO, 4 Å MS, DCE, 58%; (b) (ⅰ) HCl; (ⅱ) NaBH4 (72% for two steps); (c) 20, DIAD, Ph3P, 56%