synthesis and catalytic functionalization of biologically active indoles

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1 Palladium-catalyzed Coupling Reactions of Indoles 15 ArX: N I SO 2 polystyrene O B O N SO 2 51 52 1) Pd[P(tBu) 3] 2 DMF, K 3PO 4, 80 °C,1day 2) tBuOK, THF, rt, 5 h I I CO 2Et Br Br CO 2Et 53a (77%) 53b (91%) 53a (74%) 53b (88%) I OMe Br OMe 53c (74%) 53c (73%) 53d (60%) 53e (82%) Scheme 11. Palladium-catalyzed Suzuki-Miyaura reaction of immobilized indole. Br S I N 53a-e Because it was difficult to estimate the exact loading value (mmol/g) of the immobilized indolylboron, the three-step yield from 51 was used to evaluate the performance of the coupling reaction with various aryl halides. For the reaction of the heteroaryl halides 53d and 53e, better results were obtained by using Pd(PPh3)4 as catalyst. In general the reaction proceeded smoothly for both electron-rich and -poor aryl halides. Additionally they reported a synthesis with dibromomaleimide under the same conditions. The bisindolylmaleimide subunit is present in numerous biologically active metabolites including staurosporine and rebeccamycin. [50] Vinblastine 54 and vincristine 55 are two bisindole alkaloid natural products as well. Both possesses considerable amitotic carcinomas and thus have found use in the treatment for various carcinomas, particularly childhood leukemia and Hodgkin’s disease. [51] The following study led to the preparation of a number of structurally novel vindolin analogues 58a-j and opened also the door to new strategies for the synthesis of vinblastine, vincristine, and related anti-cancer agents. [52] N H Ar
1 Palladium-catalyzed Coupling Reactions of Indoles 16 The authors described a general protocol for the rapid construction of C-15substituted analogues of vindoline 56 using palladium cross-coupling reactions (Figure 3, Table 4). N H N HO CO 2Me MeO N 54 R = Me vinblastine 55 R = CHO vincristine HO N R Figure 3. Vinblastine, vincristine and vindoline. OAc CO 2Me MeO N N HO 56 vindoline OAc Co 2Me The conversion of vindoline 56 (Figure 3) to 15-bromovindoline 57 (Table 4) was proved eventfully and gave nearly quantitative yield. The cross-coupling afterwards of bromovindoline 57 with a broad range of boronic acids (Table 4) led to biaryl products 58a-j in good yields (Table 4, entries 1-6). The ability to use heteroaryl boronic acids allowed the access to a wide range of arylated vindoline analogues. The introduction of functionality on these partners, which mimic the “upper” portion of vinoblastine, permitted also the identification of new bioactive analogues of this important drug. Vinylboronic acids were less effective coupling partners, giving the corresponding products in moderate to low yields. The commercially available Xphos-ligand was highly effective [53] and accepted also couplings with an alkylboronic acid (Table 4, entry 13). Table 4. Suzuki-Miyaura couplings of bromovindoline. Br MeO 57 N N HO OAc Co 2Me RB(OH) 2 Pd-cat. R MeO N 58a-j N HO OAc Co 2Me
Page 1 and 2: Leibniz-Institut für Katalyse e. V
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Page 11 and 12: Preface The search for drugs is an
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3 Publications 3.1 Titanium-Catalyz
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1092 N. Schwarz et al. LETTER Table
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1094 N. Schwarz et al. LETTER 2,6-d
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3 Publications 84 3.2 Zinc-Promoted
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Table 2: Reaction of N-methyl-N-phe
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Am. Chem. Soc. 2002, 124, 15168 - 1
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A novel palladium catalyst for the
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Table 2. Reaction of different amin
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3 Publications 94 Experimental Data
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3 Publications 96 (q); 115.3 (d, J
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3 Publications 98 3.4 Palladium-Cat
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PAPER Coupling Reactions of Electro
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3 Publications 108 3.5 Synthesis of
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Scheme 2 Ti-catalyzed synthesis of
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mixture was used for the synthesis
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7.11 (ddd, 1H, J = 8.0 Hz, J = 7.0
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FULL PAPER DOI: 10.1002/ejoc.200800
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Synthesis of Potential 5-HT 6 Recep
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FULL PAPER DOI: 10.1002/ejoc.200700
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Synthesis of Indole-2,3-dicarboxyla
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3 Publications 132 3.8 Selective Re
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8 7 N R N R OH CO2Et CO2Et OH indol
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mixture was stirred at 78 C for 3 m
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3.89 (s, 2H, H-10), 4.27 (s, 2H, H-
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DOI: 10.1002/cssc.200700160 General
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Zn-Catalyzed Hydroamination of Term
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Zn-Catalyzed Hydroamination of Term
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3 Publications 146 3.10 Zn-Catalyze
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Over the past years, we investigate
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3 Publications 150 3.11 First Synth
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4608 K. Alex et al. / Tetrahedron L
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Publikationen 1 Titanium-Catalyzed
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