- Stereospecific total synthesis of the indole alkaloid ervincidine. Establishment of the C-6 hydroxyl stereochemistry
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The total synthesis of the indole alkaloid ervincidine (3) is reported. This research provides a general entry into C-6 hydroxy-substituted indole alkaloids with either an α or a β configuration. This study corrects the errors in Glasby's book (Glasby, J. S. Encyclopedia of the Alkaloids; Plenum Press: New York, 1975) and Lounasmaa et al.'s review (Lounasmaa, M.; Hanhinen, P.; Westersund, M. In The Alkaloids; Cordell, G. A., Ed.; Academic Press: San Diego, CA, 1999; Vol. 52, pp 103-195) as well as clarifies the work of Yunusov et al. (Malikov, V. M.; Sharipov, M. R.; Yunusov, S. Yu. Khim. Prir. Soedin. 1972, 8, 760-761. Rakhimov, D. A.; Sharipov, M. R.; Aripov, Kh. N.; Malikov, V. M.; Shakirov, T. T.; Yunusov, S. Yu. Khim. Prir. Soedin. 1970, 6, 724-725). It establishes the correct absolute configuration of the C-6 hydroxyl function in ervincidine. This serves as a structure proof and corrects the misassigned structure reported in the literature.
- Rallapalli, Sundari K.,Namjoshi, Ojas A.,Tiruveedhula, V. V. N. Phani Babu,Deschamps, Jeffrey R.,Cook, James M.
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supporting information
p. 3776 - 3780
(2014/05/20)
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- General approach for the synthesis of sarpagine indole alkaloids. Enantiospecific total synthesis of (+)-vellosimine, (+)-normacusine B, (-)-alkaloid Q3, (-)-panarine, (+)-Na-methylvellosimine, and (+)-Na-methyl-16-epipericyclivine
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The first total synthesis of (+)-Na-methyl-16-epipericyclivine (9) was completed [from D-(+)-tryptophan methyl ester] in an overall yield of 42% (eight reaction vessels). The optical rotation [[α]D +22.8 (c 0.50, CHCl3)] obtained on this material confirmed that the reported optical rotation [[α]D 0 (c 0.50, CHCl 3)]47 was biogenetically unreasonable. The total syntheses of (+)-vellosimine, (+)-normacusine B, (-)-alkaloid Q3, (-)-panarine, and (+)-Na-methylvellosimine are also described. Moreover, a mixed sample (1:1) of synthetic (-)-panarine and natural (-)-panarine yielded only one set of signals in the 13C NMR; this indicated that the two compounds are identical and further confirmed the correct configuration of (+)-vellosimine, (+)-normacusine B, and (-)-alkaloid Q3. In this approach, the key templates, (-)-Na-H,N b-benzyltetracyclic ketone 15a and (-)-Na-methyl,N b-benzyltetracyclic ketone 43 were synthesized on multihundred gram scale by the asymmetric Pictet-Spengler reaction and a stereocontrolled Dieckmann cyclization via improved sequences. An intramolecular palladium (enolate-mediated) coupling reaction was employed to introduce the C(19)-C(20) E-ethylidene function in the sarpagine alkaloids for the first time in stereospecific fashion.
- Yu, Jianming,Wang, Tao,Liu, Xiaoxiang,Deschamps, Jeffrey,Flippen-Anderson, Judith,Liao, Xuebin,Cook, James M.
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p. 7565 - 7581
(2007/10/03)
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- General approach for the total synthesis of the sarpagine related indole alkaloids (+)-Na-methyl-16-epipericyclivine, (-)-alkaloid Q3 and (-)-panarine via the asymmetric Pictet-Spengler reaction
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The stereospecific total synthesis of (+)-Na-methyl-16-epipericyclivine (1) was completed [from D-(+)-tryptophan methyl ester] in an overall yield of 42% (eight reaction vessels). The optical rotation {[α]D +22.8 (c 0.50, CHCl3
- Yu, Jianming,Wearing, Xiangyu Z.,Cook, James M.
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p. 543 - 547
(2007/10/03)
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- Deoxysarpagine hydroxylase--a novel enzyme closing a short side pathway of alkaloid biosynthesis in Rauvolfia.
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Microsomal preparations from cell suspension cultures of the Indian plant Rauvolfia serpentina catalyze the hydroxylation of deoxysarpagine under formation of sarpagine. The newly discovered enzyme is dependent on NADPH and oxygen. It can be inhibited by typical cytochrome P450 inhibitors such as cytochrome c, ketoconazole, metyrapone, tetcyclacis and carbon monoxide. The CO-effect is reversible with light (450 nm). The data indicate that deoxysarpagine hydroxylase is a novel cytochrome P450-dependent monooxygenase. A pH optimum of 8.0 and a temperature optimum of 35 degrees C were determined. K(m) values were 25 microM for NADPH and 7.4 microM for deoxysarpagine. Deoxysarpagine hydroxylase activity was stable in presence of 20% sucrose at -25 degrees C for >3 months. The analysis of presence of the hydroxylase in nine cell cultures of seven different families indicates a very limited taxonomic distribution of this enzyme.
- Yu, Bingwu,Ruppert, Martin,Stoeckigt, Joachim
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p. 2479 - 2483
(2007/10/03)
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- General approach for the synthesis of sarpagine/macroline indole alkaloids. Enantiospecific total synthesis of the indole alkaloid trinervine.
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[structure: see text] The total synthesis of the indole alkaloid trinervine 1 was accomplished in enantiospecific fashion in an overall yield of 20% (from the tetracyclic ketone 8) in 10 reaction vessels (12.5% from tryptophan methyl ester). The synthesis of the N(a)-H substituted macroline equivalent 2 was also completed in high yield via the same intermediate 13. The unique protection/hydroboration process developed here should provide a method to functionalize the C(19)-C(20) double bond in similar systems.
- Liu,Cook
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p. 4023 - 4026
(2007/10/03)
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- Stereoselective Transformation of Ajmaline into Three Minor Gelsemium Alkaloids, Koumidine, (19Z)-Anhydrovobasinediol and N-Demethoxyrankinidine and their Absolute Configuration
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Ajmaline was converted into new Gelsemium alkaloids, 19Z-anhydrovobasinediol and N-demethoxyrankinidine, via koumidine along the biomimetic sequence, and the absolute configuration of these alkaloids was determined by these transformations.
- Kitajima, Mariko,Takayama, Hiromitsu,Sakai, Shin-ichiro
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p. 1773 - 1779
(2007/10/02)
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- Studies on Gelsemium alkaloids. Total synthesis of (+)-koumine, (+)-taberpsychine, and (+)-koumidine
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The total synthesis of the Gelsemium alkaloids (+)-koumine (2), (+)-taberpsychine (4), and (+)-koumidine (50) has been accomplished starting from (S)-(-)-tryptophan (21), All the synthetic alkaloids are antipodal to the natural compounds. N′ -Benzyltryptophan ((-)-22) was methylated to give 23 which was reductively benzylated to provide (-)-25. Pictet-Spengler condensation of (-)-25 with 2-ketoglutaric acid followed by esterification gave a mixture of diastereomeric methyl esters 27/28. Exposure of (+)-27 and (-)-28 to Dieckmann cyclization conditions provided (+)-29 and (-)-29, respectively. Thus starting from a single enantiomer of tryptophan both antipodes of the tetracyclic β-ketoesters (+)-29/(-)-29 are available. Since (+)-29 was the more readily available antipode, subsequent reactions were conducted with this compound. Conversion of (+)-29 into (+)-31 followed conventional lines. N-Alkylation of (+)-31 with propargyl bromide gave (+)-33 which was converted into (+)-36 by treatment with t-BuMe2SiOTf/Et3N, n-BuLi/CICO2Me, and LiBF4. Exposure of (+)-36 to pyrrolidine/ trifluoroacetic acid gave the (Z)- and (E)-quinuclidines (+)-37 and (+)-38. Methylenation of 38 with Tebbe's reagent gave 39. Both E and Z isomers were taken through the series of transformations to give 43, 45, 47, and 49 and 44, 46, 48, and 50. The structures of (+)-37 and (+)-43 were conclusively established by single-crystal X-ray crystallography. Fragmentation of 49 with methyl chloroformate gave 51 which was reduced with LiAlH4 to give (+)-taberpsychine (4). Treatment of 47 with methyl chloroformate gave the 18-hydroxytaberpsychine derivative 52 which was reduced with LiAlH4 to give 53. Similarly 48 gave 55. When the Z isomer 55 was exposed to the Mitsunubo conditions, (+)-koumine (2) was formed (40%, 72% based upon recovered 55). The E isomer 53 gave (+)-koumine (2) in lower yields at a much reduced rate.
- Magnus, Philip,Mugrage, Benjamin,DeLuca, Mark R.,Cain, Gary A.
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p. 5220 - 5230
(2007/10/02)
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- CHARACTERISTICS OF VELLOSIMINE REDUCTASE, A SPECIFIC ENZYME INVOLVED IN THE BIOSYNTHESIS OF THE RAUWOLFIA ALKALOID SARPAGINE
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A plant enzyme - vellosimine reductase - has been isolated from Rauwolfia cell suspension cultures.This new enzyme has been purified (110-fold) and characterized.The reductase is a specific enzyme of the sarpagine pathway catalyzing the NADPH dependent conversion of vellosimine into 10-deoxysarpagine.The latter alkaloid is the immediate biogenetic precursor of sarpagine as shown by its high in vivo incorporation rate (86percent) into sarpagine.
- Pfitzner, Artur,Krausch, Brigitte,Stoeckigt, Joachim
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p. 1691 - 1700
(2007/10/02)
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- VELLOSIMINE REDUCTASE. A SPECIFIC ENZYME INVOLVED IN THE CELLFREE BIOSYNTHESIS OF SARPAGINE TYPE ALKALOIDS.
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Vellosimine reductase is a substrate and cofactor specific enzyme which catalyzes the NADPH-dependent reduction of vellosimine (4) forming 10-deoxy-sarpagine type alkaloids.
- Pfitzner, Arthur,Stoeckiqt, Joachim
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p. 1695 - 1698
(2007/10/02)
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