- Synthesis and glucose-stimulate insulin secretion (GSIS) evaluation of vindoline derivatives
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It is demonstrated that natural product vindoline can enhance the glucose-stimulated insulin secretion (GSIS) in MIN6 cells with the EC50 value of 50.2?μM. In order to improve the activities, a series of vindoline derivatives are synthesized an
- Xiao, Chengqian,Tian, Yunan,Lei, Min,Chen, Fanglei,Gan, Xianwen,Yao, Xingang,Shen, Xu,Chen, Jing,Hu, Lihong
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- Conversion of vindoline into 11-mesyloxytabersonine
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Conversion of readily available vindoline to 11-mesyloxytabersonine, a versatile synthetic intermediate for indole alkaloids, has been achieved by a 9-step sequence in 39% overall yield.
- Han-Ya, Yuki,Inui, Tomohiko,Yokoshima, Satoshi,Tokuyama, Hidetoshi,Fukuyama, Tohru
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- Synthesis of Novel Vindoline-Chrysin Hybrids
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Vinca alkaloids are well-known microtubule targeting agents, which are used against some types of cancer. Vindoline is one of the monomeric Vinca alkaloids which does not have anti-tumor effect, although its derivatives have serious impact on the field of
- Mayer, Szabolcs,Nagy, Nóra,Keglevich, Péter,Szigetvári, áron,Dékány, Miklós,Szántay Junior, Csaba,Hazai, László
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- Medical use of medicine derivant wen Duo
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The invention relates to an application of a vindoline derivative with a structure as shown in the formula I or pharmaceutically acceptable salts thereof in preparing pharmaceuticals for promoting insulin secretion and/or preventing or treating diabetes m
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Paragraph 0103; 0104; 0105
(2016/10/08)
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- Total synthesis and evaluation of vinblastine analogues containing systematic deep-seated modifications in the vindoline subunit ring system: Core redesign
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The total synthesis of a systematic series of vinblastine analogues that contain deep-seated structural modifications to the core ring system of the lower vindoline subunit is described. Complementary to the vindoline 6,5 DE ring system, compounds with 5,5, 6,6, and the reversed 5,6 membered DE ring systems were prepared. Both the natural cis and unnatural trans 6,6-membered ring systems proved accessible, with the latter representing a surprisingly effective class for analogue design. Following Fe(III)-promoted coupling with catharanthine and in situ oxidation to provide the corresponding vinblastine analogues, their evaluation provided unanticipated insights into how the structure of the vindoline subunit contributes to activity. Two potent analogues (81 and 44) possessing two different unprecedented modifications to the vindoline subunit core architecture were discovered that matched the potency of the comparison natural products and both lack the 6,7-double bond whose removal in vinblastine leads to a 100-fold drop in activity.
- Schleicher, Kristin D.,Sasaki, Yoshikazu,Tam, Annie,Kato, Daisuke,Duncan, Katharine K.,Boger, Dale L.
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supporting information
p. 483 - 495
(2013/04/24)
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- Inhibitors of tubulin polymerization: Synthesis and biological evaluation of hybrids of vindoline, anhydrovinblastine and vinorelbine with thiocolchicine, podophyllotoxin and baccatin III
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A series of novel hybrid compounds obtained by the attachment of anhydrovinblastine, vinorelbine, and vindoline to thiocolchicine, podophyllotoxin, and baccatin III are described. Two types of diacyl spacers are introduced. The influence of the hybrid compounds on tubulin polymerization is reported. The results highlight the importance of the length of the spacer. Immunofluorescence microscopy and flow cytometry measurements that compound with the best in vitro activity could disrupt microtubule networks in cell and prevent the formation of the proper spindle apparatus, thereby causing cell cycle arrest in the G2/M phase. The newly synthesized compounds were tested in the human lung cancer cell line A549.
- Passarella, Daniele,Giardini, Alessandra,Peretto, Bruno,Fontana, Gabriele,Sacchetti, Alessandro,Silvani, Alessandra,Ronchi, Cristina,Cappelletti, Graziella,Cartelli, Daniele,Borlak, Jurgen,Danieli, Bruno
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p. 6269 - 6285
(2008/12/21)
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- Total synthesis of (-)- and ent-(+)-vindoline and related alkaloids
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A concise 11-step total synthesis of (-)- and ent-(+)-vindoline (3) is detailed based on a unique tandem intramolecular [4 + 2]/[3 + 2] cycloaddition cascade of a 1,3,4-oxadiazole inspired by the natural product structure, in which three rings and four C-C bonds are formed central to the characteristic pentacyclic ring system setting all six stereocenters and introducing essentially all the functionality found in the natural product in a single step. As key elements of the scope and stereochemical features of the reaction were defined, a series of related natural products of increasing complexity were prepared by total synthesis including both enantiomers of minovine (4), 4-desacetoxy-6,7-dihydrovindorosine (5), 4-desacetoxyvindorosine (6), and vindorosine (7) as well as /V-methylaspidospermidine (11). Subsequent extensions of the approach provided both enantiomers of 6,7-dihydrovindoline (8), 4-desacetoxyvindoline (9), and 4-desacetoxy-6,7-dihydrovindoline (10).
- Ishikawa, Hayato,Elliott, Gregory I.,Velcicky, Juraj,Choi, Younggi,Boger, Dale L.
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p. 10596 - 10612
(2007/10/03)
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- Total synthesis of (-)- and ent-(+)-vindoline
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(Chemical Equation Presented) Two exceptionally concise total syntheses of (-)- and ent-(+)-vindoline are detailed enlisting a diastereoselective tandem [4 + 2]/[3 + 2] cycloaddition of a 1,3,4-oxadiazole. The unique reaction cascade assembles the fully functionalized pentacyclic ring system of vindoline in a single step that forms four C-C bonds and three rings while introducing all requisite functionality and setting all six stereocenters within the central ring including three contiguous and four total quaternary centers.
- Choi, Younggi,Ishikawa, Hayato,Velcicky, Juraj,Elliott, Gregory I.,Miller, Michael M.,Boger, Dale L.
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p. 4539 - 4542
(2007/10/03)
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- On the reaction of deacetylvindoline with thionyl chloride
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Reaction of deacetylvindoline (2) with excess thionyl chloride gave rise to hexacyclic 6,10-dichloro-6,17-epithio-11-methoxy-1-methyltabersonine (4) as a single product in 43.5% yield. The structure was deduced from 1H and 13C 1D and 2D NMR experiments as well as from mass spectra. A tentative mechanism of this complex transformation was also proposed.
- Hajicek, Josef,Hanus, Vladimir
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p. 789 - 796
(2007/10/03)
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- An efficient total synthesis of (-)-vindoline
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A highly efficient total synthesis of the title compound is described. Our synthesis features a highly efficient preparation of the key intermediate 11 using our novel indole synthesis methodology. A novel amine protecting protocol by means of 2,4-dinitrobenzenesulfonamides has been developed to ensure the formation of the elusive secodine-type intermediate 15 under very mild conditions.
- Kobayashi, Satoshi,Ueda, Toshihiro,Fukuyama, Tohru
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p. 883 - 886
(2007/10/03)
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- Biomimetic Alkaloid Syntheses. 15. Enantioselective Syntheses with Epichlorohydrin: Total Syntheses of (+)-, (-)-, and (+/-)-Vindoline and a Synthesis of (-)-Vindorosine
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Total syntheses of vindoline (1) in racemic as well as in each enantiomeric form and of (-)-vindorosine (2) are described.They were achieved by generation and diastereoselective cyclizations of 14-hydroxysecodine intermediates 6 and 7.The subsequent oxidative elaboration of ring E was also studied with 3-oxotabersonine (24), 3-oxovincadifformine (26), and 14β-hydroxyvincadifformine (15).Na-Methyltabersonine (22) was oxidized to a ring-D-contracted α-keto lactam, 23.
- Kuehne, Martin E.,Podhorez, David E.,Mulamba, Tshilundu,Bornmann, William G.
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p. 347 - 353
(2007/10/02)
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- A New Efficient Total Synthesis of Vindorosine and Vindoline
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Highly stereoselective total syntheses of indole alkaloids vindorosine (1a) and vindoline (1b) are described.An imino Diels-Alder reaction, a stereospecific alkylation, and a rearrangement induced by the Pummerer reaction are the key steps of these short and high overall yield sequences.
- Andriamialisoa, Ratremaniaina Zo,Langlois, Nicole,Langlois, Yves
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p. 961 - 967
(2007/10/02)
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- Rapid Access to the Highly Oxygenated Aspidosperma Alkaloids Vindoline, Vindorosine, and Cathovaline
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A highly expedient and efficient synthesis of vindoline (1a) and vindorosine (1b), via the hitherto unknown azadienes (3a,b), is reported.
- Danieli, Bruno,Lesma, Giordano,Palmisano, Giovanni,Riva, Renata
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p. 909 - 911
(2007/10/02)
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- INDOLE ALKALOID BIOSYNTHESIS
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The early and late stages of indole alkaloid biosynthesis in Catharanthus roseus were studied by cell-free enzymes from the plant and its tissue culture.The intermediacy of strictosidine (isovincoside), geissoschizine and other compounds in the formation of ajmalicine is discussed.Vinblastine, the antineoplastic dimeric alkaloid, was synthesized enzymically from a semi-synthetic precursor, anhydrovinblastine.
- Scott, A. Ian,Lee, Siu-Leung,Culver, Michael G.,Wan, Winnie,Hirata, Toshifumi,et al.
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p. 1257 - 1274
(2007/10/02)
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