A total synthesis of (.+-.)-cephalotaxinamide.

Yasuda, Shingo; Yamamoto, Youichi; Yoshida, Shuji; Hanaoka, Miyoji

doi:10.1248/cpb.36.4229

Cited by 30 publications

(9 citation statements)

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“…Several elegant syntheses of 1 have been reported over the past three decades. The racemic approaches have embodied several key transformations, including Nazarov cyclization, [19] photo-stimulated S RN 1 cyclization, [20] Claisen rearrangement, [21,22] oxidative ring contraction, [23] acylnitroso Diels-Alder cycloaddition, [24,25] transannular N-conjugate addition, [26,27] intramolecular alkyne hydroamination, [28] and reductive ring expansion of tetrahydrosioquinoline intermediates. [29,30] Non-racemic routes have featured electrophilic aromatic substitution, [31] Heck arylation, [32,33] Pummerer-electrophilic aromatic substitution cascade, [34][35][36] and acid catalyzed ring expansion of cyclobutanol derivatives.…”

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confidence: 99%

Synthesis of Antiproliferative Cephalotaxus Esters and Their Evaluation against Several Human Hematopoietic and Solid Tumor Cell Lines: Uncovering Differential Susceptibilities to Multidrug Resistance

Eckelbarger

Wilmot

Epperson

et al. 2008

Chemistry A European J

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Deoxyharringtonine (2), homoharringtonine (3), homodeoxyharringtonine (4), and anhydroharringtonine (5) are reported to be among the most potent members of the antileukemia alkaloids isolated from the Cephalotaxus genus. Convergent syntheses of these four natural products are described, each involving novel synthetic methods and strategies. These syntheses enabled evaluation of several advanced natural and non-natural compounds against an array of human hematopoietic and solid tumor cells. Potent cytotoxicity was observed in several cell lines previously not challenged with these alkaloids. Variations in the structure of the ester chain within this family of alkaloids confer differing activity profiles against vincristine-resistant HL-60/RV+, signalling new avenues for molecular design of these natural products to combat multi-drug resistance.

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confidence: 99%

Synthesis of Antiproliferative Cephalotaxus Esters and Their Evaluation against Several Human Hematopoietic and Solid Tumor Cell Lines: Uncovering Differential Susceptibilities to Multidrug Resistance

Eckelbarger

Wilmot

Epperson

et al. 2008

Chemistry A European J

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“…In 2013, Zhang et al proposed two pathways for the formal synthesis of rac-CET (AE)-(1) targeting Li's enone (AE)-174 100 and Hanaoka's enone (AE)-180 96 based on conventional alkylations and aldol condensations from known benzazepines 101 165 and 166 obtained in four steps from aryl amine 83 (bearing a methylenedioxy substituent) or 158 (bearing two methoxy substituents), respectively (Scheme 11). 102 The C ring was elaborated via an N-and C-alkylating annulation by treatment of benzazepine 165 with 1,3-dibromopropane (167) Cs 2 CO 3 giving product 168 in one step.…”

Section: Zhang and Liu's Formal Synthesis (2013)mentioning

confidence: 99%

“…131 In 2004, these authors developed an enantioselective synthesis of (À)-CET (À)-(1) from spirolactam ketal (À)-306, 132 relying on Kuehne 94 301 furnished the desired spiro compound (À)-303. A further modification consisted in the use of AlH 3 96 at 0 C instead of LiAlH 4 in refluxing tetrahydrofuran (THF) for the reduction of (À)-308 to avoid any racemization of sensitive CET (1). The major diastereoisomer was recrystallized and also easily recovered by chromatography, and thus azaspirononanedione (À)-303 was obtained in 70% yield and de surpassing 99%.…”

Section: Royer's Total Synthesis (2004)mentioning

confidence: 99%

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Cephalotaxus Alkaloids

Pérard-Viret

Quteishat

Alsalim

et al. 2017

The Alkaloids: Chemistry and Biology

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Cephalotaxus alkaloids represent a family of plant secondary metabolites known for 60 years. Significant activity against leukemia in mice was demonstrated for extracts of Cephalotaxus. Cephalotaxine (CET) (1), the major alkaloid of this series was isolated from Cephalotaxus drupacea species by Paudler in 1963. The subsequent discovery of promising antitumor activity among new Cephalotaxus derivatives reported by Chinese, Japanese, and American teams triggered extensive structure elucidation and biological studies in this family. The structural feature of this cephalotaxane family relies mainly on its tetracyclic alkaloid backbone, which comprises an azaspiranic 1-azaspiro[4.4]nonane unit (rings C and D) and a benzazepine ring system (rings A and B), which is linked by its C3 alcohol function to a chiral oxygenated side chain by a carboxylic function alpha to a tetrasubstituted carbon center. The botanical distribution of these alkaloids is limited to the Cephalotaxus genus (Cephalotaxaceae). The scope of biological activities of the Cephalotaxus alkaloids is mainly centered on the antileukemic activity of homoharringtonine (HHT) (2), which in particular demonstrated marked benefits in the treatment of orphan myeloid leukemia and was approved as soon as 2009 by European Medicine Agency and by US Food and Drug Administration in 2012. Its exact mechanism of action was partly elucidated and it was early recognized that HHT (2) inhibited protein synthesis at the level of the ribosome machinery. Interestingly, after a latency period of two decades, the topic of Cephalotaxus alkaloids reemerged as a prolific source of new natural structures. To date, more than 70 compounds have been identified and characterized. Synthetic studies also regained attention during the past two decades, and numerous methodologies were developed to access the first semisynthetic HHT (2) of high purity suitable for clinical studies, and then high grade enantiomerically pure CET (1), HHT (2), and analogs.

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“…[48] The only comparable reactions are methanol elimination from 2,2-dimethoxycyclopentanone on treatment with FeCl 3 /SiO 2 , affording 2-methoxy-2cyclopentenone in 71 % yield, [49] and an elimination caused by DMSO at elevated temperature. [50] The oxidative deacetalization mentioned above was tried next. [42,43] When rac-19 was treated with 1.3 equivalents of trityl tetrafluoroborate for 18 h, the substituted derivative rac-22 of the target complex was obtained in 48 % yield along with rac-21, which was formed in 10 % yield.…”

Section: Introductionmentioning

confidence: 99%

Synthesis of Enantiopure Tricarbonyl(indan‐1,2‐dione)chromium

et al. 2005

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A multistep synthesis of the planar chiral tricarbonyl(η 6 -indan-1,2-dione)chromium, based on acetal protection of the keto groups, is presented. Since common deacetalization procedures failed, an oxidative deprotection with triphenylcarbenium tetrafluoroborate was used. Tricarbonyl(η 6 -indan-1,2-dione)chromium is regarded as a potential precursor for dianionic oxy-Cope rearrangements upon alkenyllithium diaddition. As an unexpected side product in the synthesis, an indan-1,2-dione complex with a triphenylmethyl substituent at C-3 was obtained. Attempts directed towards the formation of enantiomerically pure material include the first reported investigation into an enantiose-

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A total synthesis of (.+-.)-cephalotaxinamide.

Cited by 30 publications

References 0 publications

Synthesis of Antiproliferative Cephalotaxus Esters and Their Evaluation against Several Human Hematopoietic and Solid Tumor Cell Lines: Uncovering Differential Susceptibilities to Multidrug Resistance

Synthesis of Antiproliferative Cephalotaxus Esters and Their Evaluation against Several Human Hematopoietic and Solid Tumor Cell Lines: Uncovering Differential Susceptibilities to Multidrug Resistance

Cephalotaxus Alkaloids

Synthesis of Enantiopure Tricarbonyl(indan‐1,2‐dione)chromium

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