Asymmetric Synthesis of the Nakijiquinones—Selective Inhibitors of the Her-2/Neu Protooncogene

Stahl, Petra; Waldmann, Herbert

doi:10.1002/(sici)1521-3773(19991216)38:24<3710::aid-anie3710>3.0.co;2-h

Cited by 26 publications

(14 citation statements)

References 11 publications

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“…The first enantioselective access to nakajiquinones, a group of bioactive sesquiterpene quinones, was explored, essentially relying on the (36b AE 37 AE 38 AE 39) route. 107 A novel method for the synthesis of sesquiterpene quinones, which utilized the coupling of a neopentyl type radical with quinones, was developed. 108 In this way, the enantioselective syntheses of avarol 18 and avarone 52 was achieved effectively.…”

Section: 111mentioning

confidence: 99%

Synthesis of Clerodane Diterpenoids and Related Compounds - Stereoselective Construction of the Decalin Skeleton with Multiple Contiguous Stereogenic Centers

Tokoroyama

2000

Synthesis

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Stereoselective construction of contiguous stereogenic centers in the decalin ring -usually four -is central to the synthesis of clerodane diterpenoids and the present review surveys the methods utilized to meet this task. Major strategies for the stereocontrol are: (i) diastereoface-selective reactions on a rigid ring, (ii) conformational preference of a rigid ring structure in an equilibrium condition, and (iii) diastereoselective cyclization. According to the classification based on the methods for construction of the stereogenic centers, an overview will be presented to various synthetic studies on clerodane and related natural products, which are of current interest in view of biological activity. Use of Oxy-Cope Reactions 6.2 Use of Stereocontrolled Ring-Closure Reactions 7Concluding Remarks

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Section: 111mentioning

confidence: 99%

Synthesis of Clerodane Diterpenoids and Related Compounds - Stereoselective Construction of the Decalin Skeleton with Multiple Contiguous Stereogenic Centers

Tokoroyama

2000

Synthesis

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“…Owing to their unique structural features coupled with their attractive biological activities, these natural products are exceptionally intriguing and timely targets for total synthesis. Total syntheses of unnatural (–)‐ 1 , natural (–)‐ 2 , and natural (+)‐ 4 have been reported; however, the total synthesis of 3 has not been reported to date . In this study, we describe the unified total syntheses of compounds 1 – 4 , all with the natural absolute configurations.…”

Section: Introductionmentioning

confidence: 99%

Unified Synthesis of the Marine Sesquiterpene Quinones (+)‐Smenoqualone, (–)‐Ilimaquinone, (+)‐Smenospongine, and (+)‐Isospongiaquinone

et al. 2017

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The marine sesquiterpene quinones (+)‐smenoqualone, (–)‐ilimaquinone, (+)‐smenospongine, and (+)‐isospongiaquinone were efficiently synthesized in a unified manner starting from a known trans‐decalin derivative, which is accessible from (+)‐5‐methyl Wieland–Miescher ketone. The synthetic method involved the following key steps: (i) assembly of the whole carbon skeleton by coupling the decalin segment to an aromatic moiety; (ii) p‐quinone formation by strategic salcomine oxidation of phenolic intermediates; (iii) direct conversion of (–)‐ilimaquinone into (+)‐isospongiaquinone by pTsOH‐induced isomerization of the C‐4 olefinic double bond; (iv) site‐selective amination of a dimethoxy‐p‐quinone intermediate by substitution of the C‐18 methoxy group with an amino group; and (v) one‐step construction of the requisite tetracyclic core structure by sequential BF3·Et2O‐induced rearrangement/cyclization of an olefinic decalin intermediate having an aromatic moiety. The syntheses of (+)‐smenoqualone and (+)‐smenospongine are reported here for the first time.

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“…The crude product was purified by flash chromatography (5% EtOAc—95% hexanes). The title compounds were obtained as orange and red crystalline solids, respectively, with identical spectral data to the previous report [ 31 , 32 ].…”

Section: Methodsmentioning

confidence: 55%

“…Synthetic routes to sesquiterpenes ( 1 – 7 ) are either complex and low yielding, or yet to be reported [ 29 – 32 ]. Thus, herein we explore a scaffold simplification approach in our efforts to develop the cytotoxicity structure–activity relationship of bolinaquinone analogues.…”

Section: Introductionmentioning

confidence: 99%

A focused library synthesis and cytotoxicity of quinones derived from the natural product bolinaquinone

et al. 2018

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Bolinaquinone is a natural product that is a structurally complex, cytotoxic sesquiterpene quinone. A scaffold simplification and focused library approach using a microwave-assisted Suzuki coupling gave 32 bolinaquinone analogues with good-to-excellent cytotoxicity profiles. Mono-arylbenzoquinones, Library A, were preferentially toxic towards BE2-C (neuroblastoma) cells with growth inhibition (GI50) values of 4–12 µM; only the 3,4-dimethoxyphenyl 23 and 3-biphenyl 28 variants were broad-spectrum active—HT29 (colon carcinoma), U87 and SJ-G2 (glioblastoma), MCF-7 (breast carcinoma), A2780 (ovarian carcinoma), H460 (lung carcinoma), A431 (skin carcinoma), Du145 (prostate carcinoma), BE2-C (neuroblastoma), MIA (pancreatic carcinoma) and SMA (spontaneous murine astrocytoma). Library B with a second aryl moiety exhibited broad-spectrum cytotoxicity with MCF-7 cells’ GI50 values of 5.6 ± 0.7 and 5.1 ± 0.5 µM for 2,5-dimethoxy-3-(naphthalene-1-yl)-6-(naphthalene-3-yl) 33 and 2,5-dimethoxy-3-(biaryl-2-yl)-6-(naphthalene-3-yl) 36, respectively. Similar potencies were also noted with 2,5-dimethoxy-3,6-diphenyl 30 against A2780 (GI50 = 5.9 ± 0.0 µM) and with 2,5-dimethoxy-3-(biaryl-3-yl)-6-(naphthalene-3-yl) 37 against HT29 (GI50 = 5.4 ± 0.4 µM), while the 3,4-dimethoxy mono-aryl analogue 23 exhibited good levels of activity against A2780 (GI50 = 3.8 ± 0.75 µM), the neuroblastoma cell line BE2-C (GI50 = 3 ± 0.35 µM) and SMA (GI50 = 3.9 ± 0.54 µM). Introduction of the amino-substituted Library C gave 2-(naphthalen-1-yl)-5-(naphthalen-3-yl)-3,6-bis(propylamino) 43, with excellent activity against HT29 (0.08 ± 0.0 µM), MCF-7 (0.17 ± 0.1 µM), A2780 (0.14 ± 0.1 µM), A431 (0.11 ± 0.0 µM), Du145 (0.16 ± 0.1 µM), BE2-C (0.08 ± 0.0 µM) and MIA (0.1 ± 0.0 µM).

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Asymmetric Synthesis of the Nakijiquinones—Selective Inhibitors of the Her-2/Neu Protooncogene

Cited by 26 publications

References 11 publications

Synthesis of Clerodane Diterpenoids and Related Compounds - Stereoselective Construction of the Decalin Skeleton with Multiple Contiguous Stereogenic Centers

Synthesis of Clerodane Diterpenoids and Related Compounds - Stereoselective Construction of the Decalin Skeleton with Multiple Contiguous Stereogenic Centers

Unified Synthesis of the Marine Sesquiterpene Quinones (+)‐Smenoqualone, (–)‐Ilimaquinone, (+)‐Smenospongine, and (+)‐Isospongiaquinone

A focused library synthesis and cytotoxicity of quinones derived from the natural product bolinaquinone

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