Synthesis Study on Marmycin A: Preparation of the C3′-Desmethyl Analogues

Ding, Chunyong; Tu, Shanghui; Li, Fuying; Wang, Yuanxiang; Yao, Qizheng; Hu, Wenxiang; Xie, Hua; Meng, Linghua; Zhang, Ao

doi:10.1021/jo9011078

Cited by 30 publications

(39 citation statements)

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“…[38] This includes silver-catalyzed decarboxylic radical alkylation [39][40][41] yielding bromide 3, palladium-catalyzed cyclization to offer tetracyclic product 4, and DBU-assisted aromatization (Scheme 1). This strategy is very efficient yielding the target compound 5 in a 40% three-step overall yield.…”

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confidence: 99%

One‐Pot Three‐Step Synthesis of Naphtho[2,3‐a]carbazole‐ 5,13‐diones using a Tandem Radical Alkylation–Cyclization– Aromatization Reaction Sequence

Ding

Yao

et al. 2010

Adv Synth Catal

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A three-step, one-pot tandem reaction including radical nucleophilic alkylation/cyclization/ aromatization was developed using 0.3 equivalents of silver(I) acetate (AgOAc) as the catalyst and 2 equivalents of ammonium persulfate [(NH 4 ) 2 S 2 O 8 ] as the oxidant. This strategy is highly efficient for the assembly of pentacyclic complex carbazoles from aryl-fused bromobenzoquinones and indol-3-ylpropanoic acid acids in 52-72% overall yields (three steps). This new approach provides a significant improvement over the previously reported methods and would greatly facilitate analog library construction of pentacyclic complex carbazoles and benefit further biological evaluation of these compounds.

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confidence: 99%

One‐Pot Three‐Step Synthesis of Naphtho[2,3‐a]carbazole‐ 5,13‐diones using a Tandem Radical Alkylation–Cyclization– Aromatization Reaction Sequence

Ding

Yao

et al. 2010

Adv Synth Catal

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“…3a,4 The formation of C -glycoside 22 is well precedented 13. Although hydroaminations of unactivated alkenes catalyzed by acid or lanthanum triflates have recently been reported, they require temperatures between 135–160 °C 14.…”

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Efficient Synthesis of the Tetracyclic Aminoquinone Moiety of Marmycin A

Maugel

Snider

2009

Org. Lett.

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An efficient four-step route to the tetracyclic aminoquinone moiety of marmycin A that proceeds in 41% overall yield from 5-nitronaphthoquinone and 5-methyl-1-vinylcyclohexene will facilitate preparation of marmycin A analogues for biological evaluation. The Diels-Alder reaction gave exclusively the desired adduct that is favored by steric considerations rather than the regioisomeric adduct that is favored by electronic considerations.Fenical and coworkers recently isolated two cytotoxic quinones of the angucycline family, marmycins A (1a) and B (2), from a marine sediment-derived actinomycete related to the genus Streptomycetes. 1 The structures were determined by spectroscopic analysis and X-ray crystallography. C-glycosidic linkages are quite common in angucyclines, 2 but the C-and Nglycosidic linkages resulting in a hexacyclic skeleton is unique to the marmycins. Marmycin A (1a) showed potent activity against 12 human tumor cell lines with a mean IC 50 value of 22 nM. The combination of the novel skeleton and potent biological activity of 1a prompted us to undertake its synthesis.We envisioned that condensation of glycal 2a with tetracyclic aminoquinone 3 would provide the acetate of 1a. Yadav has extensively studied related condensations of simple anilines with glycals such as 2b that contain hydrogen on C-3 to form the tricyclic ABC ring system of the marmycins with a hydrogen rather than a methyl group at C-3′. 3 While our work was in progress, Yao and Zhang reported a ten-step synthesis of tetracyclic aminoquinone 3 and the InBr 3 -catalyzed condensation of 3 and 2b to afford C-3′-desmethyl marmycin A (1c). 4 Our approach to tetracyclic aminoquinone 3 by the Diels-Alder reaction of 5-nitronaphthoquinone (4) 5 with 5-methyl-1-vinylcyclohexene (5) 6 will form the complete carbon skeleton in a single step. However, the regiochemistry of the proposed Diels-Alder reaction was of some concern. Naphthoquinones with electron withdrawing substituents on C-5 react preferentially with nucleophiles, including the nucleophilic end of a diene, at C-2, not C-3, which should lead to the undesired regioisomer in the Diels-Alder reaction (see Scheme 2). 7 Nitroquinone 4 reacts with 1,1-dimethoxyethylene preferentially (2.7:1) at snider@brandei.edu. Supporting Information Available: Complete experimental procedures, copies of 1 H and 13 C NMR spectral data, details of the structure determination of 3, and CIF file of 3. This material is available free of charge via the Internet at http://pubs.acs.org. NIH Public Access NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript C-2. 8 Oda studied the Diels-Alder reactions of 4 with isoprene, which gave a 9.2:1 mixture favoring the expected major isomer 6. 9 However, with piperylene the expected major isomer 8 was favored by only 1.4:1. Molecular mechanics calculations of the Diels-Alder transition states provide a possible explanation for this loss of selectivity. 10 The formation of 6 is preferred sterically by 0.34 kcal/mol in addition to the elect...

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“…In contrast to their previous report, 5 they proposed that the reaction proceed via a Ferrier rearrangement reaction first to give N-pseudoglycal product. Subsequent ring-opening followed by a 4π conrotatory electrocyclization 16 yielded cyclopentenone product (Scheme 1.26).…”

Section: Scheme 125mentioning

confidence: 68%

“…It should be noted that the condensation of primary arylamines with glycals, which contain only hydrogen on C3, to form tetrahydroquinolines have been extensively studied. 5,11,12,13 In addition, the utilization of water as solvent to mimic nature's way of making…”

Section: Resultsmentioning

confidence: 99%

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Diverse reactivity of glycals with arylamines and sulfonamides : synthesis of 4-aminocyclopentenones, cyclopentanone fused indolines and sialic acid

Wang¹

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I am thankful to Dr. Li Yongxin for the X-ray crystallographic analysis. I also thank technical staff Goh Ee Ling, Zhu Wenwei, for their support for NMR, mass spectroscopy. My biggest personal challenge is to maintain a healthy work-family balance. I would like to thank my wife, Qiongxia, for her sacrifice throughout. For almost single-handedly raising our daughter so I can accomplish my goal, I am truly grateful. I also acknowledge my parents for the support and encouragement over the past years. Without them, it is impossible for me to finish my PhD study.

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Synthesis Study on Marmycin A: Preparation of the C3′-Desmethyl Analogues

Cited by 30 publications

References 46 publications

One‐Pot Three‐Step Synthesis of Naphtho[2,3‐a]carbazole‐ 5,13‐diones using a Tandem Radical Alkylation–Cyclization– Aromatization Reaction Sequence

One‐Pot Three‐Step Synthesis of Naphtho[2,3‐a]carbazole‐ 5,13‐diones using a Tandem Radical Alkylation–Cyclization– Aromatization Reaction Sequence

Efficient Synthesis of the Tetracyclic Aminoquinone Moiety of Marmycin A

Diverse reactivity of glycals with arylamines and sulfonamides : synthesis of 4-aminocyclopentenones, cyclopentanone fused indolines and sialic acid

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