Improved synthesis of aryl 1,1-dimethylpropargyl ethers

Godfrey, Jollie D.; Mueller, Richard H.; Sedergran, Thomas C.; Soundararajan, Ν.; Colandrea, Vincent J.

doi:10.1016/s0040-4039(00)78231-1

Cited by 133 publications

(79 citation statements)

References 27 publications

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“…61,62 The reaction conditions were mild, and the yields were excellent. Although the method had not been used to form stereogenic centers, we felt that a stereochemical induction from a vicinal stereocenter might provide useful levels of selectivity.…”

Section: Discovery Of An Aziridine Ring-opening Reaction By Phenol Dementioning

confidence: 99%

Evolution of the Total Syntheses of Ustiloxin Natural Products and Their Analogues

Evans

et al. 2008

J. Am. Chem. Soc.

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Ustiloxins A-F are antimitotic heterodetic cyclopeptides containing a 13-membered cyclic core structure with a synthetically challenging chiral tertiary alkyl-aryl ether linkage. The first total synthesis of ustiloxin D was achieved in 31 linear steps using an S N Ar reaction. An nOe study of this synthetic product showed that ustiloxin D existed as a single atropisomer. Subsequently, highly concise and convergent syntheses of ustiloxins D and F were developed by utilizing a newly discovered ethynyl aziridine ring-opening reaction in a longest linear sequence of 15 steps. The approach was further optimized to achieve a better macrolactamization strategy. Ustiloxins D, F and eight analogues (14-MeO-ustiloxin D, four analogues with different amino acid residues at the C-6 position, and three (9R, 10S)-epi-ustiloxin analogues) were prepared via the second generation route. Evaluation of these compounds as inhibitors of tubulin polymerization demonstrated that variation at the C-6 position is tolerated to a certain extent. In contrast, the S configuration of the C-9 methylamino group and a free phenolic hydroxyl group are essential for inhibition of tubulin polymerization. Antimitotic agentsAntimitotic agents have long been of interest to scientists and physicians, even before their precise mechanism of action could be articulated. Most of these compounds interfere with microtubule assembly and functions thus resulting in mitotic arrest of eukaryotic cells. There are a number of natural and synthetic compounds that interfere with tubulin function to inhibit the formation of microtubules. 1 Such antimitotic agents exhibit a broad range of biological activities and can be used for medicinal and agrochemical purposes, acting as anticancer, antifungal, or anthelmintic agents. Moreover, tubulin binding compounds are valuable for understanding basic mechanisms involved in the dynamics of the microtubule network. 2 Mitotic arrest is of importance in cancer chemotherapy, since tubulin is an established chemotherapeutic target. In addition to the widely used vinca alkaloids and taxoids, many other antimitotic agents are currently in clinical or preclinical development. 3 Newer potential targets NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript that may cause mitotic arrest are in development as well. Although cancer chemotherapy is a very important goal being extensively investigated, the mechanism of action of the naturally occurring peptides that inhibit tubulin polymerization remains a challenging problem. Attempts to establish a relationship among the tubulin binding peptides have only had limited success. [4][5][6][7][8] As a result, the mechanism of action of peptidic antimitotic agents is not completely elucidated and deserves further investigation. UstiloxinsThe first peptide shown to interact with tubulin was phomopsin A (Error! Reference source not found.). [9][10][11][12][13] Since then, a number of peptides and depsipeptides were found to disrupt cellular microtubules. These compo...

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Section: Discovery Of An Aziridine Ring-opening Reaction By Phenol Dementioning

confidence: 99%

Evolution of the Total Syntheses of Ustiloxin Natural Products and Their Analogues

Evans

et al. 2008

J. Am. Chem. Soc.

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“…The preparation of the other required coupling partner, aldehyde 10, began with methyl ester 8, [11] which was converted into the corresponding bis-reversed prenylated ester 9 through a copper-catalyzed etherification [12] with 1,1-dimethylpropynyl carbonate and Lindlar hydrogenation (72 % overall yield). Chemoselective reduction of 9 with LiAlH 4 , followed by oxidation with DMP led to aldehyde 10 in 92 % overall yield for the two steps.…”

Section: Dedicated To Masakatsu Shibasaki On the Occasion Of His 60thmentioning

confidence: 99%

Cascade Reactions Involving Formal [2+2] Thermal Cycloadditions: Total Synthesis of Artochamins F, H, I, and J

Nicolaou¹,

Lister²,

Denton³

et al. 2007

Angew Chem Int Ed

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Dedicated to Masakatsu Shibasaki on the occasion of his 60th birthdayThe Artocarpus genus encompasses approximately 60 species of trees that are distributed throughout the tropical regions of Asia. Selected members of this family of plants have been used as traditional folk medicines in Sri Lanka, Taiwan, Thailand, and Indonesia. [1][2][3][4] A search for the bioactive ingredients of these plants led to the isolation of several bioactive prenylated flavanoids from the roots of Artocarpus chama, [5] and more recently a number of weakly cytotoxic prenylated stilbenes and their derivatives.[6] Artochamins F, H, I, and J (1-4, Scheme 1) are among the most structurally fascinating members of this group of compounds. Herein we describe the total synthesis of all four natural products through an expedient route that involves a cascade sequence featuring a novel formal [2+2] thermal cycloaddition reaction.The unique bicyclo[3.2.0]heptane carbon frameworks of artochamins H-J (2-4) would appear to be biogenetically derived from artochamin F (1), or a derivative thereof, through a formal [2+2] cycloaddition reaction between the stilbene alkene and one of the prenyl groups.[6] Furthermore, the racemic nature [7] of 2-4 could implicate a non-enzymatic process for this transformation, given the pairwise enantiotopic relationship between both the top and bottom faces of the two prenyl moieties. We were intrigued by the possibility of accomplishing the required cycloaddition under thermal conditions [8] since we speculated that the realization of such a reaction would lead to a concise synthetic approach to the artochamins from stilbenes 5 a and/or 5 b through a cascade sequence that involved, in addition to the key cyclobutaneforming process, two consecutive Claisen rearrangements. Furthermore, protecting-group design on the intermediates was expected to modulate the cascade reaction and allow selective pathways so as to deliver any of the four targeted natural products (1-4).The first objective was the stereoselective construction of an appropriately functionalized stilbene derivative from which the formal [2+2] cycloaddition reaction within the projected cascade could be investigated. The Julia-Kocienski olefination [9] was chosen [10] as the key step for this initial construction as shown in Scheme 2.Thus, the substituted phenyltetrazolesulfones 7 a and 7 b were prepared from 3,4-dihydroxybenzaldehyde (6) in a straightforward manner that involved protection (either as the corresponding Boc derivative or silyl ether), reduction with NaBH 4 , and Mitsunobu coupling with 1-phenyl-1H-tetrazole-5-thiol, followed by molybdenum-catalyzed oxidation of the resulting sulfides to the desired sulfones 7 a (73 % overall yield from 6) and 7 b (77 % overall yield from 6). The preparation of the other required coupling partner, aldehyde 10, began with methyl ester 8, [11] which was converted into the corresponding bis-reversed prenylated ester 9 through a copper-catalyzed etherification [12] with 1,1-dimethylpropynyl carbonate and Lindlar h...

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“…The structures of 7 and 8 were determined by two dimensional (2D)-NMR analysis. After separation, propargyl group was introduced to 7 in the presence of Cu(II) catalyst and 1,8-diazabicyclo [5.4.0] undec-7-ene (DBU) 9,10) by using propargyl ester 9, derived from alcohol 10 and trifluoroacetic anhydride (TFAA) in situ, to afford propargyl ether 5. The regioselectivity of the thermal Claisen rearrangement of 5 was unexpectedly low and a mixture of the desired product 11 and the regioisomer 12 was obtained in a 2 : 1 ratio, 11) estimated from the 1 H-NMR integrals.…”

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confidence: 99%

Synthesis of a Natural Chromenoquinone <i>via</i> the Diels–Alder Reaction of Pyranobenzyne and Furan

Katakawa

Sato

Iwasaki

et al. 2014

CHEMICAL & PHARMACEUTICAL BULLETIN

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Improved synthesis of aryl 1,1-dimethylpropargyl ethers

Cited by 133 publications

References 27 publications

Evolution of the Total Syntheses of Ustiloxin Natural Products and Their Analogues

Evolution of the Total Syntheses of Ustiloxin Natural Products and Their Analogues

Cascade Reactions Involving Formal [2+2] Thermal Cycloadditions: Total Synthesis of Artochamins F, H, I, and J

Synthesis of a Natural Chromenoquinone <i>via</i> the Diels–Alder Reaction of Pyranobenzyne and Furan

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