Total Synthesis of (−)‐Ulapualide A: The Danger of Overdependence on NMR Spectroscopy in Assignment of Stereochemistry

Pattenden, Gerald; Ashweek, Neil J.; Baker-Glenn, Charles; Walker, Gary M.; Yee, James G. K.

doi:10.1002/anie.200700459

Cited by 47 publications

(24 citation statements)

References 37 publications

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“…In this case, synthetic studies have demonstrated that this approach is unreliable for distinguishing ulapualide diasteromers. 12 However, all of the tris-oxazole compounds characterized by X-ray crystallography have the same absolute configuration (with the omission of position 9), 13 this suggests that those stereocenters are conserved via a shared biogenesis. In addition, the two other stereocenters in 5 are most likely 30 R, 37 R consistent with 2 and the structurally-related mycalolides.…”

Section: Resultsmentioning

confidence: 99%

Ulapualides C–E Isolated from a Hawaiian Hexabranchus sanguineus Egg Mass

et al. 2017

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Three new ulapualides (3–5) were isolated from egg masses of the nudibranch Hexabranchus sanguineus. The structures of 3–5 were deduced by analyses of physical and spectroscopic data in comparisons with ulapualides A (1) and B (2). Ulapualide C demonstrated submicromolar cytotoxicity against select NCI cell lines (768-0, DU-145, MDA-MB-231, and A549) with the most potent activity against MDA-MB-231 (IC50 0.58 μM). Ulapualides A (1) and B (2) were two to four-fold more potent than 3.

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Section: Resultsmentioning

confidence: 99%

Ulapualides C–E Isolated from a Hawaiian Hexabranchus sanguineus Egg Mass

et al. 2017

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“…The formation of a five-membered oxazol ring was carried out, for instance, in synthesis of the macrolide ulapualide A isolated from marine nudibranch [58] and oxygen analog (79) of the anti-inflammatory thiazole-containing drug halipeptin D (80) of sea sponges Leiosella cf. arenifibrosa.…”

Section: Functionalisation Of Macrocycles With Preservation Of Their mentioning

confidence: 99%

Functionalisation of Macroheterocycles with Preserving and Changing Their Sizes

Ishmuratov¹,

Yakovleva²,

Выдрина³

et al. 2017

MHC

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“…[15] To date,t otal syntheses of mycalolide A( 2) [16] and ulapualide A [17] have been accomplished, in which Yamaguchi lactonization, cyclization of the central oxazole ring, or intramolecular Horner-Wadsworth-Emmons olefination were used to construct macrocycles.However,nototal synthesis of mycalolide Bh as been reported to date.W e describe herein the first total synthesis of (À)-mycalolide B (1)a nd the second total synthesis of mycalolide A( 2)u sing olefin metathesis as akey step.…”

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confidence: 99%

Total Synthesis of Mycalolides A and B through Olefin Metathesis

et al. 2015

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An asymmetric total synthesis of the trisoxazole marine macrolides mycalolides Aa nd Bi sd escribed. This synthesis involves the convergent assembly of highly functionalized C1-C19 trisoxazole and C20-C35 side-chain segments through the use of olefin metathesis and esterification as well as Julia-Kocienski olefination and enamide formation as key steps.Mycalolides,isolated from the marine sponge Mycale sp., are cytotoxic and antimycotic trisoxazole macrolides.[1] Mycalolides inhibit the enzyme actomyosin Mg 2+ -ATPase [2] and show potent actin-depolymerizing activity by forming a1 :1 complex with the monomeric molecule.[3] Mycalolide B( 1) contains a2 ,3-O-dimethyl-d-glyceryl ester moiety and 13 asymmetric centers as structural features,w hile ac losely related mycalolide A( 2)c ontains ak etone functionality at the C30 position (Scheme 1). Several trisoxazole macrolides that are closely related to mycalolides have been isolated, such as ulapualides, [4] halichondramides, [5] jaspisamides, [6] and kabiramides; [7] all of these exhibit actin-depolymerizing activity and potent cytotoxicity,a nd some induce apoptosis in tumor cells.[8] Thus,t hese agents may be useful for the design and development of novel pharmacological tools for analyzing actin-mediated cell functions,s uch as muscle contraction, cell motility,a nd cytokinesis,a sw ell as those of therapeutic agents. [9] Mycalolides can be divided into two structurally characteristic parts:t he C1-C24 trisoxazole macrolactone and the C25-C35 side chain functionalized by an N-methyl enamide moiety.S tudies on the structure-activity relationships [10] and photolabeling experiments [11] have established that the sidechain component of mycalolides is important for its ability to bind to and depolymerize actin. Additionally,X-ray analyses of the actin-kabiramide C, [12] actin-jaspisamide A, [12] and actin-ulapualide Ac omplexes [13] have revealed that the aliphatic side chains of the macrolides intercalate into the hydrophobic cleft between subdomains 1and 3ofactin. More recently,wesynthesized the 19E-and 19Z-lactone analogues of mycalolides that lack the C25-C35 side chain.[14] These analogues exhibited moderate cytotoxicity against tumor cells (circa 1/100 of 1), but did not show actin-depolymerizing properties or antimycotic activity against pathogenic fungi. [14] Thus,b oth the side-chain and macrolactone moieties were suggested to be essential for the potent biological activities of the parent molecules.As aresult of their extraordinary structures and biological activities,m ycalolides and their congeners have received considerable attention in the synthetic community,a nd several approaches to the construction of conformationally restricted trisoxazole macrolactone structures have been described. [15] To date,t otal syntheses of mycalolide A( 2) [16] and ulapualide A [17] have been accomplished, in which Yamaguchi lactonization, cyclization of the central oxazole ring, or intramolecular Horner-Wadsworth-Emmons olefination were used to construct macr...

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Total Synthesis of (−)‐Ulapualide A: The Danger of Overdependence on NMR Spectroscopy in Assignment of Stereochemistry

Cited by 47 publications

References 37 publications

Ulapualides C–E Isolated from a Hawaiian Hexabranchus sanguineus Egg Mass

Ulapualides C–E Isolated from a Hawaiian Hexabranchus sanguineus Egg Mass

Functionalisation of Macroheterocycles with Preserving and Changing Their Sizes

Total Synthesis of Mycalolides A and B through Olefin Metathesis

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