A versatile approach to the total synthesis of the pseudomonic acids

Mckay, Catherine; Simpson, Thomas J.; Willis, Christine L.; Forrest, Andrew K.; O’Hanlon, Peter J.

doi:10.1039/b003094p

Cited by 33 publications

(18 citation statements)

References 23 publications

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“…To confirm the structure of the novel metabolite, synthetic samples of the C-2 epimers 14 and 15 were prepared from a common alkene 19 in a cross-metathesis approach (Scheme 4). The known [26] secondary alcohol 18 was protected as the silyl ether. Reductive cleavage of the sultam auxiliary followed by Wittig olefination gave alkene 19 [27] in good yield.…”

Section: Structure Elucidation Of Mupiric Acidmentioning

confidence: 99%

In vivo Mutational Analysis of the Mupirocin Gene Cluster Reveals Labile Points in the Biosynthetic Pathway: the “Leaky Hosepipe” Mechanism

Hothersall

Mazzetti

et al. 2008

ChemBioChem

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A common feature of the mupirocin and other gene clusters of the AT-less polyketide synthase (PKS) family of metabolites is the introduction of carbon branches by a gene cassette that contains a beta-hydroxy-beta-methylglutaryl CoA synthase (HMC) homologue and acyl carrier protein (ACP), ketosynthase (KS) and two crotonase superfamily homologues. In vivo studies of Pseudomonas fluorescens strains in which any of these components have been mutated reveal a common phenotype in which the two major isolable metabolites are the truncated hexaketide mupirocin H and the tetraketide mupiric acid. The structure of the latter has been confirmed by stereoselective synthesis. Mupiric acid is also the major metabolite arising from inactivation of the ketoreductase (KR) domain of module 4 of the modular PKS. A number of other mutations in the tailoring region of the mupirocin gene cluster also result in production of both mupirocin H and mupiric acid. To explain this common phenotype we propose a mechanistic rationale in which both mupirocin H and mupiric acid represent the products of selective and spontaneous release from labile points in the pathway that occur at significant levels when mutations block the pathway either close to or distant from the labile points.

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Section: Structure Elucidation Of Mupiric Acidmentioning

confidence: 99%

In vivo Mutational Analysis of the Mupirocin Gene Cluster Reveals Labile Points in the Biosynthetic Pathway: the “Leaky Hosepipe” Mechanism

Hothersall

Mazzetti

et al. 2008

ChemBioChem

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“…In 2000, Willis and coworkers published a novel total synthesis of pseudomonic acid C (144) that featured two Baeyer-Villiger oxidations to prepare the tetrahydropyran core of the molecule (151,Scheme 19). [91] Dihydroxylation and subsequent silyl protection of optically active ketone 147 gave compound 148, which was subjected to Baeyer-Villiger oxidation conditions to furnish lactone 149. Reductive opening of the lactone and capping of the resulting primary hydroxy group afforded secondary alcohol 150, which was oxidized to the corresponding ketone and subjected to a second Baeyer-Villiger oxidation to give lactone 151.…”

Section: Pseudomonic Acidsmentioning

confidence: 99%

“…Cross-coupling partner 172 was prepared from phenol 169 as . [91] Scheme 21. Highlights of the synthesis of the thiomarinol core 162 (Gao and Hall, 2005).…”

Section: Kinamycin Cmentioning

confidence: 99%

Recent Advances in the Chemistry and Biology of Naturally Occurring Antibiotics

et al. 2009

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Ever since the world-shaping discovery of penicillin, nature's molecular diversity has been extensively screened for new medications and lead compounds in drug discovery. The search for anti-infective agents intended to combat infectious diseases has been of particular interest and has enjoyed a high degree of success. Indeed, the history of antibiotics is marked with impressive discoveries and drug development stories, the overwhelming majority of which have their origins in nature. Chemistry, and in particular chemical synthesis, has played a major role in bringing naturally occurring antibiotics and their derivatives to the clinic, and no doubt these disciplines will continue to be key enabling technologies for future developments in the field. In this review article, we highlight a number of recent discoveries and advances in the chemistry, biology, and medicine of naturally occurring antibiotics, with particular emphasis on the total synthesis, analog design, and biological evaluation of molecules with novel mechanisms of action.

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“…[170]; the vinca alkaloid (+)-catharanthine [171]; 2-epibotcinolide (primary alcohol to aldehyde TPAP oxidation also involved) [89]; the spirobicyclic sesquiterpene (±)-erythrodiene (nitro to ketone oxidation also involved; cf. 5.6.4) [172]; a secondary alcohol to an enone as a step in the synthesis of the biologically active sequiterpene (−)-diversifolin [51]; the cytotoxic fasicularin [173]; the limonoid fraxinellone [174]; the plasmodial pigment fuligorubin A [160]; the antifungal gambieric acids A and C (also a primary alcohol to aldehyde step) [90]; the ether toxin gambierol (two primary alcohol to aldehyde steps) [91]; the cytotoxic gymnocin-A (also a primary to aldehyde step) [92]; the alkaloid (±)-lapidilectine B [175]; the antiparasitic and insecticide (+)-milbemycin-b 1 , (involving both oxidation of a primary alcohol group to an aldehyde and, in a later step, of a secondary alcohol to a ketone) [98]; the acetogenin muricatetrocin C [176] and the sesquiterpenes nortrilobolide, thapsivillosin F and trilobolide [64]; the glutamate receptor neodysiherbaine [177]; the marine alkaloid norzoanthamine (primary alcohol to aldehyde step also) [99]; the anticarcinogenic agent ovalicin [178]; the cytotoxic agent phorboxazole (hemi-acetal to lactone) [179]; the antibacterial agent pseudomonic acid C [180]; the antifungal agent rapamycin (cf. 1.11) [181,182]; the antigen daphane diterpene (+)-resiniferatoxin [183]; the antitumour macrolide (+)-rhizoxin D [184]; the heliobactericidal (+)-spirolaxine methyl ether [185]; the SERCA thapsigargin inhibitors [112,152,153]; the antitumour agent tonatzitlolone [186] and the therapeutic hypercholesterolemia agent zaragozic acid A [187].…”

Section: Natural Product/pharmaceutical Syntheses Involving Secondarymentioning

confidence: 99%

Oxidation of Alcohols, Carbohydrates and Diols

Griffith

2009

Catalysis by Metal Complexes

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This is one of the most important classes of oxidation effected by Ru complexes, particularly by RuO 4 , [RuO 4 ] − , [RuO 4 ] 2− and RuCl 2 (PPh 3 ) 3 , though in fact most Ru oxidants effect these transformations. The chapter covers oxidation of primary alcohols to aldehydes (section 2.1), and to carboxylic acids (2.2), and of secondary alcohols to ketones (2.3). Oxidation of primary and secondary alcohol functionalities in carbohydrates (sugars) is dealt with in section 2.4, then oxidation of diols and polyols to lactones and acids (2.5). Finally there is a short section on miscellaneous alcohol oxidations in section 2.6.In this chapter the first of the two most important categories of oxidations catalysed by Ru complexes (the other being alkene and alkyne oxidations in Chapter 3) are considered. The approach in this and subsequent chapters differs from that of Chapter 1, concentrating here on the substrate rather than on the oxidant. The text is divided into the categories of alcohols and their oxidations. There are summaries in section 2.3.6 of systems of limited applicability which are mentioned only in Chapter 1, and in section 2.3.7 of large-scale (>1 g) oxidations.The first oxidations of alcohols by stoicheiometric RuO 4 /H 2 O were reported in 1958, of primary alcohols to aldehydes or carboxylic acids and secondary alcohols to ketones [1]. The first Ru-catalysed oxidation of an alcohol was reported in 1965 when Parikh and Jones used RuO 2 /aq. Na(IO 4 )/CCl 4 1 ( Table 2.3) [2] to oxidise secondary alcohol groups in carbohydrates.Oxidation of alcohols is the most frequently reviewed topic for Ru-catalysed oxidations [3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18][19][20]. Mechanisms of alcohol oxidation by Ru complexes have been reviewed [21].

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A versatile approach to the total synthesis of the pseudomonic acids

Cited by 33 publications

References 23 publications

In vivo Mutational Analysis of the Mupirocin Gene Cluster Reveals Labile Points in the Biosynthetic Pathway: the “Leaky Hosepipe” Mechanism

In vivo Mutational Analysis of the Mupirocin Gene Cluster Reveals Labile Points in the Biosynthetic Pathway: the “Leaky Hosepipe” Mechanism

Recent Advances in the Chemistry and Biology of Naturally Occurring Antibiotics

Oxidation of Alcohols, Carbohydrates and Diols

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