Total Synthesis of Rapamycin

Ley, Steven V.; Tackett, Miles N.; Maddess, Matthew L.; Anderson, James C.; Brennan, P.E.; Cappi, Michael W.; Heer, Jag; Helgen, Céline; Kori, Masakuni; Kouklovsky, Cyrille; Marsden, Stephen P.; Norman, Joanne; Osborn, David P.; Palomero, M. Angel; Pavey, John B. J.; Pinel, Catherine; Robinson, Lesley A.; Schnaubelt, Jiirgen; Scott, James S.; Spilling, Christopher D.; Watanabe, Hidenobu; Wesson, Kieron E.; Willis, Michael C.

doi:10.1002/chem.200801656

Cited by 63 publications

(19 citation statements)

References 134 publications

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“…During synthesis of the protein phosphatase inhibitor okadaic acid three oxidations with TPAP/NMO/PMS/CH 2 Cl 2 were used, two of primary alcohol to aldehydes and one of a diol to a lactone [109], and in the synthesis of the immunoadjuvant QS-21A api a diol-to-lactone step is involved [360], as in the case of the lypophilic macrolide rapamycin (cf. 1.11) [181]. In the synthesis of cis-solamin the reagent oxidised a triol to a lactone aldehyde (an RuO 4 -catalysed cyclisation of a 1,3-diene is also involved, cf.…”

Section: Specific Examplesmentioning

confidence: 99%

“…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]. For synthesis of a fragment of the protein phosphatase inhibitor calyculin A the TPAP/NMO/PMS/CH 2 Cl 2 reagent was involved [188].…”

Section: Natural Product/pharmaceutical Syntheses Involving Secondarymentioning

confidence: 99%

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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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Section: Specific Examplesmentioning

confidence: 99%

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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“…Epoxy chalcone and its derivatives are inimitable pharmacophore [15] for drug synthesis (e.g. diltiazem [16], rapamycin [17], epoxomicin [18], eponemycine [19], carmaphycin [20]) with virtuous anti-oxidant [21], anti-bacteria [22], anticancer [23], anti-depressant [24], anti-fungi [25] and antimicrobial [26] activities. Epoxy chalcone derivatives also offers numerous synthetic strategies of organic compounds via ring opening reaction under specific conditions to form C-C bond [27][28][29].…”

Section: Introductionmentioning

confidence: 99%

One Pot and Two Pot Synthetic Strategies and Biological Applications of Epoxy-Chalcones

Farooq

Ngaini

2020

Chemistry Africa

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Epoxy chalcone is a heterocyclic molecule and an important precursor for the synthesis of biologically active compounds. This mini-review is elucidating the synthetic strategies of chalcone epoxide via one pot and two pot routes including nature of reactants, nature of catalyst and variety of catalyst to improve yield of desired product, biological applications and advantages and drawbacks of these synthetic strategies. One pot route has wide variety of reactants and efficient one is the condensation of aldehyde and ketone. However, two pot route is consisted of chalcone synthesis preceding to epoxy chalcone. The synthetic routes for the preparation of epoxy chalcone and the usage as a precursor for the synthesis of various organic molecules with biological application is comprehensively discussed. This review is outstanding in organic chemistry and pharmaceutical industries to produce new molecules with various applications. Graphic AbstractO O

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“…Rapamycin is a highly complex molecule and although total syntheses of rapamycin have been reported, 15 , 16 these syntheses are unlikely to deliver the quantities of rapalogs that would be required for drug development. While semi-synthetic rapalogs have received FDA-approval, the scope and flexibility of this approach is limited with regards to amenable diversification of the rapamycin scaffold.…”

Section: Introductionmentioning

confidence: 99%