Convergent stereospecific total synthesis of Monocillin I and Monorden (or Radicicol)

Lampilas, Maxime; Lett, Robert

doi:10.1016/s0040-4039(00)77713-6

Cited by 53 publications

(39 citation statements)

References 16 publications

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“…8). 100,101 Although RDC has been synthesized previously, 102 recent work by Danishefsky and co-workers led to the development of a succinct synthesis of this natural product and identification of the first structure-activity relationships for RDC and Hsp90. 103 In an effort to remove the potential liabilities associated with the allylic epoxide, these investigators prepared a cyclopropyl analog of RDC, cycloproparadicicol (c-RDC, Fig.…”

Section: E Radicicol Derivativesmentioning

confidence: 99%

Hsp90 inhibitors: Small molecules that transform the Hsp90 protein folding machinery into a catalyst for protein degradation

Blagg

Kerr

2005

Medicinal Research Reviews

174

119

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The 90 kDa heat shock proteins (Hsp90) are responsible for the conformational maturation of nascent polypeptides and the renaturation of denatured proteins. In transformed cells, numerous mutated and overexpressed proteins rely on the Hsp90 protein folding machinery for tumor progression. The Hsp90-mediated protein folding process is dependent upon ATP, and when inhibitors of ATP are present, the Hsp90 machinery is unable to fold client proteins into their biologically active form, which results in the degradation of protein substrates via the ubiquitin-proteasome pathway. Consequently, Hsp90 has evolved into a promising anti-cancer target because multiple oncogenic proteins can be simultaneously degraded as a consequence of Hsp90 inhibition. This review serves to explain the Hsp90 protein folding process, the impact of Hsp90 inhibition, the identification of natural product inhibitors, and the development of rationally designed inhibitors of the Hsp90 protein folding machinery.

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Section: E Radicicol Derivativesmentioning

confidence: 99%

Hsp90 inhibitors: Small molecules that transform the Hsp90 protein folding machinery into a catalyst for protein degradation

Blagg

Kerr

2005

Medicinal Research Reviews

174

119

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“…Compound 70 was converted to radicicol according to known procedures. [6] Conversely, the acid 47 could be esterified with alcohol 14 a by using polymer-bound DEAD (Scheme 13) followed by MOM protection to obtain toluate 48 a which could be used in the subsequent coupling without further purification. Deprotonation of the crude toluate 48 a with LDA and reaction with polymer bound Weinreb amide 59 afforded the polymer bound diene 71.…”

Section: Wwwchemeurjorgmentioning

confidence: 99%

“…[3] The absolute stereochemistry of its three chiral centers was assigned by X-ray crystallography [4] and confirmed by total synthesis. [5,6] The reported biological activity initially attributed to this compound did not arouse much interest until it was reported that radicicol was a tyrosine kinase inhibitor. [7] It was later discovered that the inhibitory effect of radicicol for certain kinases stemmed from the fact that radicicol was an inhibitor of HSP90; [8,9] this molecular chaperone is necessary for the maturation and function of the kinases whose inhibition was originally observed.…”

Section: Introductionmentioning

confidence: 99%

Solution‐ and Solid‐Phase Synthesis of Radicicol (Monorden) and Pochonin C

Barluenga

Moulin

López

et al. 2005

Chemistry A European J

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A modular synthesis for pochonin C and radicicol is reported. The two natural products were prepared in seven and eight steps, respectively, from three readily available fragments. Alternative syntheses of these compounds were achieved using a combination of polymer-bound reagents and solid phase reactions. The conformation of the two natural products was studied and compared by using 2D NMR spectroscopy.

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“…6,7 The sequence leading to installation of the enamide side chain began with a two-step conversion of the protected primary allylic alcohol (+)-16 to the corresponding enal (DDQ then Dess Martin periodinane 27 ). Cleavage of the anisole methyl ether with boron tribromide 28 provided phenol (+)-17. 13 Subsequent oxidation of the enal to the carboxylic acid, followed by silylation of both the C(3) hydroxyl and acid moieties and base-mediated hydrolysis 29 of the TBS ester furnished carboxylic acid (-)- 18.…”

Section: Methodsmentioning

confidence: 99%

A First Generation Total Synthesis of (+)-Salicylihalamide A

Smith¹,

Zheng²

2001

Synlett

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Dedicated to Professor Ryoji Noyori with admiration and respect for his many seminal contributions to chemistry.Abstract: An efficient total synthesis of (+)-salicylihalamide (1) is described. The synthetic strategy features a highly E-selective ringclosing metathesis to construct the 12-membered salicylihalamide A macrocycle and a practical method for installation of the labile ene-hepta-(Z,Z)-dienamide side chain, which relies on a Curtius rearrangement to forge the C18-N bond with subsequent N-acylation.

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Convergent stereospecific total synthesis of Monocillin I and Monorden (or Radicicol)

Cited by 53 publications

References 16 publications

Hsp90 inhibitors: Small molecules that transform the Hsp90 protein folding machinery into a catalyst for protein degradation

Hsp90 inhibitors: Small molecules that transform the Hsp90 protein folding machinery into a catalyst for protein degradation

Solution‐ and Solid‐Phase Synthesis of Radicicol (Monorden) and Pochonin C

A First Generation Total Synthesis of (+)-Salicylihalamide A

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