Total Synthesis of Pseudolaric Acid A

Geng, Zhe; Chen, Bin; Chiu, Pauline

doi:10.1002/anie.200602056

Cited by 79 publications

(51 citation statements)

References 54 publications

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“…3-Chloro-2-(chloromethyl)prop-1-ene was reacted with the sodium salt of p-methoxybenzyl alcohol in THF to give the known 3-chloro-2-(4-methoxybenzyloxy)methylpropene (10). [38] Copper-catalyzed reaction [39] of the allyl chloride 10 and the organozinc derived from ethyl iodobutyrate [40] gave ester 11 in good yield. Direct conversion into the Weinreb amide 9 was achieved in excellent yield using the isopropylmagnesium chloride mediated reaction with N,O-dimethylhydroxylamine hydrochloride developed by Williams et al [41] The known ortho-toluate ester 8 [37] in THF was treated with LDA (2.5 equiv) at À78 8C, and the deep red colored solution was immediately treated with the Weinreb amide 9.…”

Section: Resultsmentioning

confidence: 99%

Inhibition of Hsp90 with Resorcylic Acid Macrolactones: Synthesis and Binding Studies

Day

Sharp

Rowlands

et al. 2010

Chemistry A European J

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A series of resorcylic acid macrolactones, analogues of the natural product radicicol has been prepared by chemical synthesis, and evaluated as inhibitors of heat shock protein 90 (Hsp90), an emerging attractive target for novel cancer therapeutic agents. The synthesis involves acylation of an ortho-toluic acid dianion, esterification, followed by a ring-closing metathesis to form the macrocycle. Subsequent manipulation of the protected hydroxymethyl side chain allows access to a range of new analogues following deprotection of the two phenolic groups. Co-crystallization of one of the new macrolactones with the N-terminal domain of yeast Hsp90 confirms that it binds in a similar way to the natural product radicicol and to our previous synthetic analogues, but that the introduction of the additional hydroxymethyl substituent appears to result in an unexpected change in conformation of the macrocyclic ring. As a result of this conformational change, the compounds bound less favorably to Hsp90.

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Section: Resultsmentioning

confidence: 99%

Inhibition of Hsp90 with Resorcylic Acid Macrolactones: Synthesis and Binding Studies

Day

Sharp

Rowlands

et al. 2010

Chemistry A European J

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“…Tandem Rh(II)-catalyzed intramolecular carbonyl ylide formation followed by 1,3-dipolar cycloaddition of -diazocarbonyl compounds with dipolarophiles, 1 which can efficiently provide epoxybridged complex polycyclic products in a one-pot reaction (Scheme 1), has been applied toward the syntheses of various biologically important oxygen-containing polycyclic natural products, such as brevicomin, 2 zaragozic acids, 3 komaroviquinone, 4 polygalolides, 5 pseudolaric acid A, 6 and aspidophytine 7 ( Figure 1). To improve the asymmetric synthesis of optically active oxygen-containing polycyclic compounds, Hodgson 8 and Hashimoto 9 have independently developed a highly enantioselective variant of this methodology featuring a chiral Rh(II)-associated carbonyl ylide in the transition state.…”

Section: Introductionmentioning

confidence: 99%

Inverse electron demand asymmetric cycloadditions of cyclic carbonyl ylides catalyzed by chiral Lewis acids—Scope and limitations of diazo and olefinic substrates

et al. 2010

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ABSTRACT. High enantioselectivities (94 -96% ee) were obtained for the inverse electron-demand 1,3-dipolar cycloadditions between cyclohexyl vinyl ether and 2-benzopyrylium-4-olate generated via Rh 2 (OAc) 4 -catalyzed decomposition of o-methoxycarbonyl--diazoacetophenone. The reactions were effectively catalyzed by Eu(OTf) 3 , Ho(OTf) 3 , or Gd(OTf) 3 complexes (10 mol%) of chiral 2,6-bis[(4S,5S)-4,5-diphenyl-2-oxazolinyl]pyridine. The reactions with the other electron-rich dipolarophiles such as allyl alcohol, 2,3-dihydrofuran, and butyl-t-butyldimethylsilylketene acetal showed moderate enanantioselectivities (60 -73% ee). Good to high enantioselectivities (73 -97% ee) were also obtained for the cycloadditions between 3-acyl-2-benzopyrylium-4-olates, generated from methyl 2-(2-diazo-1,3-dioxoalkyl)benzoates and butyl or cyclohexyl vinyl ethers, in the presence of binaphthyldiimine (BINIM)-Ni(II) complexes (10 mol%). Under similar conditions, the reaction between methyl 2-(2-diazo-1,3-dioxohexyl)benzoate and 2,3-dihydrofuran was highly endo-selective, and moderately enantioselective (70% ee). For the BINIM-Ni(II)-catalyzed reactions of cyclohexyl vinyl ether, the use of an epoxyindanone as the 3-acyl-2-benzopyrylium-4-olate precursor revealed that the chiral Lewis acid can function as a catalyst for asymmetric induction. The scope of the cyclic carbonyl ylides was extended to those generated from 1-diazo-2,5-pentanedione derivatives, which were reacted with butyl or TBS vinyl ether and catalyzed using the (4S,5S)-Pybox-4,5-Ph 2 -Lu(OTf) 3 complex to give good levels of asymmetric inductions (75 -84% ee).

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“…From the root bark of Pseudolarix kaempferi, used in folk medicine in China [4,5], the antifungal compound pseudolaric acid A (4) was isolated. This has been a synthetic target [6][7][8] due to its complex structure and biological activities [9]. It has a trans fused bicyclo [5.3.0]decene system, the juncture position of which has an acetoxy group.…”

mentioning

confidence: 99%

Synthesis of a Key Intermediate, 10-Acetyl-7-(t-butyldiphenylsilyloxymethyl)-4-methylbicyclo[5.3.0]dec-4-en-1-ol, in the Synthesis of Pseudolaric Acid A

Nakashima

Kikuchi

Takehara

et al. 2013

Natural Product Communications

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Total Synthesis of Pseudolaric Acid A

Cited by 79 publications

References 54 publications

Inhibition of Hsp90 with Resorcylic Acid Macrolactones: Synthesis and Binding Studies

Inhibition of Hsp90 with Resorcylic Acid Macrolactones: Synthesis and Binding Studies

Inverse electron demand asymmetric cycloadditions of cyclic carbonyl ylides catalyzed by chiral Lewis acids—Scope and limitations of diazo and olefinic substrates

Synthesis of a Key Intermediate, 10-Acetyl-7-(t-butyldiphenylsilyloxymethyl)-4-methylbicyclo[5.3.0]dec-4-en-1-ol, in the Synthesis of Pseudolaric Acid A

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