Asymmetric synthesis of (+)-trachyspic acid

Morokuma, Kenji; Taira, Yuko; Uehara, Yumiko; Shibahara, Setsuya; Takahashi, Keisuke; Ishihara, Jun; Hatakeyama, Susumi

doi:10.1016/j.tetlet.2008.07.004

Cited by 22 publications

(11 citation statements)

References 21 publications

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“…Finally, pyrrolidine thiourea derivative (296, 50 mol%; Scheme 3.69) gave the best result, among several proline derivatives, in aldol reaction of α-keto ester 298 and 4-pentenal (297), yielding compound 299 (49% yield, 33% de, and 85% ee), which was a key step intermediate in the total synthesis of (+)-trachyspic acid (300) [353]. …”

Section: Application To Natural Product Synthesismentioning

confidence: 99%

Organocatalyzed Aldol Reactions

Guillena¹

2013

Modern Methods in Stereoselective Aldol Reactions

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The use of catalytic enantioselective methods to perform an aldol reaction provides a direct entry for the synthesis of chiral compounds and is probably the most attractive way to achieve this goal with high control of the chemo-, regio-, diastereo-, and enantioselectivity. The application of biochemical methods based on enzyme aldolases or antibodies, which are discussed in other chapters, avoid the use of preformed enolates or their equivalents for enhancing the global atom efficiency of the process [1] for which the narrow substrate scope is a major drawback. The discovery of methodologies to carry out the enantioselective direct aldol reaction [2] has eluded the production of stoichiometric by-products increasing the substrate scope. This task could be accomplished by using small molecules as catalysts, such as metal complexes (which are covered along this book) and organic molecules, also known as organocatalysts [3]. The growth of this last research area and the direct aldol reaction are closely linked [4], with the report on the use of (S)-proline as catalyst for the intermolecular aldol [5] definitely being the push for the development of the organocatalytic methods as a competitive methodology for the synthesis of chiral compounds.In a strict sense, an organocatalyzed reaction is a process in which all the involved reagents and catalysis are purely organic compounds of low-molecular weight, excluding boron-and silicon-containing derivatives. However, in some cases, the presence of a silyl group only plays a steric role and therefore can also be considered as an organocatalyzed process. Also, if the organocatalyst involved in a reaction is immobilized in a polymer, a dendrimer, or even an inorganic material that serves only as a support to facilitate its recovery [6], it could still be considered as an organocatalyst, although those types of derivatives have been scarcely used in the natural product synthesis and therefore will be excluded from this chapter. Therefore, a comprehensive overview of the direct aldol reaction [7], emphasizing the reactivity, scope, selectivity, and limitations of the methodology and giving several examples of their application to the synthesis of biologically active compounds, is discussed in this chapter.

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Section: Application To Natural Product Synthesismentioning

confidence: 99%

Organocatalyzed Aldol Reactions

Guillena¹

2013

Modern Methods in Stereoselective Aldol Reactions

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“…[6a] Its synthesis commenced with ester 13 (Scheme 3 ), which was converted into epoxide 14 through alkyne carbocupration[ 15 ] with 3-trimethylsilylpropynylmagnesium bromide,[ 16 ] ester reduction, and Sharpless asymmetric epoxidation (83 % over 3 steps, 92 % ee ). [ 17 ] Ring-opening of 14 with allylmagnesium chloride,[ 18 ] followed by oxidation and β-lactone formation, afforded 15 in good yield (74 % over 4 steps). [ 19 ] Double nucleophilic addition of methylmagnesium bromide to the β-lactone smoothly installed the gem- dimethyl group of the B ring ( 16 );[ 20 ] oxidative cleavage of the terminal alkene in 16 , methyl acetal formation, and oxidation of the remaining primary alcohol afforded aldehyde regioisomers 17 and 18 (1.9:1 ratio, 72 % yield from 16 ).…”

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confidence: 99%

Total Synthesis of (+)‐Rubriflordilactone A

et al. 2015

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Two enantioselective total syntheses of the nortriterpenoid natural product rubriflordilactone A are described, which use palladium- or cobalt-catalyzed cyclizations to form the CDE rings, and converge on a late-stage synthetic intermediate. These key processes are set up through the convergent coupling of a common diyne component with appropriate AB-ring aldehydes, a strategy that sets the stage for the synthetic exploration of other members of this family of natural products.

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“…2–6 The contiguous C3 and C4 chiral centers and the efficient management of the unusual C6–C9 β,γ-diketoaldehyde have proven to be the principle hurdles to synthesis. For construction of the former subunit, previous syntheses of trachyspic acid have employed either aldol 2,3,6 or Ireland-Claisen rearrangement 4,5 strategies. The occurrence of the fully substituted C3 glycolic acid suggested the opportunity to develop a new silyl glyoxylate-based three-component coupling 7–13 that might permit efficient access to the core substructure.…”

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confidence: 99%

Three-Component Coupling Approach to Trachyspic Acid

2011

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Three-component coupling of the lithium enolate of t-BuOAc, silyl glyoxylate, and an α,β-unsaturated ketone enables the rapid construction of the trachyspic acid carbon skeleton. A 3,4-disubstituted isoxazole is utilized to mask the C7/C9 dicarbonyl. New enolsilane/nitrile-oxide cycloadditions enable the preparation of various 3,4-disubstituted isoxazoles that are challenging to access by other means.

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Asymmetric synthesis of (+)-trachyspic acid

Cited by 22 publications

References 21 publications

Organocatalyzed Aldol Reactions

Organocatalyzed Aldol Reactions

Total Synthesis of (+)‐Rubriflordilactone A

Three-Component Coupling Approach to Trachyspic Acid

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