Formal Synthesis of Merrilactone A Using a Domino Cyanide 1,4-Addition–Aldol Cyclization

Nazef, Naim; Davies, Robert D. M.; Greaney, Michael F.

doi:10.1021/ol301513h

Cited by 38 publications

(15 citation statements)

References 30 publications

(18 reference statements)

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“…[16] Despite various successful syntheses of similar sesquiterpenes such as anisatin [17] and merrilactone, [18] the synthetic efforts toward the majucin-subtype seco -prezizaane-type sesquiterpenes are rather limited. [19] To date, two impressive syntheses of jiadifenin ( 3 ) have been reported by the Danishefsky [20] and Zhai groups.…”

Section: Introductionmentioning

confidence: 99%

Illicium Sesquiterpenes: Divergent Synthetic Strategy and Neurotrophic Activity Studies

Trzoss

Lacoske

et al. 2013

Chemistry A European J

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Majucin-type sesquiterpenes from Illicium sp., such as jiadifenolide (2), jiadifenin (3) and (1R,10S)-2-oxo-3,4-dehydroxyneomajucin (4, ODNM), possess a complex caged chemical architecture and remarkable neurotrophic activities. As such, they represent attractive small molecule leads against various neurodegenerative diseases. We present an efficient, enantioselective and unified synthesis of 2, 3 and 4 and designed analogues that diverge from tetracyclic key intermediate 7. The synthesis of 7 is highlighted by the use of an enantioselective Robinson annulation reaction (construction of AB rings), a Pd-mediated carbomethoxylation reaction (construction of C ring) and a one-pot oxidative reaction cascade (construction of D ring). Evaluation of the neurotrophic activity of these compounds led to the identification of several highly potent small molecules that significantly enhanced the activity of nerve growth factor (NGF) in PC-12 cells. Moreover, efforts to define the common pharmacophoric motif suggest that substitution at the C-10 center significantly affects bioactivity, while the hemiketal moiety of 2 and 3 and the C-1 substitution might not be critical to the neurotrophic activity.

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Section: Introductionmentioning

confidence: 99%

Illicium Sesquiterpenes: Divergent Synthetic Strategy and Neurotrophic Activity Studies

Trzoss

Lacoske

et al. 2013

Chemistry A European J

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“…Since its isolation in 2000, merrilactone A has been consistently appealing to researchers. Over the years, several different routes towards the total synthesis of merrilactone A have been reported [77,78,79,80,81]. Most recently, Liu and Wang [82] designed and achieved a concise synthesis of merrilactone A in a racemic form (Scheme 6).…”

Section: Oxetanesmentioning

confidence: 99%

An Overview of Saturated Cyclic Ethers: Biological Profiles and Synthetic Strategies

Harmalkar

Choi

et al. 2019

Molecules

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Saturated oxygen heterocycles are widely found in a broad array of natural products and other biologically active molecules. In medicinal chemistry, small and medium rings are also important synthetic intermediates since they can undergo ring-opening and -expansion reactions. These applications have driven numerous studies on the synthesis of oxygen-containing heterocycles and considerable effort has been devoted toward the development of methods for the construction of saturated oxygen heterocycles. This paper provides an overview of the biological roles and synthetic strategies of saturated cyclic ethers, covering some of the most studied and newly discovered related natural products in recent years. This paper also reports several promising and newly developed synthetic methods, emphasizing 3–7 membered rings.

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“…79 The 1-iodo-3,3-(ethylenedioxy)butane isotopologue is routinely prepared from MVK upon treatment with concentrated aqueous hydriodic acid, followed by addition of ethylene glycol (49%, 35-g scale). 80 Since no 13 C-labeled MVK preparation has been reported in the literature, due to its volatility and its tendency to dimerize or polymerize, the use of [1,2-13 C 2 ]-ethylene gas (250 mL/€612) has provided the most expedient and convenient preparation of the required masked MVK 118 in the context of 13 C-labeled synthesis. It should be mentioned that a preparation of 1-iodo-3,3-(ethylenedioxy)butane from ethyl acetoacetate has also been reported 81 following a four-step sequence.…”

Section: Syn Thesismentioning

confidence: 99%

Synthesis of 13C-Labeled Steroids

Dénès

Farard²,

Lebreton

2019

Synthesis

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Due to the wide spectrum of biological activities of steroids, the detection and quantification of steroidal residues in various biological materials are crucial for drug development, doping prevention, and environmental protection. In addition, the analytical technique of stable isotopic dilution (SID) by Liquid Chromatography-Mass Spectrometry (LC-MS) requires 13C-labeled steroids as standards to provide accurate and reproducible steroid quantification. In this context, the synthesis of 13C-labeled steroids is reviewed. The approaches based on partial synthesis starting from commercially available steroids have been, by far, the most commonly employed strategy.1 Introduction2 Hemisynthesis of 13C3-Labeled Steroids via Partial Degradation of the A Ring2.1 Degradation of the A Ring to an Enol Lactone2.1.1 Introduction of 13C Atom(s) via Claisen Condensation: Turner’s Strategy2.1.2 Introduction of 13C Atom(s) with 13C-Labeled 5-(Diethylphosphono)pentan-2-one Ethylene Ketal Based on the Fujimoto–Belleau Reaction2.2 Degradation of the A Ring and Introduction of 13C Atom(s) with [13C3]-1-(Triphenylphosphoranylidene)propan-2-one3 Construction of the A Ring from an α,β-Unsaturated Ketone with 13C-Labeled 1-Iodo-3,3-(ethylenedioxy)butane as Electrophile4 Construction of the A and B rings: Stork’s Strategy5 Hemisynthesis with Introduction of 13C Atom(s) in the C17 Side Chain6 Conclusion

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Formal Synthesis of Merrilactone A Using a Domino Cyanide 1,4-Addition–Aldol Cyclization

Cited by 38 publications

References 30 publications

Illicium Sesquiterpenes: Divergent Synthetic Strategy and Neurotrophic Activity Studies

Illicium Sesquiterpenes: Divergent Synthetic Strategy and Neurotrophic Activity Studies

An Overview of Saturated Cyclic Ethers: Biological Profiles and Synthetic Strategies

Synthesis of 13C-Labeled Steroids

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