An Enantiospecific Synthesis of Jiadifenolide

Siler, David A.; Mighion, Jeffrey D.; Sorensen, Erik J.

doi:10.1002/ange.201402335

Cited by 26 publications

(6 citation statements)

References 37 publications

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“…A simple crystallization of 18 from hexane elevated its optical purity to > 99 % ee. Hydrogenation and methylation [19] of 18 provided ketone 19 in 82 % overall yield. Reduction of 19 with LAH followed by hydrogenation formed compound 20 in 83 % overall yield.…”

Section: Methodsmentioning

confidence: 99%

Enantioselective Palladium‐Catalyzed Dearomative Cyclization for the Efficient Synthesis of Terpenes and Steroids

Guo

Chen

et al. 2015

Angewandte Chemie

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A novel enantioselective palladium-catalyzed dearomative cyclization has been developed for the efficient construction of a series of chiral phenanthrenone derivatives bearing an all-carbon quaternary center. The effectiveness of this method in the synthesis of terpenes and steroids was demonstrated by a highly efficient synthesis of a kaurene intermediate, the facile construction of the skeleton of the anabolic steroid boldenone, and the enantioselective total synthesis of the antimicrobial diterpene natural product (À)-totaradiol.Tricyclic skeletons bearing chiral all-carbon quaternary centers, such as chiral phenanthrenone derivatives, exist in numerous complex terpenes and steroids with interesting biological activities ( Figure 1). [1] For example, kaurene [2] is the biosynthetic precursor of the plant hormones gibberellins, boldenone [3] is an anabolic steroid, totaradiol [4a-d] is a diterpene natural product that exhibits good antimicrobial properties, and triptoquinone B exhibits a remarkable inhibitory activity against interleukin-1 release. [4e-f] Their syntheses have attracted a great deal of attention with the emergence of various excellent methods. [5] Among them, the asymmetric intramolecular Heck reaction [6] has become a powerful method for constructing chiral polycyclic skeletons bearing all-carbon quaternary centers ( Figure 2). However, a number of synthetic steps are often required either in constructing the olefin moiety necessary for the Heck cyclization or for the post-modification of the Heck product to the target molecule. Alternatively, asymmetric intramolecular dearomative cyclizations [7,8] between two aryl systems can offer better synthetic efficiency owing to the availability of aryl systems as well as the convenience in the post-modification of the cyclization product. Herein, we present a powerful asymmetric palladium-catalyzed dearomative cyclization that has led to a series of chiral phenanthrenone derivatives bearing an allcarbon quaternary center in excellent enantioselectivities. The new method has been successfully applied in the highly efficient synthesis of a chiral kaurene intermediate, the facile construction of the skeleton of the anabolic steroid boldenone, and an enantioselective total synthesis of the diterpene natural product (À)-totaradiol.Although dearomative cyclizations have been frequently applied in natural product synthesis, the asymmetric transition-metal-catalyzed dearomative cyclization has remained underdeveloped, and only a few examples of efficient intramolecular dearomative arylations have been reported thanks to the pioneering work from the Buchwald, [9] Bedford, [10] and You [11] groups. Buchwald [9] and co-workers developed efficient dearomative cyclizations to form chiral benzocarbazole derivatives and spirocyclohexadienones bearing all-carbon quaternary centers. You [11e] et al. recently reported an interesting dearomative cyclization to form a tetracyclic spiroamine framework. However, to the best of our knowledge, enantioselective dearomative...

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Section: Methodsmentioning

confidence: 99%

Enantioselective Palladium‐Catalyzed Dearomative Cyclization for the Efficient Synthesis of Terpenes and Steroids

Guo

Chen

et al. 2015

Angewandte Chemie

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“…108 Among this large family, jiadifenolide ( 81 , Scheme 7) has recently attracted significant synthetic attention owing to its compact and highly oxidized molecular framework coupled with its ability to promote neurite outgrowth at very low concentrations. 109 To date, total syntheses of 81 have been disclosed by the groups of Theodorakis, 110,111 Paterson, 112 Sorensen, 113 Shenvi, 114 and Zhang, 115 in addition to a recent formal synthesis by Gademann. 116 Herein we discuss the three chiral pool-based total syntheses of 81 by Sorensen (2014), Zhang (2015), and Shenvi (2015).…”

Section: Syntheses From the 21st Centurymentioning

confidence: 99%

Navigating the Chiral Pool in the Total Synthesis of Complex Terpene Natural Products

et al. 2017

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The pool of abundant chiral terpene building blocks (i.e. “chiral pool terpenes”) has long served as a starting point for the chemical synthesis of complex natural products, including many terpenes themselves. As inexpensive and versatile starting materials, such compounds continue to influence modern synthetic chemistry. This review highlights 21st century terpene total syntheses which themselves use small, terpene-derived materials as building blocks. An outlook to the future of research in this area is highlighted as well.

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“…Although Sanford's catalytic CÀH acetoxylation protocol proved scalable for oxidation of C-23, [27][28][29] the alkene in 1 does not tolerate strong oxidants. We therefore developed a one-pot sequence to 3 30 consisting of protection via halolactonization with N-bromosuccinimide (NBS), oxidation of C-3-OH with trichloroisocyanuric acid (TCCA), and oxime formation with hydroxylamine in quantitative yield without the need for any further purification (Scheme 1).…”

Section: Càh Oxidation Sequence For Functionalization Of Ring Bmentioning

confidence: 99%

Application of Relay C−H Oxidation Logic to Polyhydroxylated Oleanane Triterpenoids

Berger

Knittl-Frank

Bauer

et al. 2020

Chem

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Although biological applications of abundant feedstock triterpenoids such as oleanolic acid are limited because of poor solubility, synthetic access to higher hydroxylated metabolites is challenging. We use relay CÀH oxidation logic to mimic the processes carried out in Nature by P450 monooxygenase enzymes. To this end, we use the C-23-OH as natural handle for a hydrogen-atom-transfer access to C-6, enabling the first syntheses of highly oxidized natural products as well as uncovering the anti-leukemic activity of a synthetic intermediate.

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An Enantiospecific Synthesis of Jiadifenolide

Cited by 26 publications

References 37 publications

Enantioselective Palladium‐Catalyzed Dearomative Cyclization for the Efficient Synthesis of Terpenes and Steroids

Enantioselective Palladium‐Catalyzed Dearomative Cyclization for the Efficient Synthesis of Terpenes and Steroids

Navigating the Chiral Pool in the Total Synthesis of Complex Terpene Natural Products

Application of Relay C−H Oxidation Logic to Polyhydroxylated Oleanane Triterpenoids

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