Toward the Synthesis of Phomoidride D

Murphy, Graham K.; Shirahata, Tatsuya; Hama, Naoto; Bedermann, Aaron A.; Dong, Ping; McMahon, Travis C.; Twenter, Barry M.; Spiegel, David A.; McDonald, Ivar M.; Taniguchi, Nobuaki; Inoue, Munenori; Wood, John L.

doi:10.1021/jo302353g

Cited by 17 publications

(10 citation statements)

References 33 publications

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“…The triterpenoid phainanoid F ( 1 ) was found to have potent immunosuppressive activity. Phomoidride B (also known as CP-263,114, 2 ) and related analogs were shown to inhibit squalene synthase as well as Ras farnesyl transferase and have attracted plenty of synthetic attention . Massarinolin A ( 3 ) and its analogs expansolides A ( 4 ) and B ( 5 ) have shown potent antibacterial activity against drug resistant strains.…”

Section: Introductionmentioning

confidence: 99%

Catalytic Carbonylative Spirolactonization of Hydroxycyclopropanols

et al. 2016

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A palladium-catalyzed cascade carbonylative spirolactonization of hydroxycyclopropanols has been developed to efficiently synthesize oxaspirolactones common to many complex natural products of important therapeutic value. The mild reaction conditions, high atom economy, broad substrate scope, and scalability of this new method were highlighted in expedient total syntheses of the Turkish tobacco natural products α-levantanolide and α-levantenolide in two and four steps respectively. The hydroxycyclopropanol substrates are readily available in one step via a Kulinkovich reaction of the corresponding lactones. Mechanistic studies utilizing high-resolution electrospray ionization mass spectrometry (ESI-MS) identified several key intermediates in the catalytic cycle as well as those related to catalyst decomposition and competitive pathways.

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Section: Introductionmentioning

confidence: 99%

Catalytic Carbonylative Spirolactonization of Hydroxycyclopropanols

et al. 2016

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“…Due to the unique structure of isotwistanes, the total syntheses of biologically active compounds with isotwistane skeletons have been studied by many research groups. [19][20][21][22][23] Most of these studies have used the intramolecular DielsAlder reaction to build the fused structure of isotwistane. Based on these previous studies, we planned the synthesis of a chiral isotwistane skeleton by two Diels-Alder reactions: our asymmetric Diels-Alder reaction and a sequential intramolecular Diels-Alder reaction.…”

Section: Resultsmentioning

confidence: 99%

Construction of Optically Active Isotwistanes and Aminocyclitols Using Chiral Cyclohexadiene as a Common Intermediate

Harada

Kino

et al. 2016

CHEMICAL & PHARMACEUTICAL BULLETIN

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We have developed a new method for synthesizing chiral isotwistane and homoisotwistane skeletons as well as aminocyclitols in a highly stereoselective manner. These results were achieved through the use of a common intermediate, which was derived from the ytterbium-catalyzed asymmetric Diels-Alder reaction of Danishefsky diene.Key words isotwistane; homoisotwistane; aminocyclitol; Diels-Alder; asymmetric catalysis; hetero-DielsAlder Many biologically active compounds possess a cyclic skeleton with center chirality in their structure. Therefore, the stereoselective synthesis of optically active carbon frameworks is in high demand for synthetic and medicinal chemists. The Diels-Alder reaction has been widely used for this purpose to construct six-membered carbocycles, and the catalytic and enantioselective variant of this reaction has been studied for decades. 1) Our group reported the first example of the catalytic and asymmetric Diels-Alder reaction of Danishefsky diene (1) 2,3) (Chart 1). Functionalized cyclohexene 3 was obtained in optically pure form, and 3 could be transformed to cyclohexenone 4 in quantitative yield. Both functionalized compounds could be potential synthetic intermediates, and we have previously demonstrated the synthetic utility of this reaction. 4-7)In the present study, silyloxy-substituted cyclohexadiene 7 derived from 4 was shown to be a key intermediate for two types of synthetically useful chiral building blocks, i.e., the tricyclo[4.3.1.0 3,7 ] decane (isotwistane 8, n=1) and tricyclo[5.3.1.0 3,8 ] undecane (homoisotwistane 8, n=2) skeletons via the intramolecular Diels-Alder reaction, and aminocyclitol 10 via the intermolecular hetero-Diels-Alder reaction with nitrosobenzene (Chart 2). Results and DiscussionConstruction of Isotwistane and Homoisotwistane Skeletons Isotwistane is an all-carbon tricyclic compound, and its structural motif is found in natural products such as pupukeananes, [8][9][10][11][12] palhinines, [13][14][15] and seychellene. [16][17][18] These types of compounds with (homo) isotwistane skeleton were attracted by their potential for perfumery, and the difference of scent derived from their chirality could be an important research target. Due to the unique structure of isotwistanes, the total syntheses of biologically active compounds with isotwistane skeletons have been studied by many research groups. [19][20][21][22][23] Most of these studies have used the intramolecular DielsAlder reaction to build the fused structure of isotwistane. Based on these previous studies, we planned the synthesis of a chiral isotwistane skeleton by two Diels-Alder reactions: our asymmetric Diels-Alder reaction and a sequential intramolecular Diels-Alder reaction.Dienophiles 2a-d with an olefin in the side chain (R) were prepared. We expected that Lewis acidic activation of the dienophile would occur site-specifically only at the acyloxazolidinone moiety, and the Diels-Alder reaction would take place at the adjacent olefin. With the application of our ytterbium catalyst, 3) the asy...

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“…Recently, Wood reported an elegant example of a SmI 2 -mediated cascade initiated by a single-electron reduction of an α,β-unsaturated ester under very mild reaction conditions in the studies directed toward a total synthesis of phomoidride D (Scheme ) . Initially, other reagents were tested for the transformation with the aim of initiating the cascade by bromide reduction (e.g., Bu 3 SnH); however, the yields were compromised by the undesired 6- endo cyclization into the methylenebutyrolactone.…”

Section: Cross-coupling As Part Of Sequential and Cascade Reactionsmentioning

confidence: 99%