Hydroboration of Terpenes. III. Isomerization of (+)-3-Carene to (+)-2-Carene. Hydroboration of (+)-2-Carene ([UNK]<sup>4</sup>-Carene). Nuclear Magnetic Resonance Spectra with Absolute Configurational and Conformational Assignments for the 2-Caranols and 2-Caranones

Acharya, Shrinivas P.; Brown, Herbert C.

doi:10.1021/ja00984a030

Cited by 52 publications

(6 citation statements)

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“…Interestingly, 2-carene 9 is widely found in nature albeit in small concentrations. The isolation of 9 from essential oils, or from reaction mixtures after 3-carene 8 isomerization, is difficult, making 9 expensive and therefore not attractive for use in organic synthesis [ 25 , 26 , 27 , 28 , 29 ]. Recently, we developed a method for the isomerization of readily available 3-carene 8 to 2-carene 9 using montmorillonite clays as a catalyst [ 30 ].…”

Section: Resultsmentioning

confidence: 99%

Design, Synthesis, and Biological Investigation of Novel Classes of 3-Carene-Derived Potent Inhibitors of TDP1

et al. 2020

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Two novel structural types of tyrosyl-DNA phosphodiesterase 1 (TDP1) inhibitors with hexahydroisobenzofuran 11 and 3-oxabicyclo [3.3.1]nonane 12 scaffolds were discovered. These monoterpene-derived compounds were synthesized through preliminary isomerization of (+)-3-carene to (+)-2-carene followed by reaction with heteroaromatic aldehydes. All the compounds inhibit the TDP1 enzyme at micro- and submicromolar levels, with the most potent compound having an IC50 value of 0.65 μM. TDP1 is an important DNA repair enzyme and a promising target for the development of new chemosensitizing agents. A panel of isogenic clones of the HEK293FT cell line knockout for the TDP1 gene was created using the CRISPR-Cas9 system. Cytotoxic effects of topotecan (Tpc) and non-cytotoxic compounds of the new structures were investigated separately and jointly in the TDP1 gene knockout cells. For two TDP1 inhibitors, 11h and 12k, a synergistic effect was observed with Tpc in the HEK293FT cells but was not found in TDP1 −/− cells. Thus, it is likely that the synergistic effect is caused by inhibition of TDP1. Synergy was also found for 11h in other cancer cell lines. Thus, sensitizing cancer cells using a non-cytotoxic drug can enhance the efficacy of currently used pharmaceuticals and, concomitantly, reduce toxic side effects.

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Section: Resultsmentioning

confidence: 99%

Design, Synthesis, and Biological Investigation of Novel Classes of 3-Carene-Derived Potent Inhibitors of TDP1

et al. 2020

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“…This use of Frémy's salt compares very favourably with the yield of 20% achieved in the early oxygenation of cannabidiol in aqueous 5% KOH to give HU-331. could not be deduced from NMR data owing to overlapping multiplets in the relevant regions, only one diastereoisomer was detected, and by analogy with the hydroborationoxidation of (+)-2-carene to give (-)-2-isocaranol (92%), [45] hydroboration on the face opposite to the bulky isopropyl group would be expected, affording the triequatorially substituted stereoisomer 8h, and hence 9h.…”

Section: )mentioning

confidence: 99%

Monocyclic Quinone Structure‐Activity Patterns: Synthesis of Catalytic Inhibitors of Topoisomerase II with Potent Antiproliferative Activity

et al. 2019

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The monocyclic 1,4-benzoquinone, HU-331, the direct oxidation product of cannabidiol, inhibits the catalytic activity of topoisomerase II but without inducing DNA strand breaks or generating free radicals, and unlike many fused-ring quinones exhibits minimal cardiotoxicity. Thus, monocyclic quinones have potential as anti-cancer agents, and investigation of the structural origins of their biological activity is warranted. New syntheses of cannabidiol and (±)-HU-331 are here reported. Integrated synthetic protocols afforded a wide range of polysubstituted resorcinol derivatives; many of the corresponding novel 2-hydroxy-1,4-benzoquinone derivatives are potent inhibitors of the catalytic activity of topoisomerase II, some more so than HU-331, whose monoterpene unit replaced by a 3-cycloalkyl unit conferred increased anti-proliferative properties in cell lines with IC50 values extending below 1 mM, and greater stability in solution than HU-331. The principal pharmacophore of quinones related to HU-331 was identified. Selected monocyclic quinones show potential for the development of new anticancer agents. Financial support from the Engineering and Physical Sciences Research Council for a PhD studentship to T. D.W. is gratefully acknowledged.

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“…This is in contrast to the 94:4 cis:trans ratio reported by Brown. [ 42 ] The difference in product distribution may be due to the use of acetic acid or the higher hydrogen pressure in the current work. For comparison purposes, 1,1,4‐trimethylcycloheptane 4 was synthesized from 3‐carene with 10% Pd/C at 150 °C and 500 psi H 2 .…”

Section: Resultsmentioning

confidence: 99%

“…Hydrogenation of sabinene with Pd/C results in the isolation of tetrahydrosabinene (2), [ 15,40 ] whereas the hydrogenation of sabinene with PtO 2 and NaBH 4 at low temperature (−20 °C) was reported to result in chemoselective hydrogenation of the double bond, affording thujane (1). [ 40 ] Similarly, the hydrogenation of 3‐carene with a Pt catalyst has been reported to yield primarily cis‐carane (3), [ 41–43 ] whereas reaction with Pd‐based catalysts resulted in conversion to 1,1,4‐trimethylcycloheptane (4). This work describes our efforts to control the hydrogenation of sabinene and 3‐carene at preparative scale by selecting catalysts and reaction conditions (temperature/pressure) to allow for chemoselective hydrogenation of these two bio‐based substrates.…”

Section: Introductionmentioning

confidence: 99%

Chemoselective Hydrogenation of Ring‐Strained Monoterpenes: A Route to High‐Performance Sustainable Aviation Fuels

Woodroffe

Harvey

2021

Energy Tech

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Sabinene and 3‐carene, bio‐based monoterpene precursors to high‐performance jet fuels, are chemoselectively hydrogenated with reduced PtO2 at low temperatures (263–298 K), to yield products in which the alkene groups are saturated, whereas cyclopropane rings from the parent hydrocarbons are conserved. Sabinene is selectively converted to a 79:21 mixture of cis:trans‐thujane (1), whereas 3‐carene is converted to a 72:28 mixture of cis:trans‐carane (3). For comparison, the fully hydrogenated species tetrahydrosabinene (2) and 1,1,4‐trimethylcycloheptane (4) are prepared by hydrogenation with Pd/C. To evaluate 1−4 as advanced jet fuel blendstocks, several key fuel properties are measured. Compared with conventional jet fuel, the hydrogenated monoterpenes exhibit up to 8.6% higher density, 1.3% higher gravimetric net heat of combustion (NHOC), 9.7% higher volumetric NHOC, and 64% lower kinematic viscosity at −20 °C. These properties suggest that 1−4 are valuable blendstocks for conventional jet fuel or sustainable aviation fuel, providing enhanced operability and performance.

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Hydroboration of Terpenes. III. Isomerization of (+)-3-Carene to (+)-2-Carene. Hydroboration of (+)-2-Carene ([UNK]⁴-Carene). Nuclear Magnetic Resonance Spectra with Absolute Configurational and Conformational Assignments for the 2-Caranols and 2-Caranones

Cited by 52 publications

References 0 publications

Design, Synthesis, and Biological Investigation of Novel Classes of 3-Carene-Derived Potent Inhibitors of TDP1

Design, Synthesis, and Biological Investigation of Novel Classes of 3-Carene-Derived Potent Inhibitors of TDP1

Monocyclic Quinone Structure‐Activity Patterns: Synthesis of Catalytic Inhibitors of Topoisomerase II with Potent Antiproliferative Activity

Chemoselective Hydrogenation of Ring‐Strained Monoterpenes: A Route to High‐Performance Sustainable Aviation Fuels

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Hydroboration of Terpenes. III. Isomerization of (+)-3-Carene to (+)-2-Carene. Hydroboration of (+)-2-Carene ([UNK]4-Carene). Nuclear Magnetic Resonance Spectra with Absolute Configurational and Conformational Assignments for the 2-Caranols and 2-Caranones

Cited by 52 publications

References 0 publications

Design, Synthesis, and Biological Investigation of Novel Classes of 3-Carene-Derived Potent Inhibitors of TDP1

Design, Synthesis, and Biological Investigation of Novel Classes of 3-Carene-Derived Potent Inhibitors of TDP1

Monocyclic Quinone Structure‐Activity Patterns: Synthesis of Catalytic Inhibitors of Topoisomerase II with Potent Antiproliferative Activity

Chemoselective Hydrogenation of Ring‐Strained Monoterpenes: A Route to High‐Performance Sustainable Aviation Fuels

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About

Hydroboration of Terpenes. III. Isomerization of (+)-3-Carene to (+)-2-Carene. Hydroboration of (+)-2-Carene ([UNK]⁴-Carene). Nuclear Magnetic Resonance Spectra with Absolute Configurational and Conformational Assignments for the 2-Caranols and 2-Caranones