The selective oxidation of the terminal double bonds in squalene

Tamelen, E. E. Van; Curphey, Thomas J.

doi:10.1016/s0040-4039(00)71112-9

Cited by 134 publications

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“…The first step in this sequence consists of the formation of the terminal epoxide (2,3-oxidosqualene) by the squalene epoxidase enzyme (3). Although the synthetic production of this epoxide is unusually demanding owing to the similarity of the double bonds in the molecule, some authors have succeeded in the high-yield production of the terminal epoxide using N-bromosuccinimide (NBS) in a glyme/water solvent mixture followed by a base-catalyzed dehydrobromination (4,5).…”

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The use of ¹H NMR for yield determination in the regioselective epoxidation of squalene

Aerts

Sels

Jacobs

2005

J Americ Oil Chem Soc

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1 H NMR can be used to determine the epoxide yield rapidly in the oxidation of squalene. Moreover, unequivocal distinction can be made between internal and terminal epoxide bonds. To underline the power of this technique, different stoichiometric and catalytic epoxidation procedures were carried out using squalene as substrate. They were characterized in terms of substrate conversion and regioselectivity of the epoxide fraction.Paper no. J10990 in JAOCS 82, 409-413 (June 2005).Besides the double bond epoxidation of fatty compounds (1), we became interested in the epoxidation of squalene and more specifically in the search for new catalytic regioselective epoxidation procedures for this compound. Squalene is a key intermediate in the biosynthesis of steroids such as lanosterol and cholesterol (2). The first step in this sequence consists of the formation of the terminal epoxide (2,3-oxidosqualene) by the squalene epoxidase enzyme (3). Although the synthetic production of this epoxide is unusually demanding owing to the similarity of the double bonds in the molecule, some authors have succeeded in the high-yield production of the terminal epoxide using N-bromosuccinimide (NBS) in a glyme/water solvent mixture followed by a base-catalyzed dehydrobromination (4,5). A great deal of research has been done on the driving force behind this unique regioselectivity. Although the first studies ascribed the selective formation of the terminal epoxide to a specific coiling of the squalene molecule, it is also accepted that the polarity of the oxidant plays a role in the product selectivity. Thus, the formation of both internal and terminal epoxides is associated with the ability of the oxidant to penetrate the coiled molecule. Charged or highly polarized oxidants such as NBS only affect the ends of the squalene molecule, yielding only the terminal epoxides. A third explanation for the highly selective NBS/glyme/water system (6) is based on the heat of formation of internal and terminal epoxides, which is reduced in the latter case by 5 kcal/mmol. During our research we encountered the problem of analysis. Because a facile analysis by GC is not possible, we screened the literature thoroughly. Surprisingly, only one procedure for the analysis of the epoxide isomers is reported (4). Although this method is widely applied, it is time-consuming and not very accurate. For example, the epoxide is first hydrolyzed to obtain the diol using aqueous perchloric acid. In a second step, the diol is quantitively converted into acetone and aldehydes. Finally, the terminal epoxide yield can be determined by measuring the amount of acetone present, whereas the internal epoxides are quantified based on the aldehydes. Nowadays, different types of NMR can be used to identify and characterize squalene and its epoxides. Although important work has been reported (7,8), no effort has been made to quantify the molar ratio of the internal vs. terminal epoxides when present in an isomeric mixture.In this article, we report the determination of the inter...

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confidence: 99%

“…Because a facile analysis by GC is not possible, we screened the literature thoroughly. Surprisingly, only one procedure for the analysis of the epoxide isomers is reported (4). Although this method is widely applied, it is time-consuming and not very accurate.…”

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confidence: 99%

The use of ¹H NMR for yield determination in the regioselective epoxidation of squalene

Aerts

Sels

Jacobs

2005

J Americ Oil Chem Soc

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“…85 : 15) of (2E)-and (2Z)-geranylgeranyl acetates 16 (Scheme 3) [13]. This mixture was treated with N-bromosuccinimide (NBS) followed by K 2 CO 3 according to the procedure of Van Tamelen and Curphey [14] to provide the mixture of compounds 17a and 17b. This mixture was separated by column chromatography on silica gel.…”

Section: Methodsmentioning

confidence: 99%

“…The 1 H-NMR spectra of both molecules displayed signals of two vinylic Me groups (Me (12) and Me(20)) and two olefinic Hatoms (HÀC (7) and HÀC(17)), indicating the presence of two trisubstituted C¼C bonds. In addition to the signal attributed to the terminal CH 2 (19) group, two 3-H singlets due to the Me groups, Me (13) and Me (14), linked to quaternary sp 3 -C-atoms, were also observed in both 1 H-NMR spectra that were completed by the presence of an ABX system attributed to a OH-bearing CH 2 methylene group (CH 2 (11)) and further connected with an allylic CH moiety (HÀC (9)). These data indicated that both cyclization products retained two of the four C¼C bonds of the starting compound 12, and that the two remaining unsaturation degrees required by the molecular formula were due to two rings.…”

Section: Methodsmentioning

confidence: 99%

A Biomimetic Synthesis of Sacculatane Diterpenoids

Grinco

Kulciţki

Ungur

et al. 2008

Helvetica Chimica Acta

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The biomimetic synthesis of sacculatane‐type epimeric compounds 14a and 14b is reported. The key synthetic step is the low‐temperature superacidic cyclization of (all‐E)‐ω‐acetoxygeranylgeraniol 12 obtained in nine steps from geranyllinalool (13). The 19‐acetoxysacculata‐7,17‐dien‐11‐ol (14a) could be an important and convenient starting compound for the synthesis of other sacculatane diterpenoids.

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“…The bromohydrin was prepared using a modified procedure of van Tamelen and Curphey (17). To a stirred solution of silyl protected farnesol (500 mg, 1.1 mmol), in a 3:l mixture of THF and water (9 rnL of THF), was added Kbromosuccinimide (1.05 equiv).…”

Section: Se Sen and Gm Gaminmentioning

confidence: 99%

Synthesis of (2E,6E)‐[10‐³H]farnesol and (2E6E)‐[10‐³H]farnesal for insect dehydrogenase studies

Sen¹,

Garvin²

1995

Labelled Comp Radiopharmac

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SUMMARY110-3H1Farnesol ((2€,60-3,7,11-trimethyl-2,6,1O-dodecatrien-l-ol~ and I1 7,6, were synthesized by sequential reduction and oxidation of the corresponding tert-butyldiphenylsilyl protected 1 1'1 2,13-trisnoraldehyde, followed by Wittig homologation using isopropyltriphenylphosphorane. Direct reduction of the C-12 allylic bromide or allylic chloride proved to be an nonviable method, resulting in either multiple decomposition products or significant double bond transposition. Oxidation of the I1 O-3Hllabelled trisnoralcohol with pyridinium chlorochromate resulted in essentially complete retention of the radiolabel as was established for the corresponding deuterated material. 13Hllabelled farnesol and farnesal were obtained in 78% and 74% yields. respectively, from the trisnoraldehyde. These materials were used as radiotracers for examining the enzymatic activity of insect farnesol and farnesal dehydrogenase, key enzymes in the biosynthesis of juvenile hormone.

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The selective oxidation of the terminal double bonds in squalene

Cited by 134 publications

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The use of ¹H NMR for yield determination in the regioselective epoxidation of squalene

The use of ¹H NMR for yield determination in the regioselective epoxidation of squalene

A Biomimetic Synthesis of Sacculatane Diterpenoids

Synthesis of (2E,6E)‐[10‐³H]farnesol and (2E6E)‐[10‐³H]farnesal for insect dehydrogenase studies

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The selective oxidation of the terminal double bonds in squalene

Cited by 134 publications

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The use of 1H NMR for yield determination in the regioselective epoxidation of squalene

The use of 1H NMR for yield determination in the regioselective epoxidation of squalene

A Biomimetic Synthesis of Sacculatane Diterpenoids

Synthesis of (2E,6E)‐[10‐3H]farnesol and (2E6E)‐[10‐3H]farnesal for insect dehydrogenase studies

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The use of ¹H NMR for yield determination in the regioselective epoxidation of squalene

The use of ¹H NMR for yield determination in the regioselective epoxidation of squalene

Synthesis of (2E,6E)‐[10‐³H]farnesol and (2E6E)‐[10‐³H]farnesal for insect dehydrogenase studies