91418-95-0Relevant academic research and scientific papers
Highly stereoselective construction of the C2 stereocentre of α-tocopherol (Vitamin E) by asymmetric addition of Grignard reagents to ketones
Bieszczad, Bartosz,Gilheany, Declan G.
, p. 6483 - 6492 (2017/08/16)
Tertiary alcohol precursors of both C2 diastereoisomers of α-tocopherol were prepared in three ways by our recently reported asymmetric Grignard synthesis. The versatility of Grignard chemistry inherent in its three-way disconnection was exploited to allow the synthesis of three product grades: 77:23 dr (5 steps), 81:19 dr (5 steps) and 96:4 dr (7 steps, one gram scale) from readily available and abundant starting materials. The products were converted to their respective α-tocopherols in 3 steps, which allowed a definitive re-assignment of their absolute configurations.
Asymmetric Grignard Synthesis of Tertiary Alcohols through Rational Ligand Design
Bieszczad, Bartosz,Gilheany, Declan G.
supporting information, p. 4272 - 4276 (2017/04/03)
A simple, general and practical method is reported for highly enantioselective construction of tertiary alcohols through the direct addition of organomagnesium reagents to ketones. Discovered by rational ligand design based on a mechanistic hypothesis, it has an unprecedented broad scope. It utilizes a new type of chiral tridentate diamine/phenol ligand that is easily removed from the reaction mixture. It is exemplified by application to a formal asymmetric synthesis (>95:5 d.r.) of vitamin E.
Towards a modern definition of vitamin e - Evidence for a quinone hypothesis
Shrader, William D.,Amagata, Akiko,Barnes, Adam,Hinman, Andrew,Jankowski, Orion,Lee, Edgar,Kheifets, Viktoria,Komatsuzaki, Ryo,Mollard, Paul,Murase, Katsuyuki,Rioux, Patrice,Wesson, Kieron,Miller, Guy
, p. 391 - 395 (2012/03/11)
We report on the synthesis, biological and pharmacological activity of the tocoquinone natural product, α-tocopherol quinone (ATQ); an oxidative metabolite of α-tocopherol. ATQ is a potent cellular protectant against oxidative stress, whose biological activity is dependent upon its ability to undergo reversible two-electron redox cycling. ATQ is orally bioavailable, with a favorable pharmacokinetic profile and has demonstrated a beneficial clinical response in patients with Friedreich's ataxia. ATQ is a member of a broader class of vitamin E derived quinone metabolites which may be ascribable in whole or in part to the activity of vitamin E.
Total synthesis of naturally occurring α-tocopherol. Assymetric alkylation and asymmetric epoxidation as means to introduce (R)-configuration at C(2) of the chroman moiety
Hubscher,Barner
, p. 1068 - 1086 (2007/10/02)
Based on the reductive, stereospecific ring closure of (2R,4'R,8'R)-α-'Tocopherylquinone' or corresponding analogues with a short, functionalized side chain (B, Scheme 1) to 1 resp. the chroman system of 1 (C), two different approaches for the introduction of the required tertiary methyl-substituted alcohol structure in the side chain of the aromatic precursors (A, Scheme 1) were developed. The first approach uses asymmetric alkylation in three different versions featuring a) diastereoselective steering with chiral auxiliaries I-IV (Scheme 2) attached as esters to α-keto acids, b) intermediate transfer of chirality in an ester enolate (from 18, Scheme 4) derived from an optically active α-hydroxyacid, c) enantioselective alkylation of phytenal (20) and subsequent ring closure with chirality transfer (Schemes 5-7). The second approach is based on the asymmetric epoxidation of β-metallylalcohol (Sharpless epoxidation), the corresponding epoxyalcohol being converted in situ to the (S)- or (R)-chlorodiol (S)- and (R)-29, respectively, for isolation (Schemes 8 and 9). Nucleophilic epoxide opening with a (3R,7R)-3,7,11-trimethyldodecyl (C15**) and an ArCH2 unit in appropriate sequence is used to assemble the C-framework of the target molecule via corresponding epoxide intermediates from either chlorodiol. Combined with the use of the methoxymethyl-ether function for protection of the hydroquinone system, the epoxide approach provides a short route to 1 (Scheme 10).
Hydroquinone derivatives useful in the production of vitamin E
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, (2008/06/13)
The present invention is directed to novel hydroquinone derivatives which are useful as intermediates for the manufacture of (R,R,R)-α-tocopherol (natural vitamin E) as well as of racemic α-tocopherol. The invention is also directed to a process for the preparation of the hydroquinone derivatives of the invention.
