Synthesis of (+)-(1R,2R,4R,6S )-1,6-epoxy-4-benzyloxycyclohexan-2-ol, a key precursor to inositol monophosphatase inhibitors, from (−)-quinic acid

Schulz, Jürgen; Beaton, Martin W.; Gani, David

doi:10.1039/a909292g

Cited by 16 publications

(12 citation statements)

References 18 publications

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“…[8] Alternatively, the use of N,N-dimethylaminopyridine (DMAP) as a nucleophilic catalyst was also reported. [9] Transition metal catalysts such as Cu(II), LaA C H T U N G T R E N N U N G (III), FeA C H T U N G T R E N N U N G (III), CrA C H T U N G T R E N N U N G (III), Ti(IV), Zr(IV), YA C H T U N G T R E N N U N G (III), and Sn(IV) have been widely employed for the hydrolysis of phosphonates, fluorophosphates, and phosphate esters. [10] However, relatively fewer efforts have been devoted to studies of the catalytic phosphorylation of alcohols.…”

Section: Introductionmentioning

confidence: 99%

Substitution‐ and Elimination‐Free Phosphorylation of Functionalized Alcohols Catalyzed by Oxidomolybdenum Tetrachloride

et al. 2010

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Among 14 oxidometallic species examined for catalytic phosphorylation of the tested alcohols, oxidomolybdenum tetrachloride (MoOCl 4 ) was found to be the most efficient with a negligible background reaction mediated by triethylamine (Et 3 N). The new catalytic protocol can be applied to the chemoselective phosphorylations of primary, secondary and tertiary alcohols as well as the substitution-free phosphorylations of allylic, propargylic, and benzylic alcohols. Functionalized alcohols bearing acetonide, tetrahydropyranyl ether, tert-butyldimethylsilyl ether, or ester group are also amenable to the new catalytic protocol. The most difficult scenarios involve substitution-free phosphorylations of 1-phenylethanol and 1-(2-naphthyl)ethanol which can be effected in 95 and 90% yields, respectively. ESI-MS, IR, 1 H, and 31 P NMR spectroscopic analyses of the reaction progress suggest the intermediacy of an alkoxyoxidomolybdenum trichloride-triethylamine adduct such as [(RO)Mo(O)Cl 3 -Et 3 N] to be responsible for the catalytic turnover.

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Section: Introductionmentioning

confidence: 99%

Substitution‐ and Elimination‐Free Phosphorylation of Functionalized Alcohols Catalyzed by Oxidomolybdenum Tetrachloride

et al. 2010

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“…5c It is now relatively easy to prepare such compounds and we have used epoxide 4 as a common precursor to all such inhibitors. 18 These materials have proved invaluable as probes for elucidation of the mechanism of action of IMPase but they are of no use in vivo. In common with all known organic phosphate inhibitors of IMPase there are bioavailability limitations that preclude their use as drugs.…”

Section: Introductionmentioning

confidence: 99%

Removal of the phosphate group in mechanism-based inhibitors of inositol monophosphatase leads to unusual inhibitory activity

et al. 2004

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Inositol monophosphatase is widely held to be the therapeutic target for inhibition by lithium ion in the treatment of bipolar disorder. In a continued effort to improve the bioavailability of alternative inhibitors, we have designed and tested two new series of compounds; phosphonates and product-like mimics. Phosphonate substrate mimics were competitive inhibitors of reduced potency as compared to phosphate based inhibitors. Product mimics however, showed various inhibitory modes of action. The 6-butylamino derivative 6p was an uncompetitive inhibitor when acting alone (K(i)= 0.3 mM) but displayed non-competitive inhibition in the presence of inorganic phosphate. This compound represents a new lead in the search for a viable replacement for lithium ion therapy.

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“…However, in these reactions carried out in DCM at room temperature, special catalysts, such as Ti(O t Bu) 4 and 4-dimethylaminopyridine (DMAP) were used beside triethylamine. 7 8 If an isolated monohydroxyphosphate ( F ) is the starting material, before esterification, the acid function was converted into chloride (as in C ) by reaction with oxalyl chloride (or an inorganic acid chloride). 9 In other cases, e.g.…”

Section: Table 1 Direct Esterification Of Monobutylphos...mentioning

confidence: 99%

P-Chloride-Free Synthesis of Phosphoric Esters: Microwave-Assisted Esterification of Alkyl- and Dialkyl Phosphoric Ester-Acids Obtained from Phosphorus Pentoxide

Harsági¹,

Kiss²,

Keglevich³

2022

Synthesis

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It is a reasonable endeavour to replace P-chloride starting materials (e.g. POCl3) by greener and cheaper reagents. Our purpose was to start from phosphorus pentoxide, i.e. to utilize its reaction with alcohols in the preparation of (HO)2P(O)(OR) and HOP(O)(OR)2, and to convert the mixtures of the corresponding monoester and diester so obtained to the target trialkyl esters. Separate experiments showed that the monobutylphosphate undergo microwave (MW)-assisted esterification with butanol in the presence of [bmim][BF4] catalyst at 200 °C to afford dibutylphosphate in a selective manner (~95%) that, in turn, may be converted to tributylphosphate by alkylation under MW irradiation. In this way, the mixtures of (HO)2P(O)(OR) and HOP(O)(OR)2 obtained by the practical reaction of phosphorus pentoxide and alcohol (ROH) could also be converted in two additional steps to the corresponding trialkyl esters. The three-step synthesis of trialkylphosphates starting from phosphorus pentoxide was also transformed in a one-pot (step 1: preparation of the monoester diester mixture, step 2: diesterification) and telescoping (step 3: triesterification) variation avoiding the isolation and purification of the intermediates, and affording the triesters in 86-93% yields. The three- and two-step P-chloride-free methods developed are “green” and of more general value.

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Synthesis of (+)-(1R,2R,4R,6S )-1,6-epoxy-4-benzyloxycyclohexan-2-ol, a key precursor to inositol monophosphatase inhibitors, from (−)-quinic acid

Cited by 16 publications

References 18 publications

Substitution‐ and Elimination‐Free Phosphorylation of Functionalized Alcohols Catalyzed by Oxidomolybdenum Tetrachloride

Substitution‐ and Elimination‐Free Phosphorylation of Functionalized Alcohols Catalyzed by Oxidomolybdenum Tetrachloride

Removal of the phosphate group in mechanism-based inhibitors of inositol monophosphatase leads to unusual inhibitory activity

P-Chloride-Free Synthesis of Phosphoric Esters: Microwave-Assisted Esterification of Alkyl- and Dialkyl Phosphoric Ester-Acids Obtained from Phosphorus Pentoxide

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