Orally active PDE4 inhibitor with therapeutic potential

Ochiai, Hiroshi; Ohtani, Tazumi; Ishida, Akiharu; Kishikawa, Katsuya; Yamamoto, Sachiko; Takeda, Hiroshi; Obata, Takaaki; Nakai, Hisao; Toda, Masaaki

doi:10.1016/j.ejmech.2004.02.010

Cited by 13 publications

(8 citation statements)

References 17 publications

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“…rel ‐((1 R , 2 R , 3 S , 4 S )‐7‐oxabicyclo[2.2.1]hept‐5‐ene‐2,3‐diyl)dimethanol (6) . Oxabicyclodiol 6 was realized according to the same procedure as described in the literature [38] . Lithium aluminum hydride (1.48 g, 39.13 mmol) in dry THF (50 mL) was added portion wise to phthalic anhydride 5 (5 g, 30.10 mmol) dissolved in THF at 0 ° C. The mixture was warmed to reflux for 6 h then cooled to 0 °C.…”

Section: Methodsmentioning

confidence: 99%

Versatile Synthesis of rac‐ and meso‐Hydroxymethyl Cyclohexenoids Containing Phenyl Groups: α‐/β‐Glucosidase Activities, Inhibition Kinetics and Molecular Docking Studies

et al. 2022

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The effective strategy has been developed to synthesize a series of monophenyl and diphenyl carbasugar analogues, from the cycloadduct reaction of furan and maleic anhydride, containing halogen groups based on the conduritol scaffold. The strategy mainly consists of reduction, esterification, bromination, formation of new double bond and replacement of bromine with phenyl by Suzuki coupling reaction. New phenyl-substituted carbasugars were obtained by cleavage of the oxo bridge and subsequent hydrolysis of the esters. The structures of the target compounds were defined using different chemical methods. In vitro inhibitory activity studies, kinetic and molecular docking studies were performed against α-, β-glucosidase enzymes for the final compounds.

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Section: Methodsmentioning

confidence: 99%

Versatile Synthesis of rac‐ and meso‐Hydroxymethyl Cyclohexenoids Containing Phenyl Groups: α‐/β‐Glucosidase Activities, Inhibition Kinetics and Molecular Docking Studies

et al. 2022

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“…At the outset, a synthetic route permitting access to large amounts of lactone (−)- 32 was developed and implemented (Scheme ). To this end, meso diol 36 , obtained via lithium aluminum hydride reduction of commercially available anhydride 35 in cold tetrahydrofuran, was subjected to a modification of a known enzymatic asymmetrization employing porcine pancreatic lipase in a reaction medium of methyl acetate containing 4 Å sieves; the latter were introduced to scavenge the methanol byproduct of enzyme acylation, thus permitting a manageable amount of methyl acetate to be employed as solvent upon reaction scale-up . Without separation, the resultant mixture of monoacetate (+)- 37 and diacetate 38 (3.4:1) was directly treated with toluenesulfonyl chloride in pyridine and dichloromethane (1:1 v/v) at room temperature to furnish tosylate (−)- 39 .…”

Section: Resultsmentioning

confidence: 99%

Access to the Akuammiline Family of Alkaloids: Total Synthesis of (+)-Scholarisine A

2012

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The planning and implementation of an enantioselective total synthesis of (+)-scholarisine A is presented. Key tactics employed include a novel cyclization, consisting of a nitrile reduction coupled with concomitant addition of the resultant amine to an epoxide; a modified Fischer indolization; an oxidative-lactonization of a diol in the presence of an indole ring; and a late stage cyclization to complete the caged ring scaffold. The development of a possible “retrobiosynthetic” approach to other members of the akuammiline alkaloid family is also described.

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“…Di-Grignard reagents were prepared from Mg flakes that were freshly washed with 1 M HCl, followed sequentially by washing with water, EtOH, THF, and Et 2 O before being dried for 20 min under high vacuum. 1-Bromo-2-(2-chloroethyl)benzene, 1-bromo-2-(2-chloroethyl)naphthalene, (±)- trans -4,5-bis(bromomethyl)cyclohex-1-ene, and cis -4,5-bis(bromomethyl)cyclohex-1-ene were prepared according to literature procedures. Phenylphosphonic dichloride (POPhCl 2 ), tert -butylphosphonic dichloride (PO( t -Bu)Cl 2 ), and N , N -dimethylphosphoramide dichloride (PO(NMe 2 )Cl 2 ) were obtained commercially.…”

Section: Methodsmentioning

confidence: 99%

Cyclic Phosphine Oxides and Phosphinamides from Di-Grignard Reagents and Phosphonic Dichlorides: Modular Access to Annulated Phospholanes

et al. 2015

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. (2015). Cyclic phosphine oxides and phosphinamides from digrignard reagents and phosphonic dichlorides: modular access to annulated phospholanes. Journal of Organic Chemistry, 80 (19),[9774][9775][9776][9777][9778][9779][9780] Cyclic phosphine oxides and phosphinamides from di-grignard reagents and phosphonic dichlorides: modular access to annulated phospholanes AbstractThe reaction between 1,4-di-Grignard reagents and phosphonous(III) dichlorides is a classical method for the direct synthesis of phospholanes. Reported here is an extension of this approach to the preparation of valueadded, annulated phospholane oxides, achieved through the combination of carbocyclic-fused di-Grignard reagents and readily available phosphonic(V) dichlorides. The procedure is amenable to (benz)annulation at both the 2,3-and 3,4-positions of the phospholane ring, and a variety of aliphatic, cyclic and aryl Pelectrophiles are tolerated in reasonable to excellent yields. Corresponding author, *email: keller@uow.edu.au (PAK) Abstract: The reaction between 1,4-di-Grignard reagents and phosphonous(III) dichlorides is a classical method for the direct synthesis of phospholanes. Reported here is an extension of this approach to the preparation of value-added,

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Orally active PDE4 inhibitor with therapeutic potential

Cited by 13 publications

References 17 publications

Versatile Synthesis of rac‐ and meso‐Hydroxymethyl Cyclohexenoids Containing Phenyl Groups: α‐/β‐Glucosidase Activities, Inhibition Kinetics and Molecular Docking Studies

Versatile Synthesis of rac‐ and meso‐Hydroxymethyl Cyclohexenoids Containing Phenyl Groups: α‐/β‐Glucosidase Activities, Inhibition Kinetics and Molecular Docking Studies

Access to the Akuammiline Family of Alkaloids: Total Synthesis of (+)-Scholarisine A

Cyclic Phosphine Oxides and Phosphinamides from Di-Grignard Reagents and Phosphonic Dichlorides: Modular Access to Annulated Phospholanes

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