62182-73-4Relevant academic research and scientific papers
Identification of novel mammalian squalene synthase inhibitors using a three-dimensional pharmacophore
Fairlamb, Ian J.S.,Dickinson, Julia M.,O'Connor, Rachael,Higson, Seamus,Grieveson, Lynsey,Marin, Veronica
, p. 2641 - 2656 (2002)
Squalene synthase (E.C. 2.5.1.21) catalyses the reductive dimerisation of farnesyl diphosphate in a [1-4] head to head fashion to form squalene, and is the first committed step in cholesterol biosynthesis. Specific inhibitors of squalene synthase would inhibit cholesterol formation and allow production of other important compounds derived from the cholesterol biosynthetic pathway, namely the ubiquinones (co-enzyme Q10), dolichol, and would also allow the isoprenylation process of ras by farnesyl-protein transferase. The construction of a hypothetical squalene synthase three-dimensional pharmacophore is presented. It serves as a template for the identification of several new potential classes of inhibitors. The synthesis, anti-microbial and mammalian pig liver squalene synthase activities of analogues based on the bicyclo[3.2.0]heptane and bicyclo[3.3.0]octane ring systems are reported. Analogues of the latter system are pro-drug type inhibitors and exhibit promising biological activity.
Thermal rearrangement of 7-methylbicyclo[3.2.0]hept-2-ene: An experimental probe of the extent of orbital symmetry control in the [1,3] sigmatropic rearrangement
Bender, Jared D.,Leber, Phyllis A.,Lirio, Ruel R.,Smith, Randall S.
, p. 5396 - 5402 (2007/10/03)
The gas-phase thermal rearrangement of exo-7-methylbicyclo[3.2.0]hept-2-ene yields almost exclusively 5-methylnorbornene products. Inversion (i) of configuration dominates this [1,3] sigmatropic shift although some retention (r) is also observed. Because the [1,3] migration can only occur suprafacially (s) in this geometrically constrained system, the si/sr ratio of 7 observed for the migration of C7 in exo-7-methylbicyclo[3.2.0]hept-2-ene indicates that the orbital symmetry rules are somewhat permissive for the [1,3] sigmatropic migration of carbon.
Biological Baeyer-Villiger Oxidation of Some Monocyclic and Bicyclic Ketones using Monooxygenases from Acinetobacter calcoaceticus NCIMB 9871 and Pseudomonas putida NCIMB 10007
Gadnon, Rene,Grogan, Gideon,Levitt, Melissa S.,Roberts, Stanley M.,Wan, Peter W. H.,Willetts, Andrew J.
, p. 2537 - 2544 (2007/10/02)
A. calcoaceticus NCIMB 9871 and Ps. putida NCIMB 10007 have been utilized as biocatalysts in Baeyer-Villiger oxidations.The former microorganism oxidized the racemic ketone 6 non-selectively but transformed the dihalogeno ketone (+/-)-8 into optically active lactone 10 and recovered ketone.Ps. putida NCIBM 10007 oxidized the two enantiomers of the ketone 6 at different rates while both enantiomers of ketone (+/-)-1 were converted into lactones, one enantiomer giving 3-oxabicyclooctenone preferentially, while the other enantiomer gave 2-oxabicyclooctenone.Ps. putida NCIMB 10007 contains two quite different types of monooxygenase enzyme, one using NADH as cofactor (labelled MO1) the other employing NADPH as cofactor (labelled MO2).Monooxygenase MO1 proved to be a selective efficient biocatalyst for the oxidation of bicyclic ketones such as 1 and 6 while monooxygenase MO2 is a useful catalyst for the oxidation of cyclopentanones 15 - 17.Cofactor recycling was effected using dehydrogenase enzymes in preparative-scale experiments.
BIOCATALYTIC PREPARATION OF BICYCLOHEPTANE DERIVATIVES
Klempier, Norbert,Geymayer, Paul,Stadler, Peter,Faber, Kurt,Griengl, Herfried
, p. 111 - 118 (2007/10/02)
Bicyclohept-2-en-6-ols, central building blocks for the synthesis of chiral cyclobutane and -pentane systems, were prepared with up to >99percent e.e. by lipase catalysed resolution of their acetates, butyrates, or isobutyrates.Substituents at C-7 vicinal to the reaction site reduced both enantioselectivity and reaction rate, whereas variation of the acid moiety showed a smaller influence.Among the lipases tested, those from Pseudomonas sp. were shown to be superior to those from Candida cylindracea, Mucor sp. and porcine pancreas.
REDUCTION OF 7-CHLOROBICYCLOHEPT-2-EN-6-ONES CATALYSED BY 3α,20β-HYDROXYSTEROID DEHYDROGENASE
Davies, H. Geoff,Gartenmann, Thomas C. C.,Leaver, Jeff,Roberts, Stanley M.,Turner, Michael K.
, p. 1093 - 1094 (2007/10/02)
7,7-Dichlorobicyclohept-2-en-6-one and 7endo-chlorobicyclohept-2-en-6-one are reduced regio-specifically and with high substrate enantioselectivity using a 3α,20β-hydroxysteroid alcohol dehydrogenase.
Reduction of Bicyclohept-2-en-6-one with Dehydrogenase Enzymes in Whole Cell Preparations of some Fungi and Yeasts
Dawson, Michael J.,Lawrence, Gordon C.,Lilley, Gerald,Todd, Martin,Noble, David,at al.
, p. 2119 - 2125 (2007/10/02)
(+/-)-Bicyclohept-2-en-6-one (1) was reduced using a variety of fungi and yeasts.Bakers' yeast gave 6-exo-(1R,5S,6S)-bicyclohept-2-en-6-ol (2a) and 6-endo-(1S,5R,6S)-bicyclohept-2-en-6-ol (3b) while Curvularia lunata and Mortierella ramanniana gave only the 6-endo-alcohol (3b) and optically active bicycloheptenone (1a).Under slightly modified reaction conditions (+/-)-6-endo-bicyclohept-2-en-6-ol was oxidized by bakers' yeast to give (1S,5R)-bicyclohept-2-en-6-one (1b) and the endo-alcohol (3a).
Total Synthesis of Prostaglandin-F2α involving Stereocontrolled and Photo-induced Reactions of Bicycloheptanones
Howard, Colin C.,Newton, Roger F.,Reynolds, Derek P.,Wardsworth, Alan H.,Kelly, David R.,Roberts, Stanley M.
, p. 852 - 857 (2007/10/02)
A short total synthesis of prostaglandin-F2α from cyclopentadiene is described.Acetalisation of bicyclohept-2-en-6-one (1) followed by formation of a singal bromohydrin gave on treatment with base the epoxyacetal (4).Reaction of (4) with the appropriate organocuprate reagent introduced both the 12β side-chain and 11α-hydroxy-group of the embryonic prostaglandin.The fused cyclobutane ring is important as it controls both the stereoselectivity of epoxide formation and the regioselectivity of the subsequent ring-opening reaction.Furthermore, the unusual photochemical behaviour of cyclobutanones was exploited in this synthesis.Irradiation of the bicycloheptan-6-one (9) in aqueous solution and subsequent Wittig olefination afforded prostaglandin-F2α.Baeyer-Villiger oxidation of the same ketone (9) furnished the lactone (16), a known precursor of prostaglandin-E.
