71155-04-9

Usage

Uses

Used in Organic Synthesis:
Bicyclo[3.2.0]hept-2-en-6-one,(1S,5R)is used as a building block in organic synthesis for the creation of complex natural products and pharmaceuticals. Its unique structure and reactivity make it a valuable tool for chemists in developing new chemical compounds.
Used in Medicinal Chemistry:
Due to its potential biological activities, Bicyclo[3.2.0]hept-2-en-6-one,(1S,5R)may have applications in the field of medicinal chemistry. Its chiral nature and specific configuration could contribute to the development of novel therapeutic agents with targeted effects.
Used in Pharmaceutical Industry:
In the pharmaceutical industry, Bicyclo[3.2.0]hept-2-en-6-one,(1S,5R)is used as a key intermediate in the synthesis of various drugs. Its unique structural features allow for the creation of molecules with specific pharmacological properties, enhancing the effectiveness and selectivity of medications.
Used in Research and Development:
Bicyclo[3.2.0]hept-2-en-6-one,(1S,5R)is utilized in research and development for exploring its potential applications and understanding its chemical behavior. This knowledge can lead to the discovery of new reactions and the creation of innovative synthetic routes for the production of complex molecules.

Upstream product

• 925211-06-9 bicyclo(3.2.0)hept-2-en-6-one 
• 13173-09-6 bicyclo[3.2.0]hept-2-en-6-one 
• 79-36-7 dichloroacethyl chloride 
• 542-92-7 cyclopenta-1,3-diene 
• 20836-85-5 7endo-chlorobicyclo<3.2.0>hept-2-en-6-one 
• 4591-28-0 dichloroketene 
• 13259-28-4 (+/-)-exo-bicyclo<3.2.0>hept-2-en-6-ol 
• 13259-28-4 (rac)-6-endo-bicyclo<3.2.0>hept-2-en-6-ol 
• 5307-99-3 7,7-dichlorobicyclo[3.2.0]hept-2-en-6-one 

Downstream Products

• 34638-25-0 (1R,5S)-2-oxabicyclo[3.3.0]oct-6-en-3-one 
• 128946-78-1 3-oxabicyclo[3.3.0]oct-6-en-2-one 
• 103618-27-5 (+)-(1S,5R)-3-oxabicyclo<3.3.0>oct-6-en-2-one 
• 76704-05-7 <3aS(3aα,4α,5β,6aα)>-(+)-5-hydroxy-4-hydroxymethyl-hexahydro-2H-cyclopentafuran-2-one 
• 130520-29-5 C₂₀H₂₅NO₇S 
• 130520-28-4 C₂₁H₂₇NO₇S 
• 54483-30-6 (1aS,2aR,5aR,5bR)-hexahydro-4H-oxireno[3,4]cyclopenta[1,2-b]furan-4-one 
• 130520-22-8 [(1S,5S)-5-(Toluene-4-sulfonylamino)-cyclopent-2-enyl]-acetic acid methyl ester 
• 130520-23-9 N-((3aR,4S,6R,6aR)-6-Iodo-2-oxo-hexahydro-cyclopenta[b]furan-4-yl)-4-methyl-benzenesulfonamide 
• 130520-24-0 [(1R,2R,3S,5S)-3-(Toluene-4-sulfonylamino)-6-oxa-bicyclo[3.1.0]hex-2-yl]-acetic acid methyl ester 
• 130520-26-2 (Z)-7-[(1R,2R,3S,5S)-3-(Toluene-4-sulfonylamino)-6-oxa-bicyclo[3.1.0]hex-2-yl]-hept-5-enoic acid 
• 130520-21-7 C₂₀H₂₇NO₆S 
• 130520-25-1 (Z)-7-[(1R,2R,3S,5S)-3-(Toluene-4-sulfonylamino)-6-oxa-bicyclo[3.1.0]hex-2-yl]-hept-5-enoic acid methyl ester 

Relevant academic research and scientific papers

E. coli cells expressing the Baeyer-Villiger monooxygenase 'MO14' (ro03437) from Rhodococcus jostii RHA1 catalyse the gram-scale resolution of a bicyclic ketone in a fermentor

The Baeyer-Villiger monooxygenase (BVMO) 'MO14' from Rhodococcus jostii RHA1, is an enantioselective BVMO that catalyses the resolution of the model ketone substrate bicyclo[3.2.0]hept-2-en-6-one to the (1S,5R)-2-oxa lactone and the residual (1S,5R)-substrate enantiomer. This regio-plus enantioselective behaviour is highly unusual for BVMOs, which often perform enantiodivergent biotransformations of this substrate. The scaleability of the transformation was investigated using fermentor-based experiments, in which variables including gene codon optimisation, temperature and substrate concentration were investigated. E. coli cells expressing MO14 catalysed the resolution of bicyclo[3.2.0]hept-2-en-6-one to yield (1S,5R)-2-oxa lactone of >99% ee and (1S,5R)-ketone of 96% ee after 14 h at a temperature of 16 °C and a substrate concentration of 0.5 g L-1 (4.5 mM). MO14 is thus a promising biocatalyst for the production of enantio-enriched ketones and lactones derived from the [3.2.0] platform.

Functional divergence between closely related Baeyer-Villiger monooxygenases from Aspergillus flavus

Baeyer-Villiger monooxygenases (BVMOs) catalyse the chemo-, regio- and enantioselective oxidation of ketones to esters and lactones. To date, most of the cloned BVMOs available are derived from bacteria, although Baeyer-Villiger oxidations using fungi have frequently been demonstrated. Here we report the cloning and characterization of four BVMOs from the fungus Aspergillus flavus NRRL3357. Phylogenetic analysis shows these four BVMOs to cluster in a distinct group apart from other well-characterized BVMOs including cyclohexanone, phenylacetone and 4-hydroxyacetophenone monooxygenase. Building on the Grogan classification/clustering of BVMOs, we have designated this new group of BVMOs, Group VI. Group VI BVMOs show an early divergence from the cyclopentanone monooxygenase (CPMO) type BVMOs (Group I). Substrate profiling using cyclic, bicyclic, aliphatic and aryl ketones show a clear divergence in function and specificity not only between this new group of BVMOs and the CPMO-type BVMOs, but also between the four A. flavus BVMO paralogues despite their high sequence similarity. This study not only contributes to the growing number of available BVMOs, but also addresses the current classification of Type I BVMOs, and the usefulness of phylogenetic clustering and prediction of function and selectivity when genome-mining is used to search for new biocatalysts.

Identification of novel mammalian squalene synthase inhibitors using a three-dimensional pharmacophore

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.

Preparation of TADOOH, a hydroperoxide from TADDOL, and use in highly enantioface- and enantiomer-differentiating oxidations

Replacement of one OH group in TADDOL ( = a,a,a′,a′-tetraaryl-1,3-dioxolane-4.5-dimethanol) by an OOH group gives a stable, crystalline chiral hydroperoxy alcohol TADOOH ( = [(4R,5R)-5-[(hydroperoxydiphenyl)methyl]-2,2-dimethyl-1,3-dioxolan-4-yl] diphenylmethanol) 3, the crystal structure of which resembles those of numerous other TADDOL derivatives (Fig. 2). The new hydroperoxide was tested as chiral oxidant in three types of reactions: the epoxidation of enones with base catalysis (Scheme 2), the sulfoxidation of methyl phenyl sulfide (Scheme 3), and the Baeyer-Villiger oxidation of bicyclic and tricyclic cyclobutanones, rac-10a-d with kinetic resolution (Scheme 4, Fig. 3, and Table). Products of up to 99% enantiomer purity were isolated (the highest values yet observed for oxidations with a chiral hydroperoxide!). Mechanistic models are proposed for the stereochemical courses of the three types of reactions (Schemes 5 and 6, and Fig. 4). Results of AM1 calculations of the relative transition-state energies for the anionic rearrangements of the exo Criegee adducts of TADOOH to the enantiomeric bicyclo[3.2.0]heptan-6-ones are in qualitative agreement with the observed relative rates (Table and Fig. 5).

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

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

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

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

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

(+/-)-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

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.