1‐Phosphabicyclo[2.2.1]heptane

1‐Phosphabicyclo[2.2.1]heptanes Exo‐endo‐ and exo‐exo‐2.6‐dimethyl‐1‐phosphabicyclo [2.2.1]heptane have been obtained by cyclization of 2‐methyl‐4‐(2‐propenyl)phospholane in the presence of the complex base, sodium salt of diethylenglycolmonoethylether ‐ sodium amide in THF (NAMEDEG). The bicyclic phosphanes are characterized by reac‐tions with selenium, sulfur, (CH₃)₂SeO, CH₃I and HSO₃F, respectively, elemental analysis, X‐ray crystal structure analysis as well as ¹H, ¹³C, ³¹P NMR spectral measurements. The steric demand of these phosphanes as complex ligands has been estimated from the P, H coupling constants of the phosphonium fluorosulphates according to the Tolman model. The phosphane selenides were found to display the lowest values for the ¹J(Se, P) coupling constant, found up to now for alicyclic and cyclic aliphatic tertiary phosphane selenides. The ⁿJ(P, H)‐ and ⁿJ(H, H)_{n=2, 3} coupling constants have been extracted from the proton spectra at 600 MHz by computerized analysis.     

Preparation of 2,5,7-trithiabicyclo[2.2.1]heptane from 1,2-bis-triisopropylsilanylsulfanyl alkenes

[reaction: see text] The chemical behavior of 1,2-bis-triisopropylsilanylsulfanyl alkenes 1 is relatively unexplored, and the weak sulfur-silicon bonds give rise to various transformations. Under acidic conditions (HCl) and in the presence of a Lewis acid at room temperature the bicyclic adduct 2 is obtained in good yield. The structure was confirmed by X-ray crystal analysis with R = benzyl.     

7-Selenabicyclo[2.2.1]heptane

Thermolysis of a benzene solution of N-[4-(p-(methoxybenzyl)seleno)cyclohexanoyl]-N,S-dimethyldithiocarbonate affords the hitherto unknown 7-selenabicyclo[2.2.1]heptane in 48% conversion and in 20% yield after chromatography. G3(MP2)-RAD calculations predict a rate constant of 5 × 10(4) s(-1) at 80 °C (3.8 × 10(6) s(-1) at 200 °C) for the intramolecular homolytic substitution process involved in this cyclization.     

Synthesis of 7‐azabicyclo[2.2.1]heptane derivatives by transformation of tropinone

The bromination (CuBr₂, AcOEt/CHCI₃) plus Favorskii rearrangement (EtONa, EtOH) of N‐carbethoxytropinone ( 4 ), readily available from tropinone ( 3 ), affords mixtures of exo‐ and endo‐isomers of 2,7‐dicarbethoxy‐7‐azabicyclo[2.2.1]heptane ( 1b ) in variable and moderate chemical yield (maximum 37%). The bromination (Br₂, HBr/AcOH) reaction of compound 4 gives ethyl trans‐2,4‐dibromo‐3‐oxo‐8‐azabicyclo[3.2.1]octane‐8‐carboxylate ( 5 ) in 99% yield, a product that on Favorskii rearrangement (EtONa/EtOH) affords ethyl 2,2‐diethoxy‐3‐oxo‐8‐azabicyclo[3.2.1]octane‐8‐carboxylate in moderate yield ( 6 ) (52%).     

Chiral 7-Oxabicyclo[2.2.1]heptane Building Blocks for Prostanoids

Russian Journal of Organic Chemistry - Methyl (Z)-3-[(2R,3R,4S,5S)-5-(2-methoxy-2-oxoethyl)-3,4-(isopropylidenedioxy)tetrahydrofuran-2-yl]-prop-2-enoate was synthesized, and its intramolecular...     

Biohydroxylation d'un aza-2 bicyclo [2.2.1] heptane

Biohydroxylation with Beauveria sulfurescens of the 5-exo position of the 2-aza bicyclo [2.2.1] heptane ring system gives rise to a precursor of carbocyclic 2-deoxy nucleosides.     

Preparation of 1,2exo- and 1,2endo-Diiodo-bicyclo[2.2.1]heptane

1,2 exo-Diiodo-norbornane ( 4 ) was prepared from norcamphor hydrazone by oxidative iodination and subsequent rearrangement of the 2,2-diiodo-bicyclo [2.2.1]heptane ( 2 ). The stable α-iodohydrazone 11 was obtained from 1-iodo-bicyclo[2.2.1]heptan-2-one ( 10 ), which itself was prepared from 1-iodo-norbornene ( 5 ). Subsequent treatment of 11 with iodine lead to 1,2,2-triiodo-norbornane ( 12 ) and l,2-diiodo-norborn-2-ene ( 13 ). 1,2 endo-Diiodo-norbornane ( 14 ) was obtained by stereoselective reduction of 12 with tribtityltinhydride or by reaction of 13 with diimide.     

Development of a New Class of Inhibitors for the Malarial Aspartic Protease Plasmepsin II Based on a Central 7‐Azabicyclo[2.2.1]heptane Scaffold

Plasmepsin II (PMII), a malarial aspartic protease involved in the catabolism of hemoglobin in parasites of the genus Plasmodium, and renin, a human aspartic protease, share 35% sequence identity in their mature chains. Structures of 4‐arylpiperidine inhibitors complexed to human renin were reported by Roche recently. The major conformational changes, compared to a structure of renin, with a peptidomimetic inhibitor were identified and subsequently modeled in a structure of PMII (Fig. 1). This distorted structure of PMII served as active‐site model for a novel class of PMII inhibitors, according to a structure‐based de novo design approach (Fig. 2). These newly designed inhibitors feature a rigid 7‐azabicyclo[2.2.1]heptane scaffold, which, in its protonated form, is assumed to undergo ionic H‐bonding with the two catalytic Asp residues at the active site of PMII. Two substituents depart from the scaffold for occupancy of either the S1/S3 or S2′‐pocket and the hydrophobic flap pocket, newly created by the conformational changes in PMII. The inhibitors synthesized starting from N‐Boc‐protected 7‐azabicyclo[2.2.1]hept‐2‐ene ( 6 ; Schemes 1–5) displayed up to single‐digit micromolar activity (IC₅₀ values) toward PMII and good selectivity towards renin. The clear structure? activity relationship (SAR; Table) provides strong validation of the proposed conformational changes in PMII and the occupancy of the resulting hydrophobic flap pocket by our new inhibitors.     

7-oxabicyclo[2.2.1]heptane hydrochloride and hydrofluoride: Quantum-chemical investigation

Structural parameters, IR spectra and energy of H-bonds for binary complexes of 7-oxabicyclo[2.2.1]heptane molecule with molecules of HCl and HF are calculated by quantum-chemical B3LYP/cc-pVTZ method with inclusion to the basis of diffuse “aug”-orbitals of halogen, oxygen and bridgehead hydrogen.     

The electronic structure of bicyclo [2.2.1] heptane and of bicyclo [2.2.2] octane

An ab initia SCF-LCAO-MO study of bicyclo [2.2.1] heptane(I) and of bicyclo [2.2.2] octane(II) has been performed. The electronic structure and the nature of the molecular orbitals and of the bonds have been analyzed. Interactions between fragment orbitals may be recognized. The bridgehead C-H bonds interact dominantly “through-space” in I and “through-bond” in II. Some relations between electronic structure and molecular properties are discussed.     

Enzymatic preparation of optically active 7-oxabicyclo[2.2.1] heptane derivatives

Enzymatic resolution of endo-7-oxabicyclo [2.2.1] hept-2-yl butyrates 3 and 5 using lipase from Candida cylindracea led to optically pure bicyclic alcohols and esters being important intermediates for the synthesis of biologically active compounds.     

An Improved Procedure for the Synthesis of Chiral 2-Aza-Bicyclo[2.2.1]heptane

Grieco's protocol for the synthesis of 2-aza-bicyclo[2.2.1]heptane is modified and adapted for large scale preparation. The optical purity of the material is readily upgraded by purification through a chiral salt.     

Synthesis of opioid ligands having oxabicyclo[2.2.2]octane and oxabicyclo[2.2.1]heptane skeletons

Two types of novel skeletons were synthesized from morphinan and 4,5-epoxymorphinan derivatives by using stable and unstable sulfur ylide.     

Conversion of bicyclo[2.1.0]pentane into 2,3-dioxabicyclo[2.2.1]heptane via t-butyl peroxymercuriation

Bicyclo[2.1.0]pentane has been converted in 45% yield into 2,3-dioxabicyclo-[2.2.1]heptane by the sequence t-butyl peroxymercuriation, iododemercuriation, epimerisation of the resultant 1-t-butylperoxy-3-iodocyclopentane, and reaction of the trans isomer with silver trifluoroacetate.