Tricyclic Portion Research Articles

A very short O-H⋯O hydrogen bond in the structure of clozapinium hydrogen bis-(3,5-di-nitro-benzoate).

In the title salt {systematic name: 4-[6-chloro-2,9-di-aza-tri-cyclo-[9.4.0.03,8]penta-deca-1(15),3(8),4,6,9,11,13-heptaen-10-yl]-1-methyl-piperazin-1-ium 3,5-di-nitro-benzoate-3,5-di-nitro-benzic acid (1/1)}, C18H20ClN4 +·C7H3N2O6 -·C7H4N2O6, there is a very short, asymmetric, O-H⋯O hydrogen bond [O⋯O = 2.453 (3) Å] within the anion. The oxygen atoms of one of the nitro groups of the anion are disordered over two sets of sites having occupancies of 0.56 (3) and 0.44 (3). The fused tricyclic portion of the cation adopts a butterfly conformation, with a dihedral angle of 45.59 (6)° between the planes of the two aryl rings. In the crystal, a combination of O-H⋯O, N-H⋯O and C-H⋯O hydrogen bonds links the component species into a three-dimensional framework. Comparisons are made with the structures of some related compounds.

Synthetic studies toward the kempane diterpenes. Construction of a key tricyclic intermediate

A synthetic sequence is described for construction of the tricyclic portion (35) of kempane diterpenes. The central stereochemistry was established by a Diels-Alder addition of 2,6-dimethyl-para-benzoquinone to a 5-membered, dithiane-protected diene, and the addition of acetylide, with very high chemoselectivity, provided a suitably functionalized handle that will be incorporated into the final seven-membered ring. The remaining stereogenic centres about the decalin moiety were established by a series of equilibration and reduction steps.

Synthetic studies on azadirachtin (Part 3): Asymmetric synthesis of the tricyclic dihydrofuran moiety of azadirachtin

An asymmetric synthesis of the tricyclic dihydrofuran moiety of azadirachtin is reported. The Diels-Alder adduct, which was catalyzed by Evans' chiral Cu-bisoxazoline complex, was easily converted to the tricyclic portion via SmI 2 reductive cleavage and selective functionalization.

Application of the Tethered Biginelli Reaction for Enantioselective Synthesis of Batzelladine Alkaloids. Absolute Configuration of the Tricyclic Guanidine Portion of Batzelladine B.

Tethered Biginelli condensation of enantioenriched hexahydropyrrolopyrimidines 8 with beta-ketoesters provides efficient asymmetric access to tricyclic guanidines 9 having a syn relationship of the angular C2a and C8a hydrogens. This reaction was employed to realize the first practical enantioselective access to this fragment of batzelladine alkaloids B (2) and E (5). The efficiency of this strategy is illustrated in the synthesis of the dextrorotatory enantiomer of batzelladine B methanolysis product 10 in 10 steps and 25% overall yield from 2-nonanone and methyl acetoacetate. The asymmetric synthesis of 10 establishes that the absolute configuration of the tricyclic portion of batzelladine B (2) is 25aR,28S,30R. The 4-methyl-7-alkyl-1,2,2a,3,4,5,6,7,8,8a-decahydro-5,6,8b-triazaacenaphthalene-3-carboxylic acid subunit, e.g., 29, of batzelladine alkaloids A (1), D (4), F (6), and G was also prepared for the first time by catalytic hydrogenation of tricyclic guanidines 26 having the 2a,8a-anti stereochemistry.

Synthesis of the tricyclic portions of batzelladines A, B and D. Revision of the stereochemistry of batzelladines A and D

The tricyclic portion 4 of batzelladine B ( 2) is obtained from 10a, which differs in one side chain from the ptilomycalin A model 10c that we prepared several years ago, by reduction with NaBH 3CN in buffered MeOH. Hydrogenation of 11b over Rh Al 2O 3 at 50 PSI H 2 affords the proposed tricyclic portion 12b of batzelladine A ( 1). Epimerization of 12b and hydrolysis affords acid 3, which is similar to, but different from, the acid obtained from hydrolysis of 1. A five step sequence converts 7b to the anti tricyclic acid 15, which is identical to the hydrolysis product of 1. The stereochemistry of the hydrolysis product 15 was confirmed by NOE experiments.

Chemical modification of ring c of himbacine: Discovery of a pharmacophoric element for M 2-selectivity

Removal of the carbonyl oxygen of himbacine furnishes a molecule which binds with 20-fold and 4-fold lower affinity at the M 2 and M 1 receptor sites, respectively. Thus, the carbonyl oxygen constitutes an important pharmacophoric element responsible for some of the M 2 selectivity of himbacine. Other modifications of the C-ring of the tricyclic portion of himbacine were examined and tested for potency at M 1 and M 2 sites, and the data confirm that M 2 selectivity is optimal with a closed heterocyclic ring and with the presence of a proximal carbonyl oxygen.

Synthesis of the Enantiomeric Furobenzofurans, Late Precursors for the Synthesis of (+)- and (-)-Aflatoxins B1, B2, G1, and G2

Enantiomeric tetrahydrofuro[2,3-b]benzofurans, representing the ABC tricyclic portion of aflatoxins B 1 , B 2 , G 1 , and G 2 , were generated from the oxaza-Cope rearrangement of a suitably functionalized O-aryl- oxime. The O-aryloxime was, in turn, made from the condensation of an enantiomerically pure aldehyde derived from glutamic acid and a substi- tuted phenoxyamine. High regioselectivity with respect to the A-ring substituents of the ABC tricycle was achieved through the use of elec- trochemistry. The regioselective electrochemical cleavage of 4,6-bis (tosyloxy)-2-(methoxycarbonyl)-2,3,3a,8a-tetrahydrofuro[2,3-b]benzofuran (22) resulted in a 97/3 mixture of regioisomeric phenols. The regio- chemical assignements of the resulting phenols were determined by 2D NOESY NMR. The enantiomeric ratio of the final product was determined to be 96/4 by NMR analysis of diastereomers resulting from the coupling of (31a) to (+)- and (±)phenethylamine

Studies of nonsteroidal anti-inflammatory drugs: azapropazone

The structure of azapropazone, 5-(dimethylamino)-9-methyl-2-propyl-1H-pyrazolo[1,2-a][1,2,4]benzotriazine-1,3(2H)-dione, was determined by single crystal X-ray diffraction. Crystals were orthorhombic (P212121), with a = 5.570(1) Å, b = 14.593(3) Å, c = 19.270(4) Å, and Z = 4. Intensities were measured on a Rigaku AFC6-R diffractometer with Cu-Kα radiation and 2316 reflections were used to determine the structure. Contrary to previous postulates, the tricyclic portion of the molecule is not planar. Azapropazone is a zwitterion with the negative charge delocalized over the β-keto-enol system and with the proton on N(6) of the triazine ring. The nonplanarity of the molecule is caused by steric interaction of a methyl group on the exocyclic dimethylamino group with O(3) of the keto-enol system. Bond lengths and angles are normal. NMR studies showed that at room temperature rapid inversion occurs between the two enantiomers, but this inversion slows at low temperatures with ΔG≠ = 44.9(2) kJ mol−1. The product derived from opening of the pyrazolidine ring of azapropazone by formic acid is not as previously formulated. The compound is 3-dimethylamino-7-methyl-1-valeryl-1,4-dihydro-1,2,4-benzotriazine. Its structure was determined by single crystal X-ray diffraction. Crystals were monoclinic (P21/n), with a = 10.240(2) Å, b = 12.608(3) Å, c = 13.176(3) Å, β = 108.46(3)°, and Z = 4. Intensities were measured on a Rigaku AFC6-R diffractometer with Cu-Kα radiation and 2209 reflections were used to determine the structure. The conformation of the benzotriazine ring system was very similar to that observed in azapropazone and bond lengths and angles were normal.

Biomimetic synthesis of the central tricyclic portion of ptilomycalin A

Abstract The central tricyclic portion 20 of ptilomycalin A ( 1 ) is formed from bis enone 16 in two steps. Addition of O -methylisourea in DMF to 16 affords a mixture of 17 and 18 that are both converted to a single tricyclic aminal 20a on treatment with NH 3 and NH 4 OAc in methanol at reflux.