Studies on the Diels-Alder reaction of maleic anhydride and β-trans-ocimene

The structure of the by-product, obtained in the Diels-Alder condensation of maleic anhydride with β-trans-ocimene followed by distillation of the adduct formed, has been established as 2-isopropylidene-4-methyl-7-carboxy- ,3,3a,6,7,7a-hexahydroindanone (IVa) and the mechanism of its formation from the adduct (II) discussed. Some hitherto unreported reactions of the maleic anhydride adduct (II) and its derivatives are described. These throw light on the stereochemistry of the adduct and derived products.

An Eventful Synthetic Approach Towards the Biologically Potent Natural Product Ottelione A: Enantio-, Regio- and Stereoselective Construction of the Bicyclic Core

A novel synthetic approach towards the recently reported anti-tumor and anti-tuberculor natural product ottelione A from the readily available Diels-Alder adduct of cyclopentadiene and p-benzoquinone is delineated. Our short strategy, besides being enantio-, regio- and stereoselective, charts an eventful course and is inherently well-suited for adaptation towards diverse synthetic analogues of this biologically potent natural product.

Bile-Acids in Asymmetric-Synthesis.2. Cholic-Acid Derived Novel Chiral Auxiliaries For Asymmetric Diels-Alder Reactions

Cholic acid-based chiral acrylate 5 yields a Diels-Alder adduct with cyclopent

Reaction of spironaphthalenones with hydroxylamine: Part III. A novel mechanism for the formation of products and trapping of an intermediate.

A mechanism involving the intermediacy of nitrene 5, formed from the oxime of spironaphthalenone 1 by acid catalysed dehydration, has been proposed to explain the formation of pyrrolotropones/pyrrolo esters from spironaphthalenones. The initially formed nitrene rearranges to the isopyrrole 6, which either undergoes sigmatropic migration to the pyrrolotropone 2 or adds alcohol to form the pyrrolo ester depending on substitution at 1′ position. The isopyrrole intermediate 6 has been trapped as a Diels-Alder adduct 8.

Stereochemical properties and x-ray structure of a water-soluble diastereomeric (arene)ruthenium(II) Schiff-base complex: [Ru(.eta.-MeC6H4Pri-p)(H2O)(L*)](ClO4), containing a weakly bound aqua ligand [HL* = (S)-(.alpha.-methylbenzyl)salicylaldimine]

An air-stable and water-soluble diastereomeric half-sandwich ruthenium(I1) complex, [Ru(s-MeCsH4Pr'-p)(H*O)-(L*)] (C104) (l), has been isolated and structurally characterized [HL* = (27)-(a methylbenzyl)salicylaldimine,2-HOC6H4CH-NCHMePhI. Complex 1, Czd-I3oNO&lRu, crystallizes in the noncentric triclinic space group P1 with a = 9.885(1) A, b = 10.185(1) A, c = 14.187(2) A, a = 110.32(1)', 6 = 102.17(1)', y = 102.41(1)O, V=1243( 1) A3, and 2 = 2. The X-ray structure shows the presence of two diastereomers in a 1:l ratio having RR,,,SCand SR,,,&c onfigurations. The Ru-OHz bond distances are considerably long, and the values for RR, - a~n d SRu-1isomers are 2.1 19(5) and 2.203(5) A, respectively. The aqua complex (1) exists as a single diastereomer in solution,and it forms stable adducts with P-, N-, and halide-donor ligands. The stereochemical changes associated with adduct-forming reactions follow an inversion order: PPhs >> P(OMe)3 > pyridine bases >> halides (I, Br, Cl) >H20.

Interaction of EcoP1 modification methylase with S-adenosyl-L-methionine: a UV-crosslinking study

EcoP1 modification methylase was radioactively labeled when incubated with S-adenosyl-L-[methyl-3H]methionine in the presence of ultraviolet light. Crosslinking of the enzyme as detected by electrophoresis on sodium dodecyl sulfate-polyacrylamide gel followed by fluorography and autoradiography, was shown to be specific by a number of criteria. More importantly, EcoP1 modification methylase was also radioactively labeled with S-adenosyl-L-[carboxyl-14C]methionine demonstrating that labeling involved binding of the entire AdoMet molecule rather than methylation of the protein. Further, c2 EcoP1 mutant DNA modification methylases which show negligible or very little methylation activity, correspondingly formed a weak or no adduct upon crosslinking. These results suggest that photolabeling of EcoP1 DNA modification methylase occurs at the AdoMet binding site.

Photolabeling of the EcoP15 DNA methyltransferase with S-adenosyl-l-methionine

Radioactivity from S-adenosyl-L-[methyl-H-3] methionine ([methyl-H-3]AdoMet) was bound to the EcoP15 DNA methyltransferase (M.EcoP15) following short-wave ultraviolet (UV) irradiation. The labeled protein was subjected to polyacrylamide-gel electrophoresis in the presence of sodium dodecyl sulfate (SDS-PAGE), and detected by fluorography and autoradiography. Labeling was found to be dependent on the concentration of AdoMet and time of UV irradiation. The photolabeling by [methyl-H-3]AdoMet was specific and blocked by S-adenosyl-L-homocysteine (AdoHcy) and sinefungin which are known to function as competitive inhibitors. Limited digestion of the M EcoP15-AdoMet adduct by Staphylococcus aureus protease V8 generated three peptides of approx. 50, 32 and 30 kDa; Interestingly, only the 30-kDa peptide fragment contained radioactivity, as detected by SDS-PAGE, followed by fluorography and autoradiography. Further, sequencing of a few amino acids at the N-terminus of these peptides showed that the 30-kDa fragment was the N-terminal portion of M.EcoP15, These results suggest that photolabeling is at the AdoMet-binding site and that the N-terminal half of M.EcoP15 may be involved in substrate binding.

Asymmetric Diels-Alder Reactions of Chiral Acrylates of Cholic Acid Derivatives

New steroid-based chiral auxiliaries 6, 9, and 12 have been synthesized from readily available cholic acid. These new chiral auxiliaries place the reactive and the shielding sites in a 1,5 relationship to each other. Diels-Alder reaction of cyclopentadiene with corresponding acrylate esters (7, 10, and 13) have been examined. Acrylates 7 and 10 yielded cycloadducts with 29-88% diastereomeric excess with excellent endo selectivity in the presence of an excess of Lewis acids such as AlCl3, BF3.OEt(2), FeCl3, SnCl4, TiCl4, and ZnCl2. Treatment of acrylate 7 with cyclopentadiene in the presence of BF3.OEt(2) at -80 degrees C gave the endo adduct (>99%) with 88% de. Lewis acid catalyzed and uncatalyzed reactions of acrylates 7 and 10 with cyclopentadiene yielded cycloadducts with opposite stereochemistry. The chiral auxiliary was recovered in a nondestructive manner only via iodolactonization. Acrylate ester of alcohol 12 did not show any selectivity in either catalyzed and uncatalyzed reactions with cyclopentadiene. The presence of a flat aromatic surface at C-7 of the steroid was found to be essential to effect high diastereoselection.

Ab initio studies of the structure and vibrational spectra of methyl isocyanide-borane and acetonitrile-borane

The SCF/DZP and MP2/DZP methods of ab initio quantum chemistry have been utilized to study the structure, vibrational spectra, binding energy, and barrier to internal rotation of methyl isocyanide-borane and acetonitrile-borane adducts. The eclipsed conformation of the complexes was predicted to be a minimum, and the staggered form is a transition state with a barrier height of about 10 cal/mol. The vibrational analyses of CH3NC-BH3 and CH3CN-BH3 and several of their isotopomers have been carried out by the GF matrix method. Computations have also been carried out for free CH3NC and CH3CN in order to investigate the changes in CH3NC and CH3CN as a result of their complex formation with BH3. To obtain an acceptable set of force constants, a recently proposed procedure ''RECOVES'' has been utilized. The increase in the N=C/C=N stretching force constant of CH3NC/CH3CN on adduct formation is interpreted with the help of Parr and Borkman's model. The binding energies for the two adducts have been determined taking basis set superposition error (BSSE) into consideration. The effect of the BSSE on structure, dipole moment, and vibrational frequencies of CH3CN and CH3NC is also evaluated. The predicted infrared band intensities for the two complexes are in good agreement with the experimentally observed features, and they have been utilized in the assignment of vibrational frequencies.

Investigations Of Iron Adducts Of C-60 - Novel Fec60 In The Solid-State With Fe Inside The C-60 Cage

By carrying out contact-arc vaporization of graphite in a partial atmosphere of Fe(CO)5, an iron-adduct with C60 has been obtained. The adduct has been characterized by various techniques including mass spectrometry, Fe-57 Mossbauer spectroscopy and Fe K-EXAFS. Properties of this adduct are compared with those of an adduct prepared by solution method where Fe is clearly outside the cage. Results suggest that FeC60 obtained from the gas phase reaction has the Fe atom in the cage.

Synthesis Based on Cyclohexadienes. 5. A New Approach to the Synthesis of a-Ring Aromatic Steroids - a Formal Total Synthesis of (+/-)-Estrone

A new strategy for the construction of A-ring aromatic steroids which resulted in the formal total synthesis of estrone is described. Thus reaction of the adduct (9), obtained from 1-methoxy-4-methylcyclohexa-1,4-diene and acrolein, with 3-(m-methoxyphenyl)propylmagnesium bromide followed by oxidation afforded the bicyclo[2.2.2]octene derivative (14). Acid-catalysed rearrangement of (14) followed by an intramolecular Michael addition resulted in the cis tetraenone (18) which was dehydrogenated with palladium chloride to the pentaenone (22). Li/NH3 reduction of (22) gave 3-methoxy-D-homoestra-1,3,5(10)-trien-16-one (31) which has been converted into the methyl ether (37) of marrianolic acid, and its methyl ester (38).

Synthesis, properties and crystal structures of diastereomeric areneruthenium(II) chiral Schiff-base complexes

Diastereomers (SRu,Sc)-1a and (RRu,Sc)-1b, in a ratio of 85: 15 and formulated as [Ru(η-MeC6H4Pri-p)Cl(L*)], have been prepared by treating [{Ru(η-MeC6H4Pri-p)Cl2}2] with the sodium salt of (S)-α-methylbenzylsalicylaldimine (HL*) in tetrahydrofuran at –70 °C. The reaction of 1(1a+1b) with AgClO4 in acetone followed by an addition of PPh3 or 4-methylpyridine (4Me-py) leads to the formation of adducts [Ru(η-MeC6H4Pri-p)(PPh3)(L*)]ClO42[(SRu,Sc)2a, (FRu,Sc)2b] and [Ru(η-MeC6H4Pri-p)(4Me-py)(L*)]ClO43[(SRu,Sc)3a, (RRu,Sc)3b] in the diastereomeric ratios (SRu,Sc) : (RRu,Sc) of 2 : 98 and 76 : 24, respectively. Complex 1 crystallises with equal numbers of 1a and 1b molecules in an asymmetric unit of monoclinic space group P21 with a= 10.854(1), b= 17.090(1), c= 12.808(4)Å, β= 110.51(1)°, and Z= 4. The structure was refined to R= 0.0552 and R′= 0.0530 with 2893 reflections having I[gt-or-equal] 1.5σ(I). The absolute configurations of the chiral centres in the optically pure single crystal of the PPh3 adduct have been obtained from an X-ray study. Crystals of formulation [Ru(η-MeC6H4Pri-p)-(PPh3)(L*)]2[ClO4][PF6]·1.5 CHCl3, obtained in presence of both ClO4 and PF6 anions, belong to the non-centric triclinic space group P1 with a= 10.852(2), b= 14.028(1), c= 15.950(2)Å, α= 91.51(1), β= 105.97(1), γ= 106.11(1)°, and Z= 2. The final residuals were R= 0.0713, R′= 0.0752 with 7283 reflections having I[gt-or-equal] 2.5σ(I). The crystal structures of 1a,1b, and the PPh3 adduct (2b,2b′) consist of a ruthenium(II) centre bonded to a η-p-cymene, a bidentate chelating Schiff base, and a unidentate ligand (Cl or PPh3). The chirooptical properties of the complexes have been studied using 1H NMR and CD spectral data. The presence of a low-energy barrier for the intermediate involved in these reactions, showing both retention as well as inversion of the metal configuration, is discussed.

Synthetic Studies Towards Prismanes - Rearrangements In Some Pentacyclic Precursors And X-Ray Crystal-Structure Of A Novel Heptacyclic Ether

In order to gain access to the heptacyclic tetraone 3, efforts were directed towards the utilisation of the major 'unwanted' [4 + 2]-adduct 11 of tetrachlorodimethoxycyclopentadiene and norbornenobenzoquinone. Epoxides derived from the diol and dimethoxy derivatives of the adduct 11 undergo facile Wagner-Meerwein rearrangement resulting in the required endo, syn, endo stereochemistry as well as methano-bridge functionalisation to deliver 18 and 24, respectively. However, intramolecular ether formation, occurring via the capture of carbocation intermediate with the transannularly poised oxygen functionality, is a more facile process. Attempts to cleave the ether linkage resulted in the formation of a novel transannularly cyclised twisted bowl shape heptacyclic compound 30 and its structure has been established through X-ray crystallography.

Synthesis, X-ray structure and properties of (eta(6)-p-cymene)ruthenium(II) Schiff-base complexes of vinylpyridine and vinylimidazole ligands

Complexes of the formulation [(eta(6)-p-cymene)Ru(O-2-C6H4-CH=NC6H4-4-CH3)(L)](ClO4), where L is gamma-picoline, 4-vinylpyridine, 1-methylimidazole and 1-vinylimidazole have been prepared and characterised. The molecular structure of the vinylpyridine adduct has been determined by X-ray crystallography. The crystal belongs to the monoclinic space group P2(1) with the following cell dimensions for the C31H33CIN2O5Ru(M = 650.11): a = 10.890(2)Angstrom, b = 22.295(9)Angstrom, c = 12.930(2)Angstrom, beta = 109.30(2)degrees(3), V = 2964(l)Angstrom 3, Z = 4; D-c = 1.457g cm(-3), lambda(Mo-K alpha) = 0.7107 Angstrom; mu(Mo-K alpha)= 6.61 cm(-1); T = 293 K; R = 0.0359 (wR(2) = 0.0981) for 4819 reflections with I > 2 sigma(I). The structure shows the non-bonding nature of the double bond of the 4-vinylpyridine ligand in the complex in which the metal is bonded to the eta(6)-p-cymene, the N, O-bidentate chelating schiff-base and the unidentate N-donor pyridine ligands.

Synthetic studies directed towards the potent cytotoxic natural product ottelione A: stereoselective construction of the complete framework

A stereoselective strategy for the rapid acquisition of the complete framework (dideoxyottelione A) of the promising cytotoxic agent ottelione A, with four contiguous stereogenic centres on a hydrindane skeleton and a sensitive 4-methylenecyclohex-2-enone functionality, from the readily available Diels-Alder adduct of 1,2,3,4-tetrachloro-5,5-dimethoxycyclopentadiene and norbornadiene, is delineated.