Search

The regioselective synthesis of isoquino(1,2-b)(3)benzazepines or homoprotoberberines using 11-membered stilbene lactams as key intermediates has been undertaken. The lactams were prepared by the intramolecular addition of an aryl radical to a trimethylsilylacetylene. The homoprotoberberines are formed when the amide of both lactams is reduced to an amide functionality and results in a regioselective (7,6)-transannular cyclization.

One of the challenges of modern organic synthesis is coming up with high efficiency in terms of maximized target-relevant molecular complexity and minimal synthetic steps. One option is the manipulation of the rich oxygenation pattern of the cycloadducts, which suggest an immediate entry to cis-2,5-disubstituted tetrahydrofurans by oxidative cleavage of the carbocycle. The results showed that the rich oxygenation and conformational rigidity of the oxabicyclic (5C + 2C) pyrone-alkene adducts offers rich unique opportunities for speeding up the synthesis of tetrahydrofurans.

Fused 6,7,5-tricarboxylic compounds have been synthesized by one-pot coupling of an intramolecular thermal (5C + 2C) pyrone-alkene cycloaddition to a (4C + 2C) Diels-Alder reaction. The compounds consist of a 1,4-oxa-bridge in the seven-membered carbocycle and undergoes transformation involving the net formation of four carbon-carbon bonds. Three new cycles and at least five new stereocenters are also formed during the transformation. Deoxygenated and aromatized products can be formed by opening the oxa-bridge through reaction of the adducts with samarium diiodide and trimethylsilyl triflate.

Silylated stilbene lactams were synthesized by intramolecular addition of an aryl radical to a trimethylsilylacetylene and subsequently converted into protoberberines via dimethyldioxirane epoxidation and acid-catalyzed cyclization of the epoxysilane with HCl. The nonsilylated trans- and cis-stilbene analogues were treated with dimethyldioxirane to produce 13-hydroxytetrahydroprotoberbirines and 13a-hydroxy-13-ketotetrahydroprotoberberines as the major compounds.

The unnecessary length dependent local minima in the autoregressive channels of finite-length constant modulus algorithm (CMA) equalizers can be removed by modifying the CMA cost function. The approach takes advantage of the fact that the equalizer output in autoregressive channels is associated with a delayed input at the length dependent local minima. This correlation is nonzero in the undesired equilibria points and disappears in the desired ones. The validity of the method was demonstrated through a stability analysis of the modified CMA cost function for a first-order autoregressive noiseless channel and a two-tap equalizer.

Vitamin D3 becomes 1alpha,25-dihydroxyvitamin D3 (calcitriol, 1alpha,25-(OH)sub2-Dsub3) in the liver and the kidney. Calcitriol can inhibit the multiplication of malignant cells and suppresses tumor growth, and has been used in the treatement of several diseases. There is increasing interest in developing new vitamin D analogs with strong cell differentiation and weak calcemic effects. Two short, practical synthetic routes to 1alpha-25-dihydroxyvitamin D2 and analogs modified at C24 have been developed.

There has been much research aimed at developing nontoxic vitamin D derivatives to be used in the treatement of hyperproliferative diseases, although there is a need for more practical and flexible approaches. A new approach based on the conjugated triene system of vitamin D and applied to the synthesis of 3-deoxy-1alpha- and 1beta hydroxyvitamin D3 is described. The method has potential for the synthesis of thermally labile derivatives.

A novel method for the synthesis of annelated 3- and 3,3''-substituted bipyridines and terpyridines was developed based on the utilization of Co(I) complexes as catalysts for the formation of the pyridine nuclei. The synthetic process was characterized by the CpCo(CO)2-catalyzed cocyclization of 5-hexanenitrile and unsubstituted 2-ethynylpyridine. The irradiation of the intermediate product led to the formation of a mixture of 2,2'-bipyridine and its 3,2'-bipyridine isomer.

A new method for separating instantaneous linear mixtures of signals is proposed. The technique is based on the constant modulus criterion and uses a linear memoryless multiple input multiple output system. It is particularly suitable for multiuser communications since it requires only statistical signal independence to perform separation and also because adaptation is performed with a convergent stochastic gradient algorithm.

3-Hydroxy-pyridone in 58% yield was produced by the reaction of methylamine and allyl thioether which was derived from the addition of chloropyrone with allylmercaptan and triethylamine. The pyridone that was derived from the chemical reaction was utilized to develope a second pyridone product. The pyridone did not undergo thermal pyrone-alkene cycloaddition due to its aromatic characteristics. Cycloadditions with 4-unsubstituted oxydopyridinium ylides exhibited chemical reactions with high regioselectivity.

The alkaloid (+/-)-clavizepine was prepared from dibenzopyranazepine in nine steps in 17% overall yield. 2,3-Dihydroxybenzaldehyde formed aldehyde after benzylation. Treatment of the aldehyde with 1,3-propanedithiol produced a phenolic dithioketal, which gave a coupled product after -nBuLi treatment and alkylation. Ullman reaction produced a complex mixture of products that formed alkenes by reduction with Raney nickel. Debenzylation of the hydroxylated alkenes gave a phenolic compound which afforded a cyclic compound after treatment with acetic acid. Catalytic hydrogenation of the cyclic compound, reductive cleavage and N-methylation, in that order, gave the amine resembling the structure of (+/-)-clavizepine.

The synthesis and characterization of antitumor lycorines are described. The scheme involves an intramolecular Diels-Alder reaction between an alpha-pyrone and an alkyne, and subsequent loss of carbon dioxide in a retro Diels-Alder reaction. The method has been applied to prepare benzophenanthridine alkaloids via the cycloaddition reactions of alpha-pyrones with benzyne.

Intramolecular Diels-Alder reactions between the aryne and azadiene derivatives result in the formation of lycorine alkaloids. Aryne-azadiene can be obtained by base-activated dehydrohalogenation of an haloarene and enolization of an amide. Alterations in the nature or position of the substituents provide different products due to change in regioselectivity. Cyclization involves a two-step ionic mechanism initiated by nucleophilic attack on the benzyne by the nitrogen atom followed by intramolecular addition of the phenyl carbanion to the promoted benzene ring.

The generation of spectral lines by cyclostationary signals passing through certain nonlinear transformations provides the basis for a new method of adaptive beamforming. A novel optimization objective is used to determine the coefficients of the beamformer. The optimization objective involves minimization of the mean square error between array output after the nonlinearity and a complex exponential. By this method, any signal that produces a spectral line at the frequency of the reference complex exponential will be optimally extracted. The beamformer also eliminates the radiocommunication channel's distortion.

Pyrrolinediones were reacted with two benzyne molecules to produce 4-phenylisoquinolones. Subsequentreaction of the bromopyrrolinedione produced the bromoadduct, phenylated adductand a minor unexpected compound. Results showed a more complex mechanism than those previously cited. New mechanisms for the reaction are suggested. Variation in the R2 groups resulted in corresponding variations in the reactionmechanisms.

N-(phenylfluorenyl)-2-amino-1-indanones were synthesized from cyclization of bromophenylalanine oxazolidinones by lithium-bromine exchange followed by intramolecular acylation of the aryllithium intermediate. A nitrogen-protecting group 9-phenylfluoren-9-yl was used to preserve the integrity of the chiral center by preventing deprotonation of the alpha-carbon.

An improved synthetic route to 1alpha,25-dihydroxyvitamin D2 involves the nucleophilic attack of stannylacetylene on a pregnyl dioxanone, obtained from a dinorcholanol and (3R)-3-hydroxybutyric acid. The attack cleaves the ketone's dioxo-ring and installs the acetylene. Conversion of the resulting alcohol into a ketone and construction of the triene by cross-coupling with a cyclohexenylinyne leads to the target 1alpha,25-dihydroxyvitamin D2.

Aunique synthetic route to C-25 analogues of 1alpha,25-dihydroxyvitamin D3 involves the ultrasound induced conjugate addition of an iodo triflate to electron-deficient olefins under aqueous conditions. The triflate is prepared in three steps from the Inhoffen-Lythgoe diol. The vinyl triflate adducts of the zinc-copper induced sonochemical step then undergo a dienyne convergent process to yield the various C-25 derivatives of 1alpha,25-(OH)2-D3.

Reaction of pyrrolinediones with arynes yields oxoprotoberberines. With the use of chlorine or bromine as protecting groups for the pyrrolinediones, 2, 3-dimethoxy-8-oxyprotoberberine, norketoyobirine and decarbomethoxydehydrogambirtannine were synthesized. 13-bromo-8- oxyprotoberberine was likewise prepared by hydrogenolysis.

Intermolecular benzyne cycloaddition (IBC) is a convergent, regioselective, flexible approach to the synthesis of benzophenanthridines. The process involves the use of pyrrolinediones as aza diene equivalents in the cycloaddition reactions with arynes. The use of IBC in the synthesis of 2,3,8,9- and 2,3,7,8-tetrasubstituted alkaloids leads to the preparation of nitidine, avicine and chelerythrine.

Ashort, simple and efficient synthesis of benzophenathridine alkaloids is described. The process involves a convergent Diels-Alder reaction between a tricyclic alpha-pyrone obtained from phthalimide and arynes derived from the aprotic diazotization of anthranilic acids. It is applied to the synthesis of antineoplastic benzophenanthridines such as nitidine, which is prepared from 4,5-dioxyanthranilic acid.

The preparation of 1-(OPPh2)ethenyl-2-(Me)-5-(OTBS)-cyclohexane and of its enantiomer provides the A-ring fragment for the convergent syntheses of dihydrotachysterol2 (DHT2), its 25-hydroxy analogue (25-OH-DHT2), 10(R),19-dihydro-(5E)-3-epivitamin D2 and the latter's 19-dihydroxy analogue. The cyclohexane is obtained in 32% yield from the Ganem reaction of (+)- and (-)-carvone followed by a seven-step process involving a stereo-directing ozonolysis. From the A-ring fragment, DHT2 is prepared in 74% yield and 25-OH-DHT2 in 84% yield. The enantiomer produces the two epivitamins D2 in 70% and 80% yields.

Trans-hydrindanol and trans-hydrindanone served as precursors in the synthesis of the CD and side-chain fragments of vitamin D metabolites and analogues. An enedione and a tosylate compound provided the starting materials for the corresponding syntheses of the hydrindanol and the hydrindanone. The key procedure in the hydrindanol synthesis involved Wilkinson catalyst-mediated hydrogenation of the hydrindenol intermediates which led to the formation of the desired trans-product in 65% yield. Both hydrindanol and hydrindanone compounds produced the diol form of the CD fragment in 81% and 80% yields, respectively.

A new high-yielding synthetic route to phthalides involves a Parham-type ring formation with the use of a carbamate as an internal electrophilic trap. The addition (at -95 degrees C) of tert-butyllithium to o-bromocarbamates in a tetrahydrofuran solution causes a metal-halogen interchange, yielding the ortho-lithiated intermediates which are trapped on their side chain. The synthetic technique also leads to lactones that may be used as precursors to aristocularine alkaloids.