Carbomethoxy Group Research Articles

Synthesis of totally chiral, multiple armed, poly Glu and poly Asp scaffoldings on bifunctional adamantane core

Three successive generations of peptidic scaffoldings consisting of two, six and fourteen chiral (all L) centres and four, eight and sixteen carbomethoxy groups, respectively, at the periphery with adamantane nucleus as the central core have been constructed by linking the two halves of corresponding Asp/Glu dendrons by 1,3 - bifunctional adamantane unit. Energy minimization and 1H NMR studies have shown these scaffoldings to adopt increasingly globular and compact architecture with each succeeding generation.

Enzymatic Conversion of Pheophorbide a to the Precursor of Pyropheophorbide a in Leaves of Chenopodium album

Soluble proteins extracted from leaves of Chenopodium album catalyzed the conversion of pheophorbide a to a precursor of pyropheophorb ide a, putatively identified as C-132-carboxyl-pyropheophorbide a. The precursor was then decarboxylated non-enzymatically to yield pyropheophorbide a. Soluble proteins and pheophorbide a, as the substrate, were required for the formation of the precursor, and boiled proteins were enzymatically inactive. The maximum rate of conversion of pheophorbide a to the precursor occurred at pH 7.5. The Km for pheophorbide a was 12.5 fiM at pH 7.0. Both pheophorbide b and bacteriopheophorbide a could serve as substrates, but protopheophorbide a could not. Formation of methanol was detected during the enzymatic reaction, an indication that the enzyme is an esterase. Among seven alcohol analogs tested, only methanol inhibited the enzymatic activity uncompetitively, with a K, of 71.6 mM. Mass-spectrometric (MS) analysis of the precursor yield a peak at m/z 579 that indicated the release of a methyl group from pheophorbide a. It appears therefore that the enzyme catalyzes the demethylation of the carbomethoxy group at C-13 2 of pheophorbide a by hydrolysis to yield methanol and the precursor, C-132carboxyl-pyropheophorbide a, which is converted to pyropheophorbide a by spontaneous decarboxylation. We have tentatively designated the enzyme pheophorbidase. The presence of the enzyme was dependent on plant species and it was expressed constitutively.

Application of organolithium and related reagents in synthesis. Part 18. Synthetic strategies based on aromatic metallation. A conversion of methyl ortho-pyridoylbenzoates into aza-anthra-5,10-quinones

The synthesis of the aza-anthraquinones (16) and (17) via metallation (LDA / THF) of the pyridine nucleus at the C3-carbon atom of the methyl ortho-pyridinecarbonyl benzoates (12) and (13), and then the intramolecular cross addition of the generated lithiated species to the carbomethoxy group is described.

Intramolecular Diels–Alder reactions of 2H-thiopyran dienes

A systematic survey of IMDA reactions of 4-[tris(2-methylethyl)silyl]oxy-2H-thiopyran derivatives with potential dienophiles tethered at the C-2, C-3, C-5, and C-6 positions is presented. Cycloaddition was not observed with a C3 or C4 tether and an unactivated terminal olefin as dienophile. IMDA adducts could be obtained when dienophiles activated by a carbomethoxy group were employed. Compounds having the activated dienophile attached via a C3 tether to C-2 of the 2H-thiopyran gave adducts with high stereoselectivity. Substrates having the dienophile attached to C-3 with a C3 or C4 tether cyclized readily. With an (E)-enoate as the dienophile, the stereoselectivity was poor (endo:exo = 1.1–2.5:1) and essentially independent of reaction conditions (i.e., thermal vs. Lewis acid mediated). With the(Z)-enoate, a 7:1 mixture of endo:exo IMDA adducts was obtained under thermal conditions; with Lewis acid catalysis, isomerization of the dienophile was competitive with cycloaddition. Type II IMDA adducts were not observed with C-5 tethered substrates. Compounds having the dienophile attached to C-6 via a C3 or a five-atom tether also failed to give IMDA adducts. No evidence for isomerization of the 2H-thiopyran dienes by [1,5] sigmatropic rearrangement was observed. The endo adducts from IMDA reactions of the C-3 tethered substrates can be desulfurized to obtain synthetically useful trans-fused hydrindans and decalins with angular methyl groups. Key words: intramolecular Diels–Alder, 2H-thiopyran, cis-substituted 1,3-diene surrogate, trans-octahydro-3a-methyl-1H-indene derivatives, trans-decahydro-4a-methylnapthalene derivatives.

Design and synthesis of a cocaine-diamide hapten for vaccine development

A cocaine-diamide hapten was designed in an effort to obtain a potent, long-lasting anti-cocaine immune response for the treatment of cocaine abuse. The analogue incorporated an amido linker functionality in place of the carbomethoxy group at C-2 and a benzoylamino replacement of the benzoyloxy group at C-3 of the cocaine framework. Compound 3 was synthesized in 6 chemical steps starting from (+)-2-carbomethoxy-3-tropinone.

Conformational Studies of a Six-Membered Phostone

Abstract Although 1,3,2-dioxaphosphorinanes generally assume chair conformations,1 there are examples in which the ring adopts the boat or twist-boat form.1 Recent studies on the synthesis, stereochemistry, and reactivity of 2-alkoxy-2-oxo-1,2-oxaphosphorinanes (phostones) have revealed both cis and trans isomers of 3-(diphenylhydroxymethyl)-2-ethoxy-2-oxo-1,2-axaphosphorinane2 to assume a chair conformation in the solid state. In the present work, the conformational properties of cis and trans-3-methoxycarbonyl-2-methoxy-2-oxo-1,2-oxaphosphorinanes were investigated by X-ray analysis, variable temperature 31P, 1H and 1H{31P} NMR spectroscopy, molecular mechanics, and semiempirical calculations. The X-ray crystal structure of the trans isomer revealed a chair dormation with equatorial phosphoryl and carbomethoxy groups. No changes were observed in the 31P NMR spectra of either isomer in the temperature range of 183–333 K. A complete set of vicinal JHH coupling constants was extracted from the 1H{31P} spec...

Molecular and crystal structure of azadirachtin-H

Azadirachtin-H, isolated from the seed kernels of Azadirachta indica (neem), crystallizes in space group I4, Z = 8, with disordered ethyl acetate solvent filling channels along the fourfold rotation axes. The crystal structure determination showed that the previously reported molecular structure deduced from NMR studies was correct except for the stereochemistry at C(11). Azadirachtin-H, which belongs to a group of C-seco-tetranortriterpenoids (C-seco-limonoids) of great interest for their insect antifeedant and ecdysis-inhibiting activity, has some unusual features: the absence of a carbomethoxy group at C(11); the presence of a cyclic hemiacetal function at C(11); the α-orientation of the hydroxyl group on C(11), opposite to that in all other known azadirachtins with a hydroxyl group on C(11), except azadirachtin-I. There is no intramolecular hydrogen bonding. In this crystal the rotation of the two major moieties of the azadirachtin-H molecule about the single connecting C(8)—C(14) bond is quite different from that in azadirachtin-A, whose crystal structure has recently been determined.

Studies Directed to the Synthesis of the Unusual Cardiotoxic Agent Kalmanol. Enantioselective Construction of the Advanced Tetracyclic 7-Oxy-5,6-dideoxy Congener

The first synthesis of a highly functionalized B-homo-C-nor grayanotoxin closely related to kalmanol is reported. An enantiocontrolled route to the diquinane sector was first developed from (4R)-(+)-tert-butyldimethylsiloxycyclopentenone by taking advantage of the Michael acceptor properties of this enone and an α,β-unsaturated ester subsequently derived from it, viz., 4 → 7 → 8. These experiments formed the basis for more advanced substitution of the bicyclo[3.3.0]octane core. In fact, ready access was gained to the α-hydroxy esters 24−27. In these advanced intermediates, it is imperative that the acetyl and carbomethoxy groups bear a trans 1,3-relationship. The neighboring OR substituent should preferably be larger than methoxy in order to guarantee 100% facial selectivity during the ensuing capture by 1 (as its lithiated derivative). This condensation leads unidirectionally to tricyclic lactones represented by 30 and 31 and sets the stage for implementation of sequential Tebbe olefination and Claisen rearrangement. This pivotal two-step process gives rise directly to the targeted tetracyclic framework. The further oxygenation of 35 can be accomplished in a highly stereoselective manner to give 3. The characteristics of the [3.3] sigmatropic event that results in ring expansion plays a significant role in defining absolute configuration at key carbon centers which would otherwise be difficult to establish unequivocally. A total of 25 synthetic steps was involved.

Mass spectral study of diastereomers by electron impact

AbstractThe electron impact mass spectra of some diastereomeric dialkyl tartrates and isopropylidine derivatives of dimethyl tartrate show diagnostic differences in the relative abundances of some ions. The differences have been explained based on preferred conformations of these isomers. The configuration of the carbomethoxy groups has been correlated with the configuration of carbomethoxy groups in dimethyl maleate and fumarate. The interaction between the two carbomethoxy groups is relatively larger in conformations where there is a gauche interaction between them. The results could also be correlated with the solution phase conformations of these compounds reported in the literature using nuclear magnetic resonance techniques. The difference, which is small in diastereomeric dimethyl tartrates, is very reproducible and has been confirmed using six different mass spectrometers.

Influence of Lewis Acids on the Cycloaddition Reactions of Cyano- and Carbomethoxy-Substituted Olefins

The reactions of electrophilic olefins substituted with cyano and/or carbomethoxy groups with donor olefins are investigated. The donor ole- fins include, in order of decreasing donor character, phenyl vinyl sul- fide, isobutyl vinyl ether, tert-butyldimethylsilyl vinyl ether, p-me- thoxy- and p-methylstyrene, and styrene. The reactions vary from [2+2] cycloadditions to Diels-Alder reactions to spontaneous free radical co- polymerizations. The course of the reaction is determined by both the electron disparity between the two reacting olefins and by the substi- tution pattern on the electrophilic olefin. Lewis acids (ZnCl 2 or ethe- real LiClO 4 ) are added to form complexes with the acceptor olefins, resulting in a larger electron disparity between the reactants

An Approach to 6-Oxygenated Shikimic Acid Derivatives by Photolysis of the Pyruvate Ester of Dimethyl Epoxychorismate

We report an unusual rearrangenaent of a synthetic epoxychorismic acid derivative which provides access to the 6-substituted shikimic acid framework. Photolysis of the pyruvate ester of dimethyl epoxychorismate triggered an intramolecular Paterno-Buchi photocyclization of the enol pyruvate alkene and the ketone group of the pyruvate ester, leading to a 2,2,3,3-tetrasubstituted oxetane ring. Upon standing for 1 week in CDCl 3 or in the presence of CF 3 CO 2 D, the primary photoproduct under- went a slow epoxide-opening reaction with participation by the oxetane- substituted carbomethoxy group to form an unusual fused tetracyclic lactone. The chemistry described here suggests at least one plausible pathway, with appropriate stereoelectronic constraints, by which oxi- dation of shikimic acid at C6 might be achieved

THE EFFECT OF PERIPHERAL SUBSTITUTION ON THE BATHOCHROMIC SHIFT OF THE Qy TRANSITION OF BACTERIOCHLOROPHYLL DIMERS; in vitro MODELS OF THE PROTEIN EFFECT ON THE SPECTRUM OF PIGMENT CENTERS IN THE LIGHT‐HARVESTING COMPLEXES*

Abstract— The effect of chemical modifications in the side groups of the isocyclic ring V on the formation, optical absorption and circular dichroism of bacteriochlorophyll (Bchl) dimers was examined in a mixture of formamide and water containing TritonX–100 and variable amounts of pyridine. Substitution of the carbomethoxy group in the C132 position with a hydrogen atom, had no effect on the dimerization constant but increased the shift of the Qy transition by 1000 cm‐1 with respect to the native Bchl. Substitution of the C13 hydrogen atom with OH decreased the shift of the Qy transition by 400 cm‐1. The similarity between the spectra of the modified Bchl dimers and Bchl dimers in vivo indicates that protein binding to the side groups at Bchl dimers may profoundly affect the energy of their Qy transition but have minor effects on the Qy transitions of the monomelic Bchl.

Preparation of Porous Spherical Poly(γ-methyl L-glutamate) Particles Containing β-Structure

Porous poly(γ-methyl L-glutamate) spherical particles underwent transition α-helix-to-β-structure in the main chain as a result of heat treatment in water or methanol. The particles obtained maintained their sphericity and characteristic porosity after the heat treatment, while the transition increased insolubility against organic solvents. The amount of β-structure depended on the temperature. The transition in water included hydrolysis of the residual carbomethoxy groups. Adsorption capacity of the particles for cytochrome C depended remarkably on the content of β-structure as well as the amount of carboxyl groups produced.

Conformational analysis of cocaine, the potent analog 2β‐carbomethoxy‐3β‐(4‐fluorophenyl)tropane (CFT), and other dopamine reuptake blockers

AbstractUsing the MM2‐87 program and parameter set, conformational analyses have been performed on cocaine (1), the potent analog 2β‐carbomethoxy‐3β‐(4‐fluorophenyl)tropane (CFT, 2), and a group of dopamine reuptake blockers that contain two phenyl rings. The latter includes LU 19‐005 (3), a 1‐amino‐4‐phenyltetralin (4), a hexahydropyrrolo[2,1‐a]isoquinoline (5), diclofensine (6), and a hexahydro[1,2‐b]pyridine (7). Using different values for the dielectric constant, the global minimum of 1 and 2 is a conformer in which there is a favorable electrostatic interaction between the ammonium hydrogen and the carbonyl of the carbomethoxy group. The N‐methyl groups in 1 and 2 are found to strongly prefer the equatorial position of the piperidine ring. These results were also related to four crystal structures of 1 and its close derivatives. Compounds 3–7 are found to have a common conformation that was used to define the pharmacophore for dopamine reuptake blockers including the required orientation of the ammonium hydrogen. The pharmacophore provides an explanation for why the tertiary amine analogs of 3 and 4 are less potent than the secondary amines because the added N‐methyl group occupies the position required for the ammonium hydrogen. This explanation, however, does not work for 7, in which the tertiary amine is again less active than the secondary amine. However, this last series appears to have a number of anomalous features. Superposition of 2 with the pharmacophore suggests that its carbomethoxy may occupy the same region of the receptor as the second phenyl ring in compounds 3–7. © 1993 John Wiley & Sons, Inc.

Concise total syntheses of dl-camptothecin and related anticancer drugs

The readily available tricyclic ester 10 has been converted to dl-camptothecin (1) in 39% yield. It was discovered that, with the C 5 carbomethoxy group in place, the C 6 benzylic position of 10 (pyridone numbering) is selectively deprotonated by sodium hexamethyldisilazide. This allows for condensation with benzaldehyde to produce acid 17 which, after ozonolysis and methylation,afforded the tricyclic keto ester 16

Spontaneous homopolymerization competes with Diels-Alder cycloaddition of 1-aryl-1,3-butadienes to dienophiles containing a leaving group

The competition between Dies-Alder cycloaddition and spontaneous concurrent polymerization was investigated in the reactions of 1-phenyl-1,3-butadiene (1) and 1-p-anisyl-1,3-butadiene (2) with electrophilic olefins. The reactions of 1 and 2 with electrophilic olefin trisubstituted with cyano and/or carbomethoxy groups have only concerted [4+2] cycloaddition products

Use of methyl 2-iodo-2-(phenylsulfonyl)-4-pentenoate in atom-transfer radical cyclizations. Entry into annulation products containing carbonyl or exo-methylene functionality

Methyl 2-iodo-2-(phenylsulfonyl)-4-pentenoate ( 8 )is reacted with N-BOC-allylamine to afford substituted 3-azabicyclo-[3.3.0]octanes ( 10 ) in a process which involves an initial iodine atom-transfer annulation followed by an ionic cyclization. The geminal carbomethoxy and phenylsulfonyl groups are then efficiently converted to either an exocyclic olefin or to a carbonyl group. The latter transformation allows phenylsulfonylacetates to be used as surrogates for acyl radicals in synthesis.

Solid-state and solution conformational analysis of tartrate-derived 1,3-dioxolanes and 1,3,2-dioxaborolanes

Solid-state (X-ray) and solution conformational analyses of tartrate ester derived 1,3-dioxolanes and 1,3,2-dioxaborolanes are described. The solid-state conformation of dimethyl benzylidenetartrate (5) was found to be one in which the two carbomethoxy groups are pseudaxial and the ester carbonyls eclipse the adjacent dioxolane C-O bonds. This parallels exactly the conformation previously proposed for the 1,3,2-dioxaborolane unit in the transition state of the reactions of tartrate ester modified allylboronates 1-3 and aldehydes

13C-NMR spectra of positional isomers of long-chain conjugated diacetylenic fatty esters

The 13C-NMR spectra of a set of 14 positional isomers of conjugated diacetylenic fatty esters were studied. Full interpretation of the spectroscopic results was only possible after sub-sets of symmetrical dialkyl and dialkanoate substituted conjugated diacetylenes were prepared and the effects of the ω-methyl and carbomethoxy group on the chemical shifts of the acetylenic carbon nuclei were assessed. The chemical shift of the outer and inner acetylenic carbon atoms of the methyl alkadiynoates appeared at about 75–79 and 65–66 ppm, respectively. Strong shielding α-effects of the diacetylenic system on the immediately adjacent carbon nuclei were observed. In general, the carboxylic ester group caused a strong shielding effect on the outer carbon nuclei of the diacetylenic systems, but a strong deshielding effect on the inner carbon nuclei. The position of the conjugated diacetylenic system in the alkyl chain could be determined for isomers, where the number of methylene groups between the diacetylenic system and the ester group was less than 7; and in isomers where the number of methylene groups between the ω-methyl group and the diacetylenic system was less than 4. Twelve of the 14 conjugated diacetylenic fatty ester isomers were identified by this technique.

Photochemical and acid-catalyzed dienone-phenol rearrangements. The effect of substituents on the regioselectivity of 1,4-sigmatropic rearrangements of the type A intermediate

Birch reduction of isophthalic acid and 3-cyanobenzoic acid followed by (1) methylation of the resulting enolate with methyl iodide and (2) esterification with diazomethane provided 2-carbomethoxy- and 2-cyano-6-methyl-6-carbomethoxy-1,4-cyclohexadienes 9 and 25. Type A photorearrangements of a series of 2-carbomethoxy-, 2-cyano-, 2-methoxy-, and 2-methyl-4-carbomethoxy-4-methyl-2,5-cyclohexadien-1-ones 11, 26, 45a, and 45b gave 4-carbomethoxy-3-methyl-2-substituted-phenols 12, 28, 46, and 31. It has been demonstrated that the regioselectivity of type A photorearrangement of C(2) substituted 2,5-cyclohexadien-1-ones is governed by electronic rather than steric effects to give the intermediate C(1) rathen than C(3) substituted bicyclo[3.1.0 1,5 ]hex-3-en-2-ones. Regioselectivities of the acid-catalyzed dienone-phenol rearrangements of C(2) substituted 2,5-cyclohexadienones 11,45a, and 45b appear to be dependent upon the relative stabilities of carbocations resulting from migration of the C(4) carbomethoxy group