Azaindole derivatives. 59. Synthesis and chemical properties of 1-benzyl-4-dimethylamino-6-chloro-7-cyano-5-azaindoline

The condensation of 1-benzyl-2-cyanocarbamoylmethylene-pyrrolidine with tetramethylurea diethylacetal and subsequent cyclization gave 1-benzyl-4-dimethyl-amino-6-chloro-7-cyano-5-azaindoline, for which nucleophilic substitution and dehydrogenation reactions are described. The reactivity of this product is compared with that of 1-benzyl-6-chloro-7-cyano-5-azaindoline.See [1] for Communication 58.Translated from Khimiya Geterotsiklicheskikh Soedinenii, No. 2, pp. 215–220, February, 1981.     

Synthesis and binding activity of 4-azanicotine

4-Azanicotine ( 1 ) has been synthesized by the cyclopropylimine rearrangement. A study of several Lewis acids as possible catalysts for the NMF-mediated cyclopropyl imine rearrangement of cyclopropyl-2-pyrazinylmethanone ( 4 ) indicated that both aluminum chloride and magnesium chloride are suitable catalysts, lithium bromide shows only a trace of activity and zinc chloride, titanium tetrachloride, and titanium tetra-isopropoxide show no activity. Compound 1 , in which the aromatic ring is less basic than in nicotine, and 6-aminonicotine ( 5 ), in which the aromatic ring is more basic, have been compared with the binding properties of nicotine in the P2 rat brain preparation. Compound 1 binds with an affinity very similar to that of nicotine at two of the receptor sites, 5 binds at these sites but with a lower affinity. Unlike nicotine, 1 and 5 do not bind at the very high affinity ‘upregulatory’ site.     

A convenient synthesis of 5-(1,2,4-oxadiazol-5-yl)pyrimidine-2,4(1H,3H)-diones

The synthesis of 5-heteroaryl-substituted uracil derivatives is presented. The 1,3-dipolar cycloaddition reaction was applied for the construction of a heterocyclic ring. The nitrile oxides were obtained from the appropriate 4-substituted benzaldoximes using N-chlorosuccinimide (NCS) under basic conditions. [2+3] Cycloaddition of nitrile oxides with 5-cyanouracil as a dipolarophile gave the corresponding 5-(3-substituited-1,2,4-oxadiazol-5-yl)uracils in satisfactory yields under mild conditions. 5-Substituted uracils having an additional heterocyclic ring were obtained as a result of the [2+3] cycloaddition of 5-cyanouracil to nitrile oxides generated from thiophene-2-carbaldehyde and 5-formyluracil derivatives.     

1H n.m.r. study and conformation of 3,3-dimethyl-3-sila-1-heterocyclohexanes and derivatives (heteroatom SiCl2, SiMe2, O,NMe, S,Se, Te)

It is found that the basic form of the 3,3-dimethyl-3-sila-1-heterocyclohexane family (heteroatom X = O, NMe, S, Se, Te, SiMe₂, SiCl₂) is the chair, having ring torsion angles in the aliphatic region tending to be somewhat more puckered (up to 7°) than in cyclohexane, except next to Si when the other heteroatom is relatively small. The 5-tertiarybutyl-, 6-methyl- and 2-phenyl derivatives are all anancomeric, except for the latter two derivatives when X = NMe. A 5-tertiarybutyl group causes an additional deformation, e.g. an increased puckering of the aliphatic C-4? C-5? C-6 region (buttressing effect). Other ¹H n.m.r. features are discussed in detail, and the behaviour of the 3-sila-1-heterocyclohexanes is compared with other 1,3-diheterocyclohexanes.     

Unexpected behavior of the reaction between 1,2-diaza-1,3-butadienes and 3-dimethylaminopropenoates: a useful entry to new pyrrolines, pyrroles, and oxazolines

We observed a nucleophilic attack by the ene-amino carbon of 3-dimethylaminopropenoates at the terminal carbon of the azo-ene system of 1,2-diaza-1,3-butadienes. In tetrahydrofuran at 65 degrees C, this attack produced 1-aminopyrrolines with a high degree of cis-stereoselectivity by means of an unusual zwitterionic adduct intermediate followed by intramolecular ring closure. In toluene under reflux, 1-aminopyrrolines produced oxazoline-fused 1-aminopyrrolines. Oxazoline-fused 1-aminopyrrolines were directly obtained by reaction of 1,2-diaza-1,3-butadienes with 3-dimethylaminopropenoates in toluene under reflux. The ring opening of oxazoline-fused 1-aminopyrrolines in acidic or basic media provides highly substituted 1-aminopyrroles. 5-Unsubstituted 1-aminopyrrole derivatives were obtained from 1-aminopyrrolines under basic conditions by loss of dimethylamino and ester groups. We discuss the plausible mechanisms of the ring closure and opening.     

Structural Effects on the Intrinsic Basicities of alpha,beta-Unsaturated Lactones and Ketones

The proton affinities of 2(5H)-furanone, 1 (836 kJ/mol), 5,6-dihydro-2H-pyran-2-one, 2 (862 kJ/mol), cyclopentenone, 3 (857 kJ/mol), and cyclohexenone, 4 (863 kJ/mol), have been measured by Fourier transform ion cyclotron resonance techniques. A comparison is made with (reexamined) data concerning saturated cyclic and unsaturated aliphatic analogs. Three general observations are made. First, the basicity is found to increase with the size of the ring. Second, unsaturated lactones are more basic than their corresponding aliphatic unsaturated esters. Third, unsaturated and saturated lactones have almost identical gas-phase basicities, while unsaturated and saturated lactones have almost identical gas-phase basicities, while unsaturated cyclic ketones are more basic than their saturated analogs. All these experimental findings have been rationalized by means of ab initio calculations up to the G2(MP2,SVP) level. The basicity trends along the series are the result of two main factors: the different hybridization pattern of the carbonyl carbon as the size of the ring changes and, in the case of lactones, the nonbonding interaction between the proton attached to the carbonyl group and the ether-like oxygen which contributes to the enhanced stability of the protonated form. For unsaturated ketones the C=C double bond participates fully in the change in charge distribution induced by the protonation, while for unsaturated lactones the existence of an oxygen atom within the ring impedes this shift of the electron density.     

Molecular orbital study of the ring nitrogen basicity of various dihydrofolate reductase inhibitors

We present molecular orbital (CNDO /2) calculations on the key fragments of different dihydrofolate reductase inhibitors. Distance geometry analysis, physicochemical parameter dependent QSAR , and molecular shape analysis raised some questions regarding the basicity of the ring nitrogen (N1) in these inhibitors and the effect of the various substituents on the basicity. We show that the ring nitrogen N1 of methotrexate has a considerably higher tendency to be protonated compared to that of folic acid. However, not all 2,4-diamino inhibitors are equally basic. Even 2-amino-4-hydroxyquinazoline is sufficiently basic to be protonated, but not the 2,4-diamino-5-sulfonyl derivatives. The pyrimidinium ion seems to be highly solvated, since in spite of its high protonation energy it is strongly basic. Triazines were found to be the most basic of all the classes studied.     

Investigations on the Reactivity of Fascaplysin,Part II,General Stability Considerations and Products Formed with Nucleophiles

Reversible deprotonation of fascaplysin ( 1 ) was achieved with non‐nucleophilic bases (Scheme 1). Under basic aqueous conditions, opening of ring D of 1 occurred, yielding zwitter‐ionic reticulatine 2a , whereas, in a methoxide‐containing MeOH solution, an unexpected addition of three molecules of MeOH to the pyridinium ring produced an isomer mixture 3 of a trimethoxy‐substituted compound (Scheme 2). Transformation of the keto group of 1 to the oxime 4A took place in the presence of pyridine as base (Scheme 3). Grignard and alkyllithium reagents added as expected to the keto group of 1 , providing tertiary alcohols 5 and 6 (Scheme 4).     

Reaktionen von 3-Dimethylamino-2,2-dimethyl-2H-azirin mit. NH-aciden Heterocyclen; Synthese von 4H-imidazolen

Reactions of 3-Dimethylamino-2,2-dimethyl-2H-azirine with NH-Acidic Heterocycles; Synthesis of 4H-Imidazoles In this paper, reactions of 3-dimethylamino-2,2-dimethyl-2H-azirine ( 1 ) with heterocyclic compounds containing the structure unit CO? NH? CO? NH are described. 5,5-Diethylbarbituric acid ( 5 ) reacts with 1 in refluxing 2-propanol to give the 4H-imidazole derivative 6 (Scheme 2) in 80% yield. The structure of 6 has been established by X-ray crystallography. Under similar conditions 1 and isopropyl uracil-6-carboxylate ( 7 ) yield the 4H-imidazole 8 (Scheme 3), the structure of which is deduced from spectral data and the degradation reactions shown in Scheme 3. Hydrolysis of 8 with 3N HCl at room temperature leads to the α-ketoester derivative 9 , which in refluxing methanol gives dimethyl oxalate and 5-dimethyl-amino-2,4,4-trimethyl-4H-imidazole ( 10 ). On hydrolysis the latter is converted to the known 2,4,4-trimethyl-2-imidazolin-5-one ( 11 ) [6]. Quinazolin-2,4 (1H, 3H)-dione ( 12 ) and imidazolidinetrione (parabanic acid, 14 ) undergo with 1 a similar reaction to give the 4H-imidazoles 13 and 15 , respectively (Schemes 4 and 5). In Scheme 6 two possible mechanisms for the formation of 4H-imidazoles from 1 and heterocycles of type 16 are formulated. The zwitterionic intermediate f corresponds to b in Scheme 1. Instead of dehydration as in the case of the reaction of 1 with phthalohydrazide [3], or ring expansion as with saccharin and cyclic imides [1] [2], f , undergoes ring opening (way A or B). Decarboxylation then leads to the 4H-imidazoles 17 .     

An efficient scalable synthesis of 2,3-epoxypropyl phenylhydrazones

A series of mono and di-N-2,3-epoxypropyl N-phenylhydrazones have been prepared on a large scale by reaction of the corresponding N-phenylhydrazones of 9-ethyl-3-carbazolecarbaldehyde, 9-ethyl-3,6-carbazoledicarbaldehyde, 4-dimethyl-amino-, 4-diethylamino-, 4-benzylethylamino-, 4-(diphenylamino)-, 4-(4,4-4'-dimethyl-diphenylamino)-, 4-(4-formyldiphenylamino)- and 4-(4-formyl-4'-methyldiphenyl-amino)benzaldehyde with epichlorohydrin in the presence of KOH and anhydrous Na(2)SO(4).     

Synthesis,structural elucidation,and antioxidant activity of new phenolic derivatives containing piperidine moiety: Experimental and theoretical investigations

The incorporation of the piperidine ring into drugs may play an interesting role to fulfill significant tasks and act as an active ingredient in various treatments. Herein, three novel derivatives of 3-acetyl-2-hydroxybenzoic acid ( 3-5 ) containing a piperidine ring were synthesized through the rearrangement of triacetic acid lactone in the presence of piperidine. Their molecular structures were characterized by ¹H and ¹³C NMR and single crystal X-ray diffraction techniques. The experimental data were compared with the predicted ones obtained in the polarizable continuum model at the B3LYP/6-311++G(d,p) level of theory. Relatively good correlations were obtained between the experimental data (spectral and Z-matrix coordinates) and the predicted ones, with correlation coefficients higher than 97%. The intercontacts between the closest units of 3-5 were identified through the analysis of the Hirshfeld surface and electrostatic potentials (ESP) maps. Hirshfeld surface and ESPs analyses reveal that the closest interactions between the units of the compounds are between hydrogen atoms (59%-67%). The antioxidant activity of 3-5 was evaluated using DPPH free radical scavenging and ABTS assays. They exhibit moderate antioxidant activity, which probably is attributable to the presence of a phenolic moiety in their basic skeleton. Molecular docking calculations suggest that 3-5 may mainly bind to the active binding site of peroxiredoxin 5 through strong and weak intermolecular hydrogen bonds.     

Synthesis and Crystal Structure of 2,3-Diethoxycarbonyl-4-phenyl-5-morpholinyl Thiophene

1INTRoDUCTIONa-Thiocarbonylthioformamidesweresynthesizedin198o[l~2i,however,thereisnoreportofthesecompoundsconcerningtheirpropertiesandreactionactivitiest33.Accordingtotheirstructure,theyseemtohavereactionwithdienophi1es,likesubsti-tutedolefinicandacetylenicdienophilestoleadcorrespondingDiels-Alderproduct.xylene(15ml),diethylbutynedioicester(O.2g,1.2mmol)wasadded,themix-turewasrefluxedfor20h,thencooledtoroomtemperatureandconcentrated.Theresiduewaspurifiedbysilicagelcolumnusingacetone/petr…     

The regiochemistry of cyclization of alpha-sulfenyl-, alpha-sulfinyl-, and alpha-sulfonyl-5-hexenyl radicals: procedures leading to regioselective syntheses of cyclic sulfones and sulfoxides

A study of the cyclization of alpha-sulfenyl-, alpha-sulfinyl-, and alpha-sulfonyl-5-hexenyl and 5-methyl-5-hexenyl radicals reveals a unique contrast in the mode of ring closure of the radicals. In the case of the 5-hexenyl radicals, the sulfinyl-substituted species displays unexpected regioselectivity relative to its analogues. Thus, while the alpha-S- and alpha-SO(2)-5-hexenyl radicals give measurable and increasing quantities of 6-endo product, the alpha-sulfinyl species cyclizes with high selectivity (95.5:4.5) via a 5-exo mode. By contrast, ring closure of the 5-methyl-5-hexenyl radicals is found to give substantially the 6-endo product in all cases. It is the alpha-sulfonyl-5-methyl-5-hexenyl radical that now exhibits high regioselectivity (97.5:2.5) for 6-endo closure: an illustration of the synthetic value of this observation is the independent synthesis of the model cyclohexyl sulfone 61 in high yield. It is found that ring closure under the conditions employed occurs irreversibly in all cases.     

Ringöffnung von Nitrothiazolen

The reaction between 2-halogeno-5-nitro-thiazoles and amines has been studied. Especially the sterically hindered strongly basic secondary aliphatic amines tend to cause opening of the thiazole ring system, resulting in the formation of the heretofore unknown (1-nitro-2-amino-vinyl)-thiocyanates. The ring opening is favored by a highly polar solvent, such as dimethyl sulfoxide. A simple reaction mechanism is proposed and some properties of these new compounds are discussed.     

Sensitization of europium(III) luminescence by benzophenone-containing ligands: regioisomers, rearrangements and chelate ring size, and their influence on quantum yields

A series of europium(III) complexes based on the macrocyclic azacarboxylate structure, DO3A, have been investigated, incorporating benzophenone appended at N10 of the macrocycle via linkers containing amide bonds (H3DO3A = 1,4,7,10-tetraazacyclododecane-1,4,7-tris-acetic acid). Complexes [EuL(1-3)] incorporate N10-CH2CONH-BP linkers (BP = benzophenone), which allow formation of a five-membered chelate ring containing the metal ion upon chelation of the amide oxygen; these three isomeric complexes differ from one another in the substitution position of the BP unit, namely para, meta, and ortho for L1, L2, and L3 respectively. The quantum yields of europium luminescence sensitized via the chromophore are found to be highly dependent upon the position of substitution, being 20 times smaller for the ortho compared to the para-substituted complex. A related para-substituted BP complex [EuL(4)], prepared by an unusual Michael reaction of the azamacrocycle with a BP-containing acrylamide, incorporates an additional methylene unit in the linker, namely N10-CH2CH2CONH-BP. Despite the longer linker, this complex equals the luminescence quantum yield achieved with [EuL(1)] (Phi(lum) = 0.097 and 0.095, respectively, in H2O at 298 K). Analysis of the pertinent kinetics reveals that the decreased energy transfer efficiency in this complex, arising from the longer donor-acceptor distance, is compensated by an increased radiative rate constant. Under basic conditions, the ortho-substituted complex [EuL(3)] undergoes an intramolecular rearrangement to generate an unprecedented complex [EuL(5)] incorporating a 4-phenyl-2-hydroxyquinoline unit directly bound to the ring nitrogen. Although this complex is a poor emitter, an analogous complex obtained from 2-amino-acetophenone, which generates 4-methyl-2-hydroxyquinoline during the corresponding rearrangement, is an order of magnitude more emissive while still benefiting from relatively long-wavelength absorption. The emission from this complex is pH sensitive, being dramatically quenched under mildly basic conditions.     

On ring carbomers of cyclobutane, cyclopentane, and cyclodecane and cyclization reactions through bis(alkynyl-propargyl) coupling

A copper-mediated procedure for terminal alkynyl-propargyl coupling has been applied to "skipped" bis-terminal undecatetrayne and 1,4-bis(pseudo)halobut-2-ynes with the aim of preparing ring carbomers of representative strained and loose cycloalkanes, namely [N]pericyclynes. Two unprecedented, cyclic. "skipped" polyynes with CH2 vertices have been isolated as mixtures of diastereoisomers: an isomer 1b and a dimer 2a of [5]pericyclyne 1a. The isomer 1b is a cyclotetrayne with an exocyclic allene function resulting from a unique formal SN process. Its structure has been established by 1H/13C HMQC and HMBC two-dimensional NMR analysis. According to density functional theory calculations, it is about 6 kcalmol(-1) more stable than [5]pericyclyne (1a). Compound 1b can also be regarded as a C13-relaxed [4]pericyclyne, a long sought "skipped" C12 tetrayne. The dimer 2a is a C30 ring that results from a formal SN process. It is a stable ring carbomer of cyclodecane, that is, a [10]pericyclyne, with four CH2 vertices.     

A New Type of Heterobimetallic Compound Containing Tungstenocene: Synthesis, Reactivity, NMR, and Stereochemical Studies

Reaction of [PPh(2)M(CO)(5)]Li salts (M = Cr or W) toward tungstenocene dichloride occurs via a cyclopentadienyl ring substitution and yields the corresponding binuclear compounds (eta(5)-C(5)H(5))[eta(5)-C(5)H(4)PPh(2)M(CO)(5)]W(H)Cl, 2. They react with LiAlH(4) to give the corresponding dihydride complexes (eta(5)-C(5)H(5))[eta(5)-C(5)H(4)PPh(2)M(CO)(5)]WH(2), 3. These species have been proven to be photosensitive leading to the cyclic heterobimetallic (eta(5)-C(5)H(5))[eta(5)-C(5)H(4)PPh(2)M(CO)(4)]W(&mgr;-H)H compounds, 4; analytical data and spectroscopic measurements on complexes 4 indicate that a hydride group functions as a bridging ligand. Crystals of 4a (M = Cr) were obtained as red needles, grown from toluene solution. An isotropic refinement of only 1243 data (F > 5sigma(F)) from a low resolution data set (3707 data, d(min) = 0.9 ?) indicated significant systematic error. Thus it was possible only to ascertain that the connectivity of the non-hydrogen atoms is not inconsistent with the model proposed from solution NMR and that the Cr.W separation of 3.30 ? precludes a direct Cr-W bond. 4a crystallizes in space group Pbca(No. 61), with a = 19.693(8) ?, b = 20.34(1) ?, c = 11.695(5) ?, V = 46823 ?(3), and Z = 8. Further information on this preliminary structure determination is provided in the Supporting Information. These reactions have been investigated with stereochemical factors in mind using the ring substituted tungtenocene complex (eta(5)-C(5)H(4)Me)(2)WCl(2); the 1-3 regioselectivity of the ring disubstitution reaction is proposed on the basis of (1)H NMR experiments. The temperature dependent relaxation time measured between 295 and 213 K by the inversion recovery method makes it possible to determine a proton-proton distance between the two H ligands of 2.0 ? in 4'a.     

Synthesis, spectroscopy, and reactivity of meso-unsubstituted azuliporphyrins and their heteroanalogues. Oxidative ring contractions to carba-, oxacarba-, thiacarba-, and selenacarbaporphyrins

This paper reports the first detailed study on meso-unsubstituted azuliporphyrins, an important family of porphyrin-like molecules where one of the usual pyrrole rings has been replaced by an azulene subunit. Although the azulene moiety introduces an element of cross-conjugation, zwitterionic resonance contributors with tropylium and carbaporphyrin substructures give azuliporphyrins diatropic character that falls midway between true carbaporphyrins and nonaromatic benziporphyrins. Protonation affords an aromatic dication where this type of resonance interaction is favored due to the associated charge delocalization. Two different "3 + 1" syntheses of meso-unsubstituted azuliporphyrins have been developed. Acid-catalyzed reaction of readily available tripyrrane dicarboxylic acids with 1,3-azulenedicarbaldehyde, followed by oxidation with DDQ or FeCl(3), affords good yields of azuliporphyrins. Alternatively, azulene reacted with acetoxymethylpyrroles (2 equiv) in refluxing acetic acid/2-propanol to give tripyrrane analogues, and following a deprotection step, condensation with a pyrrole dialdehyde in TFA-CH(2)Cl(2) gave the azuliporphyrin system. The latter approach was also used to prepare 23-thia- and 23-selenaazuliporphyrins. However, reaction of the azulitripyrrane with 2,5-furandicarbaldehyde produced a mixture of three oxacarbaporphyrins in moderate yield. The free base forms of thia- and selenaazuliporphyrins both showed intermediary aromatic character that was considerably enhanced upon protonation. The UV-vis spectra for azuliporphyrins and their heteroanalogues showed four bands between 350 and 500 nm and broad absorptions at higher wavelengths. Addition of TFA gave dications that showed porphyrin-like spectra with Soret bands between 460 and 500 nm. In the presence of pyrrolidine, azuliporphyrins and their heteroanalogues undergo nucleophilic attack on the seven-membered ring to give carbaporphyrin adducts. These systems also undergo oxidative rearrangements under basic conditions with t-BuOOH to give benzocarbaporphyrins. The selenaazuliporphyrin afforded two benzoselenacarbaporphyrins, a previously unknown core-modified carbaporphyrin system. The proton NMR spectra for these compounds showed strong diatropic ring currents with the internal CH resonance upfield above -5 ppm, while the meso-protons resonated downfield near 10 ppm. The UV-vis spectra were also porphyrin-like and gave strong Soret bands at ca. 440 nm.     

Crystal structure of 2-aminopyridine-5-sulfonic acid and its 2D coordination polymer [Ag(C5H5N2O3S)] n

The crystal structure of an organosulfonate ligand 2-aminopyridine-5-sulfonic acid is reported here. Reaction of AgNO₃ and the 2-aminopyridine-5-sulfonic acid in basic ethanol/aqueous solution gave [Ag(C₅H₅N₂O₃S)] _n (1). X-ray crystallographic study reveals that 1 is a 2D network structure constructed by strong Ag-pyridine, Ag–NH₂ interactions and weaker Ag-sulfonate interactions. The replacement of the benzene ring by the pyridine ring causes the coordination modes of the sulfonate group to change from μ ³ to μ². Its TG/DSC property is also discussed.     

2-Deoxy-beta-D-erythro-pentofuranose: hydroxymethyl group conformation and substituent effects on molecular structure, ring geometry, and NMR spin-spin coupling constants from quantum chemical calculations.

The effect of hydroxymethyl conformation (gg, gt, and tg rotamers about the C4-C5 bond) on the conformational energies and structural parameters (bond lengths, bond angles, bond torsions) of the 10 envelope forms of the biologically relevant aldopentofuranose, 2-deoxy-beta-D-erythro-pentofuranose (2-deoxy-D-ribofuranose) 2, has been investigated by ab initio molecular orbital calculations at the HF/6-31G level of theory. C4-C5 bond rotation induces significant changes in the conformational energy profile of 2 (2gt and 2tg exhibit one global energy minimum, whereas 2gg exhibits two nearly equivalent energy minima), and structural changes, especially those in bond lengths, are consistent with predictions based on previously reported vicinal, 1,3- and 1,4-oxygen lone pair effects. HF/6-31G-optimized envelope geometries of 2gg were re-optimized using density functional theory (DFT, B3LYP/6-31G), and the resulting structures were used in DFT calculations of NMR spin-spin coupling constants involving 13C (i.e., J(CH) and J(CC) over one, two, and three bonds) in 2gg according to methods described previously. The computed J-couplings were compared to those reported previously in 2gt to assess the effect of C4-C5 bond rotation on scalar couplings within the furanose ring and hydroxymethyl side chain. The results confirm prior predictions of correlations between 2J(CH), 3J(CH), 2J(CC) and 3J(CC), and ring conformation, and verify the usefulness of a concerted application of these couplings (both their magnitudes and signs) in assigning preferred ring and C4-C5 bond conformations in aldopentofuranosyl rings. The new calculated J-couplings in 2gg have particular relevance to related J-couplings in DNA (and RNA indirectly), where the gg rotamer, rather than the gt rotamer, is observed in most native structures. The effects of two additional structural perturbations on 2 were also studied, namely, deoxygenation at C5 (yielding 2,5-dideoxy-beta-D-erythro-pentofuranose 4) and methyl glycosidation at O1 (yielding methyl 2-deoxy-beta-D-erythro-pentofuranoside 5) at the HF/6-31G level. The conformational energy profile of 4 resembles that found for 2gt, not 2gg, indicating that 4 is an inappropriate structural mimic of the furanose ring in DNA. Glycosidation failed to induce differential stabilization of ring conformations containing an axial C1-O1 bond (anomeric effect), contrary to experimental data. The latter discrepancy indicates that either the magnitude of this differential stabilization depends on ring configuration or that solvent effects, which are neglected in these calculations, play a role in promoting this stabilization.