Synthesis and conformational investigation of methyl 4a-carba-D-arabinofuranosides.

The synthesis of carbasugar analogues of methyl alpha-D-arabinofuranoside and methyl beta-D-arabinofuranoside (3 and 4) is reported. The route developed involves the conversion of D-mannose into a suitably protected diene (13), which is then cyclized via olefin metathesis. The resulting cyclopentene (14) is stereoselectively hydrogenated to provide an intermediate that can be used for the synthesis of both targets. Through the use of NMR spectroscopy, we have probed the ring conformation of 3 and 4, as well as the rotamer populations about the C(4)-C(5) and C(1)-O(1) bonds. These studies have demonstrated that there are differences in ring conformation between these carbasugars and their glycoside parents (1 and 2). However, only minor differences are seen in the rotameric equilibrium about the C(4)-C(5) bond in 3 and 4 relative to 1 and 2. In regard to the C(1)-O(1) bond, NOE data from 3 and 4 suggest that the favored position about this bond is similar to that in the glycosides; that is, the methyl group is anti to C(2). However, confirmation of this preference through measurement of (3)J(C,C) between the methyl group and C(2) or C(4a) was not successful.

Computational analysis of the potential energy surfaces of glycerol in the gas and aqueous phases: effects of level of theory, basis set, and solvation on strongly intramolecularly hydrogen-bonded systems.

The 126 possible conformations of 1,2,3-propanetriol (glycerol) have been studied by ab initio molecular orbital and density functional theory calculations in the gas and aqueous phases at multiple levels of theory and basis sets. The partial potential energy surface for glycerol as well as an analysis of the conformational properties and hydrogen-bonding trends in both phases have been obtained. In the gas phase at the G2(MP2) and CBS-QB3 levels of theory, the important, low-energy conformers are structures 100 and 95. In the aqueous phase at the SM5.42/HF/6-31G* level of theory, the lowest energy conformers are structures 95 and 46. Boltzmann distributions have been determined from these high-level calculations, and good agreement is observed when these distributions are compared to the available experimental data. These calculations indicate that the enthalpic and entropic contributions to the Gibbs free energy are important for an accurate determination of the conformational and energetic preferences of glycerol. Different levels of theory and basis sets were used in order to understand the effects of nonbonded interactions (i.e., intramolecular hydrogen bonding). The efficiency of basis set and level of theory in dealing with the issue of intramolecular hydrogen bonding and reproducing the correct energetic and geometrical trends is discussed, especially with relevance to practical computational methods for larger polyhydroxylated compounds, such as oligosaccharides.

Sensitivity of (1)J[C(1)-H(1)] magnitudes to anomeric stereochemistry in 2,3-anhydro-O-furanosides.

The magnitude of the one-bond coupling constant between C(1) and H(1) in 2,3-anhydro-O-furanosides has been shown to be sensitive to the stereochemistry at the anomeric center. A panel of 24 compounds was studied and in cases where the anomeric hydrogen is trans to the epoxide moiety, (1)J[C(1)-H(1)] = 163-168 Hz; and when this hydrogen is cis to the oxirane ring, ((1)J[C(1)-H(1)] = 171-174 Hz. In contrast, for 2,3-anhydro-S-glycosides, the size of the (1)J[C(1)-H(1)] is not sensitive to C(1) stereochemistry. Computational studies on all four methyl 2,3-anhydro-O-furanosides (5-8) demonstrated that (1)J[C(1)-H(1)] was inversely proportional to the length of the C(1)-H(1) bond. A previously reported equation, which relates C(1)-H(1) bond distance and atomic charges to (1)J[C(1)-H(1)] magnitudes, could be used to accurately predict the J values in the alpha-lyxo (5) and beta-ribo (8) isomers. In contrast, with the beta-lyxo (6) and alpha-ribo isomers (7), this equation underestimated the size of these coupling constants by 10-20 Hz.

Stereocontrolled synthesis of 2,3-anhydro-beta-d-lyxofuranosyl glycosides.

[reaction: see text] The stereocontrolled synthesis of 2,3-anhydro-beta-D-lyxofuranosyl glycosides from thioglycoside 2 and glycosyl sulfoxide 3 is reported.

An efficient synthesis of methyl 2,3-anhydro-alpha-D-ribofuranoside.

An efficient synthesis of methyl 2,3-anhydro-alpha-D-ribofuranoside is reported. Its preparation is achieved via a four-step sequence from methyl 2,3,5-tri-O-benzoyl-alpha-D-arabinofuranoside in 74% overall yield.

Total synthesis of both methyl 4a-carba-D-arabinofuranosides.

[reaction: see text] The total synthesis of methyl 4a-carba-alpha-D-arabinofuranoside (1) and methyl 4a-carba-beta-D-arabinofuranoside (2) has been achieved starting from D-mannose (5). Key transformations included a ring-closing metathesis of diene 11 employing Schrock's catalyst followed by a stereoselective hydrogenation with Wilkinson's catalyst.