ABSTRACT
The synthesis of 1,3,5-13C3- and 2,4-13C2-labeled 5-O-bromobenzyl-2-deoxyribonolactones 2, precursors to 13C-enriched nucleoside phosphoramidites for solid-phase synthesis of DNA oligonucletides, is described. An equimolar combination of these two multiply labeled lactones affords a "population-labeled" mixture of isotopomers which exhibits an approximately 50-fold increase in the sensitivity of 13C-NMR compared to natural abundance measurements. The 13C-13C 2-bond and 4-bond coupling constants are reported for the lactones; all are <2Hz, confirming that this labeling scheme should be especially useful for NMR-relaxation measurements.
Subject(s)
Biochemistry/methods , Lactones/chemistry , Carbon Isotopes , Isotope Labeling/methods , Magnetic Resonance Spectroscopy/methods , Sugar Acids/chemistryABSTRACT
C26H41NO7, Mr = 479.61, triclinic, P1, a = 11.894 (4), b = 12.360 (2), c = 9.969 (2) A, alpha = 106.11 (2), beta = 100.68 (2), gamma = 99.02 (2) degrees, V = 1349.5 (6) A3, Z = 2, Dx = 1.180 Mg m-3, Mo K alpha, lambda = 0.71069 A, mu = 0.079 mm-1, F(000) = 520, T = 296 K, R = 0.041, wR = 0.047 for 3196 observed unique reflections. A new approach to the total synthesis of the nargenicin macrolide system employing a [2,3] Wittig rearrangement to control the remote C16-C17 stereochemistry required characterization of a pivotal intermediate by X-ray single-crystal methods. The structure is characterized by the formation of strong intermolecular alcohol to dihydrooxazole-N hydrogen bonds, an essentially strain-free tricyclic oxa-bridged octalin nucleus, and low-energy conformations of the methoxymethyl ether side chains.
Subject(s)
Anti-Bacterial Agents/chemistry , Macrolides , Lactones/chemistry , Models, Molecular , Molecular Structure , X-Ray DiffractionABSTRACT
C20H30O6, Mr = 366.45, monoclinic, P2l/n, a = 10.411 (2), b = 16.084 (3), c = 11.991 (1) A, beta = 100.98 Mg m-3, Mo Ka, lambda V 0.71069 A, mu = 0.097 (2) degrees, V = 1971 (6) A3, Z = 4, Dx = 1.23 Mg m-3, Mo Ka, lambda = 0.71069 A, mu = 0.097 mm-1, F(000) = 792, T = 296 K, R = 0.050, wR = 0.065 for 3430 observed unique reflections. The structure of a key synthetic intermediate for use in a total synthesis of the nargenicin antibiotics has been established by X ray single-crystal methods. Its structure is characterized by an essentially strain-free tricyclic oxa-bridged octalin nucleus, low-energy methoxymethyl ether side-chain conformations and an intramolecular hydrogen bond between the hydroxyl group hydrogen atom and a methoxymethyl ether oxygen atom. Intermolecular packing contacts less than the sum of van der Waals radii consist of weak C-H...O interactions.
