Conformational analysis of sulfur-containing 6-deoxy-l-hexose derivatives by molecular modeling and NMR spectroscopy. A theoretical study and experimental evidence of intramolecular nonbonded interactions between sulfur and oxygen.
6-Deoxy-l-mannose diphenyldithioacetal (1) unexpectedly gave the rearranged products phenyl 3,4-di-O-acetyl-2-S-phenyl-1,2-dithio-6-deoxy-beta-l-glucopyranoside (9) and 3,4-di-O-acetyl-2,5-anhydro-6-deoxy-l-glucose diphenyldithioacetal (10) upon treatment with acetyl chloride, while 6-deoxy-l-mannose ethylenedithioacetal (3) yielded (4aR,6S,7S,8R,8aS)-7,8-diacetyloxy-6-methylhexahydro-4aH-[1,4]dithiino[2,3b]pyran (11), whose structure was further confirmed by X-ray diffraction, and 3,4-di-O-acetyl-2,5-anhydro-l-rhamnose ethylenedithioacetal (12). The geometry of the four rearranged products as well as that of 1-thio-6-deoxy-l-mannopyranosides 5 and 7 and their acetyl derivatives 6 and 8 was studied by density functional theory (B3LYP/6-31G) molecular models, in combination with a Karplus-type analysis of the NMR vicinal coupling constants, revealing that the six-membered ring of pyranosides 5-9 and 11 exists in a slightly distorted chair conformation (6-13% distortion) and that the conformational behavior of the 2,5-anhydro-6-deoxy-l-glucose dithioacetals 10 and 12 is strongly influenced by the presence of stabilizing intramolecular nonbonded sulfur-oxygen 1,4- and 1,5-interactions. Compounds 9-12 were formed by a molecular rearrangement via sulfonium ion intermediates followed by stereoselective intramolecular cyclizations as formulated by the quantum chemical calculations performed in the present study.
Fragoso-Serrano
Mabel
M
Departamento de Química, Centro de Investigación y de Estudios Avanzados del Instituto Politécnico Nacional, Apartado 14-740, Mexico City 07000, Mexico.
Guillén-Jaramillo
Georgina
G
Pereda-Miranda
Rogelio
R
Cerda-García-Rojas
Carlos M
CM
D003500:Cyclization; D003837:Deoxy Sugars / Q000737:chemistry*; D006601:Hexoses; D008958:Models, Molecular; D008968:Molecular Conformation; D019906:Nuclear Magnetic Resonance, Biomolecular; D010100:Oxygen / Q000737:chemistry; D013237:Stereoisomerism; D013455:Sulfur / Q000737:chemistry
D003837:Deoxy Sugars; D006601:Hexoses; D013455:Sulfur; D010100:Oxygen