Anomeric effects in carbohydrates: non equivalence of endocyclic oxygen lone pairs

Insights into furanose solution conformations: beyond the two-state model

“…In contrast, in the case of 1 α, both quantum and classical mechanical methods indicate a barrier only in the West, enabling the ring to populate a continuous distribution of conformations from North to South via the East. Previous NMR (Angyal 1979; Serianni and Barker 1984; Taha et al 2010), as well as QM (D'Souza et al 2000; Gordon et al 1999) studies, have also been shown to be consistent with conformations in the North, East, and South and it has been proposed that the anomeric effect (Cosse-Barbi and Dubois 1987; Cossé-Barbi et al 1989; D'Souza et al 2000; Ellervik and Magnusson 1994; Juaristi and Cuevas 1992; Plavec et al 1993; Richards et al 2013; Thibaudeau and Chattopadhyaya 1997) and the gauche effect (Callam and Lowary 2001; D'Souza et al 2000; Houseknecht et al 2003a; Plavec et al 1994; Plavec et al 1996; Plavec et al 1993; Thibaudeau and Chattopadhyaya 1997; Thibaudeau et al 1994) among the vicinal hydroxyl groups and the ring oxygen atom were the key influences on ring conformation in furanoses. In the case of 1 α, it has been argued that the anomeric and gauche effects both stabilize the South conformation (Callam and Lowary 2001; D'Souza et al 2000; Gordon et al 1999; Houseknecht et al 2003a).…”

“…Its presence in furanoses has been invoked as contributing to ring conformational preferences (Callam and Lowary 2001; Cosse-Barbi and Dubois 1987; Cossé-Barbi et al 1989; D'Souza et al 2000; Ellervik and Magnusson 1994; Houseknecht et al 2003a; Plavec et al 1994; Plavec et al 1996; Plavec et al 1993; Thibaudeau and Chattopadhyaya 1997; Thibaudeau et al 1994), and is consistent with the observation that electronegative substituents at C1 in furanoses prefers a pseudoaxial over a pseudoequatorial configuration, 29–34 but it has not been quantified computationally. We address this here by noting that, over the course of the pseudorotational itinerary for 13 , the endocyclic C4-O4-C1-O torsion angle spans a range of 80 to 160°, or pseudo- gauche to pseudo- anti .…”

“…Torsion terms derived from fitting to 13 ( Cf-Of-Cf-Os and Cf-Cf-Cf-Os ), implicitly include any contributions from the anomeric effect (Callam and Lowary 2001; Cosse-Barbi and Dubois 1987; Cossé-Barbi et al 1989; D'Souza et al 2000; Ellervik and Magnusson 1994; Plavec et al 1993; Thibaudeau and Chattopadhyaya 1997). In GLYCAM06, both the endo - and exo -anomeric torsion terms were parameterized by fitting to small acyclic molecular fragments, leading to the same set of terms for both applications.…”

“…In carbohydrates, the anomeric effect relates to the preference of the endocyclic C-O-C-O torsion angle to adopt the gauche orientation over the anti conformation (Cossé-Barbi et al 1989; Jeffrey et al 1978; Juaristi and Cuevas 1992), and has been estimated from quantum mechanical calculations for pyranoses (Lii et al 2003; Senderowitz et al 1996) and related acyclic fragments (Jeffrey et al 1978; Lii et al 2005) to be 1–2 kcal/mol. Its presence in furanoses has been invoked as contributing to ring conformational preferences (Callam and Lowary 2001; Cosse-Barbi and Dubois 1987; Cossé-Barbi et al 1989; D'Souza et al 2000; Ellervik and Magnusson 1994; Houseknecht et al 2003a; Plavec et al 1994; Plavec et al 1996; Plavec et al 1993; Thibaudeau and Chattopadhyaya 1997; Thibaudeau et al 1994), and is consistent with the observation that electronegative substituents at C1 in furanoses prefers a pseudoaxial over a pseudoequatorial configuration, 29–34 but it has not been quantified computationally.…”

“…Further analysis indicated that, for the two-state model to be applicable, barriers in the East and West must exist to confine the conformations to low-energy regions in the northern and southern quadrants of the pseudorotational surface. The relative stability of northern and southern conformations has been rationalized in terms of the numbers of stabilizing gauche effects between vicinal oxygen atoms (Callam and Lowary 2001; D'Souza et al 2000; Plavec et al 1993; Thibaudeau and Chattopadhyaya 1997) as well as the presence of the anomeric effect (Callam and Lowary 2001; Cosse-Barbi and Dubois 1987; Cossé-Barbi et al 1989; D'Souza et al 2000; Ellervik and Magnusson 1994; Houseknecht et al 2003a; Plavec et al 1994; Plavec et al 1996; Plavec et al 1993; Thibaudeau and Chattopadhyaya 1997; Thibaudeau et al 1994). Here, we find that whether or not there is a barrier in the eastern or western regions depends on the absence of an anomeric effect, as well as the presence of unfavorable syn -orientations of vicinal hydroxyl groups.…”