Delphirine, a new alkaloid from L.

Structural Studies of Norditerpenoid Alkaloids: Conformation Analysis in Crystal and in Solution States

“…The degree of twist of the conformations of the A/E-rings (not only the A-or E-ring) is the key to explain why these 2-H a atoms experience less steric compression. All the synthetic [3.3.1]azabicyclic analogues (15)(16)(17)(18) adopt true-chair/true-chair conformations in both crystal and solution conformations, Table 2. Key 1 H NMR che0mical shifts (δ, ppm) and key torsion angles (θ,°) of the selected NDA free bases (1), ( 3), ( 4), ( 6), (7), and their synthetic [3.3.1] bicyclic analogues (12)(13)(14)(15)(16)(17)(18).…”

“…All the synthetic [3.3.1]azabicyclic analogues (15)(16)(17)(18) adopt true-chair/true-chair conformations in both crystal and solution conformations, Table 2. Key 1 H NMR che0mical shifts (δ, ppm) and key torsion angles (θ,°) of the selected NDA free bases (1), ( 3), ( 4), ( 6), (7), and their synthetic [3.3.1] bicyclic analogues (12)(13)(14)(15)(16)(17)(18). whereas the A/E-rings of the selected NDA free bases are twisted-chair/twisted-chair in both crystal and solution conformations.…”

“…whereas the A/E-rings of the selected NDA free bases are twisted-chair/twisted-chair in both crystal and solution conformations. The comparison between the frames of selected alkaloid free bases (1), ( 3), ( 4), and ( 6) extracted from the SXRD data and those of their synthetic [3.3.1]bicyclic analogues (15)(16)(17)(18) are shown in Figure 5a. In a [3.3.1]bicycle with a true-chair/ true-chair conformation, the lone-pair electrons overlap with 7-H a (Figure 5b), resulting in significant steric compression of 7-H a .…”

“…To express the degree of twist, particularly in crystal structures, torsion angles θ C1À C17À C19À C3 recorded from SXRD data of (1), ( 3), ( 4), and ( 6) are employed to compare with θ C6À C4À C2À C8 of synthetic [3.3.1]bicyclic analogues (15)(16)(17)(18) (Table 2). θ C1À C17À C19À C3 of the natural alkaloids are significantly larger than θ C6À C4À C2À C8 of their synthetic analogues indicating that the A/Eazabicycles of these natural products are more twisted than those of their synthetic analogues.…”

“…[13][14][15] The conformation of the A/E-rings is changeable in different conditions, e. g. at different pHs, and the conformation influences certain properties of these NDAs. For instance, neoline (8) with its 1α-OH has a naturally occurring 1-epimer, delphirine (9) bearing a 1β-OH, [16] and this pair of epimers have different pKa: pKa neoline (8) = 7.6, and pKa delphirine (9) = 6.7. The A-ring of neoline (8) adopts a boat conformation with 1αÀ OH (as proton donor) forming a hydrogen-bond with the basic amine of the N-ethyl piperidine E-ring (proton acceptor), but that of delphirine ( 9) is in a chair conformation.…”