Total Syntheses of Indicine N-Oxide, Intermedine N-Oxide, and Their Enantiomers Using Carbohydrate as a Chiral Educt

Abstract

The first completely enantioselective syntheses of indicine N-oxide, intermedine N-oxide, and their enantiomers have been achieved stereospecifically. A synthetic analogue modeled on indicine N-oxide showed the superior activity to indicine N-oxide itself against cancer cell in vitro test.

Isolation of the Pyrrolizidine Alkaloid Intermedine-N-oxide from Cerinthe glabra and ab initio Calculation of its 13C NMR Shifts

“…Closer inspection of the NMR data reported for this alkaloid [18] revealed some unclear and some obviously wrong correlations of resonances. Our data from 1D and 2D NMR experiments (see Supporting Information) suggested new assignments for the chemical shifts of C-5, C-7, C-8, and C-9.…”

“…tems [26]. On this account the calculated results were plotted against the reported [18] and our 13 C NMR correlations. By employing the newly assigned chemical shifts of C-5, C-7, C-8, and C-9 (see Table 1), our correlations showed, independently from the used levels of theory and basis sets, a better linear trend than the previous correlations.…”

“…By comparing the 1 H and 13 C NMR data of the alkaloid with those available for the five presently known pyrrolizidine-N-oxides of the formula C 15 H 25 NO 6 (intermedine-N-oxide 1 [18,19], lycopsamine-N-oxide 2 [20,21], echinatine-N-oxide 3 [21,22], rinderine-N-oxide 4, and indicine-N-oxide 5 [18,21]), we found a very good accordance only with the data of 1, which had previously been obtained by unambiguous total synthesis [18] (Table 1). Moreover, the optical rotation was in good accordance with the reported literature value [18], so this alkaloid was identified as intermedine-N-oxide (1).…”

“…In an extension of this methodology to the pyrrolizidine alkaloids we calculated the 13 C NMR shifts of intermedine-N-oxide (1) based on the gauge including atomic orbitals (GIAO), using the Hartree-Fock (HF) theory and the Position a Ref. [18] This work Ref. [18] This work In an initial step several optimization cycles for the full geometry optimization of 1 had to be performed [25,26].…”

“…[18] This work Ref. [18] This work In an initial step several optimization cycles for the full geometry optimization of 1 had to be performed [25,26]. The calculated average energies of each series of optimizations steps of each used level of theory and the employed basis set are presented in Table 2.…”