Synthesis of novel α-aminoecdysteroids via regio- and stereoselective oximation/hydrogenation of 20-hydroxyecdysone derivatives

Abstract

Oximation of 20-hydroxyecdysone oxo derivatives proceeds regio- and stereoselectively and provides (E)-configured oximes in quantitative yields. The Ni–Ra-catalyzed hydrogenation of the oximes affords novel α-aminoecdysteroids with the unchanged 14α-hydroxy-7-en-6-on native chromophore of ecdysteroids. The structures of synthesized compounds were confirmed by the means of homo- and heteronuclear one-dimensional and two-dimensional 1H and 13C NMR spectroscopy and X-ray crystallography.

Stereochemistry and complete 1H and 13C NMR signal assignment of C‐20‐oxime derivatives of posterone 2,3‐acetonide in solution state

“…Our HMBC measurement (see Figure S5, cross‐peaks H‐9/C‐11 and H‐17/C‐16) revealed that the assignment of the CH 2 signals in positions 11 and 16 is in fact the opposite as compared to that published . Furthermore, based on the edited‐HSQC spectrum (Figure S4), we achieved full assignment of the diastereotopic methylene hydrogen atoms as well.…”

“…Savchenko and coworkers most recently reported the 1 H and 13 C NMR data of 20‐oxime derivative of posterone 2,3‐acetonide ( 2 ), and on the basis of its X‐ray single crystal investigation, they proved the ( E )‐configuration of the oxime moiety . As in the 1 H and 13 C NMR spectra of this compound only one set of signals appeared, the measured diamagnetic change of δC‐20 (Δδ 51 ppm) supported the C═O → C═NOH conversion, but in the absence of exact data of Δδ syn ‐ anti parameters for the C‐21 signal, the unambiguous identification of the E / Z isomerism was not possible.…”

“…This value unequivocally proofs the E configuration of the oxime group. That means that compound 2 appears in solution in the same configuration as in solid phase …”

“…Our HMBC measurement (see Figure S5, cross-peaks H-9/C-11 and H-17/C-16) revealed that the assignment of the CH 2 signals in positions 11 and 16 is in fact the opposite as compared to that published. [10] Furthermore, based on the edited-HSQC spectrum ( Figure S4), we achieved full assignment of the diastereotopic methylene hydrogen atoms as well. It should be mentioned that no remarkable NOE sterical interaction could be observed between the broad OH and the H 3 -21 (1.92 s) hydrogen atoms, not even when dmso-d 6 was used as solvent.…”

“…Most recently, Savchenko and coworkers reported the regioselective preparation of this ecdysteroid oxime, along with its X-ray single crystal investigation and NMR data limited to the nonoverlapping 1 H signals. [10] In the present study, our aim was to perform an in-depth, high-resolution NMR investigation on this compound, two of its oxime ether derivatives, and two of its conjugates with long lipophilic side-chains, potentially able to self-assemble. Publication of the antitumor activity and nanoparticle forming properties of the latter two compounds is just accepted elsewhere.…”