Synthesis of a Stable Iminium Salt and Propellane Derivatives

Abstract

The treatment of morphinan 1 with NaH and MsCl provided very stable iminium salt 7 possessing propellane skeleton. One of the synthesized iminium salts 7, isobutyl derivative 7b, was crystallized and its structure was determined by X-ray crystallography. The natural bond orbital analysis suggested that the stability of the iminium should result from the stereoelectronic effect (hyperconjugation) attributed to their own structures.

Structure–Activity Relationships of (+)-Naltrexone-Inspired Toll-like Receptor 4 (TLR4) Antagonists

“…This crude oil was purified by SiO 2 column chromatography with 10% NH 4 OH in MeOH/CHCl 3 (gradient, 0 → 8%) to afford 22 (0.740 g, 26% from 1a ) as a white solid. Spectral data matched those reported by Nagase et al, 31 on the enantiomer.…”

“…(+)-Desoxynaltrexone 4 (Scheme 3) was prepared using the procedures of Nagase et al ., 30, 31 in their synthesis of the (−)-enantiomer of 24 ( 1a → 24 , Scheme 3). This synthesis began with a methylation of the C-3 hydroxy of (+)-naltrexone 1a to arrive at the 3-methoxyether 20 , which was subsequently treated with activated zinc and ammonium chloride to open the oxide bridge and afford the C-4 hydroxy compound 21 (Scheme 3).…”

“…31 To a solution of crude 20 (1.98, 5.57 mmol) in MeOH (50 mL) was added NH 4 Cl (2.98 g, 55.7 mmol). The reaction mixture was heated to reflux and activated Zn (2.55 g, 39.0 mmol) was added in 3 portions spaced 1 h apart.…”

Naltrindole derivatives with fluorinated ethyl substituents on the 17-nitrogen as δ opioid receptor inverse agonists

“…Therefore, 17-fluoroalkyl NTI and compound 1 derivatives exhibited higher selectivities toward the DOR. On the other hand, although the alkyl groups are electron-donating groups, the electron-donating property of the methyl or propyl groups was weaker than that of the CPM group, [20][21][22] which would lead to higher comparable selectivities for 4a, b and 6a, b as compared with their respective parent compounds NTI and compound 1.…”

Sodium Hydride

“…7 (F) The treatment of morphinan with NaH and MsCl provided a very stable iminium salt possessing a propellane skeleton. 8 The iminium ion is expected to be a key intermediate for the synthesis of novel opioid ligands.…”