Spirocyclic Hybrids of Nortropane and 1,3-Oxazinan-2-one Fragments

Alexandr Mandzhulo; Iryna Vashchenko; Oleg Lukin; Svetlana Shishkina; Grygoriy Dolgonos; Andrii Gerasov; Vitaliy Yepishev; Dariia Samofalova; Volodymyr Fetyukhin; Alexander Shivanyuk

doi:10.1055/a-2335-4444

Synthesis, Inhaltsverzeichnis

Synthesis 2024; 56(17): 2709-2730
DOI: 10.1055/a-2335-4444

paper

Spirocyclic Hybrids of Nortropane and 1,3-Oxazinan-2-one Fragments

Alexandr Mandzhulo

^aI.F. Lab Ltd., Representative of Life Chemicals Inc. in Ukraine, 5 Winston Churchill St., 02098 Kyiv, Ukraine

^bInstitute of Organic Chemistry, National Academy of Science of Ukraine, 5 Winston Churchill St., 02098 Kyiv, Ukraine

,

Iryna Vashchenko

^aI.F. Lab Ltd., Representative of Life Chemicals Inc. in Ukraine, 5 Winston Churchill St., 02098 Kyiv, Ukraine

,

Oleg Lukin

^aI.F. Lab Ltd., Representative of Life Chemicals Inc. in Ukraine, 5 Winston Churchill St., 02098 Kyiv, Ukraine

,

Svetlana Shishkina

^bInstitute of Organic Chemistry, National Academy of Science of Ukraine, 5 Winston Churchill St., 02098 Kyiv, Ukraine

^cSSI Institute for Single Crystals, National Academy of Science of Ukraine, 60 Nauky ave, 61001 Kharkiv, Ukraine

,

Grygoriy Dolgonos

^aI.F. Lab Ltd., Representative of Life Chemicals Inc. in Ukraine, 5 Winston Churchill St., 02098 Kyiv, Ukraine

,

Andrii Gerasov

^aI.F. Lab Ltd., Representative of Life Chemicals Inc. in Ukraine, 5 Winston Churchill St., 02098 Kyiv, Ukraine

,

Vitaliy Yepishev

^aI.F. Lab Ltd., Representative of Life Chemicals Inc. in Ukraine, 5 Winston Churchill St., 02098 Kyiv, Ukraine

,

Dariia Samofalova

^aI.F. Lab Ltd., Representative of Life Chemicals Inc. in Ukraine, 5 Winston Churchill St., 02098 Kyiv, Ukraine

,

Volodymyr Fetyukhin

^aI.F. Lab Ltd., Representative of Life Chemicals Inc. in Ukraine, 5 Winston Churchill St., 02098 Kyiv, Ukraine

,

Alexander Shivanyuk ∗

^aI.F. Lab Ltd., Representative of Life Chemicals Inc. in Ukraine, 5 Winston Churchill St., 02098 Kyiv, Ukraine

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Abstract

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Abstract

We report facile and versatile procedures for the synthesis of exo- and endo-isomeric spirocyclic hybrids of pharmacophoric (1R,5S)-8-azabicyclo[3.2.1]octane (nortropane) and 1,3-oxazinan-2-one fragments. Our approach consists of the hydrocyanation of endo- and exo-isomeric N-Cbz-protected nortropane-3-spiroepoxides, the reduction of hydroxy nitriles into amino alcohols, the synthesis of N-alkylated amino alcohols via reductive amination, the spirocyclization of the amino alcohols, N-alkylation of the unsubstituted 1,3-oxazinan-2-one fragment in the spiro compounds, and removal of the Cbz protecting groups.

Key words

nortropane - 1,3-oxazinan-2-one - oxiranes - hydrocyanation - reduction - reductive amination - spirocyclization - alkylation

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Referenzen

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