1-Adamantylamidoxime

Benjamín Diethelm,Gonzalo Recabarren-Gajardo,Carlos Lagos

doi:10.3390/m992

Benjamín Diethelm, Gonzalo Recabarren-Gajardo + Show 1 more

Open Access

https://doi.org/10.3390/m992

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Abstract

The title compound was prepared by the nucleophilic addition of hydroxylamine over 1-cyanoadamantane. The poor reactivity of the nitrile substrate, due to its scarcely electrophilic nature, prompted the need to employ several activating conditions. Energy supply via conventional heating, ultrasound, and microwave irradiation did not lead to product formation. Therefore, Lewis acid catalysis was attempted. Initial tests with ZnCl2 led to product formation in poor yields. Conversely, the use of AlCl3 led to the formation of the desired amidoxime in the moderate yield, which was further increased to an excellent yield by performing the reaction in a more concentrated medium. The structural identity of the title compound was proven by spectroscopic methods (IR, NMR). This compound was later employed as a starting material for the synthesis of 3,5-disubstituted 1,2,4-oxadiazole derivatives as potential 11β-HSD1 inhibitors.

Highlights

11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a microsomal enzyme abundantly expressed in brain, liver, and fat tissue [1]
Several researches have pointed to this enzyme as a major pathophysiological actor in diabetes and metabolic syndrome, in which its overexpression has been shown to contribute to metabolic imbalances common in those ailments, playing an important etiological role [3,4]
In our efforts to prepare potent and selective 11β-HSD1 inhibitors based on a pharmacophore structure designed in silico by the Lagos group, we set out to synthesize several

Summary

Introduction

11β-Hydroxysteroid dehydrogenase type 1 (11β-HSD1) is a microsomal enzyme abundantly expressed in brain, liver, and fat tissue [1]. 1-adamantylamidoxime as markedly whereas aliphatic nitrilesmethod are regarded as largely inert towards this reaction, synthetic route,electrophilic, but which only provide a general for the preparation of amidoximes, without to the point where the yields of aliphatic amidoxime synthesesaare seldommethod reported for [8]. 1-adamantylamidoxime as part of aand broader of amidoximes, without stating differences terms of procedure between aliphatic aromatic reports do not detail yield or physical constant information for this specific product [9,10]. These route, butreports which only provide a general method for theconstant preparation of amidoximes, ones.synthetic. Character, led us several approaches totoincrease towardsthe thenucleophile, nucleophile, such as character, ledtouspursue to pursue several approaches increaseits itsreactivity reactivity towards such as heating, energy irradiation, and, and most successfully, Lewis acid catalysis

Discussion nitrile group of

Synthesis

Materials and Methods

Instrumentation