Synthesis of novel 13α-18-norandrostane-ferrocene conjugates via homogeneous catalytic methods and their investigation on TRPV1 receptor activation

Eszter Szánti-Pintér; Johan Wouters; Ágnes Gömöry; Éva Sághy; Éva Szőke; Zsuzsanna Helyes; László Kollár; Rita Skoda-Földes

doi:10.1016/j.steroids.2015.10.016

Synthesis of novel 13α-18-norandrostane-ferrocene conjugates via homogeneous catalytic methods and their investigation on TRPV1 receptor activation

Steroids. 2015 Dec:104:284-93. doi: 10.1016/j.steroids.2015.10.016. Epub 2015 Oct 28.

Authors

Eszter Szánti-Pintér¹, Johan Wouters², Ágnes Gömöry³, Éva Sághy⁴, Éva Szőke⁴, Zsuzsanna Helyes⁴, László Kollár⁵, Rita Skoda-Földes⁶

Affiliations

¹ University of Pannonia, Institute of Chemistry, Department of Organic Chemistry, Egyetem u. 10 (P.O. Box 158), H-8200 Veszprém, Hungary.
² University of Namur, Department of Chemistry, Rue de Bruxelles 61, B-5000 Namur, Belgium.
³ Hungarian Academy of Sciences, Research Centre for Natural Sciences, Magyar tudósok körútja 2, H-1117 Budapest, Hungary.
⁴ Department of Pharmacology and Pharmacotherapy, Szentágothai Research Center, MTA-PTE Chronic Pain Research Group, University of Pécs, Ifjúság u. 6 (P.O. Box 266), H-7624 Pécs, Hungary.
⁵ University of Pécs, Department of Inorganic Chemistry and MTA-PTE Research Group for Selective Chemical Syntheses, Ifjúság u. 6 (P.O. Box 266), H-7624 Pécs, Hungary.
⁶ University of Pannonia, Institute of Chemistry, Department of Organic Chemistry, Egyetem u. 10 (P.O. Box 158), H-8200 Veszprém, Hungary. Electronic address: skodane@almos.uni-pannon.hu.

PMID: 26519768
DOI: 10.1016/j.steroids.2015.10.016

Abstract

13α-Steroid-ferrocene derivatives were synthesized via two reaction pathways starting from an unnatural 16-keto-18-nor-13α-steroid. The unnatural steroid was converted to ferrocene derivatives via copper-catalyzed azide-alkyne cycloaddition or palladium-catalyzed aminocarbonylation. 16-Azido- and 16-N-(prop-2-ynyl)-carboxamido-steroids were synthesized as starting materials for azide-alkyne cycloaddition with the appropriate ferrocene derivatives. Based on our earlier work, aminocarbonylation of 16-iodo-16-ene and 16-iodo-15-ene derivatives was studied with ferrocenylmethylamine. The new products were obtained in moderate to good yields and were characterized by (1)H and (13)C NMR, IR and MS. The solid state structure of the starting material 13α-18-norandrostan-16-one and two carboxamide products were determined by X-ray crystallography. Evidences were provided that the N-propargyl-carboxamide compound as well as its ferrocenylmethyltriazole derivative are able to decrease the activation of TRPV1 receptor on TRG neurons.

Keywords: 13α-18-nor-Steroid; Aminocarbonylation; Copper; Cycloaddition; Ferrocene; Palladium.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Catalysis
Cells, Cultured
Copper / chemistry
Crystallography, X-Ray
Dose-Response Relationship, Drug
Ferrous Compounds / chemical synthesis*
Ferrous Compounds / chemistry
Ferrous Compounds / pharmacology*
Metallocenes
Models, Molecular
Molecular Structure
Neurons / cytology
Neurons / drug effects
Norandrostanes / chemical synthesis*
Norandrostanes / chemistry
Norandrostanes / pharmacology*
Palladium / chemistry
Rats
Rats, Wistar
Structure-Activity Relationship
TRPV Cation Channels / metabolism*
Trigeminal Ganglion / cytology
Trigeminal Ganglion / drug effects

Substances

Ferrous Compounds
Metallocenes
Norandrostanes
TRPV Cation Channels
Trpv1 protein, rat
Palladium
Copper
ferrocene