1. Introduction
The synthesis and neuropharmacological
characterization of 10-deoxyapomorphine derivatives
are a new and important direction in the development
of potent and subtype selective dopaminergic and/or
serotonergic ligands [1-6]. Currently all the synthetic
methods towards deoxyapomorphines are based
on the preparation of 3-O-(triluoromethyl)sulfonyl-
morphine (2) or -oripavine (5), the acid-catalyzed
rearrangement of these morphinans into aporphinoids
and further manipulations on the sensitive aporphine
backbone. Earlier procedures involved the synthesis
and transformation of 3-(1-phenyltetrazoyl)morphine (3)
[7,8], however the rearrangement of this compound gave
rise to a mixture of aporphines and the hydrogenolytic
removal of the (phenyltetrazolyl)oxy moiety from the
aporphines was reported to be ‘erratic and capricious’ in
both catalytic hydrogenolysis reactions and in catalytic
hydrogen-transfer reactions [8,9].
Here we report a new, eficient and versatile route
to 10-deoxyaporphines based on hitherto unknown
3-deoxyoripavine (7). The practical signiicance of
this procedure is even higher due to the fact that the
starting derivative of our procedure, oripavine (4), is
now one of the major industrial poppy alkaloids [10-12];
especially since the discovery and growing cultivation
of the poppy mutant known as top1 (for ‘thebaine
oripavine poppy 1’) which led the island state of
Tasmania to produce the major part of the world’s licit
thebaine and oripavine directly from natural sources
[10].
Central European Journal of Chemistry
The irst synthesis of 3-deoxyoripavine
and its utilization in the preparation
of 10-deoxyaporphines and cyprodime
#
* E-mail: sipos.attila@pharm.unideb.hu
#
This paper is dedicated to the memory of Prof. Sándor Makleit who passed away on 27.09.2012
Received 14 January 2013; Accepted 19 March 2013
Abstract:
© Versita Sp. z o.o.
Keywords: Oripavine • Cyprodime • 10-deoxyaporphines • Reduction • Acid-catalyzed rearrangement
1
Department of Pharmaceutical Chemistry,
Medical and Health Science Centre,
University of Debrecen, H-4010 Debrecen, Hungary
2
Department of Physical Chemistry,
University of Debrecen, H-4010 Debrecen, Hungary
3
Department of Organic Chemistry,
University of Debrecen, H-4010 Debrecen, Hungary
Attila Sipos
1*
, Antal Udvardy
2
,
Attila C. Bényei
1,2
, Sándor Berényi
3
Research Article
The synthesis of 3-deoxyoripavine (7) was realized as a novel and promising intermediate towards the synthesis of the important class of
dopaminergic and/or serotonergic 10-deoxyaporphines and the special pharmacological tool µ opioid antagonist cyprodime. Generally,
the preparation of these valuable biologically active compounds was achieved in remarkable yields.
1278
Cent. Eur. J. Chem. • 11(8) • 2013 • 1278-1285
DOI: 10.2478/s11532-013-0256-x
Author copy