Synthesis 2016; 48(21): 3646-3658
DOI: 10.1055/s-0035-1562481
short review
© Georg Thieme Verlag Stuttgart · New York

Preparation of Reduced Pyrazino[2,1-a]isoquinoline Derivatives: Important Heterocycles in the Field of Bioactive Compounds

Lorenzo Zani*
a  Istituto di Chimica dei Composti Organometallici (CNR-ICCOM), Via Madonna del Piano 10, 50019 Sesto Fiorentino, Italy   Email: [email protected]   Email: [email protected]
,
Alessandro Mordini
a  Istituto di Chimica dei Composti Organometallici (CNR-ICCOM), Via Madonna del Piano 10, 50019 Sesto Fiorentino, Italy   Email: [email protected]   Email: [email protected]
b  Dipartimento di Chimica ‘Ugo Schiff’, Via della Lastruccia 13 , 50019 Sesto Fiorentino, Italy
,
Massimo Calamante
a  Istituto di Chimica dei Composti Organometallici (CNR-ICCOM), Via Madonna del Piano 10, 50019 Sesto Fiorentino, Italy   Email: [email protected]   Email: [email protected]
b  Dipartimento di Chimica ‘Ugo Schiff’, Via della Lastruccia 13 , 50019 Sesto Fiorentino, Italy
,
Gianna Reginato*
a  Istituto di Chimica dei Composti Organometallici (CNR-ICCOM), Via Madonna del Piano 10, 50019 Sesto Fiorentino, Italy   Email: [email protected]   Email: [email protected]
› Author Affiliations
Further Information

Publication History

Received: 22 June 2016

Accepted: 24 June 2016

Publication Date:
16 August 2016 (online)


Abstract

Partially hydrogenated pyrazino[2,1-a]isoquinoline derivatives, such as praziquantel, have been the subject of significant research efforts in the field of medicinal chemistry, thanks to their antihelmintic, antiprotozoal, and antifungal activities. Nevertheless, methods for their efficient synthesis (and especially for their stereoselective preparation) can be traced back to just a few general procedures. In this short review we will summarize the approaches developed so far to access pyrazino[2,1-a]isoquinolines, with a particular focus on bioactive derivatives, and will highlight their features and weaknesses, aiming to stimulate further investigations in the preparation of this important class of heterocyclic compounds.

1 Introduction

2 Different Approaches to the Synthesis of Pyrazino[2,1-a]isoquinolines

2.1 1-(Aminomethyl)tetrahydroisoquinoline Ring Closure

2.2 Diketopiperazine Reduction/Cyclization

2.3 N-Acyliminium Ion Cyclizations

2.4 Radical Cyclizations

2.5 Multicomponent Reactions

2.6 Miscellaneous Routes

3 Access to Enantiomerically Pure Praziquantel

4 Conclusions

 
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