Asymmetric synthesis of highly substituted azapolycyclic compounds via 2-alkenyl sulfoximines: potential scaffolds for peptide mimetics.
The application of metalated, enantiomerically pure acyclic and cyclic 2-alkenyl sulfoximines for the synthesis of highly substituted aza(poly)cyclic ring systems is described. The method relies on a one-pot combination of a reagent-controlled allyl transfer reaction to alpha- or beta-amino aldehydes, followed by a Michael-type cyclization of the intermediate vinyl sulfoximines generated in the first step. The sulfur-free target compounds are preferentially obtained by samarium iodide treatment of the sulfonimidoyl substituted heterocycles. In addition to this methodological work, initial results on the biological activity of selected examples are reported. Furthermore, a concept for the transformation of peptidic lead structures into non-peptide mimetics is described, and the relevance of the new approach to highly substituted azaheterocycles in this context is discussed.
Clemens-Schöpf-Institute of Organic Chemistry and Biochemistry, Technical University of Darmstadt, Petersenstrasse 22, 64287 Darmstadt, Germany. re@punk.oc.chemie.tu-darmstadt.de
Michael
M
Reggelin
Bernd
B
Junker
Timo
T
Heinrich
Stefan
S
Slavik
Philipp
P
Bühle
D000447:Aldehydes / Q000737:chemistry; D000475:Alkenes / Q000737:chemistry*; D040761:Biomimetic Materials / Q000138:chemical synthesis / Q000737:chemistry; D008715:Methionine / Q000031:analogs & derivatives* / Q000737:chemistry; D008958:Models, Molecular; D010455:Peptides / Q000737:chemistry*; D010880:Piperidines / Q000138:chemical synthesis / Q000737:chemistry; D011083:Polycyclic Compounds / Q000138:chemical synthesis* / Q000737:chemistry; D011759:Pyrrolidines / Q000138:chemical synthesis / Q000737:chemistry; D013237:Stereoisomerism
D000447:Aldehydes; D000475:Alkenes; D010455:Peptides; D010880:Piperidines; D011083:Polycyclic Compounds; D011759:Pyrrolidines; D008715:Methionine