Synthesis of the Cyclostellettamines A−F and Related Bis(3-alkylpyridinium) Macrocycles

• Published in: European journal of organic chemistry Vol. 1998; no. 5; pp. 889 - 895
• Main Authors: Wanner, Martin J., Koomen, Gerrit-Jan
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag GmbH 01.05.1998; WILEY‐VCH Verlag GmbH; Wiley
• Subjects: Chemistry; Chemistry, Organic; Macrocycles; Physical Sciences; Protecting groups; Science & Technology; Sponge alkaloids; protecting groups; sponge alkaloids; macrocycles; MARINE SPONGE; ALKALOIDS
• ISSN: 1434-193X; 1099-0690
• DOI: 10.1002/(SICI)1099-0690(199805)1998:5<889::AID-EJOC889>3.0.CO;2-G

A general method was developed for the synthesis of a variety of symmetric and asymmetric macrocyclic bispyridines. 3‐Hydroxyalkylpyridines 18−20 were prepared, converted to the corresponding iodides and protected on the pyridine nitrogen with a p‐methoxybenzyl group to give the crystalline precursors 21, 22 and 23. Reaction with a second 3‐hydroxyalkylpyridine gave the corresponding bis (3‐alkylpyridinium) salts, which could easily be deprotected by refluxing in pyridine (24−29). Cyclization of the iodides in refluxing acetonitrile under high dilution conditions (1−2 mM) gave the desired macrocyles in overall yields between 65 and 74%. This efficient procedure resulted in the synthesis of the muscarinic receptor antagonists cyclostellettamines A−F (1−6) and some unnatural cyclophanes (12 and 31).