The synthesis of 12-membered macrocycles containing a C1–C8 alkene unit via ring-closing metathesis

• Published in: Tetrahedron Vol. 68; no. 25; pp. 5081 - 5086
• Main Authors: Požgan, Franc, Štefane, Bogdan, Kiđemet, Davor, Smodiš, Janez, Zupet, Rok
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 24.06.2012; Elsevier
• Subjects: Chemistry; Chemistry, Organic; Exact sciences and technology; Heterocyclic compounds; Heterocyclic compounds with o, s, se, te hetero atom and condensed derivatives; Heterocyclic compounds with only one n hetero atom and condensed derivatives; Lactams; Lactones; Metathesis; Olefines; Organic chemistry; Physical Sciences; Preparations and properties; Renin inhibitors; Science & Technology; Renin inhibitors; Lactams; Metathesis; Olefines; Lactones; SYSTEM; POTENT RENIN INHIBITOR; ACYL RADICALS; CONVERGENT SYNTHESIS; EN-ROUTE; ALISKIREN; Ring size; Enzyme; Nitrogen heterocycle; Lactam; Lactone; Oxygen heterocycle; Macrocycle; Stereoselectivity; Peptidases; Alkene; Renin; Cyclization; Cross reaction; Hydrolases; Aspartic endopeptidases; Inhibitor; Chemical synthesis; Ethylenic compound
• ISSN: 0040-4020; 1464-5416
• DOI: 10.1016/j.tet.2012.04.043

Model cross and ring-closing metathesis strategies toward the C1–C8-linear carbon skeleton are presented. The introduction of a four-atom tether enables the formation of 12-membered rings in good-to-excellent yields and stereoselectivity. Furthermore, the study revealed that the cross-metathesis approach and the formation of medium ring sizes via ring-closing metathesis are much less favorable. [Display omitted]