Synthesis of a natural product-inspired eight-membered ring lactam library via ring-closing metathesis

• Published in: Bioorganic & medicinal chemistry Vol. 18; no. 17; pp. 4876 - 4879
• Main Authors: Brown, Neil, Xie, Baohan, Markina, Nataliya, VanderVelde, David, Perchellet, Jean-Pierre H., Perchellet, Elisabeth M., Crow, Kyle R., Buszek, Keith R.
• Format: Journal Article
• Language: English
• Published: OXFORD Elsevier Ltd 01.09.2008; Elsevier
• Subjects: Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Biological and medical sciences; Biological Products - chemistry; Cell Proliferation - drug effects; Chemistry; Chemistry, Medicinal; Chemistry, Organic; Eight-membered; General aspects; HL-60 Cells; Humans; Lactam; Lactams - chemical synthesis; Lactams - chemistry; Lactones - chemistry; Library; Life Sciences & Biomedicine; Medical sciences; Medium-ring; Natural product; Octalactin; Parallel synthesis; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Physical Sciences; Ring-closing metathesis; Science & Technology; Small Molecule Libraries - chemical synthesis; Small Molecule Libraries - chemistry; Stereoisomerism; Parallel synthesis; Eight-membered; Lactam; Natural product; Octalactin; Library; Medium-ring; Ring-closing metathesis; lactam; ANALOGS; natural product; octalactin; OCTALACTIN-A; eight-membered; ring-closing metathesis; parallel synthesis; medium-ring; library; LACTONES; AMINO-ACIDS; ESTERS; DERIVATIVES; Antineoplastic agent; Leukemia; Metathesis; Combinatorial chemistry; Eight membered ring; Chemical compound library; Pancreas; Chemical synthesis; Tumor cell; Human; Promyelocytic leukemia; Sulfonamide; Rodentia; In vitro; Biological activity; HL60 cell line; L1210 cell line; Vertebrata; Eight-membered;Natural product;Lactam;Library;Ring-closing metathesis;Medium-ring;Octalactin;Parallel synthesis; Mammalia; Cell line; Cyclization; Mouse; Carboxamide; Fluorine Organic compounds
• ISSN: 0960-894X; 0968-0896; 1464-3405; 1464-3391
• DOI: 10.1016/j.bmcl.2008.07.074

We have prepared a novel speculative eight-membered lactam demonstration library inspired by the antitumor natural product octalactin A. The basic scaffold was readily constructed in a convergent fashion via RCM from the corresponding diene amides. A cursory examination of the biological properties of the library validates the relevance and significance of these structures. We have prepared a novel speculative eight-membered lactam demonstration library based on the skeletal structure of the potent antitumor marine natural product octalactin A. The basic scaffold was readily constructed in a convergent fashion via ring-closing metathesis chemistry from the corresponding diene amides. A cursory examination of the biological properties of the library validates the relevance and significance of these structures.