First stereoselective total synthesis and anticancer activity of new amide alkaloids of roots of pepper

• Published in: Bioorganic & medicinal chemistry letters Vol. 19; no. 20; pp. 5915 - 5918
• Main Authors: Srinivas, Ch, Sai Pavan Kumar, Ch.N.S., China Raju, B., Jayathirtha Rao, V., Naidu, V.G.M., Ramakrishna, S., Diwan, Prakash V.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier Ltd 15-10-2009; Elsevier
• Subjects: Alkaloids - chemical synthesis; Alkaloids - chemistry; Alkaloids - pharmacology; Amide alkaloids; Amides - chemical synthesis; Amides - chemistry; Amides - pharmacology; Anticancer activity; Antineoplastic agents; Antineoplastic Agents - chemical synthesis; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Biological and medical sciences; Cell Line, Tumor; Drug Screening Assays, Antitumor; Epoxidation; General aspects; Humans; HWE olefination; Medical sciences; Pharmacology. Drug treatments; Piperaceae - chemistry; Piperidines - chemical synthesis; Piperidines - chemistry; Piperidines - pharmacology; Plant Roots - chemistry; Sharpless asymmetric dihydroxylation; Stereoisomerism; Stereoselective synthesis; Wittig olefination; HWE olefination; Amide alkaloids; Wittig olefination; Anticancer activity; Epoxidation; Stereoselective synthesis; Sharpless asymmetric dihydroxylation; Antineoplastic agent; Osmium Complexes; Epimer; Lung; Cytotoxicity; Alkanal; Stereoselectivity; Alkaloid; Dicotyledones; Angiospermae; Vinylic compound; Piperidine derivatives; Asymmetric reaction; Colon; Mammary gland; Chemical synthesis; Tumor cell; Below ground plant part; Human; Wittig reaction; Root; Aliphatic compound; Olefination; Piperaceae; Transition metal Complexes; Aldehyde; In vitro; Biological activity; Total synthesis; Cell line; Sharpless dihydroxylation; Plant origin; Carboxamide; Platinoid Complexes; Spermatophyta; Piper; Glycol
• ISSN: 0960-894X; 1464-3405
• DOI: 10.1016/j.bmcl.2009.08.056

The first stereoselective total synthesis of new natural amide alkaloids
1–
3 and their anti cancer activity is reported.
The first stereoselective total synthesis of new natural amide alkaloids
1–
3 have been achieved from commercially available starting materials. Wittig olefination, Sharpless asymmetric dihydroxylation, epoxidation, a
trans regioselective opening of 2,3-epoxy alcohol, Horner–Wadsworth–Emmons (HWE) olefination and amide coupling are the key steps. The amide alkaloids
1–
3 are evaluated for their anticancer activity against colon (HT-29), breast (MCF-7) and lung (A-549) human cancer cell lines for the first time.