Concise Total Synthesis of (+)-Luteoalbusins A and B

• Published in: Organic letters Vol. 17; no. 17; pp. 4268 - 4271
• Main Authors: Adams, Timothy C, Payette, Joshua N, Cheah, Jaime H, Movassaghi, Mohammad
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 04.09.2015; Amer Chemical Soc
• Subjects: Chemistry; Chemistry, Organic; Cyclization; Diketopiperazines - chemical synthesis; Diketopiperazines - chemistry; Diketopiperazines - pharmacology; Drug Screening Assays, Antitumor; HeLa Cells; Humans; Indole Alkaloids - chemical synthesis; Indole Alkaloids - chemistry; Indole Alkaloids - pharmacology; Indoles - chemical synthesis; Indoles - chemistry; Indoles - pharmacology; Molecular Structure; Physical Sciences; Piperazines - chemical synthesis; Piperazines - chemistry; Piperazines - pharmacology; Science & Technology; Stereoisomerism; EPIPOLYTHIODIKETOPIPERAZINE ALKALOIDS; ANTIBIOTICS GLIOTOXIN; IN-VIVO; TRIOXOPIPERAZINE PRECURSORS; GENERAL-APPROACH; CELL PROLIFERATION; PREPARING EPIDITHIODIOXOPIPERAZINES; ENANTIOSELECTIVE TOTAL-SYNTHESIS; ARYL PYRROLOINDOLINES; MESO-CHIMONANTHINE
• ISSN: 1523-7060; 1523-7052
• DOI: 10.1021/acs.orglett.5b02059

The first total synthesis of (+)-luteoalbusins A and B is described. Highly regio- and diastereoselective chemical transformations in our syntheses include a Friedel–Crafts C3-indole addition to a cyclotryptophan-derived diketopiperazine, a late-stage diketopiperazine dihydroxylation, and a C11-sulfidation sequence, in addition to congener-specific polysulfane synthesis and cyclization to the corresponding epipolythiodiketopiperazine. We also report the cytoxicity of both alkaloids, and closely related derivatives, against A549, HeLa, HCT116, and MCF7 human cancer cell lines.