Total synthesis of diazonamide A

Angewandte Chemie - International Edition

Volumn 41, Issue 18, 2002, Pages 3495-3499

  Nicolaou, K C ^a,b   Bella, Marco ^a,b   Chen, David Y K ^a,b   Huang, Xianhai ^a,b   Ling, Taotao ^a,b   Snyder, Scott A ^a,b  

^a SCRIPPS RESEARCH INSTITUTE   (United States)

^b UNIVERSITY OF CALIFORNIA   (United States)

Author keywords

Antitumor agents; Cyclization; Macrocycles; Natural products; Total synthesis

Indexed keywords

ERRORS; MOLECULAR STRUCTURE; SYNTHESIS (CHEMICAL);

NATURAL PRODUCTS;

NITROGEN COMPOUNDS;

DIAZONAMIDE A; FUSED HETEROCYCLIC RINGS; NATURAL PRODUCT; OXAZOLE DERIVATIVE; UNCLASSIFIED DRUG;

ANIMAL; ANTINEOPLASTIC ACTIVITY; ARTICLE; ASCIDIACEA; CHEMICAL MODIFICATION; CHEMICAL STRUCTURE; CHEMISTRY; CYCLIZATION; CYTOTOXICITY; DRUG ACTIVITY; DRUG ISOLATION; DRUG SYNTHESIS; ISOLATION AND PURIFICATION; METABOLISM; STRUCTURE ACTIVITY RELATION; STRUCTURE ANALYSIS; SYNTHESIS; TUMOR CELL LINE; UROCHORDATA;

ANIMALS; HETEROCYCLIC COMPOUNDS WITH 4 OR MORE RINGS; MOLECULAR STRUCTURE; OXAZOLES; UROCHORDATA;

EID: 0037119717     PISSN: 14337851     EISSN: None     Source Type: Journal    
DOI: 10.1002/1521-3773(20020916)41:18<3495::AID-ANIE3495>3.0.CO;2-7     Document Type: Article

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48. 4]MeOH) which, in the case of 2, coincided precisely with the reported value for the natural product (δ = 3.88 ppm), whereas in the case of its C37 epimer the signal for this proton appeared at δ= 3.92 ppm. We should note that we were unable to obtain a sample of natural diazonamide A for direct comparison.
49. Synthetic diazonamide A (2) exhibited potent cytotoxic activity at single digit nM concentrations against various human cancer cell lines of distinct origin, including ovarian carcinoma 1A9, lung carcinoma A549, prostate carcinoma PC-3, breast carcinoma MCS-7, and the taxol-resistant 1A9/PTX10 cell line. Its C37 epimer, although less active, also exhibited significant activity against the same cell lines. We thank Dr. Paraskevi Giannakakou and Aurora O'Brate of the Winship Cancer Institute, Emory University School of Medicine, for these biological assays.