Isolation, structural elucidation, and absolute stereochemistry of enigmazole A, a cytotoxic phosphomacrolide from the Papua New Guinea marine sponge Cinachyrella enigmatica.
Enigmazole A (1), a novel phosphate-containing macrolide, was isolated from a Papua New Guinea collection of the marine sponge Cinachyrella enigmatica. The structure of 1, including the absolute stereochemistry at all eight chiral centers, was determined by a combination of spectroscopic analyses and a series of microscale chemical derivatization studies. Compound 1 is comprised of an 18-membered phosphomacrolide that contains an embedded exomethylene-substituted tetrahydropyran ring and an acyclic portion that spans an embedded oxazole moiety. Two additional analogues, 15-O-methylenigmazole A and 13-hydroxy-15-O-methylenigmazole A, were also isolated and assigned. The enigmazoles are the first phosphomacrolides from a marine source and 1 exhibited significant cytotoxicity in the NCI 60-cell line antitumor screen, with a mean GI(50) of 1.7 microM.
Oku
Naoya
N
Molecular Targets Laboratory, Center for Cancer Research, National Cancer Institute, NCI-Frederick, Building 1052, Room 121, Frederick, Maryland 21701-1201, USA.
Takada
Kentaro
K
Fuller
Richard W
RW
Wilson
Jennifer A
JA
Peach
Megan L
ML
Pannell
Lewis K
LK
McMahon
James B
JB
Gustafson
Kirk R
KR
D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D018942:Macrolides / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D008958:Models, Molecular; D015394:Molecular Structure; D009369:Neoplasms / Q000188:drug therapy; D009943:Organophosphorus Compounds / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D010080:Oxazoles / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology*; D010219:Papua New Guinea; D011161:Porifera / Q000737:chemistry*
D000970:Antineoplastic Agents; D018942:Macrolides; D009943:Organophosphorus Compounds; D010080:Oxazoles; C553539:enigmazole A