Anticancer agents from the Australian tropical rainforest: Spiroacetals EBC-23, 24, 25, 72, 73, 75 and 76.
EBC-23, 24, 25, 72, 73, 75 and 76 were isolated from the fruit of Cinnamomum laubatii (family Lauraceae) in the Australian tropical rainforests. EBC-23 (1) was synthesized stereoselectively, in nine linear steps in 8 % overall yield, to confirm the reported relative stereochemistry and determine the absolute stereochemistry. Key to the total synthesis was a series of Tietze-Smith linchpin reactions. The novel spiroacetal structural motif, exemplified by EBC-23 (1), was found to inhibit the growth of the androgen-independent prostate tumor cell line DU145 in the mouse model, indicating potential for the treatment of refractory solid tumors in adults.
Dong
Lin
L
School of Chemistry and Molecular Biosciences, University of Queensland, Brisbane, 4072, Queensland, Australia.
Schill
Heiko
H
Grange
Rebecca L
RL
Porzelle
Achim
A
Johns
Jenny P
JP
Parsons
Peter G
PG
Gordon
Victoria A
VA
Reddell
Paul W
PW
Williams
Craig M
CM
D000080:Acetals / Q000737:chemistry* / Q000302:isolation & purification / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D001315:Australia; D045744:Cell Line, Tumor; D027424:Cinnamomum / Q000737:chemistry; D005638:Fruit / Q000737:chemistry; D006801:Humans; D051379:Mice; D008819:Mice, Nude; D011714:Pyrans / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013141:Spiro Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013237:Stereoisomerism; D023041:Xenograft Model Antitumor Assays
D000080:Acetals; D000970:Antineoplastic Agents; C534557:EBC-23; D011714:Pyrans; D013141:Spiro Compounds