A novel approach in drug discovery: synthesis of estrone--talaromycin natural product hybrids.
Hetero-Diels-Alder reaction of the steroidal exocyclic enol ethers 14 and 15, obtained from the secoestrones 8 and 9 by reduction, iodoetherification, and elimination, with ethyl O-benzoyldiformylacetate (16) leads to the spiroacetals 17 and 18 as a mixture of four diastereomers. Reduction of the major diastereomers 17a and 18a with DIBAH and subsequent hydrogenation yields the novel natural product hybrids 21, 23, 24, and 25, which possess the structural features of the steroid estrone (7) and the mycotoxin talaromycin 6.
Tietze
L F
LF
Institut für Organische Chemie, Georg-August-Universität Göttingen, Germany. ltietze@gwdg.de
Schneider
G
G
Wölfling
J
J
Fecher
A
A
Nöbel
T
T
Petersen
S
S
Schuberth
I
I
Wulff
C
C
D000080:Acetals / Q000138:chemical synthesis / Q000737:chemistry; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D002463:Cell Membrane Permeability; D015195:Drug Design; D004970:Estrone / Q000737:chemistry* / Q000494:pharmacology; D006571:Heterocyclic Compounds / Q000138:chemical synthesis / Q000737:chemistry; D006801:Humans; D006865:Hydrogenation; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D015394:Molecular Structure; D009183:Mycotoxins / Q000737:chemistry* / Q000494:pharmacology; D010084:Oxidation-Reduction; D013141:Spiro Compounds / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D013237:Stereoisomerism; D014407:Tumor Cells, Cultured
D000080:Acetals; D000970:Antineoplastic Agents; D006571:Heterocyclic Compounds; D009183:Mycotoxins; D013141:Spiro Compounds; C416203:talaromycin B; D004970:Estrone