Unknown

Dataset Information

0

The cephalostatins. 22. synthesis of bis-steroidal pyrazine pyrones (1).

ABSTRACT: Cephalostatin 1 (1), a remarkably strong cancer cell growth inhibitory trisdecacyclic, bis-steroidal pyrazine isolated from the marine tube worm Cephalodiscus gilchristi, continues to be an important target for practical total syntheses and a model for the discovery of less complex structural modifications with promising antineoplastic activity. In the present study, the cephalostatin E and F rings were greatly simplified by replacement at C-17 with an ?-pyrone (in 12), typical of the steroidal bufodienolides, and by a dihydro-?-pyrone (in 16). The synthesis of pyrazine 12 from 5?-dihydrotestosterone (nine steps, 8% overall yield) provided the first route to a bis-bufadienolide pyrazine. Dihydro-?-pyrone 16 was synthesized in eight steps from ketone 13. While only insignificant cancer cell growth inhibitory activity was found for pyrones 12 and 16, the results provided further support for the necessity of more closely approximating the natural D-F ring system of cephalostatin 1 in order to obtain potent antineoplastic activity.

SUBMITTER: Pettit GR 

PROVIDER: S-EPMC3409868 | biostudies-literature | 2012 Jun

REPOSITORIES: biostudies-literature

Json Xml
altmetric image

Publications

The cephalostatins. 22. synthesis of bis-steroidal pyrazine pyrones (1).

Pettit George R GR   Moser Bryan R BR   Mendonça Ricardo F RF   Knight John C JC   Hogan Fiona F  

Journal of natural products 20120518 6

Cephalostatin 1 (1), a remarkably strong cancer cell growth inhibitory trisdecacyclic, bis-steroidal pyrazine isolated from the marine tube worm Cephalodiscus gilchristi, continues to be an important target for practical total syntheses and a model for the discovery of less complex structural modifications with promising antineoplastic activity. In the present study, the cephalostatin E and F rings were greatly simplified by replacement at C-17 with an α-pyrone (in 12), typical of the steroidal  ...[more]

Similar Datasets

Unknown The cephalostatins. 21. Synthesis of bis-steroidal pyrazine rhamnosides (1).
| S-EPMC3251514 | biostudies-literature
Unknown Ritterostatin G<sub>N</sub> 1<sub>N</sub> , a Cephalostatin-Ritterazine Bis-steroidal Pyrazine Hybrid, Selectively Targets GRP78.
| S-EPMC5562448 | biostudies-literature
Unknown μ-Pyrazine-bis-[tetra-aqua-cadmium(II)] μ-pyrazine-bis-[tetra-acetato-cadmium(II)].
| S-EPMC2961302 | biostudies-literature
Unknown Bis(triethyl-ammonium) bis-(μ-pyrazine-2,3-dithiol-ato)bis-(pyrazine-2,3-dithio-lato)diferrate(III) methanol disolvate.
| S-EPMC2967914 | biostudies-literature
Unknown Poly[[hepta-μ(2)-aqua-bis-(μ(2)-pyrazine-2-carboxyl-ato)dibarium] bis-(pyrazine-2-carboxyl-ate)].
| S-EPMC3051667 | biostudies-literature
Unknown Diaqua-bis-(nitrato-κ(2)O,O')bis-(pyrazine-2-carboxamide-κN(4))cadmium-pyrazine-2-carboxamide (1/2).
| S-EPMC3393246 | biostudies-literature
Unknown Bis(2-amino-pyrazine-?N)dichlorido-zinc.
| S-EPMC3212136 | biostudies-literature
Unknown Poly[bis-(cyanato-κN)bis-(μ-pyrazine-κN:N')cobalt(II)].
| S-EPMC2968858 | biostudies-literature
Unknown 2,5-Bis(pyridinium-2-yl)-3,6-bis-(2-pyrid-yl)pyrazine bis-[tetra-chlorido-aurate(III)].
| S-EPMC3201553 | biostudies-literature
Unknown Crystal structure of di-aqua-bis-(2,6-di-methyl-pyrazine-?N)bis-(thio-cyanato-?N)cobalt(II) 2,5-di-methyl-pyrazine tris-olvate.
| S-EPMC4719868 | biostudies-literature