Loading...
Please wait, while we are loading the content...
Similar Documents
The synthesis and reactivity of 3β-(2-alkynylsulfonyl)- and 3β-(2-alkynylsulfonylmethyl) androst-5-en-17-ones as inhibitors of glucose-6-phosphate dehydrogenase
| Content Provider | Semantic Scholar |
|---|---|
| Author | Williams, J. Rodman Boehm, Jeffrey Charles |
| Copyright Year | 1995 |
| Abstract | 3β-(Hexadec-2-ynylsulfonyl)androst-5-en-17-one, 2c, was designed as an analog of dehydroepiandrosterone sulfatide 1c, a potent, natural inhibitor of glucose-6-phosphate dehydrogenase (G6PDH). Nucleophilic substitution of 1-bromo hexadec-2-yne 11 with 3β-mercaptoandrost-5-en-17-one followed by oxidation afforded 2c. The propargylic sulfone 2c may tautomerize to the electrophilic allenic sulfone 3a and thus function as a masked affinity label of the steroidal binding site of G6PDH. Since 2c demonstrated low potency as an inhibitor of G6PDH, a sulfonylmethyl analog 4b was also designed and synthesized. Synthesis of 4b began by methylenation of androst-5-en-3,17-dione 17-ketal 6 with the Tebbe reagent, to yield the 3-methyleneandrost-5-ene 7. Hydroboration, followed by oxidation, gave a mixture of 3α- and 3β-hydroxymethyl isomers 8a and 8b, respectively. The 3β alcohol 8b was converted to the thiol 10. Alkylation of 10 with 1-bromo-2-hexadecyne 11, followed by selective oxidation, gave the desired acetylenic sulfone 4b. Insertion of the methylene in 4a and 4b significantly increased their G6PDH inhibitory properties over the initial compounds, 2b and 2c. |
| Starting Page | 699 |
| Ending Page | 708 |
| Page Count | 10 |
| File Format | PDF HTM / HTML |
| DOI | 10.1016/0039-128X(95)00094-7 |
| Volume Number | 60 |
| Alternate Webpage(s) | https://api.elsevier.com/content/article/pii/0039128X95000947 |
| Alternate Webpage(s) | https://www.sciencedirect.com/science/article/pii/0039128X95000947?dgcid=api_sd_search-api-endpoint |
| Alternate Webpage(s) | https://doi.org/10.1016/0039-128X%2895%2900094-7 |
| Journal | Steroids |
| Language | English |
| Access Restriction | Open |
| Content Type | Text |
| Resource Type | Article |
