Preparation of 17β-(Hydroxymethyl)-3-methoxyestra-1,3,5(10)- trien-18-oic Acid 18,20-Lactone, a New C(18)-Oxygenated Steroid
✍ Scribed by Alexander Kuhl; Wolfgang Kreiser
- Publisher
- John Wiley and Sons
- Year
- 1998
- Tongue
- German
- Weight
- 114 KB
- Volume
- 81
- Category
- Article
- ISSN
- 0018-019X
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✦ Synopsis
Lactone 13 was synthesized by intramolecular radical-mediated oxygenation of the angular Me(18) group of the 17b-configurated sterol 3. Several substrate-controlled methods for stereoselective construction of the hydroxymethyl side chain of 3 were investigated.
Helvetica Chimica Acta ± Vol. 81 (1998) 2264 1 ) Alkene 5 is obtained from estradiol 3-methyl ether or the corresponding 17-(tosyloxy) derivative (see and ). In accordance with the literature [1] [5], the D 13,14 isomer is also obtained in minor amounts (8%).
Purification by TLC with AgNO 3 -impregnated plates (22.5% AgNO 3 , cyclohexane/AcOEt 19 : 1; R f 0.60) provides pure 5 in 52 and 50% yield, respectively. Attempts to further functionalize the vinylic methyl group by treatment with SeO 2 lead to a complex mixture of oxygenation products, leaving, however, the vinylic methyl group untouched. 2 ) A hydroxymethyl group b-situated at C(17) instead of a substituted alkyl side chain has been demonstrated to have a yield-increasing effect in the pregnane series, due to missing steric hindrance [7b].