Robert G. Christiansen

Synthesis and androgen receptor affisity of steroidal methylsulfonylforans and a menthylsulfonylthiophene

Abstract Syntheses of the unsubstituted steroidal [3,2-b]furan ( 3a ), thiophene ( 3b ) and [2,3-b]furan ( 24 ) are described. Lithiation of the THP ethers 18a and 18b followed by the reaction with methyl disulfide and deprotection gave the 5′-methylsulfide derivatives 19a and 19b . Oxidation of the sulfides and ethynylation provided the compounds 2a and 2b . Swern oxidation of the [2,3-b]furan 24 with DMSO/TFAA/diisopropylethylamine resulted in oxidation to the 17-ketone and introduction of a 5′-methylthio group to give 25 . Ethynylation at C-17 followed by oxidation of the sulfide group provided the product 27 . 5′-Methylsulfonyl[3,2-b]furanosteroid 2a bound to the rat ventral prostate androgen receptor. However, the corresponding thiophene 2b and the [2,3-b]furan 27 lacked affinity for the receptor.

An Orally Active Hypocholesteremic Steroid with Reduced Uterotrophic Effect

Summary A series of reference and experimental estrogens has been evaluated in terms of the amount required to reduce total serum cholesterol 33% in mature male rats and the amount required to increase the uterine weights of weanling female rats 50 mg over those of the controls. The resultant hypocholesteremic: uterotrophic dissociations were: estrone 50, Premarin® 20, estrone methyl ether >3.2, 16α-chloroestrone methyl ether 2.4, 17-(4-hydroxy-1-butynyl)-3-methoxyestra-1,3,5 (10)-trien-17β-ol 1.6, 17-(3-hydroxypropyl)-3-methoxyestra-1,3,5 (10)-trien-17β-ol 0.2, and 17-(3-hydroxy-1-propynyl)-3-methoxyestra-1,3,5 (10) -trien-17β-ol 17α-hydrocinnamate 0.015. The hydroxy propynyl compound thus has the best dissociation of any steroid noted.