Cyclopentyl ethers

Chemical Name 3-(cyclopentyloxy)-19-nor-17a-pregna-1,3,5(10)-trien-20-yn-17-ol Common Name 17a-ethinylestradiol 3-cyclopentyl ether... 

A solution of 1.5 grams of 17a-ethynyl estradiol in 50 cc of absolute ethanol is added slowly to a mixture of 3 grams of cyclopentyl bromide and 2 grams of potassium carbonate. This mixture is heated to reflux and stirred for 3 hours, then filtered. Most of the alcohol is eliminated by distillation and the resulting solution diluted with water, and cooled in an ice-bath. The product which precipitates Is collected by filtration, washed and dried. After recrystallization from methanol the 3-cyclopentyl ether of 17a-ethynyl estradiol shows a melting point of 107° to 108°C. 

Common Name 17a-Ethinylestradiol 3-cyclopentyl ether Structural Formula ... 

Further investigations resulted in the discovery that etherification of the 3-hydroxy group of ethinyl estradiol resulted in formation of potent orally active oestrogens such as mestranol (the 3-methyl ether) and quinestrol (the 3-cyclopentyl ether), although this is not now used in oral contraceptives (Fig. 20.27). 

SAMPLE SOLUTION (a) In the reaction of dialkyl ethers with excess hydrogen bromide, each alkyl group of the ether function is cleaved and forms an alkyl bromide. Because bromocydopentane and 1-bromobutane are the products, the starting ether must be butyl cyclopentyl ether. 

Some examples will help clarify this process. Suppose the target is benzyl cyclopentyl ether ... 

Written in the forward direction, our proposed synthesis of benzyl cyclopentyl ether is as follows ... 

Ether formation often leads to enhanced oral activity. 17/8-Hydroxy-5a-androstan-3-one 17-(rmethoxy)cyclopentyl ether (D-130), 17)3-hydroxy-5a-androstan-3-one 17-(l -ethoxy)cyclopentyI ether (D-132), 17j3-hydroxy-5a-androst-l-en-3-one 17-(r-ethoxy)cyclopentyl ether (A-163), and 17j3-hydroxy-5a-androst-l-en-3-one 17-cyclopent-r-enyl ether (A-164) are all reported to possess favorable anabolic-androgenic ratios with increased anabolic and androgenic properties. The enhancement of oral activity is interesting in view of the fact that the ether bond of these compounds is easily broken, as manifested by the strongly enhanced excretion of 17-ketosteroids in humans treated with the ether derivatives [144]. 

C10H18O cyclopentyl ether 10137-73-2 480.98 42.060 2 20832 Cl OH1804 3-tert-butyl adipic acid 10347-88-3 537.22 47.471 2... 

The poiyether poiy(bisphenol F digiycidyi ether) shows a weight ioss as low as 80° C in NaOH [23]. Some other poiyethers are described in literature, such as poly[bis(2,3-epoxy-cyclopentyl)ether], poly(1,4-butandioi digiycidyi ether), poly(phenyl glycidyi ether), poly(1,2-epoxy-3-phenoxypropane), etc. The structures of the main sequence of these poiymers after curing are shown beiow ... 

Finally, a series of cyclopentyl ethers was identified as potent, metabolicaUy stable derivatives leading to the discovery of a next generation lead series. 

Steroids - The metabolism of orally administered ethynylestradiol-6,7- H (EE) and its SjT- H-S-cyclopentyl-l- C ether (EECPE) was studied in patients with externalized bile ducts.EECPE was cleaved either to EE amd cyclopentanol derivatives (urinary products) or to various conjugation products of compounds containing an intact cyclopentyl ether linkage (urinary and biliary products). In patients given EE, the unaltered compound was the main excretory product in the glucuronide and sulfate fractions of urine and bile, other more polar metabolites were also excreted, two of them presumed to be 6a-hydroxy EE and 6a-hydroxy EECPE. 

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