Patent GB-1314191-A (GB)
Title: Oestratrienes
IPC: A61K/
Filed: 1970-03-06
Abstract: 1314191 Steroid 14α,17α-acetals KONINKLIJKE NEDERLANDSCHE GISTEN SPIRITUSFABRIEK NV 19 April 1971 [6 March 1970] 10995/70 Heading C2U The invention comprises compounds of formula wherein R is H, C 1-9  aliphatic hydrocarbyl, C 3-6  cycloalkyl, aryl (up to C 10 ) which may be sub - stituted by one nitro or one or more methoxy groups, adamantyl, furyl or thienyl; R 1  is H or -OR 2  in which R 2  is H, C 1-3  aliphatic hydrocarbyl, #-dimethylaminoethyl, acetyl, -SO 2 OH- -SO 2 O(Alkali metal), or 1H-tetrazolyl which may be substituted by phenyl; R 3  is H, OH, OCOMe or OXO; and the broken lines in the 6,7- and 9,11-positions indicate optional bonds. CompoundsI are prepared by decarboxylation of compounds of Formula III, IV or VIII: followed, in the case of compounds IV by hydrolysis of the 14α,17α-phenylborylenedioxy group and acetalization of the resulting 14α,17α- diol with RCHO, and followed in the case of compounds VIII by 1,2-dehydrogenation (optionally also with 6,7-dehydrogenation) and then ring-A aromatization. The decarboxylation of III and IV with lead tetra-acetate yields 6α- and 6#-acetoxy compounds in admixture with the 6-unsubstituted product. Compounds I are interconvertible by (i) etherification, de-etherification and esterification at the 3-position; (ii) removal of a 3-hydroxy group by reduction of the 1H-tetrazol-5-yl or 1,3-oxazol-2-yl ether thereof, to give a 3-unsubstituted product; (iii) 9,11-dehydrogenation, e.g. with ohloranil/t-butanol; (iv) hydrolysis of 6-acetoxy; and (v) oxidation of 6-hydroxy. Compounds III, IV and VIII are prepared from the corresponding 14α,17α-diols by acetalization with RCHO or reaction with phenylboronic acid. 3 - Methoxy - 14α,17α - dihydroxy - 9α/# - estra- 1,3,5(10) - triene - 17# - carboxylic acid is prepared by hypobromite oxidation of 3-methoxy- 14α,17α - dihydroxy - 19 - nor - 9α/# - pregna- 1,3,5(10)-trien-20-one, the latter being prepared by reaction of dimethyl sulphate with 3,14α,17α - trihydroxy - 19 - nor - 9α/# - pregna - 1,3,5(10)- trien-20-one which is prepared as described in Specification 1,278,705. 14x,17a-Acetals (XVIII) of 14α,17α-dihydroxyandrosta - 1,4 - dien - 3 - one (XVII) are prepared from 3 - oxo - 14α,17α - dihydroxyandrost-4-ene-17#-carboxylic acid (XV) (see Specification 1,277,886) by the sequence: XV-# 3 - oxo - 14α,17α - phenylborylenedioxyandrost - 4- ene - 17# - carboxylic acid -# 14α,17α - phenylborylenedioxyandrost 4 - en - 3 - one -# 14α,- 17α - dihydroxyandrost - 4 - em - 3 - one (XVI) -# XVII -# XVIII. Compound XVI is said to be alternatively obtainable from 3-ethers of 3,14α-dihydroxy-androsta-3,5-dien- 17-one. 3 - Methoxy - 14α,17α - dihydroxyestra- 1,3,5(10)-triene (XXI) is prepared from 3,14α- dihydroxyestra - 1,3,5(10) - trien - 17 - one (XX) by the sequence XX-# 3-methoxy-14α-hydroxyestra - 1,3,5(10) - trien - 17 - one -# 3- methoxy - 14α - hydroxy - 17 - hydrazonoestra- 1,3,5(10) - triene -# 3 - methoxy - 14α - hydroxy- 17 - iodo - estra - 1,3,5(10),16 - tetraene -# 3- methoxy - 14α - hydroxyestra - 1,3,5(10),16 - tetraene -# 3 - methoxy - 14α - hydroxy - 16α,17α- epoxyestra-1,3,5(10)-triene -# XXI. Compounds I are said to possess estrogenic and hypocholesterolemic activities and may be made up with carriers into pharmaceutical compositions for oral and parenteral administration