Patent GB-1214506-A (GB)
Title: 03-alkyl-3,11,17,20,21-pentaoxygenated-18,19-dinopregnenes and their derivatives
IPC: C07J1/00
Filed: 1967-12-19
Abstract: 1,214,506. 13 - Alkyl - 3,11,17,20,21 - pentaoxygenated-18,19-dinorpregnenes and derivatives thereof. AMERICAN HOME PRODUCTS CORP. 19 Dec., 1967 [19 Dec., 1966 (2)], No. 57494/67. Heading C2U. A novel process for preparing a 13#-alkyl- 3,11,17,20,21 - penta - oxygenated - 18,19 - dinorpregnene comprises essentially the steps (a) converting a 3-hydroxy or protected hydroxy 13#- alkyl - 17# - ethylgona - 1,3,5(10), 9(11)-tetraen-17#-ol to a corresponding 13#- alkyl - 17# - ethylgona - 1,3,5(10) - trien - 11, 17#-diol by hydroboration, (b) protecting the generated 11-hydroxy function by conversion to an 11-oxo, -protected oxo or -protected hydroxy group; (c) dehydrating the product of (b) at the 17-position to form the corresponding 17-ethylidene compound and if desired removing the protecting group from the 11-oxo or 11- hydroxy group; (d) Birch reducing a 3-alkoxy- 1,3,5(10)-triene to form a 3-alkoxy-2,5(10)- diene, (e) hydrolysing the product of (d) to give a 5(10)-en- or 4-en-3-one, and (f) oxidizing the 17-ethylidene group at the 17-, 20- and 21- positions to form a 17,20,21-trioxygenated derivative, steps (a) to (c) being carried out in the given order and steps (d) to (f), of which (d) and (e) are optional being carried out in any convenient order, steps (d) and (e), if desired, being carried out intermediately of the various oxidation stages of step (f); and, if desired, carrying out one or more of the following optional steps at any convenient stage: (i) oxidizing an 11-hydroxy group to an 11-oxo group, (ii) reducing an 11-oxo group to an 11 #-hydroxy group, (iii) ketalizing or converting to an enol ether or enol ester group a 3-oxo group, (iv) esterifying or ketalizing an 11-hydroxy or 11- oxo group, (v) esterifying a 17- or 21-hydroxy group, (vi) ketalizing a 20-oxo group, (vii) isomerizing with acid or base a 5(10)-en-3-one to a 4-en-3-one, or (viii) forming a 3-alkoxy group from a 3-hydroxy group or from a 3-protected hydroxy group other than a 3-alkoxy group. Novel products have the formula where R<SP>1</SP> is C 2-5  alkyl; W is α- or #-OH or protected OH or oxo or protected oxo; Y is OH or protected OH and ring A is aromatic, or Y is etherified OH and there is a 2,5(10)-diene system, or Y is oxo and there is a 4- or 5(10)- double bond, or Y is protected oxo and there is a 4-, 5(10)- or 5(6)-double bond with or without a 2- or 3-double bond; and X is a #-(2<SP>1</SP>-halo, hydroxy or protected hydroxy-1<SP>1</SP>-oxo or protected oxo - ethyl) - α - hydroxy or protected hydroxy-methylene group. Figs. 1 to 7 illustrate the applications of the novel process which are described in detail. The term " oxygenated " is used to denote oxo or hydroxy groups or protected equivalents readily convertible to them, which protected groups do not necessarily contain oxygen, e.g. thioketals. In the novel process the nucleus of the pentaoxygenated pregnene and its precursors can contain further substituents other than those specified. The 13#-enantiomers may be in resolved or racemate form according as to whether the starting materials are resolved or racemic. The novel 13#-polycarbonalkyl-3,11,17,20,21- pentaoxygenated - 18,19 - dinorpregnenes and derivatives thereof have pharmacological, e.g. corticoidal, estrogenic, activity and may be made up into pharmaceutical compositions with suitable carriers. Specifications 1,214,507 and 1,214,508 are referred to.