Stereoselective introduction of 7 or 8-substits. in oestratriene - by reacting tetra:ene with formaldehyde, then redn. or hydrogenation, and new process intermediates

摘要

Prepn. of oestratriene-3,17-diol derivs. of formula (I) comprises (1) reacting tetraene (III) with HCHO in presence of Lewis acid to give hydroxymethyl cpds. (IIa) or (IIb), then (2) catalytic hydrogenation of (IIa) to give (I; X=alpha-CH2OH, Y=Z=alpha-H); or Birch redn. of (IIa) to give (I; X=alpha-CH2OH+ Y=beta-H; Z=alpha-H), or catalytic hydrogenation of (IIb) to give (I; Y=alpha-CH2OH; Z=alpha-H; X=H). The CH2OH can then be converted conventionally to other values of X or Y, and opt. the protecting gps. R'1 and R'2 are then removed. Cpds. (IIa) and (IIb) are new, where G+K = double bond and L=H; or G=H and K+L= double bond; R'1 and R'2= OH protecting gp.; (a) X=alpha-CH2OH, to syloxymethyl, Me, CHO, formyldithioalkyl-ketal, 2-14C alkyl or alk-1,2-enyl (which can include additional double bonds); Y=Z=alpha-H; (b) is as in (a); Y =beta-H and Z=alpha-H; (c) X=H; Y is as defined for X in (a); Z=alpha-H; R1 and R2= H or OH protecting gps.. USE/ADVANTAGE - (I) have biological activity; cpds. with 7alpha- or 8alpha- substits. have stronger activity than unsubstd. analogues. This method provides stereoselective introduction of opt. substd. 7/8 alkyl substits. in the alpha configuration, so the troublesome sepn. of alpha/beta forms is avoided.