Total steroid synthesis employing substituted isoxazole derivatives

A process for the preparation of a steroidal compound of the formula ##STR33## wherein R'.sub.15 is hydrogen or lower alkyl;

• Z is selected from the group consisting of carbonyl, lower alkylenedioxymethylene, di-lower alkoxymethylene, phendioxymethylene and a group of the formula ##STR34## wherein R.sub.7 is selected from the group consisting of hydrogen, lower alkyl, lower alkoxy-lower alkyl, phenyl-lower alkyl, tetrahydropyranyl and lower acyl;
• R.sub.8 is selected from the group consisting of hydrogen and lower alkyl;
• the configuration is trans-anti-trans-anti;
• R.sub.1 is a primary alkyl group of from 1 to 5 carbons and m is 1 or 2
• which comprises treating a starting reactant of the formula ##STR35## wherein R.sub.15 and R.sub.16 are hydrogen or lower alkyl, with the proviso that when R.sub.15 is lower alkyl, R.sub.16 equals R.sub.15, when R.sub.16 is hydrogen, R.sub.15 is lower alkyl and when R.sub.15 is hydrogen, R.sub.16 is lower alkyl;
• Z is selected from the group consisting of carbonyl, lower alkylenedioxymethylene, di-lower alkoxymethylene, phendioxymethylene and a group of the formula ##STR36## wherein R.sub.7 is as above;
• R.sub.8 is selected from the group consisting of hydrogen and lower aliphatic hydrocarbyl;
• the configuration is trans-anti-trans;
• and R.sub.1 and m are as above
• in the following manner;
• a. converting the free carbonyl group or groups of the starting reactant to a derivative of the formula ##STR37## wherein R.sub.15, R.sub.16, R.sub.1 and m are as above, the D-ring Z" is selected from the group consisting of lower alkylenedioxymethylene, phendioxymethylene, di-lower alkoxymethylene and a group of the formula ##STR38## wherein R.sub.7 is as above and R.sub.8 is selected from the group consisting of hydrogen and lower aliphatic hydrocarbyl;
• and the B-ring Z" is selected from the group consisting of lower alkylenedioxymethylene, phendioxymethylene, di-lower alkoxymethylene and a group of the formula ##STR39## wherein R.sub.7 is as above and R.sub.8 is selected from the group consisting of hydrogen;
• b. contacting the protected carbonyl compound of step (a) with hydrogen to yield a vinylogous amide of the formula ##STR40## wherein R.sub.15, R.sub.16, R.sub.1 and m are as above, the D-ring Z" is selected from the group consisting of lower alkylenedioxymethylene, phendioxymethylene, di-lower alkoxymethylene and a group of the formula ##STR41## wherein R.sub.7 is as above and R.sub.8 is selected from the group consisting of hydrogen and lower alkyl;
• and the B-ring Z" is selected from the group consisting of lower alkylenedioxymethylene, phendioxymethylene, di-lower alkoxymethylene and a group of the formula ##STR42## wherein R.sub.7 is as above and R.sub.8 is selected from the group consisting of hydrogen;
• c. contacting the vinylogous amide of step (b) with aqueous base to yield a compound of the formula ##STR43## wherein R.sub.15, R.sub.1 and m are as above, the D-ring Z" is selected from the group consisting of lower alkylenedioxymethylene, phendioxymethylene, di-lower alkoxymethylene and a group of the formula ##STR44## wherein R.sub.7 is selected from the group consisting of hydrogen, lower alkyl, lower alkoxy-lower alkyl, phenyl-lower alkyl and tetrahydropyranyl and R.sub.8 is selected from the group consisting of hydrogen and lower alkyl;
• and the B-ring Z" is selected from a group consisting of lower alkylenedioxymethylene, phendioxymethylene, di-lower alkoxymethylene and a group of the formula ##STR45##
• wherein R.sub.7 is as above and R.sub.8 is selected from the group consisting of hydrogen;
• and
• d. removing the carbonyl protecting group or groups formed in step (a), regenerating the free carbonyl group or groups to yield a B-ring ketone of the formula ##STR46## wherein R.sub.15, R.sub.1, m and the D-ring Z" are as above, cyclizing the B-ring ketone and recovering the steroid.