Novel isomers of bufalin and resibufogenin and their preparation

A compound having the general formula ##STR55## wherein R is selected from the group consisting of ##STR56## and wherein S is selected from the group consisting of sugars.

A compound having the general formula ##STR57## wherein R is selected from the group consisting of ##STR58##

A compound having the general formula ##STR59## wherein R is selected from the group consisting of ##STR60## and wherein S is selected from the group consisting of sugars.

A method of preparing isobufalin (a) of formula ##STR61## comprising the steps of:

• (a) reacting a compound having the formula ##STR62## wherein X is a blocking group, with an anion of formula ##STR63## where Z is selected from the group consisting of ##STR64## and CH.sub.3 --O--CH.sub.2 --O--CH.sub.2 --, to produce a tertiary alcohol having the formula ##STR65## (b) acetylating said tertiary alcohol and subjecting the resulting 17-acetate to treatment with base in organic solution to produce an allylic alcohol having the formula ##STR66## (c) selectively hydrogenating the 16,17 double bond of said allylic alcohol by hydrogenating over a hydrogenation catalyst containing a metal from the platinum group to produce a 16,17 saturated ketal;
• (d) hydrolyzing said 16,17 saturated ketal in acid conditions to produce a furyl aldehyde, and then reducing said furyl aldehyde with a hydride reducing agent to produce a furyl methylene alcohol having the formula ##STR67## (e) oxidizing said furyl methylene alcohol to produce a 23-hydroxy ketohemiacetal having the formula ##STR68## and then converting said ketohemiacetal to isobufalin (a).

A method of preparing isobufalin (b) of the formula ##STR73## comprising the steps of:

• (a) reacting a compound having the formula ##STR74## wherein X is a blocking group, with an anion of formula ##STR75## where Z is selected from the group consisting of ##STR76## and CH.sub.3 --O--CH.sub.2 --O--CH.sub.2 --, to produce a tertiary alcohol having the formula ##STR77## (b) acetylating said tertiary alcohol and subjecting the resulting 17-acetate to treatment with base in organic solution to produce an allylic alcohol having the formula ##STR78## (c) selectively hydrogenating the 16,17 double bond of said allylic alcohol by hydrogenating over a hydrogenation catalyst containing a metal from the platinum group to produce a 16,17 saturated ketal;
• (d) hydrolyzing said 16,17 saturated ketal in acid conditions to produce a furyl aldehyde, and then reducing said furyl aldehyde with a hydride reducing agent to produce a furyl methylene alcohol having the formula ##STR79## (e) oxidizing said furyl methylene alcohol to produce a 21-hydroxy ketohemiacetal having the formula ##STR80## and then converting said ketohemiacetal to isobufalin (b).

A method of preparing isoresibufogenin (a) of the formula ##STR85## comprising the steps of (a) reacting a compound having the formula ##STR86## , wherein X is a blocking group, with an anion of formula ##STR87## , where Z is selected from the group consisting of ##STR88## and CH.sub.3 --O--CH.sub.2 --O--CH.sub.2 --, to produce a tertiary alcohol having the formula ##STR89## (b) acetylating said tertiary alcohol and subjecting the resulting 17-acetate to treatment with base in organic solution to produce an allylic alcohol having the formula ##STR90## (c) selectively hydrogenating the 16,17 double bond of said allylic alcohol by hydrogenating over a hydrogenation catalyst containing a metal from the platinum group to produce a 16,17 saturated ketal;

• (d) hydrolyzing said 16,17 saturated ketal in acid conditions to produce a furyl aldehyde, and then reducing said furyl aldehyde with a hydride reducing agent to produce a furyl methylene alcohol having the formula ##STR91## (e) oxidizing said furyl methylene alcohol to produce a 23-hydroxy ketohemiacetal having the formula ##STR92## and then converting said ketohemiacetal to isoresibufogenin (a).

A method of preparing isoresibufogenin (b) of the formula ##STR97## comprising the steps of (a) reacting a compound having the formula ##STR98## , wherein X is a blocking group, with an anion of formula ##STR99## , where Z is selected from the group consisting of ##STR100## and CH.sub.3 --O--CH.sub.2 --O--CH.sub.2 --, to produce a tertiary alcohol having the formula ##STR101## (b) acetylating said tertiary alcohol and subjecting the resulting 17-acetate to treatment with base in organic solution to produce an allylic alcohol having the formula ##STR102## (c) selectivey hydrogenating the 16,17 double bond of said allylic alcohol by hydrogenating over a hydrogenation catalyst containing a metal from the platinum group to produce a 16,17 saturated ketal;

• (d) hydrolyzing said 16,17 saturated ketal in acid conditions to produce a furyl aldehyde, and then reducing said furyl aldehyde with a hydride reducing agent to produce a furyl methylene alcohol having the formula ##STR103## (e) oxidizing said furyl methylene alcohol to produce a 21-hydroxy ketohemiacetal having the formula ##STR104## and then converting said ketohemiacetal to isoresibufogenin (b).