Patent ID: 8183376

Claim:
A synthetic method comprising: stereoselectively reducing a ketone of a morphinone to form a reduced morphinone by contacting the morphinone with a stereoselective reducing agent, wherein the morphinone has the following structure wherein: R 1 is H or a hydroxyl protecting group; wherein the stereoselective reducing agent is a single agent or combination of agents selected from the group consisting of lithium triethylborohydride, sodium triethylborohydride, potassium triethylborohydride, sodium triacetoxyborohydride, potassium triacetoxyborohydride, lithium tri-sec-butylborohydride, sodium tri-sec-butylborohydrid, potassium tri-sec-butylborohydride, lithium 9-borabicyclo[3.3.1]-nonane hydride, lithium hexylborohydride, lithium trisiamylborohydride, lithium triethylborodeuteride, and LiA1H(Cet 2 CMe 2 ) 3 ; and wherein the molar amount of the reduced morphinone in an α epimer form is at least 65% of the molar amount of morphinone contacted with the stereoselective reducing agent; and covalently attaching a water-soluble polymer to the reduced morphinone.