Peptidomimetic protease inhibitors

A compound of formula 24

• wherein:
• is optionally substituted cycloalkyl or optionally substituted fused arylcycloalkyl;
• R11 is —CO2R13;
• R12 is an iminic glycinimide derivative adduct;
• and
• R13 is acid protecting group or optionally substituted aliphatic group.

A compound of formula 25

• wherein:
• R14 is —CONR15R15, —CN;
• or —CO2R16;
• R15 is optionally substituted aliphatic group;
• and
• R16 is acid protecting group, optionally substituted aryl, or optionally substituted aliphatic group.

A compound of formula 26

• wherein:
• pO is amide protecting group;
• R14 is —CONR15R15, —CN;
• or —CO2R16;
• R15 is optionally substituted aliphatic group;
• and
• R16 is acid protecting group, optionally substituted aryl, or optionally substituted aliphatic group.

A compound of formula 27

• wherein:
• pO is selected from the group consisting of BOC, CBz, and —CO2 alkyl;
• R14 is —CONR15R15, —CN;
• or —C2R16;
• R15 is optionally substituted aliphatic group;
• and
• R16 is acid protecting group, optionally substituted aryl, or optionally substituted aliphatic group.

A process for preparing a chiral bicycloprolinate compound of formula 28

• comprising the steps of:
• (a) cleaving and cyclizing a compound of formula 24
• wherein:
• is optionally substituted cycloalkyl or optionally substituted fused arylcycloalkyl;
• R11 is —CO2R13;
• R12 is an iminic glycinimide derivative adduct;
• R13 is acid protecting group or optionally substituted aliphatic group;
• under cleaving and cyclizing conditions to form a compound of formula 25
• wherein:
• R14 is —CONR15R15, —CN;
• or —CO2R16;
• R15 is optionally substituted aliphatic group;
• R16 is acid protecting group, optionally substituted aryl, or optionally substituted aliphatic group;
• and
• (b) protecting the nitrogen of the lactam moiety in the compound of formula 25 with an amide protecting group to form a compound of formula 26
• wherein:
• pO is amide protecting group;
• R14 is as described herein;
• and
• (c) reducing the compound of formula 26 under reducing conditions to form a compound of formula 27
• wherein:
• pO and R14 are as described herein;
• and
• (d) deprotecting the compound of formula 27 under deprotecting conditions to form a compound of formula 28
• wherein:
• R14 is as described herein.