Total syntheses of specialized pro-resolving mediators (spms), structural isomers and structural analogs

A method of preparing a protectin, protectin analog, structural isomer, or a pharmaceutically acceptable salt thereof, the method comprising reacting a compound of formula (XX):

• wherein:
• X1 and X2 are each independently hydroxy or OP, wherein P is a hydroxy protecting or hydroxy activating group;
• under conditions sufficient to produce a compound of formula (XXI):
• wherein R is alkyl(C≤12), cycloalkyl(C≤12), alkenyl(C≤12), alkylidene(C≤12), alkynyl(C≤12), aryl, aralkyl, heteroaryl or heteroaralkyl.

A method of preparing a protectin, protectin analog, structural isomer, or a pharmaceutically acceptable salt thereof, the method comprising reacting a compound of formula (XXIII):

• wherein:
• X1 is hydroxy or OP, wherein P is a hydroxy protecting or hydroxy activating group;
• under conditions sufficient to produce a compound of formula (XXIV):
• wherein:
• R1 and R2 are independently H, alkyl(C≤12), cycloalkyl(C≤12), alkenyl(C≤12), alkylidene(C≤12), alkynyl(C≤12), aryl, aralkyl, heteroaryl or heteroaralkyl;
• Y is O, N, S or SO2;
• and
• n is 0 or 1.

A method of preparing a protectin, protectin analog, structural isomer, or a pharmaceutically acceptable salt thereof, the method comprising reacting a compound of formula (XXXIII):

• wherein:
• X1 and X3 are each independently hydroxy or OP, wherein P is a hydroxy protecting group or hydroxy activating group;
• with a Wittig reagent under conditions sufficient to produce the compound of formula (XXXIV):
• wherein X1 and X3 and n are as defined above.

A protectin or protectin, protectin analog, structural isomer, or a pharmaceutically acceptable salt thereof, having the structure:

• wherein:
• R1 and R2 are independently selected from alkyl(C≤12), alkoxy, alkylamino, dialkyl amino, cycloalkyl(C≤12), alkenyl(C≤12), alkylidene(C≤12), alkynyl(C≤12), aryl, aryloxy, aralkyl, heterocyclyl, heteroaryl, heterocyclyloxy, or heteroaralkyl;
• and
• Z1, Z2, Z3, Z4, Z5 and Z6 are independently selected from, H, D, T, Br76, I123 and I125, I131.

A protectin or protectin, protectin analog, structural isomer, or a pharmaceutically acceptable salt thereof, having the structure:

• wherein:
• R1 and R2 are independently selected from alkyl(C≤12), alkoxy, alkylamino, dialkyl amino, cycloalkyl(C≤12), alkenyl(C≤12), alkylidene(C≤12), alkynyl(C≤12), aryl, aryloxy, aralkyl, heterocyclyl, heteroaryl, heterocyclyloxy, or heteroaralkyl;
• and
• Z1, Z2, Z3, Z4, Z5 and Z6 are independently selected from, H, D, T, Br76, I123 and I125, I131.

A protectin or protectin, protectin analog, structural isomer, or a pharmaceutically acceptable salt thereof, having the structure:

• wherein:
• R1 and R2 are independently selected from alkyl(C≤12), alkoxy, alkylamino, dialkyl amino, cycloalkyl(C≤12), alkenyl(C≤12), alkylidene(C≤12), alkynyl(C≤12), aryl, aryloxy, aralkyl, heterocyclyl, heteroaryl, heterocyclyloxy, or heteroaralkyl;
• and
• Z1 and Z2 are independently selected from, H, D, T, Br76, I123 and I125, I131.