Synthesis of resorcylic acid lactones useful as therapeutic agents

A compound of formula II or II′, or a tautomer thereof, a pharmaceutically acceptable salt, solvate, ester or prodrug thereof:

• wherein:
• X is O, S or NR;
• Y is —OR, —O—(CH2)mCOOR, —O—(CH2)mCON(R)2, —N(R)2, —N(R)SOR or —N(R)SO2R, wherein the groups bound to the nitrogen atom may be in Z- or E-configuration;
• R1 and R2 are independently hydrogen, halogen, OR, N(R)2, SR, azido, nitro, cyano, aliphatic, aryl, alkylaryl, arylalkyl, heterocyclyl, heteroaryl, —S(O)R, —S(O)2R, —SO2N(R)2, —N(R)SO2R, —N(CO)R, —N(CO)N(R)2, —N(CO)OR, —O(CO)R, —(CO)R, —(CO)OR, —(CO)N(R)2, —O(CO)OR, or —O(CO)N(R)2;
• R3, R4, R5, R6, R7, R8, R9 and R10 are independently hydrogen, halogen, azido, nitro, cyano, aliphatic, alkylaryl, aralkyl, aryl, heteroalkyl, alkylheteroaryl, heterocyclyl, heteroaryl, OR, N(R)2, SR, —O(CH2)mN(R)C(O)(CH2)pR, —O(CH2)mOC(O)(CH2)pR, —O(CH2)mC(O)(CH2)pN(R)2, —O(CH2)mC(O)(CH2)pOR, —O(CH2)mN(R)C(O)(CH2)pOR, —O(CH2)mN(R)C(O)(CH2)pN(R)2, —O(CH2)mOC(O)(CH2)pOR, —O(CH2)mOC(O)(CH2)pN(R)2, —NR(CH2)mN(R)C(O)(CH2)pR, —NR(CH2)mOC(O) (CH2)pR, —NR(CH2)mC(O)(CH2)pN(R)2, —NR(CH2)mC(O)(CH2)pOR, —NR(CH2)mN(R)C(O)(CH2)pOR, —NR(CH2)mN(R)C(O)(CH2)pN(R)2, —NR(CH2)mOC(O)(CH2)pOR, —NR(CH2)mOC(O)(CH2)pN(R)2, —(CH2)mN(R)C(O) CH2)pR, —(CH2)mOC(O)(CH2)pR, —(CH2)mC(O)(CH2)pN(R)2, —(CH2)mC(O)(CH2)pOR, —(CH2)mN(R)C(O)(CH2)pOR, —(CH2)mN(R)C(O)(CH2)pN(R)2, —(CH2)mOC(O)(CH2)pOR, —(CH2)mOC(O)(CH2)pN(R)2, —(CH2)mN3, —O(CH2)mN3—(CH2)mN(R)2, —(CH2)mOR, —(CH2)mS(O)(CH2)pR, —(CH2)mS(O)2(CH2)pR, —(CH2)mSO2(CH2)pN(R)2, or —(CH2)mN(R)SO2(CH2)pR;
• and
• each R is independently R11, hydrogen, aliphatic, amino, azido, cyano, nitro, alkylamino, dialkylamino, OH, alkoxy, carbonylamino, aminocarbonyl, alkoxycarbonyl, carbonyloxy, carboxy, acyl, aryl, alkaryl, arylalkyl including benzyl, heteroalkyl, heteroaryl, heterocyclyl, or a protecting group;
• or two R on the same nitrogen are taken together with the nitrogen to form a 5-8 membered heterocyclic or heteroaryl ring;
• wherein where a group contains more than one R substituent;
• wherein R is optionally substituted, and each R can be the same or different;
• R11 is the group:
• where Z is an inorganic or organic counterion;
• m and p are independently 0, 1, 2, 3, 4 or 5;
• wherein in formula II′, when X is O, then at least one of R5, R6, R7, R8, R9 or R10 is not hydrogen;
• and
• provided that when Y is —OR, R is not H.