Synthesis of tetracyclines and analogues thereof

A compound of the formula:

• or salt isomer, or tautomer thereof, wherein R3 is hydrogen;
• halogen;
• cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic;
• cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic;
• substituted or unsubstituted, branched or unbranched acyl;
• substituted or unsubstituted, branched or unbranched aryl;
• substituted or unsubstituted, branched or unbranched heteroaryl;
• —ORC;
• ═O;
• —C(═O)Rc;
• —CO2RC;
• —CN;
• —SCN;
• —SRC;
• —SORC;
• —SO2RC;
• —NO2;
• —N(RC)2;
• —NHC(O)RC;
• or —C(RC)3;
• wherein each occurrence of RC is independently hydrogen, a protecting group, aliphatic, heteroaliphatic, acyl;
• aryl;
• heteroaryl;
• alkoxy;
• aryloxy;
• alkylthio;
• arylthio;
• amino, alkylamino, dialkylamino, heteroaryloxy;
• or heteroarylthio;
• R4 is hydrogen;
• halogen;
• cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic;
• cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic;
• substituted or unsubstituted, branched or unbranched acyl;
• substituted or unsubstituted, branched or unbranched aryl;
• substituted or unsubstituted, branched or unbranched heteroaryl;
• —ORD;
• ═O;
• —C(═O)RD;
• —CO2RD;
• —CN;
• —SCN;
• —SRD;
• —SORD;
• —SO2RD;
• —NO2;
• —N(RD)2;
• —NHC(O)RD;
• or —C(RD)3;
• wherein each occurrence of RD is independently hydrogen, a protecting group, aliphatic, heteroaliphatic, acyl;
• aryl;
• heteroaryl;
• alkoxy;
• aryloxy;
• alkylthio;
• arylthio;
• amino, alkylamino, dialkylamino, heteroaryloxy;
• or heteroarylthio;
• R5 is hydrogen;
• halogen;
• cyclic or acyclic, substituted or unsubstituted, branched or unbranched aliphatic;
• cyclic or acyclic, substituted or unsubstituted, branched or unbranched heteroaliphatic;
• substituted or unsubstituted, branched or unbranched acyl;
• substituted or unsubstituted, branched or unbranched aryl;
• substituted or unsubstituted, branched or unbranched heteroaryl;
• —ORE;
• —CN;
• —SCN;
• —SRE;
• or —N(RE)2;
• wherein each occurrence of RE is independently hydrogen, protecting group, aliphatic, heteroaliphatic, acyl;
• aryl;
• heteroaryl;
• alkoxy;
• aryloxy;
• alkylthio;
• arylthio;
• amino, alkylamino, dialkylamino, heteroaryloxy;
• or heteroarylthio;
• R6 is hydrogen, halogen, substituted or unsubstituted aliphatic, substituted or unsubstituted heteroaliphatic, substituted or unsubstituted alkoxy, —CN, —SCN, —SH, alkylthio, arylthio, —NO2, amino, alkyl amino, or dialkyl amino;
• and
• each occurrence of P′ is independently hydrogen or a protecting group.