Synthesis and anti-cancer activity of communesin alkaloids

A compound of Formula (V):

• or a salt, tautomer, or stereoisomer thereof, wherein
• R4 is selected from H, substituted or unsubstituted C1-C12 alkyl, substituted or unsubstituted C2-C12 alkenyl, substituted or unsubstituted C2-C12 alkynyl, —C(═O)R9, —C(═O)NR9R10, —S(═O)bR12, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted carbocyclyl, and substituted or unsubstituted heterocyclyl;
• each instance of R2 and R5 are independently selected from F, Cl, Br, I, —OH, —OR9, —OC(═O)R9, —S(═O)bR12, —NR9R10, substituted or unsubstituted C1-C12 alkyl, substituted or unsubstituted C2-C12 alkenyl, substituted or unsubstituted C2-C12 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted and heterocyclyl;
• each instance of R3 is independently selected from substituted or unsubstituted C1-C12 alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted carbocyclyl, and substituted or unsubstituted heterocyclyl;
• R6 is
• X is O, NR9, or —S(═O)bR12;
• each instance of R7 and R8 is independently selected from H, halogen, substituted or unsubstituted C1-C12 alkyl, substituted or unsubstituted C2-C12 alkenyl, substituted or unsubstituted C2-C12 alkynyl, —C(═O)R9, —C(═O)NR9R10, —S(═O)bR12, —OH, —OR9, —OC(═O)R9, —NR9R10, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted carbocyclyl, and substituted or unsubstituted heterocyclyl, or wherein two R7 or two R8 groups taken together with the carbon atoms to which they are attached form a substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted carbocyclic, or substituted or unsubstituted heterocyclic ring;
• each instance of R9 and R10 are independently selected from H, substituted or unsubstituted C1-C12 alkyl, substituted or unsubstituted C2-C12 alkenyl, substituted or unsubstituted C2-C12 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted carbocyclyl, and substituted or unsubstituted heterocyclyl, or wherein R9 and R10 taken together with the carbon atoms to which they are attached form a substituted or unsubstituted heteroaryl or substituted or unsubstituted heterocyclic ring;
• each instance of R12 is independently substituted or unsubstituted C1-C12 alkyl, substituted or unsubstituted C2-C12 alkenyl, substituted or unsubstituted C2-C12 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, —(CH2)cSiMe3, or —(CH2)cR9;
• R13 and R13′ are each independently hydrogen,
• R14 is —CN, —OH, —OR9, —NR9R10, S(═O)bR12, or P(═O)(OR9)2
• each instance of R15 and R16 is independently selected from H, substituted or unsubstituted C1-C12 alkyl, substituted or unsubstituted C2-C12 alkenyl, substituted or unsubstituted C2-C12 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted carbocyclyl, and substituted or unsubstituted heterocyclyl, or wherein R15 and R16 taken together with the carbon atoms to which they are attached form a substituted or unsubstituted carbocyclic ring, or substituted or unsubstituted heterocyclic ring;
• m and t are each independently an integer from 0 to 3, inclusive;
• n, r, and s are each independently an integer from 0 to 4, inclusive;
• v is an integer from 0 to 4, inclusive;
• each instance of c is independently an integer from 0 to 6, inclusive;
• each instance of b is independently 0, 1, or 2;
• u is 0, 1, or 2;
• and
• q is an integer from 1 to 6, inclusive.

A compound of Formula (III′):

• or a salt, tautomer, or stereoisomer thereof, wherein
• R4 is selected from H, substituted or unsubstituted C1-C12 alkyl, substituted or unsubstituted C2-C12 alkenyl, substituted or unsubstituted C2-C12 alkynyl, —C(═O)R9, —C(═O)NR9R10, —S(═O)bR12, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted carbocyclyl, and substituted or unsubstituted heterocyclyl;
• each instance of R5 is independently selected from F, Cl, Br, I, —OH, —OR9, —OC(═O)R9, —S(═O)bR12, —NR9R10, substituted or unsubstituted C1-C12 alkyl, substituted or unsubstituted C2-C12 alkenyl, substituted or unsubstituted C2-C12 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted carbocyclyl, and substituted or unsubstituted heterocyclyl;
• R6 is
• X is O, NR9, or —S(═O)bR12;
• each instance of R8 is independently selected from H, halogen, substituted or unsubstituted C1-C12 alkyl, substituted or unsubstituted C2-C12 alkenyl, substituted or unsubstituted C2-C12 alkynyl, —C(═O)R9, —C(═O)NR9R10, —S(═O)bR12, —OH, —OR9, —OC(═O)R9, —NR9R10, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted carbocyclyl, and substituted or unsubstituted heterocyclyl;
• each instance of R9 and R10 is independently selected from H, C1-C12 alkyl, C2-C12 alkenyl, C2-C12 alkynyl, aryl, heteroaryl, carbocyclyl, and heterocyclyl, or wherein R9 and R10taken together with the carbon atoms to which they are attached form a substituted or unsubstituted heteroaryl or substituted or unsubstituted heterocyclic ring;
• each instance of R12 is independently substituted or unsubstituted C1-C12 alkyl, substituted or unsubstituted C2-C12 alkenyl, substituted or unsubstituted C2-C12 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted carbocyclyl, substituted or unsubstituted heterocyclyl, —(CH2)cSiMe3, or —(CH2)cR9;
• R13 is
• each instance of R15 and R16 is independently selected from H, substituted or unsubstituted C1-C12 alkyl, substituted or unsubstituted C2-C12 alkenyl, substituted or unsubstituted C2-C12 alkynyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted carbocyclyl, and substituted or unsubstituted heterocyclyl, or wherein R15 and R16 taken together with the carbon atoms to which they are attached form a substituted or unsubstituted carbocyclic, or substituted or unsubstituted heterocyclic ring;
• m is an integer from 0 to 3, inclusive;
• v is an integer from 0 to 4, inclusive;
• r is an integer from 0 to 4, inclusive;
• each instance of c is independently an integer from 0 to 6, inclusive;
• each instance of b is independently 0, 1, or 2;
• and
• u is 0, 1, or 2.

A compound of Formula (XIV):

• or a salt, tautomer, or stereoisomer thereof, wherein
• each instance of R3 is independently substituted or unsubstituted C1-C12 alkyl, substituted or unsubstituted aryl, substituted or unsubstituted heteroaryl, substituted or unsubstituted carbocyclyl, and substituted or unsubstituted heterocyclyl;
• and
• q is an integer from 1 to 6, inclusive.