Fullerene derivatives

A method of preparing a fullerene derivative of the following formula:

• F(—E)n(—R1)p(—R2)q
• wherein
• F is a fullerene core;
• E is E1, E2, or E3;
• in which E1 is Y1,Y2-amino, (Y1,Y2-alkyl)-amino, Y1,Y2-ethylenediamino, (dihydroxymethyl)alkylamino, (X1,X3-aryl)amino, or X1,X3-aryloxy;
• E2 is Y1,Y2-alkoxy, (Y1,Y2-amino)alkoxy, (Y1,Y2,Y3-aryl)oxy, (dihydroxyalkyl)-aryloxy, (Y1,Y2,Y3-alkyl)amino, (Y1,Y2,Y3-aryl)amino, dihydroxyalkylamino, Y1,Y2,Y3-alkoxy, (trihydroxyalkyl)alkoxy, (trihydroxyalkyl)alkylamino, (dicarboxyalkyl)amino, (Y1,Y2,Y3-alkyl)thio, (X1,X3-aryl)thio, (Y1,Y2-alkyl)thio, (dihydroxyalkyl)thio, Y1,Y2-dioxoalkyl, or tri-(Y1,Y2,Y3-methylaminocarboxyethyl)methylamino;
• and E3 is ((glycosidyl)oxoheteroaryl)amino, ((glycosidyl)oxoaryl)amino, (X1,X2,X3-heteroaryl)amino, (X1-diarylketone)amino, (X,X1-oxoaryl)amino, (X,X1-dioxoaryl)amino, (Y1-alkyl,Y2-alkyldioxoheteroaryl)amino, (Y1-alkyl,Y2-alkyldioxoaryl)amino, (di(Y1,Y2-methyl)dioxoheteroaryl)amino, (di(Y1,Y2-methyl)dioxoaryl)amino, ((glycosidyl)heteroaryl)amino, ((glycosidyl)aryl)amino, ((carboxylacetylalkyl)oxo-heteroaryl)amino, ((carboxylacetylalkyl)oxoaryl)amino, ((isopropylaminohydroxy-alkoxy)aryl)amino, (X1,X2,X3-alkylaryl)amino, (X1,X2,X3-heteroaryl)oxy, (isopropylaminohydroxyalkyl)aryloxy, (X1,X2,X3-oxoheteroaryl)oxy, (X1,X2,X3-oxoaryl)oxy, (X1,Y1-oxoheteroaryl)oxy, (X1-diarylketone)oxy, (X,X1-oxoaryl)oxy, (X1,X2-dioxoaryl)oxy, (Y1,Y2,di-aminodihydroxy)alkyl, (X1,X2-heteroaryl)thio, ((tricarboxylalkyl)ethylene-diamino)alkoxy, (X1,X2-oxoaryl)thio, (X1,X2-dioxoaryl)thio, (glycosidylheteroaryl)thio, (glycosidylaryl)thio, Y1-alkyl(thiocarbonyl)thio, Y1,Y2,-alkyl(thiocarbonyl)thio, Y1,Y2,Y3-alkyl(thiocarbonyl)thio, (Y1,Y2-aminothiocarbonyl)thio, (pyranosyl)thio, cysteinyl, tyrosinyl, (phenylalainyl)amino, (dicarboxyalkyl)thio, (aminoaryl)1-100amino, (pyranosyl)amino, (Y1-aminoaryl)1-100amino, (amino(sulfoaryl))1-100amino, peptidyl, thymidinyl, uridinyl, guanosinyl, adenosinyl, cholesteryl, or biotinylalkoxy;
• wherein X is halide;
• each of X1, X2, and X3, independently, is —Y1, —O—Y1, —S—Y1, —NH—Y1, —CO—O—Y1, —O—CO—Y1, —CO—NH—Y1, —CO—NY1Y2, —NH—CO—Y1, —SO2—Y1, —CHY1Y2, or —NY1Y2;
• and each of Y1, Y2, and Y3, independently, is —Z or —B—Z;
• in which B is —Ra—O—[Si(CH3)2—O—]1-100, C1-2000 alkyl, C6-40 aryl, C7-2000 alkylaryl, C7-2000 arylalkyl, (C1-30 alkyl ether)1-100, (C6-40 aryl ether)1-100, (C7-2000 alkylaryl ether)1-100, (C7-2000 arylalkyl ether)1-100, (C1-30 alkyl thioether)1-100, (C6-40 aryl thioether)1-100, (C7-2000 alkylaryl thioether)1-100, (C7-2000 arylalkyl thioether)1-100, (C2-50 alkyl ester)1-100, (C7-2000 aryl ester)1-100, (C8-2000 alkylaryl ester)1-100, (C8-2000 arylalkyl ester)1-100, —Ra—CO—O—(C1-30 alkyl ether)1-100, —Ra—CO—O—(C6-40 aryl ether)1-100, —Ra—CO—O—(C7-2000 alkylaryl ether)1-100, —Ra—CO—O—(C7-2000 arylalkyl ether)1-100, (C4-50 alkyl urethane)1-100, (C14-60 aryl urethane)1-100, (C10-2000 alkylaryl urethane)1-100, (C10-2000 arylalkyl urethane)1-100, (C5-50 alkyl urea)1-100, (C14-60 aryl urea)1-100, (C10-2000 alkylaryl urea)1-100, (C10-2000 arylalkyl urea)1-100, (C2-50 alkyl amide)1-100, (C7-60 aryl amide)1-100, (C8-2000 alkylaryl amide)1-100, (C8-2000 arylalkyl amide)1-100, (C3-30 alkyl anhydride)1-100, (C8-50 aryl anhydride)1-100, (C9-2000 alkylaryl anhydride)1-100, (C9-2000 arylalkyl anhydride)1-100, (C2-30 alkyl carbonate)1-100, (C7-50 aryl carbonate)1-100, (C8-2000 alkylaryl carbonate)1-100, (C8-2000 arylalkyl carbonate)1-100, —Ra—O—CO—NH—(Rb or Ar—Rb—Ar)—NH—CO—O—(C1-30 alkyl ether, C6-40 aryl ether, C7-2000 alkylaryl ether, or C7-2000 arylalkyl ether)1-100, —Ra—O—CO—NH—(Rb or Ar—Rb—Ar)—NH—CO—O—(C2-50 alkyl ester, C7-60 aryl ester, C8-2000 alkylaryl ester, or C8-2000 arylalkyl ester)1-100, —Ra—O—CO—NH—(Rb or Ar—Rb—Ar)—NH—CO—O—(C1-30 alkyl ether, C6-40 aryl ether, C7-2000 alkylaryl ether, or C7-2000 arylalkyl ether)1-100—CO—NH—(Rb or Ar—Rb—Ar)—NH—CO—O—, —Ra—O—CO—NH—(Rb or Ar—Rb—Ar)—NH—CO—O—(C2-50 alkyl ester, C7-60 aryl ester, C8-2000 alkylaryl ester, or C8-2000 arylalkyl ester)1-100—Rc—O—CO—NH—(Rb or Ar—Rb—Ar)—NH—CO—O—, —Ra—NH—CO—NH—(Rb or Ar—Rb—Ar)—NH—CO—O—(C1-30 alkyl ether, C6-40 aryl ether, C7-2000 alkylaryl ether, or C7-2000 arylalkyl ether)1-100, —Ra—NH—CO—NH—(Rb or Ar—Rb—Ar)—NH—CO—O—(C2-50 alkyl ester, C7-60 aryl ester, C8-2000 alkylaryl ester, or C8-2000 arylalkyl ester)1-100, —Ra—NH—CO—NH—(Rb or Ar—Rb—Ar)—NH—CO—O—(C1-30 alkyl ether, C6-40 aryl ether, C7-2000 alkylaryl ether, or C7-2000 arylalkyl ether)1-100—CO—NH—(Rb or Ar—Rb—Ar)—NH—CO—O—, —Ra—NH—CO—NH—(Rb or Ar—Rb—Ar)—NH—CO—O—(C2-50 alkyl ester, C7-60 aryl ester, C8-2000 alkylaryl ester, or C8-2000 arylalkyl ester)1-100—Rc—O—CO—NH—(Rb or Ar—Rb—Ar)—NH—CO—O—, —Ra—O—CO—NH—(Rb or Ar—Rb—Ar)—NH—CO—NH—(C2-50 alkyl amide, C7-60 aryl amide, C8-2000 alkylaryl amide, or C8-2000 arylalkyl amide)1-100, —Ra—NH—CO—NH—(Rb or Ar—Rb—Ar)—NH—CO—NH—(C2-50 alkyl amide, C7-60 aryl amide, C8-2000 alkylaryl amide, or C8-2000 arylalkyl amide)1-100;
• and each Z, independently, is —G—D, wherein G is —Ra—, —Ra—Ar—, —Ar—Ra—, or —Ar—;
• and D is —H, —OH, —SH, —NH2, —NHOH, —SO3H, —OS03H, —CO2H, —CONH2, —CONHNH2, —CH(NH2)—CO2H, —NH—CH2—CO2H, —P(OH)3, —PO(OH)2, —O—PO(OH)2, —O—PO(OH)—O—PO(OH)2, —O—PO(O−)—O—CH2CH2NH3+, —O—PO(O−)—O—CH2CH2—N+(CH3)3, -glycoside, -oligosaccharide, —CO-glycoside, —CO-oligosaccharide, —OCH3, —OCH2(CHOH)4—CH2OH, —OCH2(CHOH)2—CH2OH, —CO—OCH2(CHOH)4—CH2OH, —C6H3(OH)2, —N(CH2CO2H)2, —CO—N(CH2CO2H)2, —CO—NH—C(CH2CH2CO2H)3, —CO—NH—C(CH2CH2OH)3, —[CH2—CH(CO2Ra)]1-100—H, —NH3+, —N+H2Ra, —N+HRaRb, or —N+RaRbRc, each of Ra, Rb, and Rc, independently, being C1-20 alkyl and Ar being aryl;
• R1 is —OH or —NH2;
• R2 is —O—;
• n is 1-30;
• p is 1-20;
• and
• q is 0-10;
• provided that when R1 is —NH2, q is 0;
• said method comprising:
• obtaining a polynitrofullerene or polycyclosulfated fullerene intermediate;
• contacting the intermediate with a nucleophilic agent to produce a fullerene derivative of the formula F(—E)n, wherein each of F, E, and n has been defined above;
• and
• contacting the resulting fullerene derivative with a hydroxylating or an aminating agent to produce a fullerene derivative of the formula F(—E)n(—R1)p(—R2)q, wherein each of F, E, R1, R2, p, q, and n has been defined above.