Nucleotide analogs

A compound of the formula (OR.sup.31).sub.2 P(O)--Z.sup.1 --B or (OR) (OR.sup.31)P(O)--Z.sup.1 --B, wherein;

• B is a heterocyclic base;
• Z.sup.1 is selected from the group consisting of --CH.sub.2 --O--CH.sub.2 --CH.sub.2 --, --CH.sub.2 --O--C--H(CH.sub.2 OH)--CH.sub.2 --, --CH.sub.2 --O--C--H(CH.sub.3)--CH.sub.2 --, --CH.sub.2--O--C--H(CH.sub.2 F)--CH.sub.2 --, --CH.sub.2 --O--C--H(CH.dbd.CH.sub.2)--CH.sub.2 --and --CH.sub.2 --O--C--H(CH.sub.2 N.sub.3)--CH.sub.2 -;
• R is H,
• C.sub.3 -C.sub.24 1-acyloxy-1-alkyl,
• C.sub.6 -C.sub.24 1-acyloxy-1-aryl-1-alkyl,
• C.sub.3 -C.sub.24 1-acyloxy-2-alkoxy-1-alkyl,
• C.sub.3 -C.sub.24 1-acyloxy-2-halo-1-alkyl,
• C.sub.1 -C.sub.20 alkyl which is unsubstituted or substituted by substituents independently selected from the group consisting of OH, O, N and halogen,
• C.sub.3 -C.sub.20 aryl which is unsubstituted or substituted by substituents independently selected from the group consisting of C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.6 haloalkyl, cyano, nitro, OH, O, N and halogen, or
• C.sub.4 -C.sub.20 aryl-alkyl which is unsubstituted or substituted in the aryl moiety by substituents independently selected from the group consisting of C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.6 haloalkyl, cyano, nitro, OH, O, N and halogen;
• R.sup.31 is 2,3-dihydro-6-hydroxyindene;
• sesamol;
• catechol monoester;
• --CH.sub.2 --S(O)(R.sup.7) wherein R.sup.2 is hydrogen or C.sub.1-4 alkyl --CH.sub.2 --S(O).sub.2 (R.sup.7);
• --CH.sub.2 --CH(OC(O)CH.sub.2 R.sup.7)--CH.sub.2 (OC(O)CH.sub.2 R.sup.7);
• cholesteryl;
• a monosaccharide;
• a disaccharide;
• an oligosaccharide (3 to 9 monosaccharide residues), enolpyruvate;
• glycerol;
• an a-D-b-diglyceride;
• trimethoxybenzyl;
• triethoxybenzyl;
• 2-alkyl pyridinyl (C.sub.1-4 alkyl);
• ##STR50## C.sub.3 -C.sub.6 aryl substituted by 3, 4 or 5 halogen atoms or 1 or 2 atoms or groups selected from the group consisting of halogen, C.sub.1 -C.sub.12 alkoxy, cyano, nitro, OH, C.sub.1 -C.sub.12 haloalkyl, C.sub.1 -Cl.sub.2 alkyl, C.sub.2 -C.sub.12 alkenyl and C.sub.2 -C.sub.12 alkynyl;
• or
• C.sub.1 -C.sub.4 alkylene-C.sub.3 -C.sub.6 aryl substituted in the aryl moiety by 3 to 5 halogen atoms or 1 to 2 atoms or groups selected from the group consisting of halogen, C.sub.1 -C.sub.12 alkoxy, cyano, nitro, OH, C.sub.1 --C.sub.12 haloalkyl, C.sub.1 -C.sub.12 alkyl, C.sub.2 -C.sub.12 alkenyl and C.sub.2 -C.sub.12 alkynyl, provided that when Z.sup.1 is --CH.sub.2 --O--CH.sub.2 --CH.sub.2 --and B is adenin-9-yl, both R.sup.31 are not 4-nitrobenzyl or 4-trifluoromethyl-benzyl.

A compound of the formula (L.sup.1).sub.2 P(O)--Z--B.sup.1 wherein

• L.sup.1 is an oxyester or a thioester;
• B.sup.1 is a protected heterocyclic base;
• and
• Z--B.sup.1 is ##STR51## wherein R.sup.27 is H, OH, halogen, N.sub.3, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy or when, R.sup.26 is S, R.sup.27 is absent;
• R.sup.28 is H, OH, halogen, N.sub.3, C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkoxy;
• R.sup.29 is S, CHF or CF.sub.2 ;
• R.sup.33 is H, OH, TBSO, halogen, cyano, CH.sub.2 N.sub.3, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, CH.sub.2 OH or azido;
• and
• R.sup.34 is H, CH.sub.2 CN or CF.sub.3.

A compound of the formula (OR.sup.35)(OR.sup.35)P(O)--Z--B, wherein;

• B is a heterocyclic base;
• R.sup.35 is independently R or R.sup.31, wherein R is independently
• H,
• C.sub.3 -C.sub.24 1-acyloxy-1-alkyl,
• C.sub.6 -C.sub.24 1-acyloxy-1-aryl-1-alkyl,
• C.sub.3 -C.sub.24 1-acyloxy-2-alkoxy-1-alkyl,
• C.sub.3 -C.sub.24 1-acyloxy-2-halo-1-alkyl,
• C.sub.1 -C.sub.20 alkyl which is unsubstituted or substituted by substituents independently selected from the group consisting of OH, O, N and halogen,
• C.sub.3 -C.sub.20 aryl which is unsubstituted or substituted by substituents independently selected from the group consisting of C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.6 haloalkyl (1 to 3 halogen atoms), cyano, nitro, OH, O, N and halogen,
• C.sub.4 -C.sub.20 aryl-alkyl which is unsubstituted or substituted in the aryl moiety by substituents independently selected from the group consisting of C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.6 haloalkyl (1 to 3 halogen atoms), cyano, nitro, OH, O, N and halogen,
• C.sub.3 -C.sub.6 aryl substituted by 3 to 5 halogen atoms or 1 to 2 atoms or groups independently selected from the group consisting of halogen, C.sub.1 -C.sub.12 alkoxy, cyano, nitro, hydroxy, C.sub.1 -C.sub.12 haloalkyl, C.sub.1 -C.sub.12 alkyl, C.sub.2 -C.sub.12 alkenyl and C.sub.2 -C.sub.12 alkynyl, or
• C.sub.1 -C.sub.4 alkylene-C.sub.3 -C.sub.6 aryl substituted in the aryl moiety by 3 to 5 halogen atoms or 1 to 2 atoms or groups independently selected from the group consisting of halogen, C.sub.1 -C.sub.12 alkoxy, cyano, nitro, hydroxy, C.sub.1 -C.sub.12 haloalkyl, C.sub.1 -C.sub.12 alkyl, C.sub.2 -C.sub.12 alkenyl and C.sub.2 -C.sub.12 alkynyl;
• R.sup.31 is 2,3-dihydro-6-hydroxyindene;
• sesamol;
• catechol monoester;
• --CH.sub.2 --C(O)--N(R.sup.7).sub.2 wherein each R.sup.7 is the same or different;
• --CH.sub.2 --S(O)(R.sup.7);
• --CH.sub.2 --S(O).sub.2 (R.sup.7);
• --CH.sub.2 --CH(OC(O)CH.sub.2 R.sup.7)--CH.sub.2 (OC(O)CH.sub.2 R.sup.7);
• cholesteryl;
• a monosaccharide;
• a disaccharide;
• an oligosaccharide (3 to 9 monosaccharide residues), enolpyruvate;
• glycerol;
• an a-D-b-diglyceride;
• trimethoxybenzyl;
• triethoxybenzyl;
• 2-alkyl pyridinyl (C.sub.1-4 alkyl);
• ##STR54## Z--B is selected from the group consisting of ##STR55## wherein R.sup.27 is H, OH, halogen, N.sub.3, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy or when, R.sup.26 is S, R.sup.27 is absent;
• R.sup.33 is H, OH, TBSO, halogen, cyano, CH.sub.2 N.sub.3, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy, CH.sub.2 OH or azido;
• and
• R.sup.34 is H, CH.sub.2 CN or CF.sub.3.

A compound of the formula (R.sup.31 O).sub.2 P(O)--CH.sub.2 --OH or (R.sup.31 O).sub.2 P(OSi(CH.sub.3).sub.3) wherein

• R.sup.31 is trimethoxybenzyl;
• triethoxybenzyl;
• 2-alkyl pyridinyl (C.sub.1 -4 alkyl);
• ##STR56## wherein R.sup.7 is hydrogen or C.sub.1-4 alkyl;
• or C.sub.3 -C.sub.6 aryl substituted by 3, 4 or 5 halogen atoms or 1 or 2 atoms or groups selected from halogen, C.sub.1 -C.sub.12 alkoxy, cyano, nitro, C.sub.1 -C.sub.12 haloalkyl, C.sub.1 -C.sub.12 alkyl or C.sub.2-12 alkynyl, provided that for compound (R.sup.31 O).sub.2 P(O)--CH.sub.2 --OH, R.sup.31 is not phenyl.

A method to synthesize a compound of structure (R.sup.3 O).sub.2 P(O)--CH.sub.2 OH comprising silylating a compound of structure (R.sup.31 O).sub.2 P(O)H with about 1 equivalent of bis(trimethylsilyl)trifluoroacetamide, drying the resulting compound and reacting the resulting compound with paraformaldehyde containing catalytic amounts of a lewis acid, wherein R.sup.31 is trimethoxybenzyl;

• triethoxybenzyl;
• 2-alkyl pyridinyl (C.sub.1-4 alkyl);
• ##STR57## wherein R.sup.7 is hydrogen or C.sub.14 alkyl;
• C.sub.3 -C.sub.6 aryl substituted by 3, 4 or 5 halogen atoms or 1 or 2 atoms or groups selected from halogen, C.sub.1 -C.sub.12 alkoxy, cyano, nitro, C.sub.1 -C.sub.12 haloalkyl, C.sub.1 -C.sub.12 alkyl or C.sub.2-12 alkynyl.

A method to synthesize a compound of structure ##STR58## by reacting a compound of structure ##STR59## with iodine and (R.sup.31 O).sub.2 P(O)--CH.sub.2 --OH at high temperature, wherein B.sup.2 is a heterocyclic base or a protected heterocyclic base;

• R.sup.31 is trimethoxybenzyl;
• triethoxybenzyl;
• 2-alkyl pyridinyl (C.sub.1-4 alkyl);
• ##STR60## wherein R.sup.7 is hydrogen or C.sub.1 -4 alkyl;
• C.sub.3 -C.sub.6 aryl substituted by 3, 4 or 5 halogen atoms or 1 or 2 atoms or groups selected from halogen, C.sub.1 -C.sub.12 alkoxy, cyano, nitro, C.sub.1 -C.sub.12 haloalkyl, C.sub.1 -C.sub.12 alkyl or C.sub.2-12 alkynyl;
• and R.sup.44 is iodine or fluorine.

A compound having the formula ##STR61## and stereoisomers and salts of such compounds wherein B is a purine or pyrimidine base;

• R.sup.35 is R or R.sup.31 ;
• R is 2-alkoxyphenyl, 3-alkoxyphenyl, 4-alkoxyphenyl (C.sub.1 -C.sub.12 alkyl), 2-halophenyl, 3-halophenyl, 4-halophenyl, 2,3-dihalophenyl, 2,4-dihalophenyl, 2,5-dihalophenyl, 2,6-dihalophenyl, 3,4-dihalophenyl, 3,5-dihalophenyl, 4-haloalkylphenyl (1-5 halogens, C.sub.1 -C.sub.12 alkyl), carboalkoxyphenyl (C.sub.1 -C.sub.4 alkyl), 2-haloalkylbenzyl, 3-haloalkylbenzyl, 4-haloalkylbenzyl (1 to 5 halogen atoms, C.sub.1 -C.sub.12 alkyl), alkylsalicylphenyl (C.sub.1 -C.sub.4 alkyl), alkoxy ethyl (C.sub.1 -C.sub.6 alkyl), aryloxy ethyl (C.sub.6 -Cg aryl optionally substituted by OH, NH.sub.2, halo, C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkyl substituted by OH or by 1 to 3 halo atoms), 2-pyrrolyl, 3-pyrrolyl, 2-thienyl, 3-thienyl, 2-imidazolyl, 4-imidazolyl, 2-oxazolyl, 4-oxazolyl, 5-oxazolyl, 3-isoxazolyl, 4-isoxazolyl, 2-thiazolyl, 4-thiazolyl, 5-thiazolyl, 3-isothiazolyl, 4-isothiazolyl, 5-isothiazolyl, 3-pyrazolyl, 4-pyrazolyl, 2-pyridinyl, 3-pyridinyl, 4-pyridinyl, 2-pyrimidinyl, 4-pyrimidinyl, 5-pyrimidinyl, 2-methoxyphenyl, 3-methoxyphenyl, 4-methoxyphenyl, 2-ethoxyphenyl, 3-ethoxyphenyl, 4-ethoxyphenyl, 2-fluorophenyl, 3-fluorophenyl, 4-fluorophenyl, 2,4-difluorophenyl, 2,4-dichlorophenyl, 2-trifluoromethylphenyl, 3-trifluoromethylphenyl, 4-trifluoromethylphenyl, 2-trichloromethylphenyl, 3-trichloromethylphenyl, 4-trichloromethylphenyl, 2-cyanophenyl, 3-cyanophenyl, 4-cyanophenyl, 2-carboethoxyphenyl, 3-carboethoxyphenyl, 4-carboethoxyphenyl, 2,3-dicarboethoxyphenyl, 2,4-dicarboethoxyphenyl, 2,5-dicarboethoxyphenyl, 2,6-dicarboethoxyphenyl, 3,4-dicarboethoxyphenyl, 3,5-dicarboethoxyphenyl, 1-pyridinyl, 2-pyridinyl, 3-pyridinyl, 4-pyridinyl, 2-nitrophenyl, 3-nitrophenyl, 4-nitrophenyl, 4-trifluoromethylbenzyl, 2-ethylsalicylphenyl, 3-ethylsalicylphenyl, 4-ethylsalicylphenyl, 2-acetylphenyl, 3-acetylphenyl, 4-acetylphenyl, 1,8-dihydroxy-naphthyl, 2,2'-dihydroxybiphenyl, methoxy ethyl, phenoxymethyl, phenoxy ethyl, --C.sub.6 H.sub.4 --CH.sub.2 --N(CH.sub.3).sub.2 or N-ethylmorpholino;
• R.sup.31 is 2,3-dihydro-6-hydroxyindene, sesamol, catechol monoester, --CH.sub.2 --S(O)(R.sup.7), wherein R.sup.7 is hydrogen or C.sub.1-4 alkyl, --CH.sub.2 --S(O).sub.2 (R.sup.7), --CH.sub.2 --CH(OC(O)CH.sub.2 R.sup.7)--CH.sub.2 (OC(O)CH.sub.2 R.sup.7), cholesteryl, enolpyruvate, glycerol, an a-D-b-diglyceride, trimethoxybenzyl, triethoxybenzyl or 2-alkyl pyridinyl (C.sub.1-4 alkyl);
• R.sup.7 is H or C.sub.1 -C.sub.4 alkyl;
• and
• the carbon atom designated # has linked substituents that are in the R, S or RS configuration.

A compound of the formula (OR.sup.35)(OR.sup.35)P(O)--Z--B, wherein;

• B is a heterocyclic base;
• R.sup.35 is independently R or R.sup.31, wherein R is independently
• H,
• C.sub.3 -C.sub.24 1-acyloxy-1-alkyl,
• C.sub.6 -C.sub.24 1-acyloxy-1-aryl-1-alkyl,
• C.sub.3 -C.sub.24 1-acyloxy-2-alkoxy-1-alkyl,
• C.sub.3 -C.sub.24 1-acyloxy-2-halo-1-alkyl,
• C.sub.1 -C.sub.20 alkyl which is unsubstituted or substituted by substituents independently selected from the group consisting of OH, O, N and halogen,
• C.sub.3 -C.sub.20 aryl which is unsubstituted or substituted by substituents independently selected from the group consisting of C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.6 haloalkyl (1 to 3 halogen atoms), cyano, nitro, OH, O, N and halogen,
• C.sub.4 -C.sub.20 aryl-alkyl which is unsubstituted or substituted in the aryl moiety by substituents independently selected from the group consisting of C.sub.1 -C.sub.6 alkyl, C.sub.1 -C.sub.6 alkoxy, C.sub.1 -C.sub.6 haloalkyl (1 to 3 halogen atoms), cyano, nitro, OH, O, N and halogen,
• C.sub.3 -C.sub.6 aryl substituted by 3 to 5 halogen atoms or 1 to 2 atoms or groups independently selected from the group consisting of halogen, C.sub.1 -Cl2 alkoxy, cyano, nitro, hydroxy, C.sub.1 -C.sub.12 haloalkyl, C.sub.1 -C.sub.12 alkyl, C.sub.2 -C.sub.12 alkenyl and C.sub.2 -C.sub.12 alkynyl, or
• C.sub.1 -C.sub.4 alkylene-C.sub.3 -C.sub.6 aryl substituted in the aryl moiety by 3 to 5 halogen atoms or 1 to 2 atoms or groups independently selected from the group consisting of halogen, C.sub.1 -C.sub.12 alkoxy, cyano, nitro, hydroxy, C.sub.1 -C.sub.12 haloalkyl, C.sub.1 -C.sub.12 alkyl, C.sub.2 -C.sub.12 alkenyl and C.sub.2 -C.sub.12 alkynyl;
• R.sup.31 is 2,3-dihydro-6-hydroxyindene;
• sesamol;
• catechol monoester;
• --CH.sub.2 --S(O)(R.sup.7) wherein R.sup.7 is hydrogen or C.sub.1-4 alkyl;
• --CH.sub.2 --S(O).sub.2 (R.sup.7);
• --O--CH.sub.2 --CH (OC(O)CH.sub.2 R.sup.7)--CH.sub.2 (OC(O)CH.sub.2 R.sup.7);
• cholesteryl;
• a monosaccharide;
• a disaccharide;
• an oligosaccharide (3 to 9 monosaccharide residues), enolpyruvate;
• glycerol;
• an a-D-b-diglyceride;
• trimethoxybenzyl;
• triethoxybenzyl;
• 2-alkyl pyridinyl (C.sub.1-4 alkyl);
• ##STR64## C.sub.3 -C.sub.6 aryl substituted by 3, 4 or 5 halogen atoms or 1 or 2 atoms or groups selected from the group consisting of halogen, C.sub.1 -C.sub.12 alkoxy, cyano, nitro, OH, C.sub.1 -C.sub.12 haloalkyl, C.sub.1 -C.sub.12 alkyl, C.sub.2 -C.sub.12 alkenyl and C.sub.2 -C.sub.12 alkynyl;
• or
• C.sub.1 -C.sub.4 alkylene C.sub.3 -C.sub.6 aryl substituted in the aryl moiety by 3 to 5 halogen atoms or 1 to 2 atoms or groups selected from the group consisting of halogen, C.sub.1 -C.sub.12 alkoxy, cyano, nitro, OH, C.sub.1 -C.sub.12 haloalkyl, C.sub.1 -C.sub.12 alkyl, C.sub.2 -C.sub.12 alkenyl and C.sub.2 -C.sub.12 alkynyl;
• Z--B is selected from the group consisting of ##STR65## wherein, R.sup.25 is CH.sub.2, CHF or O;
• R.sup.26 is CH or S, provided that when R.sup.25 is CH, R.sup.26 is not S;
• R.sup.27 is H, OH, halogen, N.sub.3, C.sub.1 -C.sub.4 alkyl, C.sub.1 -C.sub.4 alkoxy or when, R.sup.26 is S, R.sup.27 is absent;
• R.sup.28 is H, OH, halogen, N.sub.3, C.sub.1 -C.sub.4 alkyl or C.sub.1 -C.sub.4 alkoxy;
• and
• R.sup.29 is S, CHF or CF.sub.2.

A compound of the formula ##STR66## wherein substituents linked to the carbon atom designated # are in the R, S or RS configuration;

• B.sup.2 is a protected or unprotected heterocyclic base;
• and
• R.sup.31 is 2,3-dihydro-6-hydroxyindene;
• sesamol;
• catechol monoester;
• --CH.sub.2 --S(O)(R.sup.7) wherein R.sup.7 is hydrogen or C.sub.1-4 alkyl;
• --CH.sub.2 --S(O).sub.2 (R.sup.7);
• --O--CH.sub.2 --CH (OC(O)CH.sub.2 R.sup.7)--CH.sub.2 (OC(O)CH.sub.2 R.sup.7);
• cholesteryl;
• a monosaccharide;
• a disaccharide;
• an oligosaccharide containing 3 to 9 monosaccharide residues, enolpyruvate;
• glycerol;
• an a-D-b-diglyceride;
• trimethoxybenzyl;
• triethoxybenzyl;
• 2-alkyl pyridinyl (C.sub.1-4 alkyl);
• ##STR67## C.sub.3 -C.sub.6 aryl substituted by 3, 4 or 5 halogen atoms or 1 or 2 atoms or groups selected from the group consisting of halogen, C.sub.1 -C.sub.12 alkoxy, cyano, nitro, OH, C.sub.1 -C.sub.12 haloalkyl, C.sub.1 -C.sub.12 alkyl, C.sub.2 -C.sub.12 alkenyl and C.sub.2 -C.sub.12 alkynyl;
• or
• C.sub.1 -C.sub.4 alkylene-C.sub.3 -C.sub.6 aryl substituted in the aryl moiety by 3 to 5 halogen atoms or 1 to 2 atoms or groups selected from the group consisting of halogen, C.sub.1 -C.sub.12 alkoxy, cyano, nitro, OH, C.sub.1 -C.sub.12 haloalkyl, C.sub.1 -C.sub.12 alkyl, C.sub.2 -C.sub.12 alkenyl and C.sub.2 -C.sub.12 alkynyl.

A compound having the structure (OR.sup.35).sub.2 P(O)--Z--B, wherein each R.sup.35 is the same and the compound is designated by numbers assigned to (OR.sup.35).sub.2, Z and B according to the convention, R.sup.35.Z.B,

• wherein the structures for R.sup.35, Z and B are designated by numbers respectively and wherein
• R35 structure 1 is --O--C.sub.6 H.sub.4 F, 2 is --O--C.sub.6 H.sub.3 F.sub.2, 3 is --O--C.sub.6 H.sub.4 --OCH.sub.3, 4 is --O--C.sub.6 H.sub.3 --(OCH.sub.3).sub.2, 5 is --O--C.sub.6 H.sub.4 --OC.sub.2 H.sub.5, 6 is --O--C.sub.6 H.sub.3 --(OC.sub.2 H.sub.5).sub.2, 7 is --O--CH.sub.2 --C.sub.6 H.sub.4 F, 8 is --O--C.sub.6 H.sub.4 --(C(O)--O--C.sub.2 H.sub.5).sub.2, 9 is --O--C.sub.6 H.sub.4 --C(O)--O--C.sub.2 H.sub.5, 10 is --O--C.sub.6 H.sub.3 --(O--C(O)--CH.sub.3).sub.2, 11 is --O--C.sub.6 H.sub.3 --C(O)--O--C.sub.3 H.sub.7, 12 is --O--CH.sub.2 --C.sub.6 H.sub.4 --O--CO--CH.sub.3, 13 is --O--C.sub.5 H.sub.4 N, 14 is --O--C.sub.6 H.sub.3 --(OC.sub.2 H.sub.5)(OH), 15 is --O--C.sub.6 H.sub.5 and 16 is --O--CH.sub.2 --O--C(O)--C(CH.sub.3).sub.3, and
• Z--B structure 1 is --P(O)--CH.sub.2 --O--CH.sub.2 --CH.sub.2 --B, 2 is --P(O)--CH.sub.2 --O--C--H(CH.sub.2 --OR.sup.4)--CH.sub.2 --B, 3 is --P(O)--CH.sub.2 --O--C--H (CH.sub.3)--CH.sub.2 --B, 4 is --P(O)--CH.sub.2 --O--C--H(CH.sub.2 F)--CH.sub.2 --B, 5 is --P(O)--CH.sub.2 --O--C--H(CH.dbd.CH.sub.2)--CH.sub.2 --B, 6 is --P(O)--CH.sub.2 --O--C--H(CH.sub.2 N.sub.3)--CH.sub.2 --B, 7 is ##STR71## and 8 is ##STR72## and B structure 1 is adenin-9-yl, 2 is guanin-9-yl, 3 is cytosin-1-yl, 4 is 2, 6-diaminopurin-9-yl, 5 is 2-aminopurin-9-yl, 6 is thymidin-1-yl and 7 is 5-fluorocytosin-1-yl, wherein the compound is named 1.1.1, 2.1.1, 3.1.1, 4.1.1, 5.1.1, 6.1.1, 7.1.1, 8.1.1, 9.1.1, 10.1.1, 11.1.1, 12.1.1, 13.1.1, 14.1.1, 1.2.1, 2.2.1, 3.2.1, 4.2.1, 5.2.1, 6.2.1, 7.2.1, 8.2.1, 9.2.1, 10.2.1, 11.2.1, 12.2.1, 13.2.1, 14.2.1, 1.3.1, 2.3.1, 3.3.1, 4.3.1, 5.3.1, 6.3.1, 7.3.1, 8.3.1, 9.3.1, 10.3.1, 11.3.1, 12.3.1, 13.3.1, 14.3.1, 1.4.1, 2.4.1, 3.4.1, 4.4.1, 5.4.1, 6.1, 7.4.1, 8.4.1, 9.4.1, 10.4.1, 11.4.1, 12.4.1, 13.4.1, 14.4.1, 1.5.1, 2.5.1, 3.5.1, 4.5.1, 5.5.1, 6.5.1, 7.5.1, 8.5.1, 9.5.1, 10.5.1, 11.5.1, 12.5.1, 13.5.1, 14.5.1, 1.6.1, 2.6.1, 3.6.1, 4.6.1, 5.6.1, 6.6.1, 7.6.1, 8.6.1, 9.6.1, 10.6.1, 11.6.1, 12.6.1, 13.6, 1, 14.6.1, 1.7.1, 2.7.1, 3.7.1, 4.7.1, 5.7.1, 6.7.1, 7.7.1, 8.7.1, 9.7.1, 10.7.1, 11.7.1, 12.7.1, 13.7.1, 14.7.1, 15.7.1, 16.7.1, 1.8.1, 2.8.1, 3.8.1, 4.8.1, 5.8, 1, 6.8.1, 7.8.1, 8.8.1, 9.8.1, 10.8.1, 11.8.1, 12.8.1, 13.8.1, 14.8.1, 15.8.1, 16.8.1, 1.1.2, 2.1.2, 3.1.2, 4.1.2, 5.1.2, 6.1.2, 7.1.2, 8.1.2, 9.1.2, 10.1.2, 11.1.2, 12.1.2, 13.1.2, 14.1.2, 1.2.2, 2.2.2, 3.2.2, 4.2.2, 5.2.2, 6.2.2, 7.2.2, 8.2.2, 9.2.2, 10.2.2, 11.2.2, 12.2.2, 13.2.2, 14.2.2, 1.3.2, 2.3.2, 3.3.2, 4.3.2, 5.3.2, 6.3.2, 7.3.2, 8.3.2, 9.3.2, 10.3.2, 11.2, 12.32, 13.3.2, 14.3.2, 1.4.2, 2.4.2, 3.4.2, 4.4.2, 5.4.2, 6.4.2, 7.4.2, 8.4.2, 9.4.2, 10.4.2, 11.4.2, 12.4.2, 13.4.2, 14.4.2, 1.5.2, 2.5.2, 3.5.2, 4.5.2, 5.5.2, 6.5.2, 7.5.2, 8.5.2, 9.5.2, 10.5.2, 11.5.2, 12.5.2, 13.5.2, 14.5.2, 1.6.2, 2.6.2, 3.6.2, 4.6.2, 5.6.2, 6.6.2, 7.6.2, 8.6.2, 9.6.2, 10.6.2, 11.6.2, 12.6.2, 13.6.2, 14.6.2, 1.7.2, 2.7.2, 3.7.2, 4.7.2, 5.7.2, 6.7.2, 7.7.2, 8.7.2, 9.7.2, 10.7.2, 11.7.2, 12.7.2, 13.7.2, 14.7.2, 15.7.2, 16.7.2, 1.8.2, 2.8.2, 3.8.2, 4.82, 5.8.2, 6.82, 7.82, 8.8.2, 9.8.2, 10.8.2, 11.8.2, 12.8.2, 13.8.2, 14.8.2, 15.8.2, 16.8.2, 1.1.3, 2.1.3, 3.1.3, 4.1.3, 5.1.3, 6.1.3, 7.1.3, 8.1.3, 9.1.3, 10.1.3, 11.1.3, 12.1.3, 13.1.3, 14.1.3, 1.2.3, 2.2.3, 3.2.3, 4.2.3, 5.2.3, 6.2.3, 7.2.3, 8.2.3, 9.2.3, 10.2.3, 11.2.3, 12.2.3, 13.2.3, 14.2.3, 1.3.3, 2.33, 3.3.3, 4.3.3, 5.3.3, 6.3.3, 7.3.3, 8.3.3, 9.3.3, 10.3.3, 11.3.3, 12.3.3, 13.3.3, 14.3.3, 1.4.3, 2.4.3, 3.4.3, 4.4.3, 5.4.3, 6.4.3, 7.4.3, 8.4.3, 9.43, 10.4.3, 11.4.3, 12.4.3, 13.4.3, 14.4.3, 15.3, 2.5.3, 3.5.3, 4.5.3, 5.5.3, 6.5.3, 7.5.3, 8.5.3, 9.5.3, 10.5.3, 11.5.3, 12.5.3, 13.5.3, 14.5.3, 1.6.3, 2.6.3, 3.6.3, 4.6.3, 5.6.3, 6.6.3, 7.6.3, 8.6.3, 9.6.3, 10.6.3, 11.6.3, 12.6.3, 13.6.3, 14.6.3, 1.7.3, 2.7.3, 3.7.3, 4.7.3, 5.73, 6.7.3, 7.7.3, 8.7.3, 9.7.3, 10.7.3, 11.7.3, 12.7.3, 13.7.3, 14.7.3, 15.7.3, 16.7.3, 1.8.3, 2.8.3, 3.8.3, 4.8.3, 5.8.3, 6.8.3, 7.8.3, 8.8.3, 9.8.3, 10.8.3, 11.8.3, 12.8.3, 13.8.3, 14.8.3, 15.8.3, 16.8.3, 1.1.4, 2.1.4, 3.1.4, 4.1.4, 5.14, 6.1.4, 7.1.4, 8.1.4, 9.1.4, 10.1.4, 11.1.4, 12.1.4, 13.1.4, 14.1.4, 1.2.4, 2.2.4, 3.2.4, 4.24, 5.2.4, 6.2.4, 7.24, 8.2.4, 9.2.4, 10.2.4, 11.2.4, 12.2.4, 13.2.4, 14.2.4, 1.3.4 , 2.3.4, 3.3.4, 4.3.4, 5.3.4, 6.3.4, 7.3.4, 8.3.4, 9.3.4, 10.3.4, 11.3.4, 12.3.4, 13.3.4, 14.3.4, 1.4.4, 2.4.4, 3.4.4, 4.4.4, 5.4.4, 6.4.4, 7.4.4, 8.4.4, 9.4.4, 10.4.4, 11.4.4, 12.4.4, 13.4.4, 14.4.4, 1.5.4, 2.5.4, 3.5.4, 4.5.4, 5.5.4, 6.5.4, 7.5.4, 8.5.4, 9.5.4, 10.5.4, 11.5.4, 12.5.4, 13.5.4, 14.5.4, 1.6.4, 2.6.4, 3.6.4, 4.6.4, 5.6.4, 6.6.4, 7.6.4, 8.6.4, 9.6.4, 10.6.4, 11.6.4, 12.6.4, 13.64, 14.6.4, 1.7.4, 2.7.4, 3.7.4, 4.4, 5.7.4, 6.7.4, 7.7.4, 8.7.4, 9.7.4, 10.7.4, 11.7.4, 12.7.4, 13.7.4, 14.7.4, 15.7.4, 16.7.4, 1.8.4, 2.8.4, 3.8.4, 4.8.4, 5.8.4, 6.8.4, 7.8.4, 8.8.4, 9.8.4, 10.8.4, 11.8.4, 12.8.4, 13.8.4, 14.8.4, 15.8.4, 16.8.4, 1.1.5 2.1.5, 3.1.5, 4.1.5, 5.1.5, 6.1.5, 7.1.5, 8.1.5, 9.1.5, 10.1.5, 11.1.5, 12.1.5, 13.1.5, 14.1.5, 1.2, 5, 2.2.5, 3.2.5, 4.2.5, 5.2.5, 6.2.5, 7.2.5, 8.2.5, 9.2.5, 10.2.5, 11.2.5, 12.2.5, 13.2.5, 14.2.5, 1.3.5, 2.3.5, 3.3.5, 4.3.5, 5.3.5, 6.3.5, 7.3.5, 8.3.5, 9.3.5, 10.3.5, 11.3.5, 12.3.5, 13.3.5, 14.3.5, 1.4.5, 2.4.5, 3.4.5, 4.4.5, 5.4.5, 6.4.5, 7.4.5, 8.4.5, 9.4.5, 10.4.5, 11.4.5, 12.4.5, 13.4.5, 14.4.5, 1.5.5, 2.5.5, 3.5.5, 4.5.5, 5.5.5, 6.5.5, 7.5.5, 8.5.5, 9.5.5, 10.5.5, 11.5.5, 12.5.5, 13.5.5, 14.5.5, 1.6.5, 2.6.5, 3.6.5, 4.6.5, 5.6.5, 6.6.5, 7.6.5, 8.6.5, 9.6.5, 10.6.5, 11.6.5, 12.6.5, 13.6.5, 14.6.5, 1.7.5, 2.7.5, 3.7.5, 4.7.5, 5.7.5, 6.7.5, 7.7.5, 8.7.5, 9.7.5, 10.7.5, 11.7.5, 12.7.5, 13.7.5, 14.7.5, 15.7.5, 16.7.5, 1.8.5, 2.8.5, 3.8.5, 4.8.5, 5.8.5, 6.8.5, 7.8.5, 8.8.5, 9.8.5, 10.8.5, 11.8.5, 12.8.5, 13.8.5, 14.8.5, 15.8.5, 16.8.5, 1.1.6, 2.1.6, 3.1.6, 4.1.6, 5.1.6, 6.1.6, 7.1.6, 8.1.6, 9.1.6, 10.1.6, 11.1.6, 12.1.6, 13.1.6, 14.1.6, 1.2.6, 2.2.6, 3.2.6, 4.2.6, 5.2.6, 6.2.6, 7.2.6, 8.2.6, 9.2.6, 10.2.6, 11.2.6, 12.2.6, 13.2.6, 14.2.6, 1.3.6, 2.3.6, 3.3.6, 4.3.6, 5.3.6, 6.3.6, 7.3.6, 8.3.6, 9.3.6, 10.3.6, 11.3.6, 12.3.6, 13.3.6, 14.3.6, 1.4.6, 2.4.6, 3.4.6, 4.4.6, 5.4.6, 6.4.6, 7.4.6, 8.4.6, 9.4.6, 10.4.6, 11.4.6, 12.4.6, 13.4.6, 14.4.6, 1.5.6, 2.5.6, 3.5.6, 4.5.6, 5.5.6, 6.5.6, 7.5.6, 8.5.6, 9.5.6, 10.5.6, 11.5.6, 12.5.6, 13.5.6, 14.5.6, 1.6.6, 2.6.6, 3.6.6, 4.6.6, 5.6.6, 6.6.6, 7.6.6, 8.6.6, 9.6.6, 10.6.6, 11.6.6, 12.6.6, 13.6.6, 14.6.6, 1.7.6, 2.7.6, 3.7.6, 4.7.6, 5.7.6, 6.7.6, 7.7.6, 8.7.6, 9.7.6, 10.7.6, 11.7.6, 12.7.6, 13.7.6, 14.7.6, 15.7.6, 16.7.6, 1.8.6, 2.8.6, 3.8.6, 4.8.6, 5.8.6, 6.8.6, 7.8.6, 8.8.6, 9.8.6, 10.8.6, 11.8.6, 12.8.6, 13.8.6, 14.8.6, 15.8.6, 16.8.6, 1.1.7, 2.1.7, 3.1.7, 4.1.7, 5.1.7, 6.1.7, 7.1.7, 8.1.7, 9.1.7, 10.1.7, 11 1.7, 12.1.7, 13.1.7, 14.1.7, 1.2.7, 2.2.7, 3.2.7, 4.2.7, 5.2.7, 6.2.7, 7.2.7, 8.2.7, 9.2.7, 10.2.7, 11.2.7, 12.2.7, 13.2.7, 14.2.7, 1.3.7, 2.3.7, 3.3.7, 4.3.7, 5.3.7, 6.3.7, 7.3.7, 8.3.7, 9.3.7, 10.3.7, 11.3.7, 12.3.7, 13.3.7, 14.3.7, 1.4.7, 2.4.7, 3.4.7, 4.4.7, 5.4.7, 6.4.7, 7.4.7, 8.4.7, 9.4.7, 10.4.7, 11.4.7, 12.4.7, 13.4.7, 14.4.7, 1.5.7, 2.5.7, 3.5.7, 4.5.7, 5.5.7, 6.5.7, 7.5.7, 8.5.7, 9.5.7, 10.5.7, 11, 5.7, 12.5.7, 13.5.7, 14.5.7, 1.6.7, 2.6.7, 3.6.7, 4.6.7, 5.6.7, 6.6.7, 7.6.7, 8.6.7, 9.6.7, 10.6.7, 11.6.7, 12.6.7, 13.6.7, 14.6.7, 1.7.7, 2.7.7, 3.7.7, 4.7.7, 5.7.7, 6.7.7, 7.7.7, 8.7.7, 9.7.7, 10.7.7, 11.7.7, 12.7.7, 13.7.7, 14.7.7, 15.7.7, 16.7.7, 1.8.7, 2.8.7, 3.8.7, 4.8.7, 5.8.7, 6.8.7, 7.8.7, 8.8.7, 9.8.7, 10.8.7, 11.8.7, 12.8.7, 13.8.7, 14.8.7, 15.8.7 or 16.8.7.