Process for the synthesis of oligomeric compounds

A compound having Formula VII:

• 51
• wherein:
• D is a monocyclic or bicyclic aromatic ring system;
• R11 and R12 are each independently H, alkyl, aryl, heteroalkyl, heteroaryl, alkaryl, or aralkyl;
• or R11 and R12 together with the carbon atoms to which they are attached form an optionally substituted aliphatic or aromatic ring having from 4 to 6 ring atoms;
• X4 is alkaryl, aralkyl, sulfoxyl, sulfonyl, thio, substituted sulfoxyl, substituted sulfonyl, or substituted thio, wherein said substituent is alkyl, aryl, or alkaryl;
• or X4 is a group of formula —C(═O)—(O)aa—R40 where aa is 0 or 1 and R40 is lower alkyl, aryl, aralkyl, heteroaryl wherein said lower alkyl, aryl, aralkyl or heteroaryl groups are optionally substituted with one or more alkyl, aryl, aralkyl, halo or acetyl groups;
• or X4 is a group of formula —(—CH2—CH2—)dSi(R9)3 where d is 0 or 1;
• each R9 is, independently, alkyl having 1 to about 10 carbon atoms, or aryl having 6 to about 10 carbon atoms;
• X1 and X5 are each independently O or S;
• A is (R7)(R8)P— or (R7)(R8)P(═X2)—;
• X2 is O or S;
• R8 is R5, or has the Formula VIII:
• 52
• wherein:
• each R1, is, independently, H, hydroxyl, C1-C20 alkyl, C3-C20 alkenyl, C2-C20 alkynyl, halogen, thiol, keto, carboxyl, nitro, nitroso, nitrile, trifluoromethyl, trifluoromethoxy, O-alkyl, S-alkyl, NH-alkyl, N-dialkyl, O-aryl, S-aryl, NH-aryl, O-aralkyl, S-aralkyl, NH-aralkyl, amino, N-phthalimido, imidazole, azido, hydrazino, hydroxylamino, isocyanato, sulfoxide, sulfone, sulfide, disulfide, silyl, aryl, heterocycle, carbocycle, intercalator, reporter molecule, conjugate, polyamine, polyamide, polyalkylene glycol, or polyether;
• or R1 is a group of formula Z—R22—(R23)v;
• Z is O, S, NH, or N—R22—(R23)v;
• R22 is C1-C20 alkyl, C2-C20 alkenyl, or C2-C20 alkynyl;
• R23 is hydrogen, amino, halogen, hydroxyl, thiol, keto, carboxyl, nitro, nitroso, nitrile, trifluoromethyl, trifluoromethoxy, O-alkyl, S-alkyl, NH-alkyl, N-dialkyl, O-aryl, S-aryl, NH-aryl, O-aralkyl, S-aralkyl, NH-aralkyl, amino, N-phthalimido, imidazole, azido, hydrazino, hydroxylamino, isocyanato, sulfoxide, sulfone, sulfide, disulfide, silyl, aryl, heterocycle, carbocycle, intercalator, reporter molecule, conjugate, polyamine, polyamide, polyalkylene glycol, polyether, a group that enhances the pharmacodynamic properties of oligonucleotides, or a group that enhances the pharmacokinetic properties of oligonucleotides;
• v is from 0 to about 10;
• or R1 has the formula:
• 53
• y1 is 0 or 1;
• y2 is independently 0 to 10;
• y3 is 1 to 10;
• E is C1-C10 alkyl, N(Q1)(Q2) or N═C(Q1)(Q2);
• each Q1 and Q2 is, independently, H, C1-C10 alkyl, substituted C1-C10 alkyl, dialkylaminoalkyl, a nitrogen protecting group, a tethered or untethered conjugate group, a linker to a solid support;
• or Q1 and Q2, together, are joined in a nitrogen protecting group or a ring structure that can include at least one additional heteroatom selected from N and O;
• or R1 has one of formula XI or XII:
• 54
• wherein
• Z0 is O, S, or NH;
• q1 is from 0 to 10;
• q2 is from 1 to 10;
• q3 is 0 or 1;
• q4 is, 0, 1 or 2;
• Z4 is OM1, SM1, or N(M1)2;
• each M1 is, independently, H, C1-C9 alkyl, C1-C8 haloalkyl, C(═NH)N(H)M2, C(═O)N(H)M2 or OC(═O)N(H)M2;
• M2 is H or C1-C8 alkyl;
• Z1, Z2 and Z3 comprise a ring system having from about 4 to about 7 carbon atoms, or having from about 3 to about 6 carbon atoms and 1 or 2 hetero atoms wherein said hetero atoms are selected from oxygen, nitrogen and sulfur, and wherein said ring system is aliphatic, unsaturated aliphatic, aromatic, or saturated or unsaturated heterocyclic;
• and
• Z5 is alkyl or haloalkyl having 1 to about 10 carbon atoms, alkenyl having 2 to about 10 carbon atoms, alkynyl having 2 to about 10 carbon atoms, aryl having 6 to about 14 carbon atoms, N(Q1)(Q2), OQ1, halo, SQ1 or CN;
• R5 is —N(R6)2, or a heterocycloalkyl or heterocycloalkenyl ring containing from 4 to 7 atoms, and having up to 3 heteroatoms selected from nitrogen, sulfur, and oxygen;
• and
• R6 is straight or branched chain alkyl having from 1 to 10 carbons;
• each B, independently, is a naturally occurring or non-naturally occurring nucleobase or a protected naturally occurring or non-naturally occurring nucleobase;
• R2 is hydrogen, a hydroxyl protecting group, or a linker connected to a solid support;
• M is an optionally protected internucleoside linkage,
• m is 0 to about 50;
• and
• R7 is R5, or has the Formula IX:
• 55
• wherein:
• R3 is hydrogen, a hydroxyl protecting group, or a linker connected to a solid support;
• n is 0 to about 50;
• with the proviso that the sum of m and n do not exceed 50.

A compound comprising a moiety having the Formula:

• 56
• wherein:
• A is a monocyclic or bicyclic aromatic ring system;
• R11 and R12 are each independently H, alkyl, aryl, heteroalkyl, heteroaryl, alkaryl, or aralkyl;
• or R11 and R12 together with the carbon atoms to which they are attached form an optionally substituted aliphatic or aromatic ring having from 4 to 6 ring atoms;
• X4 is alkaryl, aralkyl, sulfoxyl, sulfonyl, thio, substituted sulfoxyl, substituted sulfonyl, or substituted thio, wherein said substituent is alkyl, aryl, or alkaryl;
• or X4 is a group of formula —C(═O)—(O)aa—R40 where aa is 0 or 1 and R40 is lower alkyl, aryl, aralkyl, heteroaryl wherein said lower alkyl, aryl, aralkyl or heteroaryl groups are optionally substituted with one or more alkyl, aryl, aralkyl, halo or acetyl groups;
• or X4 is a group of formula —(—CH2—CH2—)dSi(R9)3 where d is 0 or 1;
• each R9 is, independently, alkyl having 1 to about 10 carbon atoms, or aryl having 6 to about 10 carbon atoms;
• and
• X1 and X5 are each independently O or S.

A compound having Formula:

• 57
• or Formula:
• 58
• wherein:
• A is a monocyclic or bicyclic aromatic ring system;
• R11 and R12 are each independently H, alkyl, aryl, heteroalkyl, heteroaryl, alkaryl, or aralkyl;
• or R11 and R12 together with the carbon atoms to which they are attached form an optionally substituted aliphatic or aromatic ring having from 4 to 6 ring atoms;
• X4 alkaryl, aralkyl, sulfoxyl, sulfonyl, thio, substituted sulfoxyl, substituted sulfonyl, or substituted thio, wherein said substituent is alkyl, aryl, or alkaryl;
• or X4 is a group of formula —C(═O)—(O)aa—R40 where aa is 0 or 1 and R40 is lower alkyl, aryl, aralkyl, heteroaryl wherein said lower alkyl, aryl, aralkyl or heteroaryl groups are optionally substituted with one or more alkyl, aryl, aralkyl, halo or acetyl groups;
• or X4 is a group of formula (—CH2—CH2—)dSi(R9)3 where d is 0 or 1;
• each R9 is, independently, alkyl having 1 to about 10 carbon atoms, or aryl having 6 to about 10 carbon atoms;
• X1 is O or S;
• X2 is O or S;
• each R1, is, independently, H, hydroxyl, C1-C20 alkyl, C3-C20 alkenyl, C2-C20 alkynyl, halogen, thiol, keto, carboxyl, nitro, nitroso, nitrile, trifluoromethyl, trifluoromethoxy, O-alkyl, S-alkyl, NH-alkyl, N-dialkyl, O-aryl, S-aryl, NH-aryl, O-aralkyl, S-aralkyl, NH-aralkyl, amino, N-phthalimido, imidazole, azido, hydrazino, hydroxylamino, isocyanato, sulfoxide, sulfone, sulfide, disulfide, silyl, aryl, heterocycle, carbocycle, intercalator, reporter molecule, conjugate, polyamine, polyamide, polyalkylene glycol, or polyether;
• or R1 is a group of formula Z—R22—(R23)v;
• Z is O, S, NH, or N—R22—(R23)v;
• R22 is C1-C20 alkyl, C2-C20 alkenyl, or C2-C20 alkynyl;
• R23 is hydrogen, amino, halogen, hydroxyl, thiol, keto, carboxyl, nitro, nitroso, nitrile, trifluoromethyl, trifluoromethoxy, O-alkyl, S-alkyl, NH-alkyl, N-dialkyl, O-aryl, S-aryl, NH-aryl, O-aralkyl, S-aralkyl, NH-aralkyl, amino, N-phthalimido, imidazole, azido, hydrazino, hydroxylamino, isocyanato, sulfoxide, sulfone, sulfide, disulfide, silyl, aryl, heterocycle, carbocycle, intercalator, reporter molecule, conjugate, polyamine, polyamide, polyalkylene glycol, polyether, a group that enhances the pharmacodynamic properties of oligonucleotides, or a group that enhances the pharmacokinetic properties of oligonucleotides;
• v is from 0 to about 10;
• or R1 has the formula:
• 59
• y1 is 0 or 1;
• y2 is independently 0 to 10;
• y3 is 1 to 10;
• E is C1-C10 alkyl, N(Q1)(Q2) or N═C(Q1)(Q2);
• each Q1 and Q2 is, independently, H, C1-C10 alkyl, substituted C1-C10 alkyl, dialkylaminoalkyl, a nitrogen protecting group, a tethered or untethered conjugate group, a linker to a solid support;
• or Q1 and Q2, together, are joined in a nitrogen protecting group or a ring structure that can include at least one additional heteroatom selected from N and O;
• or R1 has one of formula XI or XII:
• 60
• wherein
• Z0 is O, S, or NH;
• q1 is from 0 to 10;
• q2 is from 1 to 10;
• q3 is 0 or 1;
• q4 is, 0, 1 or 2;
• Z4 is OM1, SM1, or N(M1)2;
• each M1 is, independently, H, C1-C8 alkyl, C1-C8 haloalkyl, C(═NH)N(H)M2, C(═O)N(H)M2 or OC(═O)N(H)M2;
• M2 is H or C1-C8 alkyl;
• Z1, Z2 and Z3 comprise a ring system having from about 4 to about 7 carbon atoms, or having from about 3 to about 6 carbon atoms and 1 or 2 hetero atoms wherein said hetero atoms are selected from oxygen, nitrogen and sulfur, and wherein said ring system is aliphatic, unsaturated aliphatic, aromatic, or saturated or unsaturated heterocyclic;
• and
• Z5 is alkyl or haloalkyl having 1 to about 10 carbon atoms, alkenyl having 2 to about 10 carbon atoms, alkynyl having 2 to about 10 carbon atoms, aryl having 6 to about 14 carbon atoms, N(Q1)(Q2), OQ1, halo, SQ1 or CN;
• R2 is hydrogen, a hydroxyl protecting group, or a linker connected to a solid support;
• R3 is hydrogen, a hydroxyl protecting group, or a linker connected to a solid support, provided that R2 and R3 are not both simultaneously a linker connected to a solid support;
• M is an internucleoside linkage;
• m and n are each independently from 0 to about 50, provided that the sum of m and n does not exceed 50;
• and
• each B, independently, is a naturally occurring or non-naturally occurring nucleobase or a protected naturally occurring or non-naturally occurring nucleobase.

A method for the preparation of a compound of Formula II:

• 61
• wherein:
• A is a monocyclic or bicyclic aromatic ring system;
• R11 and R12 are each independently H, alkyl, aryl, heteroalkyl, heteroaryl, alkaryl, or aralkyl;
• or R11 and R12 together with the carbon atoms to which they are attached form an optionally substituted aliphatic or aromatic ring having from 4 to 6 ring atoms;
• X4 is alkaryl, aralkyl, sulfoxyl, sulfonyl, thio, substituted sulfoxyl, substituted sulfonyl, or substituted thio, wherein said substituent is alkyl, aryl, or alkaryl;
• or X4 is a group of formula —C(═O)—(O)aa—R40 where aa is 0 or 1 and R40 is lower alkyl, aryl, aralkyl, heteroaryl wherein said lower alkyl, aryl, aralkyl or heteroaryl groups are optionally substituted with one or more alkyl, aryl, aralkyl, halo or acetyl groups;
• or X4 is a group of formula —(—CH2—CH2—)dSi(R9)3 where d is 0 or 1;
• each R9 is, independently, alkyl having 1 to about 10 carbon atoms, or aryl having 6 to about 10 carbon atoms;
• X1 and X5 are each independently O or S;
• each R1, is, independently, H, hydroxyl, C1-C20 alkyl, C3-C20 alkenyl, C2-C20 alkynyl, halogen, thiol, keto, carboxyl, nitro, nitroso, nitrile, trifluoromethyl, trifluoromethoxy, O-alkyl, S-alkyl, NH-alkyl, N-dialkyl, O-aryl, S-aryl, NH-aryl, O-aralkyl, S-aralkyl, NH-aralkyl, amino, N-phthalimido, imidazole, azido, hydrazino, hydroxylamino, isocyanato, sulfoxide, sulfone, sulfide, disulfide, silyl, aryl, heterocycle, carbocycle, intercalator, reporter molecule, conjugate, polyamine, polyamide, polyalkylene glycol, or polyether;
• or R1 is a group of formula Z—R22—(R23)v;
• Z is O, S, NH, or N—R22—(R23)v;
• R22 is C1-C20 alkyl, C2-C20 alkenyl, or C2-C20 alkynyl;
• R23 is hydrogen, amino, halogen, hydroxyl, thiol, keto, carboxyl, nitro, nitroso, nitrile, trifluoromethyl, trifluoromethoxy, O-alkyl, S-alkyl, NH-alkyl, N-dialkyl, O-aryl, S-aryl, NH-aryl, O-aralkyl, S-aralkyl, NH-aralkyl, amino, N-phthalimido, imidazole, azido, hydrazino, hydroxylamino, isocyanato, sulfoxide, sulfone, sulfide, disulfide, silyl, aryl, heterocycle, carbocycle, intercalator, reporter molecule, conjugate, polyamine, polyamide, polyalkylene glycol, polyether, a group that enhances the pharmacodynamic properties of oligonucleotides, or a group that enhances the pharmacokinetic properties of oligonucleotides;
• v is from 0 to about 10;
• or R1 has the formula:
• 62
• y1 is 0 or 1;
• y2 is independently 0 to 10;
• y3 is 1 to 10;
• E is C1-C10 alkyl, N(Q1)(Q2) or N═C(Q1)(Q2);
• each Q1 and Q2 is, independently, H, C1-C10 alkyl, substituted C1-C10 alkyl, dialkylaminoalkyl, a nitrogen protecting group, a tethered or untethered conjugate group, a linker to a solid support;
• or Q1 and Q2, together, are joined in a nitrogen protecting group or a ring structure that can include at least one additional heteroatom selected from N and O;
• or R1 has one of formula XI or XII:
• 63
• wherein
• Z0 is O, S, or NH;
• q1 is from 0 to 10;
• q2 is from 1 to 10;
• q3 is 0 or 1;
• q4 is, 0, 1 or 2;
• Z4 is OM1, SM1, or N(M1)2;
• each M1 is, independently, H, C1-C8 alkyl, C1-C8 haloalkyl, C(═NH)N(H)M2, C(═O)N(H)M2 or OC(═O)N(H)M2;
• M2 is H or C1-C8 alkyl;
• Z1, Z2 and Z3 comprise a ring system having from about 4 to about 7 carbon atoms, or having from about 3 to about 6 carbon atoms and 1 or 2 hetero atoms wherein said hetero atoms are selected from oxygen, nitrogen and sulfur, and wherein said ring system is aliphatic, unsaturated aliphatic, aromatic, or saturated or unsaturated heterocyclic;
• and
• Z5 is alkyl or haloalkyl having 1 to about 10 carbon atoms, alkenyl having 2 to about 10 carbon atoms, alkynyl having 2 to about 10 carbon atoms, aryl having 6 to about 14 carbon atoms, N(Q1)(Q2), OQ1, halo, SQ1 or CN;
• R3 is hydrogen, a hydroxyl protecting group, or a linker connected to a solid support;
• each B, independently, is a naturally occurring or non-naturally occurring nucleobase or a protected naturally occurring or non-naturally occurring nucleobase;
• n is 0 to about 50;
• M is an optionally protected internucleoside linkage;
• R5 is —N(R6)2, or a heterocycloalkyl or heterocycloalkenyl ring containing from 4 to 7 atoms, and having up to 3 heteroatoms selected from nitrogen, sulfur, and oxygen;
• and
• R6 is straight or branched chain alkyl having from 1 to 10 carbons;
• comprising:
• (a) selecting a 5′-protected nucleoside having Formula V:
• 64
• and
• (b) reacting the nucleoside with a compound having the Formula VI:
• 65
• in the presence of an acid.

A method for the preparation of a compound of Formula II:

• 66
• wherein:
• A is a monocyclic or bicyclic aromatic ring system;
• R11 and R12 are each independently H, alkyl, aryl, heteroalkyl, heteroaryl, alkaryl, or aralkyl;
• or R11 and R12 together with the carbon atoms to which they are attached form an optionally substituted aliphatic or aromatic ring having from 4 to 6 ring atoms;
• X4 is alkaryl, aralkyl, sulfoxyl, sulfonyl, thio, substituted sulfoxyl, substituted sulfonyl, or substituted thio, wherein said substituent is alkyl, aryl, or alkaryl;
• or X4 is a group of formula —C(═O)—(O)aa—R40 where aa is 0 or 1 and R40 is lower alkyl, aryl, aralkyl, heteroaryl wherein said lower alkyl, aryl, aralkyl or heteroaryl groups are optionally substituted with one or more alkyl, aryl, aralkyl, halo or acetyl groups;
• or X4 is a group of formula —(—CH2—CH2—)dSi(R9)3 where d is 0 or 1;
• each R9 is, independently, alkyl having 1 to about 10 carbon atoms, or aryl having 6 to about 10 carbon atoms;
• X1 and X5 are each independently O or S;
• each R1, is, independently, H, hydroxyl, C1-C20 alkyl, C3-C20 alkenyl, C2-C20 alkynyl, halogen, thiol, keto, carboxyl, nitro, nitroso, nitrile, trifluoromethyl, trifluoromethoxy, O-alkyl, S-alkyl, NH-alkyl, N-dialkyl, O-aryl, S-aryl, NH-aryl, O-aralkyl, S-aralkyl, NH-aralkyl, amino, N-phthalimido, imidazole, azido, hydrazino, hydroxylamino, isocyanato, sulfoxide, sulfone, sulfide, disulfide, silyl, aryl, heterocycle, carbocycle, intercalator, reporter molecule, conjugate, polyamine, polyamide, polyalkylene glycol, or polyether;
• or R1 is a group of formula Z—R22—(R23)v;
• Z is O, S, NH, or N—R22—(R23)v;
• R22 is C1-C20 alkyl, C2-C20 alkenyl, or C2-C20 alkynyl;
• R23 is hydrogen, amino, halogen, hydroxyl, thiol, keto, carboxyl, nitro, nitroso, nitrile, trifluoromethyl, trifluoromethoxy, O-alkyl, S-alkyl, NH-alkyl, N-dialkyl, O-aryl, S-aryl, NH-aryl, O-aralkyl, S-aralkyl, NH-aralkyl, amino, N-phthalimido, imidazole, azido, hydrazino, hydroxylamino, isocyanato, sulfoxide, sulfone, sulfide, disulfide, silyl, aryl, heterocycle, carbocycle, intercalator, reporter molecule, conjugate, polyamine, polyamide, polyalkylene glycol, polyether, a group that enhances the pharmacodynamic properties of oligonucleotides, or a group that enhances the pharmacokinetic properties of oligonucleotides;
• v is from 0 to about 10;
• or R1 has the formula:
• 67
• y1 is 0 or 1;
• y2 is independently 0 to 10;
• y3 is 1 to 10;
• E is C1-C10 alkyl, N(Q1)(Q2) or N═C(Q1)(Q2);
• each Q1 and Q2 is, independently, H, C1-C10 alkyl, substituted C1-C10 alkyl, dialkylaminoalkyl, a nitrogen protecting group, a tethered or untethered conjugate group, a linker to a solid support;
• or Q1 and Q2, together, are joined in a nitrogen protecting group or a ring structure that can include at least one additional heteroatom selected from N and O;
• or R1 has one of formula XI or XII:
• 68
• wherein
• Z0 is O, S, or NH;
• q1 is from 0 to 10;
• q2 is from 1 to 10;
• q3 is 0 or 1;
• q4 is, 0, 1 or 2;
• Z4 is OM1, SM1, or N(M1)2;
• each M1 is, independently, H, C1-C8 alkyl, C1-C8 haloalkyl, C(═NH)N(H)M2, C(═O)N(H)M2 or OC(═O)N(H)M2;
• M2 is H or C1-C8 alkyl;
• Z1, Z2 and Z3 comprise a ring system having from about 4 to about 7 carbon atoms, or having from about 3 to about 6 carbon atoms and 1 or 2 hetero atoms wherein said hetero atoms are selected from oxygen, nitrogen and sulfur, and wherein said ring system is aliphatic, unsaturated aliphatic, aromatic, or saturated or unsaturated heterocyclic;
• and
• Z5 is alkyl or haloalkyl having 1 to about 10 carbon atoms, alkenyl having 2 to about 10 carbon atoms, alkynyl having 2 to about 10 carbon atoms, aryl having 6 to about 14 carbon atoms, N(Q1)(Q2), OQ1, halo, SQ1 or CN;
• R3 is hydrogen, a hydroxyl protecting group, or a linker connected to a solid support;
• each B, independently, is a naturally occurring or non-naturally occurring nucleobase or a protected naturally occurring or non-naturally occurring nucleobase;
• n is 0 to about 50;
• M is an optionally protected internucleoside linkage;
• R5 is —N(R6)2, or a heterocycloalkyl or heterocycloalkenyl ring containing from 4 to 7 atoms, and having up to 3 heteroatoms selected from nitrogen, sulfur, and oxygen;
• and
• R6 is straight or branched chain alkyl having from 1 to 10 carbons;
• comprising:
• (a) selecting a 5′-protected nucleoside of Formula V:
• 69
• wherein R3 is a hydroxyl protecting group;
• (b) reacting the protected nucleoside with a chlorophosphine compund of formula ClP(R5)2 in the presence of a base;
• and
• (c) contacting the product of step (b) with a compound of Formula XX:
• 70
• in the presence of an acid;
• to form the nucleoside phosphoramidite.

A compound having the formula:

• 71
• wherein
• A is a monocyclic or bicyclic aromatic ring system;
• R11 and R12 are each H, independently alkyl, aryl, heteroalkyl, heteroaryl, alkaryl, or aralkyl;
• or R11 and R12 together with the carbon atoms to which they are attached form an optionally substituted aliphatic or aromatic ring having from 4 to 6 ring atoms;
• X4 is alkaryl, aralkyl, sulfoxyl, sulfonyl, thio, substituted sulfoxyl, substituted sulfonyl, or substituted thio, wherein said substituent is alkyl, aryl, or alkaryl;
• or X4 is a group of formula —C(═O)—(O)aa—R40 where aa is 0 or 1 and R40 is lower alkyl, aryl, aralkyl, heteroaryl wherein said lower alkyl, aryl, aralkyl or heteroaryl groups are optionally substituted with one or more alkyl, aryl, aralkyl, halo or acetyl groups;
• or X4 is a group of formula —(—CH2—CH2—)dSi(R9)3 where d is 0 or 1;
• each R9 is, independently, alkyl having 1 to about 10 carbon atoms, or aryl having 6 to about 10 carbon atoms;
• X1 and X5 are each independently O or S;
• R5 is —N(R6)2, or a heterocycloalkyl or heterocycloalkenyl ring containing from 4 to 7 atoms, and having up to 3 heteroatoms selected from nitrogen, sulfur, and oxygen;
• and
• R6 is straight or branched chain alkyl having from 1 to 10 carbons.