Bruce S Ross | University of Kansas (original) (raw)
Papers by Bruce S Ross
Nucleosides, Nucleotides and Nucleic Acids, 2005
We describe an improved process to produce 2&... more We describe an improved process to produce 2'-O-(2-methoxyethyl)-pyrimidines. Starting with commercially available O-2,2'-anhydro-5-methyluridine and tris-(2-methoxyethyl)borate, we modified the ring-opening reaction conditions and changed to a continuous extraction purification method to give 2'-O-(2-methaxyethyl)-5-methyluridine. The dimethoxytritylation 5'/3' ratios and yield were improved by the use of 2,6-lutidine as the base. Conditions to convert to the 5'-methylcytidine analog and its isolation by crystallization were optimized. Final benzoylation was improved by developing a method to selectively hydrolyze benzoyl ester impurities.
The present invention provides bicyclic cyclohexose nucleoside analogs I, wherein B is a heterocy... more The present invention provides bicyclic cyclohexose nucleoside analogs I, wherein B is a heterocyclic base moiety; Z is O or S; Q is a bridge group comprising 1 or from 2 to 8 linked bi-radical groups independently selected from O, S, N(R1), C(R1)(R2), C(R1)=C(R2), C(R1)=N, C(=NR1), Si(R1)2, S(O)2, S(O), C(O) and C(S); each R1 and R2 is independently, H, hydroxy, alkyl, alkyl, alkenyl, alkynyl, aryl, heterocycle, heteroaryl, alicyclic, alicyclic, halogen, OJ1, NJ1J2, SJ1, N3, COOJ1, acyl (C(O)-H), acyl, CN, S(O)-J1 or S(O)-J1; L1 and L2 are each, independently, H, alkyl, alkenyl, alkynyl, aryl, acyl, CHO, heterocycle, aminoalkyl, protecting group; one of E1 and E2 is H and the other of E1 and E2 is O-T2 or one of E3 and E4 is H and the other of E3 and E4 is O-T2 and the remaining two of E1-E4 are each, independently H, halogen, hydroxy, alkyl, alkenyl, alkynyl, aryl, heterocycle, heteroaryl, alicyclic, OJ3, NJ3J4, SJ3, N3, COOJ3, acyl, CHO, CN, S(O)-J3 or S(O)-J3; one of T1 and T2 i...
Journal of Medicinal Chemistry, 2008
A number of 2&amp... more A number of 2'- O-modified antisense oligonucleotides have been reported for their potential use in oligonucleotide-based therapeutics. To date, most of the in vivo data has been generated for 2'-O-MOE (2'-O-methoxyethyl)- and 2'-O-Me (2'-O-methyl)-modified ASOs (antisense oligonucleotides). We now report the synthesis and biological activity of another 2'-O-modification, namely 2'-O-[2-(methylamino)-2-oxoethyl] (2'-O-NMA). This modification resulted in an increase in the affinity of antisense oligonucleotides to complementary RNA similar to 2'-O-MOE-modified ASOs as compared to first-generation antisense oligodeoxynucleotides. The ASO modified with 2'-O-NMA reduced expression of PTEN mRNA in vitro and in vivo in a dose-dependent manner similar to 2'-O-MOE modified ASO. Importantly, toxicity parameters such as AST, ALT, organ weights, and body weights were found to be normal similar to 2'-O-MOE ASO-treated animal models. The data generated in these experiments suggest that 2'-O-NMA is a useful modification for potential application in both antisense and other oligonucleotide-based drug discovery efforts.
Biochemistry, 2013
that the T m values for native sequences M and N as well as the T m and ΔT m values for the 2′-O-... more that the T m values for native sequences M and N as well as the T m and ΔT m values for the 2′-O-DMAOE modification I are transposed in Table 1. The corrected Table 1 is given here with all affected values highlighted in bold.
Journal of Organic Chemistry, 1999
In the peptide literature, a related group, the cyano-tert-butoxycarbonyl group, has been used to... more In the peptide literature, a related group, the cyano-tert-butoxycarbonyl group, has been used to protect the amino acid glycine. This group is cleaved by aqueous potassium carbonate or triethylamine by β-elimination at pH 10. 9 Recently, a related group, (2-cyano-1-phenyl) ...
Tetrahedron Letters, 1994
Abstkaek A large-scale, facile and stereoselective synthesis of 1-[5-O-(tert-butyldiphenylsilyl~2... more Abstkaek A large-scale, facile and stereoselective synthesis of 1-[5-O-(tert-butyldiphenylsilyl~2,3~d~xy-3-u-C-f~yl-~Derytbro-pentofuranosyl] -adenine (7b) and -N2-isobutyrylguanine (7~) using an intermolecular radical C-C bond formation reaction is reported. The utility of these nucleosides (7h and 7c) as building blocks for antisense digonucleosides is discussed.
Tetrahedron Letters, 1986
... 5HYDROXYMETHYL1lMETHYL6HPYRIDO[4,3b]CARBAZOLE AND 5FORMYL11METHYL6 HPYRIDO[4,3b]CARBAZOLE (17... more ... 5HYDROXYMETHYL1lMETHYL6HPYRIDO[4,3b]CARBAZOLE AND 5FORMYL11METHYL6 HPYRIDO[4,3b]CARBAZOLE (17OXOELLIPTICINE) Bruce S. Ross and Sydney Archer* Department of Chemistry Cogswel 1 Laboratory Rensselaer Polytechnic Institute Troy, New York ...
Nucleosides, Nucleotides and Nucleic Acids, 2005
We describe an improved process to produce 2&... more We describe an improved process to produce 2'-O-(2-methoxyethyl)-pyrimidines. Starting with commercially available O-2,2'-anhydro-5-methyluridine and tris-(2-methoxyethyl)borate, we modified the ring-opening reaction conditions and changed to a continuous extraction purification method to give 2'-O-(2-methaxyethyl)-5-methyluridine. The dimethoxytritylation 5'/3' ratios and yield were improved by the use of 2,6-lutidine as the base. Conditions to convert to the 5'-methylcytidine analog and its isolation by crystallization were optimized. Final benzoylation was improved by developing a method to selectively hydrolyze benzoyl ester impurities.
The present invention provides bicyclic cyclohexose nucleoside analogs I, wherein B is a heterocy... more The present invention provides bicyclic cyclohexose nucleoside analogs I, wherein B is a heterocyclic base moiety; Z is O or S; Q is a bridge group comprising 1 or from 2 to 8 linked bi-radical groups independently selected from O, S, N(R1), C(R1)(R2), C(R1)=C(R2), C(R1)=N, C(=NR1), Si(R1)2, S(O)2, S(O), C(O) and C(S); each R1 and R2 is independently, H, hydroxy, alkyl, alkyl, alkenyl, alkynyl, aryl, heterocycle, heteroaryl, alicyclic, alicyclic, halogen, OJ1, NJ1J2, SJ1, N3, COOJ1, acyl (C(O)-H), acyl, CN, S(O)-J1 or S(O)-J1; L1 and L2 are each, independently, H, alkyl, alkenyl, alkynyl, aryl, acyl, CHO, heterocycle, aminoalkyl, protecting group; one of E1 and E2 is H and the other of E1 and E2 is O-T2 or one of E3 and E4 is H and the other of E3 and E4 is O-T2 and the remaining two of E1-E4 are each, independently H, halogen, hydroxy, alkyl, alkenyl, alkynyl, aryl, heterocycle, heteroaryl, alicyclic, OJ3, NJ3J4, SJ3, N3, COOJ3, acyl, CHO, CN, S(O)-J3 or S(O)-J3; one of T1 and T2 i...
Journal of Medicinal Chemistry, 2008
A number of 2&amp... more A number of 2'- O-modified antisense oligonucleotides have been reported for their potential use in oligonucleotide-based therapeutics. To date, most of the in vivo data has been generated for 2'-O-MOE (2'-O-methoxyethyl)- and 2'-O-Me (2'-O-methyl)-modified ASOs (antisense oligonucleotides). We now report the synthesis and biological activity of another 2'-O-modification, namely 2'-O-[2-(methylamino)-2-oxoethyl] (2'-O-NMA). This modification resulted in an increase in the affinity of antisense oligonucleotides to complementary RNA similar to 2'-O-MOE-modified ASOs as compared to first-generation antisense oligodeoxynucleotides. The ASO modified with 2'-O-NMA reduced expression of PTEN mRNA in vitro and in vivo in a dose-dependent manner similar to 2'-O-MOE modified ASO. Importantly, toxicity parameters such as AST, ALT, organ weights, and body weights were found to be normal similar to 2'-O-MOE ASO-treated animal models. The data generated in these experiments suggest that 2'-O-NMA is a useful modification for potential application in both antisense and other oligonucleotide-based drug discovery efforts.
Biochemistry, 2013
that the T m values for native sequences M and N as well as the T m and ΔT m values for the 2′-O-... more that the T m values for native sequences M and N as well as the T m and ΔT m values for the 2′-O-DMAOE modification I are transposed in Table 1. The corrected Table 1 is given here with all affected values highlighted in bold.
Journal of Organic Chemistry, 1999
In the peptide literature, a related group, the cyano-tert-butoxycarbonyl group, has been used to... more In the peptide literature, a related group, the cyano-tert-butoxycarbonyl group, has been used to protect the amino acid glycine. This group is cleaved by aqueous potassium carbonate or triethylamine by β-elimination at pH 10. 9 Recently, a related group, (2-cyano-1-phenyl) ...
Tetrahedron Letters, 1994
Abstkaek A large-scale, facile and stereoselective synthesis of 1-[5-O-(tert-butyldiphenylsilyl~2... more Abstkaek A large-scale, facile and stereoselective synthesis of 1-[5-O-(tert-butyldiphenylsilyl~2,3~d~xy-3-u-C-f~yl-~Derytbro-pentofuranosyl] -adenine (7b) and -N2-isobutyrylguanine (7~) using an intermolecular radical C-C bond formation reaction is reported. The utility of these nucleosides (7h and 7c) as building blocks for antisense digonucleosides is discussed.
Tetrahedron Letters, 1986
... 5HYDROXYMETHYL1lMETHYL6HPYRIDO[4,3b]CARBAZOLE AND 5FORMYL11METHYL6 HPYRIDO[4,3b]CARBAZOLE (17... more ... 5HYDROXYMETHYL1lMETHYL6HPYRIDO[4,3b]CARBAZOLE AND 5FORMYL11METHYL6 HPYRIDO[4,3b]CARBAZOLE (17OXOELLIPTICINE) Bruce S. Ross and Sydney Archer* Department of Chemistry Cogswel 1 Laboratory Rensselaer Polytechnic Institute Troy, New York ...