Table showing various modified oligonucleotides synthesized using UnyLinker loaded solid supports.

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Emmeline Bennett
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1 Table showing various modified oligonucleotides synthesized using UnyLinker loaded solid supports. Oligo Synthesized Sequence 5 3 Oligo 1 2 -O-Methoxyethyl modified phosphorothioate 2- nucleotide gapmer ISIS Oligo 2 [CTG]-AGTCTGTTT-[TCCATTCT] Oligo 3 Oligo 4 Oligo 5 Oligo 6 Oligo 7 Oligo 8 [GCTCC]-TTCCACTGAT-[CCTGC] [GCCTC]-AGTCTGCTTC[GCACC] [TGGAA]-AGGCTTATAC-[CCCTC] [TCCCGC]-CTGTGACA-[TGCATT] d[gcccaagctggcatccgtca] [CAGC]-AGCAGAGTCTTCA-[TCAT] Oligo Synthesized Sequence 5 3 Oligo #9 5 -PO-d[AATGCATGTCACAGGCGGGA] Oligo #1 Oligo #11 Oligo #12 Oligo #13 Oligo #14 Oligo #15 Oligo #16 Oligo #17 m C ms T m ms C mo A mo G m mo C mo A m mo C mo A mo T m mo C mo T mo A m mo C mo A mo A mo G ms A ms A ms A m C ms T m ms C ms A ms G m ms C ms A m ms C ms A ms T m ms C ms T ms A m ms C ms A ms A ms G ms A ms A ms A A ro A eo G ro C eo A ro A eo C ro G eo A ro G eo A ro A eo G ro C eo G ro A eo U ro A eo A r 5 -A m es C es A m es C es A es A es A es T es T m es C es G es G es T es T m es C es T es A m es C es A es G es G es G e PO 3 -U ro U ro A ro U ro C ro G mo C mo U ro U ro C mo U mo C ro G ro U ro U ro G ro C mo U mo U m 5 - m C es G m es C es G es T es A m es C m es C es A es A es A es A es G es T es A es A es T es A es A es T es G e m C es U m fs C es A fs G es C fs A es C fs A es U m fs C es U fs A es C fs A es A fs G es A es A e 5 -T m es C es A m es C es A es A es G es T es T es A es G es G es G es T m es C es T m es C es A es G es G es G es A e S33

2 Oligo #18 Oligo #19 Oligo #2 Oligo #21 Oligo #22 Oligo #23 Oligo #24 Oligo #25 Oligo #26 Oligo #27 Oligo #28 Oligo #29 Oligo #3 Oligo #31 Oligo #32 Oligo #33 Oligo #34 Oligo #35 Oligo #36 Oligo #37 5 -G m es C es T m es C es A es T es T es T es A es G es T m es C es T es G m es C m es C es T es G es A es T e m C ls T ls G ds C ds T ds A ds G ds C ds C ds T ds C ds T ds G ds G ds A ds T ds T ds T ds G ls A l m C lo T lo G ds C ds T ds A ds G ds C ds C ds T ds C ds T ds G ds G ds A ds T ds T ds T do G lo A l 5 -A m es C es A es T es A m es C es T m es C m es C es T es T es T es m C es T m es C es A es G es A es G es T m es C m es C es A e T ls T ls G ls T ds T ds C ds T ds G ds A ds A ds T ds G ds T ds m C ls m C ls A l 5 -A es A m es C m es C es T es A es T m es C m es C es T es G es A es A es T es T es A m es C es T es T es G es A es A e 5 -A m ms C ms A ms A ms A m ms C ms A m ms C m ms C ms A ms T ms T ms G ms T m ms C ms A m ms C ms A m ms C ms T m ms C m ms C ms A m 5 -PO-d[GAGGGGTATAAGCCTTTCCA] G m ls C ls T m ls C ls A ds T ds A m ds C ds T m ds C ds G ds T ds A ds G ds G m ls C m ls C ls A l 5 -G m es C es A m ds C ds T ds T ds T ds G ds T ds G ds G ds T ds G m ds C m ds C ds A ds A ds G ds G m es C e 5 - m C m es C ds A ds G m ds C ds A ds T m ds C ds T ds G m ds C ds T ds G m es C es T es T m es C e 5 - m C es T m ds C es A ds G m es C ds A m es C ds A es T m ds C es T ds A m es C ds A es A ds G es A ds A es A e 5 -Biotin-G es A es A es G es T es A ds G m ds C m ds C ds A ds m C m ds C ds A ds A m ds C ds T es G es T es G m es C e 5 - m C es T fs C fs A fs G fs C fs A fs C fs A fs T fs C fs T fs A fs C fs A fs A fs G fs A fs A es A e 5 -PO 3 -A ro U ro A ro G ro A ro C mo U mo U ro C ro A mo U mo C ro C ro U ro U ro G ro U mo U mo G m 5 -U ro A ro C ro G ro C ro A mo A mo A ro C ro C mo U mo U ro G ro A ro U ro G ro U mo C mo C m 5 - PO 3 -A ro A ro A ro U ro G ro U mo U mo C ro C ro A mo G mo C ro C ro C ro A ro G ro G mo G mo C m 5 -G ro G eo A ro C eo A ro U eo C ro A eo A ro G eo G ro U eo U ro U eo G ro C eo G ro U eo A r 5 -U ro C ro A ro C ro U ro C ro G ro G ro C ro U ro G ro G ro A ro U ro G ro G ro A ro G ro U rs T es T 5 -[CTCTA]-GTTCCTCTCA-[ATGTC] (for plate synthesis comparison) S34

3 Table: Oligonucleotides synthesized on GE Amersham Akta 1/1 and other automated DNA/RNA synthesizers. m C = 5-methyl C; d = 2 -deoxy; e = 2 -O-methoxyethyl; m = 2 - O-methyl; r = 2 -OH; l = LNA; f = 2 -alpha-fluoro; o = PO; s = PS; PO 3 = phosphate monoester. S35

4 IP-HPLC-MS of 2 -O-methoxyethyl modified phosphorothioate Oligo 1 ma 4 A mi B m/ Upper panel (A): HPLC-UV trace of the synthesized phosphorothioate oligonucleotide. Lower panel (B): The average mass spectrum under the parent peak. S36

5 IP-HPLC-MS of 2 -O-methoxyethyl modified phosphorothioate Oligo 2 5 -[CTG]-AGTCTGTTT-[TCCATTCT]-3 mau A mi B m/ Upper panel (A): HPLC-UV trace of the synthesized phosphorothioate oligonucleotide. Lower panel (B): The average mass spectrum under the parent peak. S37

6 IP-HPLC-MS of 2 -O-methoxyethyl modified phosphorothioate Oligo 3 5 -[GCTCC]-TTCCACTGAT-[CCTGC]-3 ma 35 A min B m/z Upper panel (A): HPLC-UV trace of the synthesized phosphorothioate oligonucleotide. Lower panel (B): The average mass spectrum under the parent peak. S38

7 IP-HPLC-MS of 2 -O-methoxyethyl modified phosphorothioate Oligo 4 5 -[GCCTC]-AGTCTGCTTC-[GCACC]-3 ma A min B m/z Upper panel (A): HPLC-UV trace of the synthesized phosphorothioate oligonucleotide. Lower panel (B): The average mass spectrum under the parent peak. S39

8 IP-HPLC-MS of 2 -O-methoxyethyl modified phosphorothioate Oligo 5 5 -[TGGAA]-AGGCTTATAC-[CCCTC]-3 ma 35 A min 18.6 B m/z Upper panel (A): HPLC-UV trace of the synthesized phosphorothioate oligonucleotide. Lower panel (B): The average mass spectrum under the parent peak. S4

9 IP-HPLC-MS of DMT-on crude 2 -O-methoxyethyl modified phosphorothioate Oligo 6 5 -[TCCCGC]-CTGTGACA-[TGCATT]-3 mau 25 A min B m/z Upper panel (A): HPLC-UV trace of the synthesized phosphorothioate oligonucleotide. Lower panel (B): The average mass spectrum under the parent peak. S41

10 IP-HPLC-MS of DMT-on reversed phase purified 2 -O-methoxyethyl modified phosphorothioate Oligo 6 5 -[TCCCGC]-CTGTGACA-[TGCATT]-3 mau 4 A min B m/z Upper panel (A): HPLC-UV trace of the synthesized phosphorothioate oligonucleotide. Lower panel (B): The average mass spectrum under the parent peak. S42

11 IP-HPLC-MS of crude DMT-on oligodeoxy phosphorothioate Oligo 7- SYN #1 5 -GCCCAAGCTGGCATCCGTCA-3 mau A min B m/z Upper panel (A): HPLC-UV trace of the crude synthesized phosphorothioate oligonucleotide. Lower panel (B): The average mass spectrum under the parent peak. S43

12 IP-HPLC-MS of oligodeoxy phosphorothioate Oligo 7- SYN #1 5 -GCCCAAGCTGGCATCCGTCA-3 ma 4 A min B m/z Upper panel (A): HPLC-UV trace of the synthesized phosphorothioate oligonucleotide. Lower panel (B): The average mass spectrum under the parent peak. S44

13 IP-HPLC-MS of crude DMT-on oligodeoxy phosphorothioate Oligo 7- SYN #2 5 -GCCCAAGCTGGCATCCGTCA-3 mau A min B m/z Upper panel (A): HPLC-UV trace of the crude synthesized phosphorothioate oligonucleotide. Lower panel (B): The average mass spectrum under the parent peak. S45

14 IP-HPLC-MS of crude DMT-on oligodeoxy phosphorothioate Oligo 7- SYN #3 5 -GCCCAAGCTGGCATCCGTCA-3 mau A min B m/z S46

15 Capillary gel electropherogram (CGE) analysis of oligodeoxy phosphorothioate 7 using da-loaded solid support. S47

16 IP-HPLC-MS analysis of 2 -O-methoxyethyl modified phosphorothioate Oligo 8 5 -[CAGC]-AGCAGAGTCTTCA-[TCAT]-3 mau 4 A min B m/z Upper panel (A): HPLC-UV trace of the synthesized phosphorothioate oligonucleotide. Lower panel (B): The average mass spectrum under the parent peak. S48

17 IP-HPLC-MS of DMT-on crude 2 -O-methoxyethyl modified phosphorothioate Oligo 9 5 -PO-d[AATGCATGTCACAGGCGGGA]-3 mau 6 A mi B m/ Upper panel (A): HPLC-UV trace of the synthesized oligonucleotide. Lower panel (B): The average mass spectrum under the parent peak. S49

18 IP-HPLC-MS analysis of 2 -O-methyl modified phosphate/phosphorothioate mixed backbone Oligo 1 using UnyLinker loaded CPG solid support 5 - m C ms T m ms C mo A mo G m mo C mo A m mo C mo A mo T m mo C mo T mo A m mo C mo A mo A mo G ms A ms A ms A-3 mau A min B m/z Upper panel (A): HPLC-UV trace of the synthesized phosphorothioate oligonucleotide. Lower panel (B): The average mass spectrum under the parent peak. S5

19 IP-HPLC-MS analysis of 2 -O-methyl modified phosphorothioate Oligo 11 using UnyLinker loaded CPG solid support 5 - m C ms T m ms C ms A ms G m ms C ms A m ms C ms A ms T m ms C ms T ms A m ms C ms A ms A ms G ms A ms A ms A-3 mau 7 A min B m/z Upper panel (A): HPLC-UV trace of the synthesized phosphorothioate oligonucleotide. Lower panel (B): The average mass spectrum under the parent peak. S51

20 IP-HPLC-MS analysis of 2 -O-methoxyethyl/RNA modified sequence with phosphate backbone Oligo 12 using UnyLinker loaded CPG solid support 5 -A ro A eo G ro C eo A ro A eo C ro G eo A ro G eo A ro A eo G ro C eo G ro A eo U ro A eo A r -3 mau 12 A min B m/z Upper panel (A): HPLC-UV trace of the synthesized phosphorothioate oligonucleotide. Lower panel (B): The average mass spectrum under the parent peak. S52

21 IP-HPLC-MS analysis of 5 -phosphate-2 -O-methyl/RNA modified sequence with phosphate backbone Oligo 13 using UnyLinker loaded CPG solid support 5 -A m es C es A m es C es A es A es A es T es T m es C es G es G es T es T m es C es T es A m es C es A es G es G es G e -3 mau 7 A min B m/z Upper panel (A): HPLC-UV trace of the synthesized phosphorothioate oligonucleotide. Lower panel (B): The average mass spectrum under the parent peak. S53

22 IP-HPLC-MS analysis of 5 -phosphate-2 -O-methyl/RNA modified phosphate Oligo 14 using UnyLinker loaded CPG solid support 5 -PO 3 -U ro U ro A ro U ro C ro G mo C mo U ro U ro C mo U mo C ro G ro U ro U ro G ro C mo U mo U m -3 mau 7 A min B m/z Upper panel (A): HPLC-UV trace of the synthesized phosphorothioate oligonucleotide. Lower panel (B): The average mass spectrum under the parent peak. S54

23 IP-HPLC-MS analysis of 2 -O-methoxyethyl/RNA modified sequence with phosphate backbone Oligo 15 using UnyLinker loaded CPG solid support 5 - m C es G es m C es G es T es A es m C es m C es A es A es A es A es G es T es A es A es T es A es A es T es G e -3 mau 8 A min B m/z Upper panel (A): HPLC-UV trace of the synthesized phosphorothioate oligonucleotide. Lower panel (B): The average mass spectrum under the parent peak. S55

24 IP-HPLC-MS analysis of 2 -O-methoxyethyl/2 -alpha-fluoro modified phosphorothioate Oligo 16 using UnyLinker loaded CPG solid support 5 - m C es U fs m C es A fs G es C fs A es C fs A es U fs m C es U fs A es C fs A es A fs G es A es A e -3 mau 1 A min B m/z Upper panel (A): HPLC-UV trace of the synthesized phosphorothioate oligonucleotide. Lower panel (B): The average mass spectrum under the parent peak. S56

25 IP-HPLC-MS analysis of 2 -deoxy/lna modified phosphorothioate Oligo 17 using UnyLinker loaded CPG solid support 5 -T es m C es A es m C es A es A es G es T es T es A es G es G es G es T es m C es T es m C es A es G es G es G es A e -3 mau 8 A min B m/z Upper panel (A): HPLC-UV trace of the synthesized phosphorothioate oligonucleotide. Lower panel (B): The average mass spectrum under the parent peak. S57

26 IP-HPLC-MS analysis of modified phosphorothioate Oligo 18 using UnyLinker loaded CPG solid support 5 -G es m C es T es m C es A es T es T es T es A es G es T es m C es T es G es m C es m C es T es G es A es T e -3 mau 6 A min B m/z Upper panel (A): HPLC-UV trace of the synthesized phosphorothioate oligonucleotide. Lower panel (B): The average mass spectrum under the parent peak. S58

27 IP-HPLC-MS analysis of modified phosphorothioate Oligo 19 using UnyLinker loaded CPG solid support 5 - m C ls T ls G ds C ds T ds A ds G ds C ds C ds T ds C ds T ds G ds G ds A ds T ds T ds T ds G ls A l -3 mau 8 A min B m/z Upper panel (A): HPLC-UV trace of the synthesized phosphorothioate oligonucleotide. Lower panel (B): The average mass spectrum under the parent peak. S59

28 IP-HPLC-MS analysis of 2 -deoxy/lna modified phosphate/phosphorothioate mixed backbone Oligo 2 using UnyLinker loaded CPG solid support 5 - m C lo T lo G ds C ds T ds A ds G ds C ds C ds T ds C ds T ds G ds G ds A ds T ds T ds T do G lo A l -3 mau 8 A min B m/z Upper panel (A): HPLC-UV trace of the synthesized phosphorothioate oligonucleotide. Lower panel (B): The average mass spectrum under the parent peak. S6

29 IP-HPLC-MS analysis of modified phosphorothioate Oligo 21 using UnyLinker loaded CPG solid support 5 -A es m C es A es T es A es m C es T es m C es m C es T es T es T es m C es T es m C es A es G es A es G es T es m C es m C es A e -3 mau 5 A min B m/z Upper panel (A): HPLC-UV trace of the synthesized phosphorothioate oligonucleotide. Lower panel (B): The average mass spectrum under the parent peak. S61

30 IP-HPLC-MS analysis of 2 -deoxy/lna modified phosphorothioate Oligo 22 using UnyLinker loaded CPG solid support 5 -T ls T ls G ls T ds T ds C ds T ds G ds A ds A ds T ds G ds T ds m C ls m C ls A l -3 mau 14 A min B m/z Upper panel (A): HPLC-UV trace of the synthesized phosphorothioate oligonucleotide. Lower panel (B): The average mass spectrum under the parent peak. S62

31 IP-HPLC-MS analysis of modified phosphorothioate Oligo 23 using UnyLinker loaded CPG solid support 5 -A es A es m C es m C es T es A es T es m C es m C es T es G es A es A es T es T es A es m C es T es T es G es A es A e -3 mau 7 A min B m/z Upper panel (A): HPLC-UV trace of the synthesized phosphorothioate oligonucleotide. Lower panel (B): The average mass spectrum under the parent peak. S63

32 IP-HPLC-MS analysis of 2 -deoxy/lna modified phosphorothioate Oligo 24 using UnyLinker loaded CPG solid support 5 -A ms m C ms A ms A ms A ms m C ms A ms m C ms m C ms A ms T ms T ms G ms T ms m C ms A ms m C ms A ms m C ms T ms m C ms m C ms A m -3 mau A min B m/z Upper panel (A): HPLC-UV trace of the synthesized phosphorothioate oligonucleotide. Lower panel (B): The average mass spectrum under the parent peak. S64

33 IP-HPLC-MS analysis of modified Oligo 25 using UnyLinker loaded CPG solid support 5 -PO-d[GAGGGGTATAAGCCTTTCCA]-3 mau 1 A min B m/z Upper panel (A): HPLC-UV trace of the synthesized oligonucleotide. Lower panel (B): The average mass spectrum under the parent peak. S65

34 IP-HPLC-MS analysis of 2 -deoxy/lna modified phosphorothioate Oligo 26 using UnyLinker loaded CPG solid support 5 -G ls m C ls T ls m C ls A ds T ds A ds m C ds T ds m C ds G ds T ds A ds G ds G ls m C ls m C ls A l -3 mau 5 A min B m/z Upper panel (A): HPLC-UV trace of the synthesized phosphorothioate oligonucleotide. Lower panel (B): The average mass spectrum under the parent peak. S66

35 IP-HPLC-MS analysis of modified Oligo 27 using UnyLinker loaded solid support 5 -G es m C es A ds m C ds T ds T ds T ds G ds T ds G ds G ds T ds G ds m C ds m C ds A ds A ds G ds G es m C e -3 mau 4 A min B m/z Upper panel (A): HPLC-UV trace of the synthesized phosphorothioate oligonucleotide. Lower panel (B): The average mass spectrum under the parent peak. S67

36 IP-HPLC-MS analysis of modified phosphorothioate Oligo 28 made using UnyLinker solid support 5 - m C es m C ds A ds G ds m C ds A ds T ds m C ds T ds G ds m C ds T ds G es m C es T es T es m C e -3 mau 6 A min B m/z Upper panel (A): HPLC-UV trace of the synthesized phosphorothioate oligonucleotide. Lower panel (B): The average mass spectrum under the parent peak. S68

37 IP-HPLC-MS analysis of modified phosphorothioate Oligo 29 made using UnyLinker solid support 5 - m C es T ds m C es A ds G es m C ds A es m C ds A es T ds m C es T ds A es m C ds A es A ds G es A ds A es A e -3 mau 7 A min B m/z Upper panel (A): HPLC-UV trace of the synthesized phosphorothioate oligonucleotide. Lower panel (B): The average mass spectrum under the parent peak. S69

38 IP-HPLC-MS analysis of modified phosphorothioate Oligo 3 made using UnyLinker solid support 5 -Biotin-G es A es A es G es T es A ds G ds m C ds m C ds A ds m C ds m C ds A ds A ds m C ds T es G es T es G es m C e -3 mau A min B m/z Upper panel (A): HPLC-UV trace of the synthesized phosphorothioate oligonucleotide. Lower panel (B): The average mass spectrum under the parent peak. S7

39 IP-HPLC-MS analysis of modified phosphorothioate Oligo 31 made using UnyLinker solid support 5 -C es U fs C fs A fs G fs C fs A fs C fs A fs U fs C fs U fs A fs C fs A fs A fs G fs A fs A es A e -3 mau A min B m/z Upper panel (A): HPLC-UV trace of the synthesized phosphorothioate oligonucleotide. Lower panel (B): The average mass spectrum under the parent peak. S71

40 IP-HPLC-MS analysis of modified Oligo 32 made using UnyLinker solid support 5 -PO 3 -A ro U ro A ro G ro A ro C mo U mo U ro C ro A mo U mo C ro C ro U ro U ro G ro U mo U mo G m -3 mau 8 A min B m/z Upper panel (A): HPLC-UV trace of the synthesized phosphorothioate oligonucleotide. Lower panel (B): The average mass spectrum under the parent peak. S72

41 IP-HPLC-MS analysis of modified Oligo 33 made using UnyLinker solid support 5 -U ro A ro C ro G ro C ro A mo A mo A ro C ro C mo U mo U ro G ro A ro U ro G ro U mo C mo C m -3 mau 7 A min B m/z Upper panel (A): HPLC-UV trace of the synthesized oligonucleotide. Lower panel (B): The average mass spectrum under the parent peak. S73

42 IP-HPLC-MS analysis of modified Oligo 34 made using UnyLinker solid support 5 - PO 3 -A ro A ro A ro U ro G ro U mo U mo C ro C ro A mo G mo C ro C ro C ro A ro G ro G mo G mo C m -3 mau A min B m/z Upper panel (A): HPLC-UV trace of the synthesized oligonucleotide. Lower panel (B): The average mass spectrum under the parent peak. S74

43 IP-HPLC-MS analysis of modified Oligo 35 made using UnyLinker solid support 5 -G ro G eo A ro C eo A ro U eo C ro A eo A ro G eo G ro U eo U ro U eo G ro C eo G ro U eo A r -3 mau 12 A min B m/z Upper panel (A): HPLC-UV trace of the synthesized oligonucleotide. Lower panel (B): The average mass spectrum under the parent peak. S75

44 IP-HPLC-MS analysis of modified phosphate/phosphorothioate Oligo 36 made using UnyLinker solid support 5 -U ro C ro A ro C ro U ro C ro G ro G ro C ro U ro G ro G ro A ro U ro G ro G ro A ro G ro U rs T es T-3 mau 6 A mi 1 B m/ Upper panel (A): HPLC-UV trace of the synthesized phosphate/phosphorothioate oligonucleotide. Lower panel (B): The average mass spectrum under the parent peak. S76

45 IP-HPLC-MS of 2 -O-methoxyethyl modified phosphorothioate Oligo synthesized using MOE A nucleoside solid support 5 -[CCGTC]-GCCCTTCAGC-[ACGCA]-3 mau 3 A min mau B min Upper panel (A): The average mass spectrum under the parent peak. Lower panel (B): HPLC-UV trace of the synthesized phosphorothioate oligonucleotide. S77

46 Table 1. Analysis of 2 -O-methoxyethyl modified phosphorothioate Oligo 1 made using UnyLinker loaded solid support on OligoProcess Sequence: Oligo 1 Results (%) Full length, n 87. Full length, (P=O) Total (n-1) 1.2 Total (n+1).54 Total depurination.95 Total TPT ND TCE ND CNET.26 EPD OCH 3 1. n Early eluting species 3.6 Late eluting species 3.3 Molecular weight is ± 1. amu amu S78

47 Table 2. Analysis of 2 -O-methoxyethyl modified phosphorothioate Oligo 2 made using UnyLinker loaded solid support on OligoProcess Sequence: Oligo 2 Results (%) Full length, n 9.2 Full length, (P=O) 1.9 Total (n-1) 2. Total (n+1).3 Total depurination.6 Total TPT ND TCE ND CNET.1 EPD.1 2 -OCH 3.7 n Early eluting species 1. Late eluting species 2.9 Molecular weight is ± 1. amu amu S79

48 Table 3. Comparison of 2 -O-methoxyethyl modified phosphorothioate Oligo 3 made using UnyLinker and MOE mec-nucleoside loaded solid support on OligoProcess Sequence: Oligo 3 PS2- UnyLinker PS2 Baseloaded Full length, n Full length, (P=O) Total (n-1) Total (n+1) ND ND Total depurination.55.4 Total TPT.26.6 TCE ND ND CNET ND ND EPD ND ND 2 -OCH n n Early eluting species Late eluting species Molecular weight is ± 1. amu amu amu S8

49 Table 4. Analysis of 2 -O-methoxyethyl modified phosphorothioate Oligo 4 made using UnyLinker loaded solid support on OligoProcess Sequence: Oligo 4 Results (%) Full length, n 88.5 Full length, (P=O) Total (n-1).94 Total (n+1) ND Total depurination.46 Total TPT ND TCE ND CNET ND EPD ND 2 -OCH 3 1. n Early eluting species 1.4 Late eluting species 3.3 Molecular weight is ± 1. amu amu S81

50 Table 5. Analysis of 2 -O-methoxyethyl modified phosphorothioate Oligo 5 made using UnyLinker loaded solid support on OligoProcess Sequence: Oligo 5 Results (%) Full length, n 87.4 Full length, (P=O) Total (n-1) 1. Total (n+1) ND Total depurination 1.43 Total TPT ND TCE ND CNET.44 EPD ND 2 -OCH n n Early eluting species 2.1 Late eluting species 1.72 Molecular weight is ± 1. amu amu S82

51 Table 6. Analysis of crude 2 -O-methoxyethyl modified phosphorothioate Oligo 6 made using UnyLinker loaded solid support on OligoProcess Sequence: Oligo 6 Results (%) Full length, n 93.7 Full length, (P=O) Total (n-1) 2.8 Total depurination.4 Total TPT.7 TCE.3 CNET.17 EPD.5 2 -OCH 3.5 n + 68 Combined UV area % of two main DMT-on peaks Molecular weight is ± 1. amu amu S83

52 Table 7. Analysis of oligodeoxy phosphorothioate Oligo 7 made using UnyLinker loaded solid support on OligoProcess Sequence: Oligo 7-SYN #1 Results (%) Full length, n 88. Full length, (P=O) Total (n-1) 2.6 Total (n+1).68 Total depurination 2.3 Total TPT.37 TCE ND CNET ND n n n Early eluting species 1.26 Late eluting species 2.11 Molecular weight is ± 1. amu amu S84

53 Table 8. Comparison of oligodeoxy phosphorothioate Oligo 7 made using UnyLinker and da-nucleoside loaded solid supports on OligoProcess Results showing reproducibility of performance of UnyLinker on OligoProcess (Oligo 7-SYN #2 & Oligo 7-SYN #3) Sequence: Oligo 7 SYN #2 Results (%) SYN #3 Results (%) da-loaded Results (%) Full length, n Full length, (P=O) Total (n-1) Total depurination Total TPT.1 ND ND TCE ND ND ND CNET n EPD Molecular weight of DMTon 667 amu amu amu oligo ± 1. amu Combined UV area % of two main DMT-on peaks S85

54 Table 9. Analysis of Oligo 8 using UnyLinker loaded solid support Sequence: Oligo 8 Results (%) Full length, n 89.1 Full length, (P=O) Total (n-1) 2.5 Total (n+1) <.1 Total depurination 1.7 Total TPT <.1 TCE <.1 CNET.27 Total other impurities.37 Early eluting species 2.4 Late eluting species 2.2 Molecular weight is ± 1. amu amu S86

55 Table 1. Analysis of Oligo 9 using UnyLinker loaded solid support Sequence: Oligo 9 Results (%) UV purity n 82.2 n depurination 3.18 n Early eluting species 3.7 Late eluting species 3.28 Molecular weight is ± 1. amu amu S87

56 Table 11. Analysis of 2 -O-methyl modified phosphate/phosphorothioate mixed backbone Oligo 1 using UnyLinker loaded CPG solid support Sequence: Oligo 1 Results (%) UV purity 97.3 n 94.1 P=O.71 (n-1) 2.57 Early eluting species 1.1 Late eluting species 1.56 Molecular weight is ± 1. amu amu S88

57 Table 12. Analysis of 2 -O-methyl modified phosphorothioate Oligo 11 using UnyLinker loaded CPG solid support Sequence: Oligo 11 Results (%) UV purity n 87.5 P=O 3.95 (n-1) 3.36 Early eluting species 1.85 Late eluting species 2.52 Molecular weight is ± 1. amu amu S89

58 Table 13. Analysis of 2 -O-methoxyethyl/RNA modified sequence with phosphate backbone Oligo 12 using UnyLinker loaded CPG solid support Sequence: Oligo 12 Results (%) UV purity 9.93 n 88.9 (n-1) 2.57 Early eluting species 8.41 Late eluting species 1.66 Molecular weight is ± 1. amu amu S9

59 Table 14. Analysis of Oligo 13 using UnyLinker loaded solid support Sequence: Oligo 13 Results (%) UV purity n 91.1 P=O 3.33 (n-1) 1.35 depurination 1.46 Early eluting species 1.8 Late eluting species.74 Molecular weight is ± 1. amu amu S91

60 Table 15. Analysis of Oligo 14 using UnyLinker loaded CPG solid support Sequence: Oligo 14 Results (%) UV purity n 85.1 CNET 6.42 (n-1) 1.3 Unknown 1.6 Early eluting species 4.2 Late eluting species 1.6 Molecular weight is ± 1. amu amu S92

61 Table 16. Analysis of Oligo 15 using UnyLinker loaded solid support Sequence: Oligo 15 Results (%) UV purity 95.9 n P=O 1.85 (n-1) 1.92 Early eluting species 1.36 Late eluting species 2.7 Molecular weight is ± 1. amu amu S93

62 Table 17. Analysis of 2 -O-methoxyethyl/2 -alpha-fluoro modified phosphorothioate Oligo 16 using UnyLinker loaded CPG solid support Sequence: Oligo 16 Results (%) UV purity n P=O 3.81 (n-1) 1.36 Unknown 1.1 Early eluting species 7.97 Late eluting species 2.58 Molecular weight is ± 1. amu amu S94

63 Table 18. Analysis of Oligo 17 using UnyLinker loaded CPG solid support Sequence: Oligo 17 Results (%) UV purity 89.8 n 8.89 P=O 2.2 (n-1) 5.4 Early eluting species 5.73 Late eluting species 4.45 Molecular weight is ± 1. amu amu S95

64 Table 19. Analysis of Oligo 18 using UnyLinker loaded CPG solid support Sequence: Oligo 18 Results (%) UV purity n P=O 1.7 (n-1) 1.88 Early eluting species.62 Late eluting species.59 Molecular weight is ± 1. amu amu S96

65 Table 2. Analysis of 2 -deoxy/lna modified phosphorothioate Oligo 19 using UnyLinker loaded CPG solid support Sequence: Oligo 19 Results (%) UV purity n P=O.42 (n-1) 1.42 Total unknowns 4.94 Early eluting species 2.58 Late eluting species 1.7 Molecular weight is ± 1. amu amu S97

66 Table 21. Analysis of 2 -deoxy/lna modified phosphate/phosphorothioate mixed backbone Oligo 2 using UnyLinker loaded CPG solid support Sequence: Oligo 2 Results (%) UV purity n depurination.67 (n-1) 3.36 unknown.43 Early eluting species 5.58 Late eluting species 1.13 Molecular weight is ± 1. amu amu S98

67 Table 22. Analysis of Oligo 21 using UnyLinker loaded CPG solid support Sequence: Oligo 21 Results (%) UV purity n P=O 1.51 (n-1) 2.22 Early eluting species.95 Late eluting species.71 Molecular weight is ± 1. amu amu S99

68 Table 23. Analysis of 2 -deoxy/lna modified phosphorothioate Oligo 22 using UnyLinker loaded CPG solid support Sequence: Oligo 22 Results (%) UV purity n 93.6 P=O 2.11 (n-1) 1.19 Unknown 1.1 Early eluting species 1.65 Late eluting species 1.45 Molecular weight is ± 1. amu amu S1

69 Table 24. Analysis of Oligo 23 using UnyLinker loaded CPG solid support Sequence: Oligo 23 Results (%) UV purity n P=O 2.1 (n-1).95 Early eluting species 1.41 Late eluting species 1.32 Molecular weight is ± 1. amu amu S11

70 Table 25. Analysis of Oligo 24 using UnyLinker loaded CPG solid support Sequence: Oligo 24 Results (%) UV purity n 9.78 P=O 1.93 (n-1) 1.26 Early eluting species 2.23 Late eluting species 1.21 Molecular weight is ± 1. amu amu S12

71 Table 26. Analysis of Oligo 25 using UnyLinker loaded CPG solid support Sequence: Oligo 25 Results (%) UV purity 95.7 n 9.68 P=O.27 (n-1) 1.18 depurination 2.9 Early eluting species 1.26 Late eluting species 3.4 Molecular weight is ± 1. amu amu S13

72 Table 27. Analysis of 2 -deoxy/lna modified phosphorothioate Oligo 26 using UnyLinker loaded CPG solid support Sequence: Oligo 26 Results (%) UV purity 94.1 n 89.1 P=O 1.55 (n-1).6 Unknown 2.29 Early eluting species 3.17 Late eluting species 2.73 Molecular weight is ± 1. amu amu S14

73 Table 28. Analysis of Oligo 27 using UnyLinker loaded solid support Sequence: Oligo 27 Results (%) UV purity 9.2 n 86.5 P=O 3.7 (n-1) 1.9 CNET.33 Early eluting species 3.5 Late eluting species 2.2 Molecular weight is 682. ± 1.2 amu amu S15

74 Table 29. Analysis of Oligo 28 using UnyLinker loaded CPG solid support Sequence: Oligo 28 Results (%) UV purity 95.9 n 93.2 P=O 1.33 (n-1).83 Early eluting species.96 Late eluting species 3.14 Molecular weight is ± 1. amu amu S16

75 Table 3. Analysis of Oligo 29 using UnyLinker loaded CPG solid support Sequence: Oligo 29 Results (%) UV purity 95.6 n P=O 2.23 (n-1) 2.84 Early eluting species.95 Late eluting species 3.46 Molecular weight is ± 1. amu amu S17

76 Table 31. Analysis of Oligo 3 using UnyLinker loaded CPG solid support Sequence: Oligo 3 Results (%) UV purity n P=O 3.81 (n+187) 1.1 Early eluting species 7.96 Late eluting species 2.58 Molecular weight is ± 1. amu amu S18

77 Table 32. Analysis of Oligo 31 using UnyLinker loaded CPG solid support Sequence: Oligo 31 Results (%) UV purity 9.6 n P=O 3.54 Early eluting species 8.5 Late eluting species 1.89 Molecular weight is ± 1. amu amu S19

78 Table 33. Analysis of Oligo 32 using UnyLinker loaded CPG solid support Sequence: Oligo 32 Results (%) UV purity n 77.3 CNET 3.22 (n+methyl).77 (n-1) 1.26 Early eluting species 1.29 Late eluting species.8 Molecular weight is ± 1. amu amu S11

79 Table 34. Analysis of Oligo 33 using UnyLinker loaded CPG solid support Sequence: Oligo 33 Results (%) UV purity n 85.2 n + methyl 5.1 (n-1) 2.75 Early eluting species 5.31 Late eluting species.87 Molecular weight is ± 1. amu amu S111

80 Table 35. Analysis of Oligo 34 using UnyLinker loaded CPG solid support Sequence: Oligo 34 Results (%) UV purity n 7.52 (n-1) 2.59 (n+methyl) 3.29 n Early eluting species Late eluting species 1.37 Molecular weight is ± 1. amu amu S112

81 Table 36. Analysis of Oligo 35 using UnyLinker loaded CPG solid support Sequence: Oligo 35 Results (%) UV purity n 9.78 P=O.3 (n-1) 1.88 n + methyl 2.46 Early eluting species 3.73 Late eluting species 1.49 Molecular weight is ± 1. amu amu S113

82 Table 37. Analysis of Oligo 36 using UnyLinker loaded CPG solid support Sequence: Oligo 36 Results (%) UV purity n 57.8 P=O 1.78 (n-1) 1.98 n + methyl 5.48 Early eluting species Late eluting species.13 Molecular weight is ± 1. amu amu S114

83 Table 38. Comparison of 2 -O-methoxyethyl modified phosphorothioate Oligo 37 made using UnyLinker and MOE mec-nucleoside loaded solid supports on 96-well plate MerMade (Bioautomation) synthesizer (Synthesis #1) Control #1 Control #2 UnyLinker Syn #1 UnyLinker Syn #2 UnyLinker Syn #3 mass % % % % % Full length P=O TPT n-t n-moe mec/moe meu Total S115

84 Table 39. Comparison of 2 -O-methoxyethyl modified phosphorothioate Oligo 37 made using UnyLinker and MOE mec-nucleoside loaded solid supports on 96-well plate MerMade (Bioautomation) synthesizer (Synthesis #2). Results showing reproducibility of performance of UnyLinker loaded on CPG Control Syn #1 Control Syn #2 Control Syn #3 Control Syn #4 UnyLinker Syn #1 UnyLinker Syn #2 UnyLinker Syn #3 UnyLinker Syn #4 % % % % % % % % Full length P=O TPT n-t n-moe mec /MOE meu shortmer full length longmer S116

85 Table 4. Crystal data and structure refinement for iris. Identification code iris Empirical formula C14 H13 N O5 Formula weight Temperature 298(2) K Wavelength.7173 Å Crystal system Monoclinic Space group P2(1)/c Unit cell dimensions a = (3) Å = 9. b = (1) Å = 92.35(13). c = (2) Å = 9. Volume 125.1(4) Å 3 Z 4 Density (calculated) Mg/m 3 Absorption coefficient.117 mm -1 F() 576 Crystal size.14 x.5 x.2 mm 3 Theta range for data collection 2.4 to Index ranges -2<=h<=2, -1<=k<=7, -14<=l<=4 Reflections collected 3555 Independent reflections 2124 [R(int) =.327] Completeness to theta = % Absorption correction None Refinement method Full-matrix least-squares on F 2 Data / restraints / parameters 2124 / / 234 Goodness-of-fit on F Final R indices [I>2sigma(I)] R1 =.393, wr2 =.993 R indices (all data) R1 =.583, wr2 =.1186 Extinction coefficient.9(2) Largest diff. peak and hole.21 and -.24 e.å -3 S117

86 Table 41. Atomic coordinates ( x 14) and equivalent isotropic displacement parameters (Å2x 13) for iris. U(eq) is defined as one third of the trace of the orthogonalized Uij tensor. x y z U(eq) N(1) 2983(1) 1984(3) 6112(1) 34(1) O(1) 457(1) -2145(3) 367(2) 51(1) O(2) -14(1) 289(3) 3527(1) 48(1) O(3) 2276(1) 5185(3) 6411(1) 44(1) O(4) 3428(1) -1347(3) 5427(1) 49(1) O(5) 1179(1) 471(2) 543(1) 34(1) C(1) 187(1) -636(4) 3574(2) 41(1) C(2) 812(1) 1851(4) 3645(2) 41(1) C(3) 1152(1) 2542(4) 486(2) 35(1) C(4) 231(1) 2978(4) 4714(2) 34(1) C(5) 2422(1) 36(3) 5831(2) 33(1) C(6) 2988(1) 224(4) 5358(2) 35(1) C(7) 2349(1) 647(4) 4468(2) 35(1) C(8) 1611(1) -82(4) 4633(2) 35(1) C(9) 352(1) 2125(3) 795(2) 33(1) C(1) 3529(1) 382(4) 7853(2) 41(1) C(11) 427(1) 555(4) 881(2) 48(1) C(12) 4485(1) 2423(5) 8967(2) 51(1) C(13) 4456(1) 4141(4) 82(2) 47(1) C(14) 396(1) 44(4) 7255(2) 39(1) S118

87 Table 42. Bond lengths [Å] and angles [ ] for iris. N(1)-C(6) 1.382(3) N(1)-C(5) 1.388(3) N(1)-C(9) 1.437(3) O(1)-C(1) 1.47(3) O(1)-H(1A).94(4) O(2)-C(2) 1.412(3) O(2)-H(2A).92(4) O(3)-C(5) 1.22(2) O(4)-C(6) 1.2(2) O(5)-C(8) 1.439(2) O(5)-C(3) 1.442(2) C(1)-C(8) 1.515(3) C(1)-C(2) 1.56(3) C(1)-H(2B).97(2) C(2)-C(3) 1.532(3) C(2)-H(1B).96(2) C(3)-C(4) 1.525(3) C(3)-H(3A).98(2) C(4)-C(5) 1.57(3) C(4)-C(7) 1.525(3) C(4)-H(4A).94(2) C(6)-C(7) 1.56(3) C(7)-C(8) 1.542(3) C(7)-H(6A).96(2) C(8)-H(8A).97(2) C(9)-C(14) 1.373(3) C(9)-C(1) 1.376(3) C(1)-C(11) 1.385(3) C(1)-H(7A).97(3) C(11)-C(12) 1.37(4) C(11)-H(11A).95(2) C(12)-C(13) 1.372(4) C(12)-H(12A).96(3) C(13)-C(14) 1.38(3) C(13)-H(13A) 1.1(3) S119

88 C(14)-H(9A).96(2) C(6)-N(1)-C(5) (16) C(6)-N(1)-C(9) 123.6(16) C(5)-N(1)-C(9) 123.2(17) C(1)-O(1)-H(1A) 16(2) C(2)-O(2)-H(2A) 15(2) C(8)-O(5)-C(3) 96.9(15) O(1)-C(1)-C(8) 18.29(18) O(1)-C(1)-C(2) 112.1(18) C(8)-C(1)-C(2) 1.62(17) O(1)-C(1)-H(2B) 111.5(13) C(8)-C(1)-H(2B) 112.2(13) C(2)-C(1)-H(2B) 111.8(14) O(2)-C(2)-C(3) (18) O(2)-C(2)-C(1) (18) C(3)-C(2)-C(1) 11.66(17) O(2)-C(2)-H(1B) 16.8(11) C(3)-C(2)-H(1B) 11.(11) C(1)-C(2)-H(1B) 112.2(11) O(5)-C(3)-C(4) 99.91(16) O(5)-C(3)-C(2) 13.69(17) C(4)-C(3)-C(2) 18.37(17) O(5)-C(3)-H(3A) 19.5(13) C(4)-C(3)-H(3A) 117.2(13) C(2)-C(3)-H(3A) 116.1(12) C(5)-C(4)-C(3) 112.6(17) C(5)-C(4)-C(7) 14.36(16) C(3)-C(4)-C(7) 12.31(17) C(5)-C(4)-H(4A) 11.9(13) C(3)-C(4)-H(4A) 112.3(13) C(7)-C(4)-H(4A) 114.4(13) O(3)-C(5)-N(1) (18) O(3)-C(5)-C(4) (18) N(1)-C(5)-C(4) 18.32(17) O(4)-C(6)-N(1) 124.7(19) O(4)-C(6)-C(7) 127.5(2) S12

89 N(1)-C(6)-C(7) 17.84(17) C(6)-C(7)-C(4) 15.55(17) C(6)-C(7)-C(8) (18) C(4)-C(7)-C(8) 11.2(16) C(6)-C(7)-H(6A) 11.1(12) C(4)-C(7)-H(6A) 117.3(13) C(8)-C(7)-H(6A) 11.2(13) O(5)-C(8)-C(1) 12.46(16) O(5)-C(8)-C(7) 13.11(16) C(1)-C(8)-C(7) 18.7(17) O(5)-C(8)-H(8A) 19.(14) C(1)-C(8)-H(8A) 117.1(13) C(7)-C(8)-H(8A) 115.4(13) C(14)-C(9)-C(1) 121.5(2) C(14)-C(9)-N(1) 119.4(18) C(1)-C(9)-N(1) (19) C(9)-C(1)-C(11) 118.7(2) C(9)-C(1)-H(7A) 118.7(14) C(11)-C(1)-H(7A) 122.5(14) C(12)-C(11)-C(1) 12.2(2) C(12)-C(11)-H(11A) 12.8(14) C(1)-C(11)-H(11A) 119.1(14) C(11)-C(12)-C(13) 12.5(2) C(11)-C(12)-H(12A) 12.3(17) C(13)-C(12)-H(12A) 119.3(17) C(12)-C(13)-C(14) 12.1(2) C(12)-C(13)-H(13A) 118.7(17) C(14)-C(13)-H(13A) 121.1(17) C(9)-C(14)-C(13) 119.(2) C(9)-C(14)-H(9A) 12.7(14) C(13)-C(14)-H(9A) 12.3(14) Symmetry transformations used to generate equivalent atoms: S121

90 Table 43. Anisotropic displacement parameters (Å2x 13) for iris. The anisotropic displacement factor exponent takes the form: -22[ h2 a*2u h k a* b* U12 ] U 11 U 22 U 33 U 23 U 13 U 12 N(1) 29(1) 35(1) 37(1) -1(1) -5(1) 3(1) O(1) 45(1) 56(1) 51(1) -6(1) -9(1) -16(1) O(2) 31(1) 58(1) 54(1) 18(1) -13(1) -4(1) O(3) 42(1) 39(1) 49(1) -6(1) -5(1) 8(1) O(4) 41(1) 43(1) 61(1) -5(1) -3(1) 14(1) O(5) 32(1) 37(1) 32(1) 5(1) -2(1) (1) C(1) 37(1) 52(1) 36(1) -2(1) -1(1) -5(1) C(2) 31(1) 52(1) 4(1) 13(1) -3(1) -6(1) C(3) 29(1) 36(1) 4(1) 5(1) -4(1) 1(1) C(4) 3(1) 35(1) 36(1) 5(1) -1(1) -1(1) C(5) 27(1) 32(1) 4(1) 4(1) (1) -1(1) C(6) 27(1) 37(1) 41(1) 1(1) 1(1) 1(1) C(7) 31(1) 4(1) 34(1) -3(1) -1(1) 2(1) C(8) 36(1) 32(1) 37(1) -2(1) -3(1) 1(1) C(9) 24(1) 39(1) 36(1) (1) (1) 3(1) C(1) 36(1) 41(1) 48(1) 5(1) 2(1) 2(1) C(11) 49(1) 56(2) 4(1) 12(1) (1) 15(1) C(12) 42(1) 68(2) 41(1) -5(1) -9(1) 1(1) C(13) 37(1) 54(2) 48(1) -7(1) -5(1) -3(1) C(14) 35(1) 41(1) 41(1) 2(1) -1(1) -1(1) S122

91 Table 44. Hydrogen coordinates ( x 14) and isotropic displacement parameters (Å2x 1 3) for iris. x y z U(eq) H(1B) 134(11) 277(3) 371(16) 22(5) H(2B) 1375(13) -92(4) 29(2) 41(6) H(4A) 2135(12) 46(4) 4165(19) 35(6) H(3A) 848(13) 365(4) 521(18) 37(6) H(11A) 439(13) -63(4) 934(2) 42(6) H(6A) 2547(12) 39(4) 3735(19) 36(6) H(7A) 322(14) -95(4) 768(2) 48(7) H(8A) 1711(13) -229(4) 4936(19) 42(6) H(9A) 3921(13) 523(4) 674(2) 44(6) H(12A) 4828(16) 255(4) 962(2) 64(8) H(13A) 479(17) 552(5) 836(2) 74(9) H(1A) 278(19) -249(6) 293(3) 96(11) H(2A) -22(2) 94(6) 395(3) 12(12) S123

92 Table 45. Torsion angles [ ] for iris. O(1)-C(1)-C(2)-O(2) -13.7(3) C(8)-C(1)-C(2)-O(2) (19) O(1)-C(1)-C(2)-C(3) 18.19(19) C(8)-C(1)-C(2)-C(3) -6.66(19) C(8)-O(5)-C(3)-C(4) (17) C(8)-O(5)-C(3)-C(2) 52.91(17) O(2)-C(2)-C(3)-O(5) 93.5(2) C(1)-C(2)-C(3)-O(5) -28.3(19) O(2)-C(2)-C(3)-C(4) (18) C(1)-C(2)-C(3)-C(4) 77.5(2) O(5)-C(3)-C(4)-C(5) -7.1(2) C(2)-C(3)-C(4)-C(5) (18) O(5)-C(3)-C(4)-C(7) 41.18(19) C(2)-C(3)-C(4)-C(7) -66.9(2) C(6)-N(1)-C(5)-O(3) (19) C(9)-N(1)-C(5)-O(3) -5.3(3) C(6)-N(1)-C(5)-C(4) -4.5(2) C(9)-N(1)-C(5)-C(4) 176.(17) C(3)-C(4)-C(5)-O(3) -6.8(3) C(7)-C(4)-C(5)-O(3) -17.8(2) C(3)-C(4)-C(5)-N(1) (18) C(7)-C(4)-C(5)-N(1) 7.9(2) C(5)-N(1)-C(6)-O(4) 179.2(2) C(9)-N(1)-C(6)-O(4) -1.2(3) C(5)-N(1)-C(6)-C(7) -1.1(2) C(9)-N(1)-C(6)-C(7) 178.4(18) O(4)-C(6)-C(7)-C(4) (2) N(1)-C(6)-C(7)-C(4) 6.1(2) O(4)-C(6)-C(7)-C(8) 76.5(3) N(1)-C(6)-C(7)-C(8) -13.1(2) C(5)-C(4)-C(7)-C(6) -8.3(2) C(3)-C(4)-C(7)-C(6) (17) C(5)-C(4)-C(7)-C(8) 18.94(17) C(3)-C(4)-C(7)-C(8) -7.97(19) C(3)-O(5)-C(8)-C(1) (18) S124

93 C(3)-O(5)-C(8)-C(7) 54.3(17) O(1)-C(1)-C(8)-O(5) -78.(2) C(2)-C(1)-C(8)-O(5) 39.6(19) O(1)-C(1)-C(8)-C(7) (17) C(2)-C(1)-C(8)-C(7) -68.8(2) C(6)-C(7)-C(8)-O(5) 84.3(2) C(4)-C(7)-C(8)-O(5) (19) C(6)-C(7)-C(8)-C(1) (18) C(4)-C(7)-C(8)-C(1) 8.2(2) C(6)-N(1)-C(9)-C(14) 125.6(2) C(5)-N(1)-C(9)-C(14) -54.9(3) C(6)-N(1)-C(9)-C(1) -54.4(3) C(5)-N(1)-C(9)-C(1) 125.1(2) C(14)-C(9)-C(1)-C(11).6(3) N(1)-C(9)-C(1)-C(11) (19) C(9)-C(1)-C(11)-C(12) -.6(3) C(1)-C(11)-C(12)-C(13).1(4) C(11)-C(12)-C(13)-C(14).3(4) C(1)-C(9)-C(14)-C(13) -.2(3) N(1)-C(9)-C(14)-C(13) (19) C(12)-C(13)-C(14)-C(9) -.3(3) Symmetry transformations used to generate equivalent atoms: S125

94 O HO HO Hc 9 8 Hb O 2 Ha 6 O N Showing C8---C7 bonding O C 9 OH H b H C C 6 o Showing C7---C6 bonding C 5 C 8 O H a H b C 2 o S126

Supplementary Information

Electronic Supplementary Material (ESI) for ChemComm. This journal is The Royal Society of Chemistry 2018 Supplementary Information Oxidative Tandem Annulation of 1 (2 Ethynylaryl)prop 2 en 1 ones Catalyzed