Attempts of coupling carbasugar to adenosine

To a solution of 3,5’-O-(1,1,3,3-tetraisopropyldisiloxane-1.3-diyl)adenosine (0.12 mmol, 0.06 g) and (1S,4R,5S)-(1)-3-[(Benzyloxy)methyl]-4,5-O-isopropylidene-2-cyclopenten-1-ol (17) (0.02 mmol, 0.01 g) dissolved in toluene was added 1,1'-(azodicarbonyl)dipiperidine (0.02 g) and tributylphosphine (0.02 mL). Reaction was keeping on ice then allowed to warm up to room temperature and stirred for 24 h. No product formation could be detected by TLC or ESI-MS.

To a solution of 3,5’-O-(1,1,3,3-tetraisopropyldisiloxane-1.3-diyl)adenosine (0.12 mmol, 0.06 g) and (1S,4R,5S)-(1)-3-[(Benzyloxy)methyl]-4,5-O-isopropylidene-2-cyclopenten-1-ol (17) (0.02 mmol, 0.01 g) dissolved in THF DEAD (0.02 mmol) with triphenylphosphine (0.02 mmol, 0.006 g) was added. Reaction was keeping on ice then allowed to warm up to room temperature and stirred for 24 h. No product formation could be detected by TLC or ESI-MS.

To a solution of 3,5’-O-(1,1,3,3-tetraisopropyldisiloxane-1.3-diyl)adenosine (0.12 mmol, 0.06 g) and (1S,4R,5S)-(1)-3-[(Benzyloxy)methyl]-4,5-O-isopropylidene-2-cyclopenten-1-ol (17) (0.02 mmol, 0.01 g) dissolved in THF DIAD (0.02mmol) with triphenylphosphine (0.02 mmol, 0.006 g) was added. Reaction was keeping on ice then allowed to warm up to room temperature and stirred for 24 h. No product formation could be detected by TLC or ESI-MS.

To a solution of 3,5’-O-(1,1,3,3-tetraisopropyldisiloxane-1.3-diyl)adenosine (0.12 mmol, 0.06 g) and (3aS,4S,6aR)-2,2-dimethyl-6-((trityloxy)methyl)-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-ol (26) (0.02 mmol, 0.01 g) dissolved in toluene was added 1,1'-(azodicarbonyl)dipiperidine (0.02 g) and tributylphosphine (0.02 mL).

Reaction was keeping on ice then allowed to warm up to room temperature and stirred for 24 h. No product formation could be detected by TLC or ESI-MS.

To a solution of 3,5’-O-(1,1,3,3-tetraisopropyldisiloxane-1.3-diyl)adenosine (0.12 mmol, 0.06 g) and (3aS,4S,6aR)-2,2-dimethyl-6-((trityloxy)methyl)-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-ol (26) (0.02 mmol, 0.01 g) dissolved in toluene was added DEAD (0.02 mmol) with triphenylphosphine (0.02 mmol, 0.006 g). Reaction was keeping on ice then allowed to warm up to room temperature and stirred for 24 h. No product formation could be detected by TLC or ESI-MS.

120

To a solution of 3,5’-O-(1,1,3,3-tetraisopropyldisiloxane-1.3-diyl)adenosine (0.12 mmol, 0.06 g) and (3aS,4S,6aR)-2,2-dimethyl-6-((trityloxy)methyl)-4,6a-dihydro-3aH-cyclopenta[d][1,3]dioxol-4-ol (26) (0.02 mmol, 0.01 g) dissolved in toluene was added DIAD with triphenylphosphine. Reaction was keeping on ice then allowed to warm up to room temperature and stirred for 24 h. No product formation could be detected by TLC or ESI-MS.

To a solution of 3,5’-O-(1,1,3,3-tetraisopropyldisiloxane-1.3-diyl)adenosine (0.03 mmol, 0.016g) dissolved in DMF, sodium hydride (0.002 g) was added than (1S,4R,5S)-(1)-3-[(Benzyloxy)methyl]-4,5-O-isopropylidene-2-cyclopenten-1-bromide (18) was added. Reaction was keeping on ice after addition of NaH, was allowed to warm up to room temperature. Reaction mixture was stirred at room temperature overnight. No product formation could be detected by TLC or ESI-MS.

To a solution of 3,5’-O-(1,1,3,3-tetraisopropyldisiloxane-1.3-diyl)adenosine (0.168 mmol, 0.09 g) and (1S,4R,5S)-(1)-3-(trityl)-4,5-O-isopropylidene-2-cyclopenten-1-bromide (30) (0.2 mmol, 0.098 g) dissolved in THF and kept on ice, sodium hydride (0.032 g) was added. Reaction mixture was stirred at room temperature overnight. No product formation could be detected by TLC or ESI-MS.

To a solution of 3,5’-O-(1,1,3,3-tetraisopropyldisiloxane-1.3-diyl)adenosine (1 eq, 0.168 mmol, 0.089 g) dissolved in DMF (0.75 mL), sodium hydride (1.4 eq, 0.235 mmol, 0.009 g) was added than (1S,4R,5S)-(1)-3-(trityl)-4,5-O-isopropylidene-2-cyclopenten-1-bromide (30) (1.5 eq, 0.252 mmol, 0.12 g) was added in DMF (1.5 mL).

Reaction was keeping on ice after addition of NaH was allowed to warm up to room temperature and stirred for 15 h than heating at 70 °C for 6 h. No product formation could be detected by TLC or ESI-MS.

To a solution of 3,5’-O-(1,1,3,3-tetraisopropyldisiloxane-1.3-diyl)adenosine (1 eq, 0.168 mmol, 0.089 g) dissolved in DMF (0.75 mL), sodium hydride (1.4 eq, 0.235 mmol, 0.009 g) was added than (1S,4R,5S)-(1)-3-(trityl)-4,5-O-isopropylidene-2-cyclopenten-1-bromide (30) (1.5 eq, 0.252 mmol, 0.12 g) was added in DMF (1.5 mL).

Reaction was keeping on ice after addition of NaH was allowed to warm up to room temperature and hetead in microweave in range of time and temperature (10 - 30 min, 70 – 120 °C). No product formation could be detected by TLC or ESI-MS.

121 To a solution of 3,5’-O-(1,1,3,3-tetraisopropyldisiloxane-1.3-diyl)adenosine (1 eq, 0.123 mmol, 0.07 g) dissolved in DMF (0.5 mL), sodium hydride (1.5 eq, 0.18 mmol, 0.0072 g) was added than (1S,4R,5S)-(1)-3-(trityl)-4,5-O-isopropylidene-2-cyclopenten-1-bromide (30) (2 eq, 0.246 mmol, 0.12 g) was added. Reaction was keeping on ice after addition of NaH was allowed to warm up to room temperature and stirred for 15 h. No product formation could be detected by TLC or ESI-MS.

To a solution of 3,5’-O-(1,1,3,3-tetraisopropyldisiloxane-1.3-diyl)adenosine (1 eq, 0.123 mmol, 0.07 g) dissolved in DMF (0.5 mL), sodium hydride (1.5 eq, 0.18 mmol, 0.0072 g) with TBAI (1.5 g, 4.06 mmol) was added than (1S,4R,5S)-(1)-3-(trityl)-4,5-O-isopropylidene-2-cyclopenten-1-bromide (30) (2 eq, 0.246 mmol, 0.12 g) was added. Reaction was keeping on ice after addition of NaH was allowed to warm up to room temperature and stirred for 15 h. No product formation could be detected by TLC or ESI-MS.

To a solution of 3,5’-O-(1,1,3,3-tetraisopropyldisiloxane-1.3-diyl)adenosine (1 eq, 0.123 mmol, 0.07 g) dissolved in DMF (0.5 mL), sodium hydride (1.5 eq, 0.18 mmol, 0.0072 g), BEMP (0.026 mmol, 0.007 g, 60 μl) than (1S,4R,5S)-(1)-3-(trityl)-4,5-O-isopropylidene-2-cyclopenten-1-bromide (30) (2 eq, 0.246 mmol, 0.12 g) was added.

Reaction was keeping on ice after addition of NaH was allowed to warm up to room temperature and stirred for 15 h. No product formation could be detected by TLC or ESI-MS.

To a solution of adenosine (1 eq, 0.056 mmol, 0.015 g) dissolved in DMF (0.5 mL), sodium hydride (1.5 eq, 0.18 mmol, 0.0072 g) than (1S,4R,5S)-(1)-3-(trityl)-4,5-O-isopropylidene-2-cyclopenten-1-bromide (30) (2 eq, 0.246 mmol, 0.12 g) was added.

Reaction was keeping on ice after addition of NaH was allowed to warm up to room temperature and stirred for 15 h. No product formation could be detected by TLC or ESI-MS.

To a solution of adenosine (1 eq, 0.056 mmol, 0.015 g) dissolved in DMF (0.5 mL), sodium hydride (1.5 eq, 0.18 mmol, 0.0072 g) with TBAI (1.5 g, 4.06 mmol) than (1S,4R,5S)-(1)-3-(trityl)-4,5-O-isopropylidene-2-cyclopenten-1-bromide (30) (2 eq, 0.246 mmol, 0.12 g) was added. Reaction was keeping on ice after addition of NaH was allowed to warm up to room temperature and stirred for 15 h. No product formation could be detected by TLC or ESI-MS.

122

To a solution of adenosine (1 eq, 0.056 mmol, 0.015 g) dissolved in DMF (0.5 mL), sodium hydride (1.5 eq, 0.18 mmol, 0.0072 g) with BEMP (0.026 mmol, 0.007 g, 60 μl) than (1S,4R,5S)-(1)-3-(trityl)-4,5-O-isopropylidene-2-cyclopenten-1-bromide (30) (2 eq, 0.246 mmol, 0.12 g) was added. Reaction was keeping on ice after addition of NaH was allowed to warm up to room temperature and stirred for 15 h. No product formation could be detected by TLC or ESI-MS.

To a solution of 3,5’-O-(1,1,3,3-tetraisopropyldisiloxane-1.3-diyl)adenosine (1.5 eq, 0.03 mmol, 0.016 g) dissolved in DCM (0.5 mL), silver oxide (0.75 eq, 0.015 mmol, 0.0035 g) than (1S,4R,5S)-(1)-3-(trityl)-4,5-O-isopropylidene-2-cyclopenten-1-bromide (30) (1 eq, 0.2 mmol, 0.1 g) was added. Reaction was stirred overnight at room temperature. No product formation could be detected by TLC or ESI-MS.

To a solution of 3,5’-O-(1,1,3,3-tetraisopropyldisiloxane-1.3-diyl)adenosine (1.5 eq, 0.03 mmol, 0.016 g) dissolved in THF (0.5 mL), silver oxide (0.75 eq, 0.015 mmol, 0.0035 g) than (1S,4R,5S)-(1)-3-(trityl)-4,5-O-isopropylidene-2-cyclopenten-1-bromide (30) (1 eq, 0.2 mmol, 0.1 g) was added. Reaction was stirred overnight at room temperature. No product formation could be detected by TLC or ESI-MS.

To a solution of 3,5’-O-(1,1,3,3-tetraisopropyldisiloxane-1.3-diyl)adenosine (1.5 eq, 0.03 mmol, 0.016 g) dissolved in toluene (0.5 mL), silver oxide (0.75 eq, 0.015 mmol, 0.0035 g) than (1S,4R,5S)-(1)-3-(trityl)-4,5-O-isopropylidene-2-cyclopenten-1-bromide (30) (1 eq, 0.2 mmol, 0.1 g) was added. Reaction was stirred overnight at room temperature. No product formation could be detected by TLC or ESI-MS.

To a solution adenosine (1eq, 0.056 mmol, 0.015 g) dissolved in DMF (0.75 mL), potassium tert butoxide (1.3 eq, 0.07 mmol, 0.008 g) than (1S,4R,5S)-(1)-3-(trityl)-4,5-O-isopropylidene-2-cyclopenten-1-bromide (30) (1.2 eq, 0.07 mmol, 0.034 g) was added. Reaction was stirred for 15 h. No product formation could be detected by TLC or ESI-MS.

To a solution adenosine (1eq, 0.056 mmol, 0.015 g) dissolved in DMF (0.75 mL), n-butyl lithium (0.07 mmol, 0.0046 g, 0.006 mL) than (1S,4R,5S)-(1)-3-(trityl)-4,5-O-isopropylidene-2-cyclopenten-1-bromide (30) (1.2 eq, 0.07 mmol, 0.034 g) was added. Reaction was stirred for 15 h. No product formation could be detected by TLC or ESI-MS.

123 To a solution adenosine (1eq, 0.056 mmol, 0.015 g) dissolved in DMF (0.75 mL), sodium metoxide (0.072 mmol, 0.039 g) than (1S,4R,5S)-(1)-3-(trityl)-4,5-O-isopropylidene-2-cyclopenten-1-bromide (30) (1.2 eq, 0.07 mmol, 0.034 g) was added.

Reaction was stirred for 15 h. No product formation could be detected by TLC or ESI-MS.

To a solution adenosine (1eq, 0.056 mmol, 0.015 g) dissolved in DMF (0.75 mL), NaHMDS (0.168 mmol, 0.03 g) with TBAI (0.0168 mmol, 0.006 g) was added than (1S,4R,5S)-(1)-3-(trityl)-4,5-O-isopropylidene-2-cyclopenten-1-bromide (30) (1.2 eq, 0.07 mmol, 0.034 g) was added. Reaction was stirred for 15 h. No product formation could be detected by TLC or ESI-MS.

To a solution adenosine (1eq, 0.056 mmol, 0.015 g) dissolved in DMF (0.75 mL), silver oxide (0.042 mmol, 0.009 g) than (1S,4R,5S)-(1)-3-(trityl)-4,5-O-isopropylidene-2-cyclopenten-1-bromide (30) (1.2 eq, 0.07 mmol, 0.034 g) was added.

Reaction was stirred for 15 h. No product formation could be detected by TLC or ESI-MS.

To a solution adenosine (1eq, 0.056 mmol, 0.015 g) dissolved in DMF (0.75 mL), AgBF4 (0.001 g) with collidine (0.7 μL) than (1S,4R,5S)-(1)-3-(trityl)-4,5-O-isopropylidene-2-cyclopenten-1-bromide (30) (1.2 eq, 0.07 mmol, 0.034 g) was added.

Reaction was stirred for 15 h. No product formation could be detected by TLC or ESI-MS.

To a solution adenosine (1eq, 0.056 mmol, 0.015 g) dissolved in DMF (0.75 mL), t-BuP₄ (2eq, 0.05 mL) than (1S,4R,5S)-(1)-3-(trityl)-4,5-O-isopropylidene-2-cyclopenten-1-bromide (30) (1.2 eq, 0.07 mmol, 0.034 g) was added. Reaction was stirred for 15 h. No product formation could be detected by TLC or ESI-MS.

To a solution adenosine (1eq, 0.056 mmol, 0.015 g) dissolved in DMF (0.75 mL), potassium hydroxide in DMSO was added than (1S,4R,5S)-(1)-3-(trityl)-4,5-O-isopropylidene-2-cyclopenten-1-bromide (30) (1.2 eq, 0.07 mmol, 0.034 g) was added.

Reaction was stirred for 15 h. No product formation could be detected by TLC or ESI-MS.

124

To a solution of 3’, 5’-O-(Di-tert-butylsilanediyl)-adenosine (1.2 eq, 0.18 mmol, 0.07 g) dissolved in 1 mL DCM then AgBF₄ with collidine was added in DCM followed by addition of (1S,4R,5S)-(1)-3-(trityl)-4,5-O-isopropylidene-2-cyclopenten-1-bromide (30) (1 eq, 0.15 mmol, 0.075 g). Reaction was stirred at room temperature overnight.

No product formation could be detected by TLC or ESI-MS.

To a solution of 3’, 5’-O-(Di-tert-butylsilanediyl)-adenosine (1.2 eq, 0.18 mmol, 0.07 g) dissolved in 1 mL acetonitrile AgBF₄ with collidine was added in acetonitrile followed by addition of (1S,4R,5S)-(1)-3-(trityl)-4,5-O-isopropylidene-2-cyclopenten-1-bromide (30) (1 eq, 0.15 mmol, 0.075 g). Reaction was stirred at room temperature overnight. No product formation could be detected by TLC or ESI-MS.

To a solution of 3’, 5’-O-(Di-tert-butylsilanediyl)-adenosine (1.2 eq, 0.18 mmol, 0.07 g) dissolved in 1 mL acetonitrile then tris(2-2methoxyethoxy)ethyl)amine (4 μL, 0.0053 mmol, 0.0017 g) in acetonitrile was added followed by addition of (1S,4R,5S)-(1)-3-(trityl)-4,5-O-isopropylidene-2-cyclopenten-1-bromide (30) (1 eq, 0.15 mmol, 0.075 g). Reaction was stirred at room temperature overnight. No product formation could be detected by TLC or ESI-MS.

(1S,4R,5S)-(1)-3-(trityl)-4,5-O-isopropylidene-2-cyclopenten-1-bromide (30) (1.5 eq, 0.11 mmol, 0.056 g) was dissolved in 1 mL of acetonitrile, then isopropanol (1 eq, 0.07 mmol, 5 μL) and silver oxide (2 eq, 0.14 mmol, 0.03 g) was added. Reaction was stirred at room temperature overnight. No product formation could be detected by TLC or ESI-MS.

(1S,4R,5S)-(1)-3-(trityl)-4,5-O-isopropylidene-2-cyclopenten-1-bromide (30) (1.5 eq, 0.11 mmol, 0.056 g) dissolved in 1 mL of DCM, then isopropanol (1 eq, 0.07 mmol, 5 μL) and silver oxide (2 eq, 0.14 mmol, 0.03 g) was added. Reaction was stirred at room temperature overnight. No product formation could be detected by TLC or ESI-MS.

(1S,4R,5S)-(1)-3-(trityl)-4,5-O-isopropylidene-2-cyclopenten-1-bromide (30) (1.5 eq, 0.11 mmol, 0.056 g) was dissolved in 1 mL of DMF, then isopropanol (1 eq, 0.07 mmol, 5 μL) and silver oxide (2 eq, 0.14 mmol, 0.03 g) was added. Reaction was stirred at room temperature overnight. No product formation could be detected by TLC or ESI-MS.

125 (1S,4R,5S)-(1)-3-(trityl)-4,5-O-isopropylidene-2-cyclopenten-1-bromide (30) (1.5 eq, 0.11 mmol, 0.056 g) was dissolved in 1 mL of THF then isopropanol (1 eq, 0.07 mmol, 5 μL) and silver oxide (2 eq, 0.14 mmol, 0.03 g) was added. Reaction was stirred at room temperature overnight. No product formation could be detected by TLC or ESI-MS.

(1S,4R,5S)-(1)-3-(trityl)-4,5-O-isopropylidene-2-cyclopenten-1-bromide (30) (1.5 eq, 0.11 mmol, 0.056 g) was dissolved in 1 mL of toluene then isopropanol (1 eq, 0.07 mmol, 5 μL) and silver oxide (2 eq, 0.14 mmol, 0.03 g) was added. Reaction was stirred at room temperature overnight. No product formation could be detected by TLC or ESI-MS.

Isopropanol (20 μL) was placed in 2 mL DCM and collidine (28 μL) followed by addition of AgBF4, (0.11 mmol, 0.025 g) reaction was placed on ice and (1S,4R,5S)-(1)-3-(trityl)-4,5-O-isopropylidene-2-cyclopenten-1-bromide (30) (1 eq, 0.11 mmol, 0.056 g) was added drop by drop in 1 mL DCM Reaction was stirred on ice overnight. No product formation could be detected by TLC or ESI-MS.

(1S,4R,5S)-(1)-3-(trityl)-4,5-O-isopropylidene-2-cyclopenten-1-

trichloroacetimidate (29) (0.2 g, 0.35 mmol) was placed with isopropyl alcohol (0.6 mmol, 0.036 g, 46 μL) as well as with 3,5’-O-(1,1,3,3-tetraisopropyldisiloxane-1.3-diyl)adenosine (0.6 mmol, 0.34 g), in dry DCM with molecular sieved under N₂ atmosphere at room temperature for 10 min followed by slow addition of TMSOTf (200 μL, 0.002 mmol). No product formation could be detected by TLC or ESI-MS.

(1S,4R,5S)-(1)-3-(trityl)-4,5-O-isopropylidene-2-cyclopenten-1-

trichloroacetimidate (29) (0.2 g, 0.35 mmol) was placed with isopropyl alcohol (0.6 mmol, 0.036 g, 46 μL) as well as with 3’, 5’-O-(Di-tert-butylsilanediyl)-adenosine (0.665 mmol, 0.27 g) in dry DCM with molecular sieved under N2 atmosphere at room temperature for 10 min followed by slow addition of TMSOTf (200 μL, 0.002 mmol). No product formation could be detected by TLC or ESI-MS.

(1S,4R,5S)-(1)-3-(trityl)-4,5-O-isopropylidene-2-cyclopenten-1-

trichloroacetimidate (29) (0.2 g, 0.35 mmol) was placed with isopropyl alcohol (0.6 mmol, 0.036 g, 46 μL) as well as with adenosine (0.3 mmol, 0.08 g) in dry DCM with molecular sieved under N₂ atmosphere at room temperature for 10 min followed by

126

slow addition of TMSOTf (200 μL, 0.002 mmol). No product formation could be detected by TLC or ESI-MS.

Adenosine (1 eq, 0.05 mmol, 0.015 g) was dissolved in DMF (0.75 mL) followed by addition of (1S,4R,5S)-(1)-3-(trityl)-4,5-O-isopropylidene-2-cyclopenten-1-mesyl (28) (1.3 eq, 0.0016 g) and sodium hydride (1.3 eq) was added. No product formation could be detected by TLC or ESI-MS.

Adenosine (1 eq, 0.05 mmol, 0.015 g) was dissolved in DMF (0.75 mL) followed by addition of (1S,4R,5S)-(1)-3-(trityl)-4,5-O-isopropylidene-2-cyclopenten-1-mesyl (28) (1.3 eq, 0.0016 g) and potassium tertbutoxide (1.3 eq) was added. No product formation could be detected by TLC or ESI-MS.

Adenosine (1 eq, 0.05 mmol, 0.015 g) was dissolved in DMF (0.75 mL) followed by addition of (1S,4R,5S)-(1)-3-(trityl)-4,5-O-isopropylidene-2-cyclopenten-1-mesyl (28) (1.3 eq, 0.0016 g) and n butyl lithium (1.3 eq) was added. No product formation could be detected by TLC or ESI-MS.

Adenosine (1 eq, 0.05 mmol, 0.015 g) was dissolved in DMF (0.75 mL) followed by addition of (1S,4R,5S)-(1)-3-(trityl)-4,5-O-isopropylidene-2-cyclopenten-1-mesyl (28) (1.3 eq, 0.0016 g) and sodium metoxide, (1.3 eq) was added. No product formation could be detected by TLC or ESI-MS.

Adenosine (1 eq, 0.05 mmol, 0.015 g) was dissolved in DMF (0.75 mL) followed by addition of (1S,4R,5S)-(1)-3-(trityl)-4,5-O-isopropylidene-2-cyclopenten-1-mesyl (28) (1.3 eq, 0.0016 g) and NaHMDS with TBAJ (1.3 eq) was added. No product formation could be detected by TLC or ESI-MS.

127