yield), 2,5-dihydropyrrole derivative (+) -3.44 (0.023 g, 40% yield and a mixture of -   - C-glycosides 3.43 and  3.43 (0.012 g, 32% yield

63.60; H, 6.06; N, 3.37. Found: C, 63.41; H, 5.79; N, 3.11.

Reaction of N-nosyl aziridine 2.3 with K-enolate of dibenzoylmethane in dry toluene by t-BuOK, as the only base

A solution of trans N-nosyl,O-mesylate (+) -2.47 (0.104 g, 0.209 mmol) in dry  toluene (3.0 mL) was treated at room temperature with t-BuOK (0.047 g, 0.42 mmol, 2 equiv) in the presence of dibenzoylmethane (0.141 g, 0.63 mmol, 3 equiv). After 12 h stirring at the same temperature, the reaction mixture was partitioned between AcOEt (40 mL) and brine (10 mL), and the aqueous layer was further extracted with AcOEt (2 x 5 mL). Evaporation of the combined organic extracts afforded a crude reaction product consisting of the excess of dibenzoylmethane and a 30:30:40 mixture of 3- (dibenzoylmethyl)- D -glucal derivative (–) -3.42 (anti-1,2-addition product), 2,5- dihydropyrrole derivative (+) -3.44 and --C-glycosides 3.43 and  3.43 (anti-1,4- addition product) (

H NMR), which was subjected to rapid filtration through silica gel, to eliminate the excess of dibenzoylmethane, and then to preparative TLC using a 7:3 hexane/AcOEt mixture, as the eluant (5 runs). Extraction of the three most intense bands (the faster moving band contained (-) -3.42 and the slower moving band contained (+) - 3.44afforded pure 3-(dibenzoylmethyl)- D -glucal derivative (–) -3.42 (0.013 g, 28%

yield), 2,5-dihydropyrrole derivative (+) -3.44 (0.023 g, 40% yield and a mixture of -   - C-glycosides 3.43 and  3.43 (0.012 g, 32% yield

6-O-Benzyl-3,4-dideoxy-4-(N-nosylamino)-3-(dibenzoyl-

methyl)- D -glucal [ (–) -3.42]: an oil, R

= 0.19 [7:3 hexane/AcOEt (3 runs)];

α

D

– 30.0 (c 1.55, CHCl

).

H NMR (CDCl

)  7.97 – 7.79 (m, 5H), 7.66 – 7.31 (m, 12H), 7.21 – 7.08 (m, 2H), 6.38 (dd, 1H, J = 6.2, 2.5 Hz), 5.76 (d, 1H, J = 4.7 Hz), 5.60 (d, 1H, J = 8.2 Hz), 4.66 (dd, 1H,

BnO O

(–)-3.42 NsNH

CH(COPh)

BnO O

(–)-3.42 NsNH

CH(COPh)

BnO O

3.43 + 3.43

CH(COPh)

NsNH

N Ns

CH(COPh)

BnO

OH

(+)-3.44

J = 6.2, 2.5 Hz,), 4.36 – 4.26 (m, 2H), 4.17 – 4.06 (m, 2H), 3.56 (ddd, 2H, J = 16.0, 11.0, 4.0 Hz), 3.32 – 3.20 (m, 1H, J = 19.1 Hz).

C NMR (CHCl

) δ 195.46, 195.26, 147.48, 143.50, 137.74, 137.06, 135.27, 134.40, 134.07, 133.52, 133.11, 131.05, 129.25, 129.04, 128.80, 128.55, 128.46, 127.89, 127.69, 125.17, 99.94, 73.48, 69.06, 55.28, 52.75, 39.31.

(2R,5S,6S)-5-[2-(benzyloxy)-1-hydroxy-ethyl]-2- (dibenzoylmethyl)-1-nosyl-2,5-dihydro-1H-pyrrole [ (+) -3.44]: an oil, R

= 0.10 [7:3 hexane/AcOEt (3 runs)];

[

α

D

+39.5 (c 0.52, CHCl

).

H NMR (CDCl

) δ 8.12 (dd, 2H, J = 5.9, 2.6 Hz), 8.04 – 7.95 (m, 2H), 7.89 (dd, 1H, J = 7.8, 1.4 Hz), 7.73 – 7.28 (m, 14H), 6.30 (d, 1H, J = 5.4 Hz), 6.17 (dt, 1H, J = 6.5, 2.0 Hz), 5.80 (dt, 1H, J = 6.4, 2.0 Hz), 5.46 (ddd, 1H, J = 5.5, 3.8, 2.0 Hz), 4.74 (td, 1H, J = 3.8, 2.0 Hz), 4.51 – 4.45 (m, 1H), 4.42 (d, 1H, J = 11.6 Hz), 3.84 – 3.73 (m, 1H), 3.52 (dd, 1H, J = 9.8, 5.5 Hz), 3.45 (dd, 1H, J = 9.8, 4.6 Hz).

C NMR (CDCl

) δ 149.34, 137.82, 136.79, 136.37, 134.42, 134.26, 133.80, 133.40, 132.03, 131.16, 130.68, 130.61, 130.00, 129.79, 129.51, 129.26, 129.03, 128.97, 128.64, 128.38, 127.99, 126.57, 124.28, 73.63, 72.75, 71.55, 71.16, 68.61, 60.95.

Reaction of N-nosyl aziridine 2.3 with K-enolate of dibenzoylmethane in dry THF by t-BuOK, as the only base

A solution of trans N-nosyl-O-mesylate (+) -2.47 (0.128 g, 0.257 mmol) in dry  THF (3.0 mL) was treated at room temperature with t-BuOK (0.087 g, 0.77 mmol, 3 equiv) in the presence of dibenzoylmethane (0.173 g, 0.77 mmol, 3 equiv). After 7 h stirring at the same temperature, the reaction mixture was partitioned between Et

O (40 mL) and brine (10 mL). Evaporation of the combined organic extracts afforded a crude

BnO O

3.46

CH

COPh

NsNH N

Ns

CH(COPh)

BnO

OH

(+)-3.44

BnO O

(–)-3.45 NsNH

CH

COPh

N Ns

CH

COPh BnO

OH

(+)-3.47

3-(benzoylmethyl)- D -glucal derivative (–) -3.45 (anti-1,2-addition product), 2,5- dihydropyrrole derivative (+) -3.47 and -C-glycoside 3.46 (anti-1,4-addition product) (

H NMR), which was subjected to rapid filtration through silica gel to eliminate the excess of dibenzoylmethane, and then to preparative TLC by using a 1:1 hexane/AcOEt mixture, as the eluant Extraction of the three most intense bands (the faster moving band contained (-) -3.45 and the slower moving band contained (+) -3.47afforded pure 3- (dibenzoylmethyl)- D -glucal derivative (–) -3.45 (0.019 g, 20% yield), 2,5-dihydropyrrole derivative (+) -3.47 (0.025 g, 35% yield and  -C-glycosides 3.46 (0.032 g, 45% yield

6-O-Benzyl-3,4-dideoxy-4-(N-nosylamino)-3-(benzoylmethyl)-

D -glucal [ (–) -3.45]: an oil, R

= 0.19 [7:3 hexane/AcOEt (3 runs)];

[

α

D

– 30.0 (c 1.55, CHCl

).

H NMR (CDCl

) δ 8.07 – 8.01 (m, 1H), 7.83 – 7.77 (m, 2H), 7.70 – 7.64 (m, 1H), 7.57 – 7.28 (m, 9H), 7.24 – 7.21 (m, 1H), 6.36 (dd, 1H, J = 6.0, 2.2 Hz), 5.54 (d, 1H, J = 9.1 Hz), 4.66 (dd, 1H, J = 6.0, 2.1 Hz), 4.34 (s, 2H), 4.08 – 3.98 (m, 1H), 3.79 (q, 1H, J = 9.6 Hz), 3.71 – 3.60 (m, 1H), 3.53 (dd, 1H, J = 10.9, 5.4 Hz), 3.28 (dd, 1H, J = 17.4, 3.3 Hz), 2.86 (dd, 1H, J = 17.3, 9.4 Hz).

C NMR (CDCl

) δ 198.13, 147.52, 143.16, 137.91, 136.67, 135.07, 133.44, 133.40, 133.04, 130.54, 128.70, 128.51, 128.40, 128.09, 127.80, 127.61, 125.28, 103.05, 73.47, 69.26, 54.51, 41.18, 37.68, 35.33.

(2R,5S,6S)-6-(Benzyloxymethyl)-5-(N-mesylamino)-2- (dibenzoylmethyl)-2H-5,6-dihydropyran [3.46]: an oil, R

= 0.31 [1:1 hexane/AcOEt].

H NMR (CDCl

) δ 8.12 – 8.05 (m, 1H), 7.97 – 7.87 (m, 2H), 7.87 – 7.80 (m, 1H), 7.75 – 7.25 (m, 10H), 5.88 (ddd, 1H, J = 10.3, 2.2, 1.4 Hz), 5.45 (d, 1H, J = 9.2 Hz), 5.39 (dt, 1H, J = 10.3, 2.1 Hz), 4.83 – 4.70 (m, 1H), 4.50 (d, 1H, J = 12.2 Hz), 4.45 (d, J = 12.2 Hz, 1H), 4.19 (t, 1H, J = 8.1 Hz), 3.73 (m, 1H), 3.61 (m, 2H), 3.39 (dd, 1H, J = 16.7, 6.0 Hz), 3.02 (dd, 1H, J = 16.8, 7.5 Hz).

C NMR (CDCl

) δ 197.50, 147.88, 138.28, 137.01, 134.55, 133.81, 133.48, 133.07, 132.88, 130.98, 128.74, 128.42, 128.32, 127.75, 127.65, 126.15, 125.47, 77.60, 73.61, 71.63, 69.38, 49.14, 43.83.

O

NsNH

CH

COPh BnO

(-)-3.45

BnO O

3.46

CH

COPh

NsNH

(2R,5S,6S)-5-[2-(benzyloxy)-1-hydroxy-ethyl]-2-

(benzoylmethyl)-1-nosyl-2,5-dihydro-1H-pyrrole [ (+) -3.47]:

an oil, R

= 0.25 [1:1 hexane/AcOEt];

α

D

+9.4 (c 0.25, CHCl

).

H NMR (CDCl

) δ 7.99 – 7.28 (m, 14H), 6.07 (dt, 1H, J = 6.2, 2.0 Hz), 5.78 (dt, 1H, J = 6.3, 1.9 Hz), 5.15 – 5.06 (m, 1H), 4.85 – 4.80 (m, 1H), 4.60 (d, 1H, J = 12.0 Hz), 4.55 (d, 1H, J = 12.0 Hz), 4.23 – 4.17 (m, 1H), 3.85 (dd, J = 1H, 18.0, 3.7 Hz), 3.72 – 3.59 (m, 2H), 3.48 (dd, 1H, J = 18.0, 9.9 Hz), 2.62 (d, 1H, J = 6.7 Hz, OH).

C NMR (CDCl

) δ 198.43, 149.18, 137.82, 136.56, 133.97, 133.60, 131.91, 131.88, 131.03, 129.80, 128.82, 128.78, 128.63, 128.59, 128.25, 128.00, 127.93, 127.90, 127.30, 125.69, 124.45, 73.74, 72.43, 71.57, 70.73, 64.45, 46.44.

Deprotection of N-nosyl functionality in glycal-derived 3.42 and 3.45 and 2,5-dihydropyrrole 3.47

A solution of 3-(dibenzoylmethyl)- D -glucal derivative (–) -3.42 (0.027g, 0.042 mmol) in anhydrous MeCN (0.2 mL) was treated with a solution of PhSH (0.1M in MeCN) (1,7 mL, 0.17 mmol, 4 equiv) and was added K

CO

at 0°C (0.024mg, 0.17 mmol, 4 equiv). The resulting reaction mixture was stirred 4 h at room temperature. Dilution with Et

O and evaporation of the filtered organic solution afforded a crude product consisting of 4-N-benzoyl-3-benzoylmethyl glycal derivative 3.48 and excess of PhSH, which was subjected to preparative TLC with a 7:3 hexane/AcOEt mixture, as the eluant. 6-O- Benzyl-3,4-dideoxy-4-benzoylamino-3-(benzoylmethyl)- D -glucal [3.48]: pure as a solid, m.p. 117-119°C;

H NMR (CDCl

) δ 7.91 – 7.84 (m, 2H), 7.67 – 7.60 (m, 2H), 7.57 – 7.31 (m, 6H), 7.23 (s, 5H), 6.43 (dd, J = 6.0, 1.9 Hz, 1H), 6.31 – 6.20 (m, 1H), 4.67 (dd, 1H, J = 6.1, 1.7 Hz), 4.53 (d, 1H, J = 11.8 Hz), 4.47 (d, 1H, J = 11.8 Hz), 4.24 (dd, 1H, J

= 19.0, 9.9 Hz), 4.07 (dt, 1H, J = 9.9, 4.8 Hz), 3.74 (d, 2H, J = 4.8 Hz), 3.25 (dd, 1H, J = 16.3, 4.7 Hz), 3.20 – 3.11 (m, 1H), 3.10 – 2.94 (m, 1H).

C NMR (CDCl

) δ 199.62, 167.70, 143.53, 137.83, 136.84, 133.93, 133.49, 131.83, 128.74, 128.69, 128.47, 128.26,

N Ns

CH

COPh BnO

OH

(+)-3.47

3.48 O

PhCOHN

CH

COPh

BnO

128.09, 127.81, 127.05, 103.46, 77.83, 73.85, 70.75, 50.98, 42.39, 34.85.

A solution of 3-(benzoylmethyl)- D -glucal derivative (–) -3.45 (0.016g, 0.030 mmol) in anhydrous MeCN (0.15 mL) was treated at 0°C with 0.1M PhSH in MeCN (1.2 mL, 0.120 mmol, 4 equiv) and K

CO

(0.016mg, 0.120 mmol, 4 equiv). The resulting reaction mixture was stirred 24 h at room temperature. Dilution with Et

O and evaporation of the filtered organic solution afforded a crude product consisting of 4-amino-D-glucal derivative 3.49 and the excess of PhSH, which was subjected to preparative TLC with a 7:3 hexane/AcOEt mixture, as the eluant. Extraction of the most intense band afforded pure 6-O-Benzyl-3,4-dideoxy-4-amino-3-(benzoylmethyl)- D -glucal [3.49] (65% yield);

as an oil, R

= 0.05 (7:3 hexane/AcOEt);

H NMR (CDCl

) δ 7.98 (d, 2H, J = 7.8 Hz), 7.62 – 7.28 (m, 8H), 6.35 (d, 1H, J = 5.2 Hz), 4.69 (d, 1H, J = 12.1 Hz), 4.64 (d, 1H, J = 5.2 Hz), 4.52 (d, 1H, J = 12.1 Hz), 3.79 (dd, 2H, J = 15.8, 7.3 Hz), 3.71 – 3.61 (m, 1H), 3.52 (dd, 1H, J = 16.9, 3.6 Hz), 2.94 – 2.80 (m, 2H), 2.73 – 2.58 (m, 1H), 1.32 – 1.19 (m, 2H, NH

).

C NMR (CDCl

) δ 199.92, 143.33, 133.22, 128.74, 128.66, 128.49, 128.27, 128.03, 127.94, 127.61, 104.03, 80.11, 73.76, 69.64, 51.43, 42.62, 36.75.

Following the same procedure used for D -glucal derivative 3.45, the treatment at 0°C of 2,5-dihydropyrrole derivative (+) - 3.47 (0.025 g, 0.047 mmol) with 0.1M PhSH in MeCN (0.9 mL, 0.094 mmol, 2 equiv) and K

CO

(0.013 mg, 0.094 mmol, 2 equiv) afforded, after 4h stirring at room temperature, a crude product which was was subjected to flash chromatography. Elution with 1:1 hexane/AcOEt mixture afforded (2R,5S,6S)-5-[2-(benzyloxy)-1-hydroxy-ethyl]-2-(benzoylmethyl)-1-amino-2,5-

dihydropyrrole [(-)-3.50] (0.019 g, 75% yield):

α

D

-24.5 (c= 0.4); R

= 0.06 (1:1 hexane/AcOEt).

H NMR (CDCl

) δ 7.99 – 7.90 (m, 2H), 7.61 – 7.52 (m, 1H), 7.50 – 7.42 (m, 2H), 7.39 – 7.27 (m, 5H), 5.99 – 5.75 (m, 2H), 4.76 – 4.66 (m, 1H), 4.59 (d, 1H, J = 12.3 Hz), 4.53 (d, 1H, J = 12.3 Hz), 4.34 – 4.25 (m, 1H), 3.73 – 3.63 (m, 1H), 3.60 – 3.54 (m, 2H), 3.21 – 3.09 (m, 2H), 2.40 (bs, 2H, OH and NH).

C NMR (CDCl

) δ 199.22, 138.23, 137.12, 136.91, 133.47, 133.40, 133.07, 128.80, 128.65, 128.61, 128.35, 128.28,

N H

CH

COPh BnO

OH

(-)-3.50 O

H

N

CH

COPh BnO

3.49

127.98, 127.97, 127.91, 73.69, 71.86, 67.13, 61.36, 60.55, 29.88.

Acetylation of the free amino derivative 3.49 by Ac

O/Py.

A solution of the 4-amino- D -glucal derivative 3.49 in anhydrous pyridine (0.1mL) was treated at 0°C with Ac

O (0.05mL) and the reaction mixture was stirred 18 h at room temperature. Evaporation with Et

O afforded the corresponding acetyl derivatives 3.49-Ac, which was subjected to preparative TLC by using a 6:4 hexane/AcOEt mixture.

Extraction of the most intense band, afforded pure 6-O-Benzyl-3,4-dideoxy-4- acetylamino-3-(benzoylmethyl)- D -glucal [3.49-Ac]:

H NMR (CDCl

) δ 7.99 – 7.88 (m, 2H), 7.58 (t, 1H, J = 7.3 Hz), 7.46 (t, 2H, J = 7.4 Hz), 7.39 – 7.28 (m, 5H), 6.39 (dd, 1H, J = 6.0, 1.9 Hz), 5.42 (d, 1H, J = 8.3 Hz), 4.62 (dd, 1H, J = 6.0, 1.4 Hz), 4.55 (s, 2H), 4.05 – 3.86 (m, 2H), 3.66 (d, 2H, J = 4.5 Hz), 3.26 – 3.08 (m, 1H), 3.08 – 2.82 (m, 2H), 1.82 (s, 3H).

C NMR (CDCl

) δ 199.53, 170.44, 143.45, 137.99, 136.89, 133.59, 128.85, 128.56, 128.25, 128.13, 127.91, 103.29, 73.80, 70.47, 50.39, 42.39, 34.60, 29.85, 23.38.

Synthesis of trans N-Cbz-O-mesylate 3.30

6-O-Benzyl-3-deoxy-3-N-(benzyloxycarbonyl)amino- D -gulal (3.34a). A solution of trans amino alcohol 2.45a (0.101 g, 0.43 mmol) in anhydrous CH

Cl

(4 mL) was treated at 0°C with Et

N (0.07 mL, 0.52 mmol) and CbzCl (0.07 mL, 0.47 mmol) and the reaction mixture was stirred 12 h at room temperature. Dilution with CH

Cl

(30 mL) and evaporation of the washed (saturated aqueous NaHCO

, 1x5 mL, and saturated aqueous NaCl, 1x5 mL) organic solution afforded a crude residue (0.168 g) consisting of the N- Cbz derivative 3.34a, which was subjected to flash chromatography. Elution with a 7:3 hexane/AcOEt mixture yielded the N-Cbz derivative 3.34a (0.031 g, 20% yield), pure as a white solid, mp 98-101°C:

α

+91.4 (c 1.09, CHCl

); R

= 0.24 (6:4 hexane/AcOEt);

1

H NMR (CDCl

) δ 7.41 – 7.27 (m, 10H), 6.59 (d, 1H, J = 6.1 Hz), 5.21 – 4.98 (m, 2H), 4.82 – 4.71 (m, 2H), 4.62 (d, 1H, J = 12.2 Hz), 4.57 (d, 1H, J = 12.1 Hz), 3.98 (s, 2H),

BnO O

NHCbz HO

3.34

O

AcHN

CH

COPh BnO

3.49-Ac

3.82 (s, 3H), 3.13 (s, 1H, OH).

C NMR (CDCl

) δ 155.21, 147.09, 137.48, 136.24, 128.69, 128.40, 128.09, 128.00, 97.62, 74.02, 72.43, 70.67, 68.70, 67.13, 47.67.

6-O-Benzyl-3-deoxy-3-N-(benzyloxycarbonyl)amino-4-O-mesyl- D - gulal (3.30). A solution of the N-Cbz derivative (+)-3.34a (0.031 g, 0.08 mmol) in anhydrous pyridine (0.15 mL) was treated at 0°C with MsCl (9.8 L, 0.13 mmol) and the reaction mixture was stirred 18 h at 0°C. Dilution with CH

Cl

(40 mL) and evaporation of the washed (brine, 3 mL) organic solution afforded a crude residue (0.04 g) consisting of pure trans N-Cbz-O-mesyl derivative 3.30 :

α

D

+64.5 (c 1.09, CHCl

); R

= 0.5 (1:1 hexane/AcOEt);

H NMR (CDCl

) δ 7.42 – 7.29 (m, 10H), 6.62 (d, 1H, J = 6.1 Hz), 5.17 (d, 1H, J = 11.9 Hz), 5.05 (d, 1H, J = 11.9 Hz), 4.88 – 4.72 (m, 3H), 4.59 (s, 2H), 4.02 (t, 1H, J = 6.1 Hz), 3.87 – 3.64 (m, 3H), 3.24 (s, 3H).

C NMR (CDCl

) δ 155.13, 147.86, 137.61, 135.76, 128.79, 128.63, 128.48, 128.37, 128.28, 128.08, 96.07, 75.08, 73.96, 71.40, 68.91, 67.49, 45.88, 38.44.

Treatment of N-Cbz-O-mesyl derivative 3.30 with t-BuOK in dry MeOH for 5 days (protocol A)

A solution of trans N-Cbz-O-mesylate (+)-3.30 (0.033 g, 0.074 mmol) in dry MeOH (0.3 mL) was treated at room temperature with several portion of t-BuOK (0.052 g, 0.46 mmol). After 5 days stirring at the same temperature, the reaction mixture was diluted with Et

O and evaporated to give a crude mixture which was subjected to preparative TLC with a 7:3 hexane/AcOEt mixture as the eluant (2 runs). Extraction of the most intense band afforded a 90:10 mixture of - and - anomers 3.36 and 3.36

(0.009 g, 30% yield) which turned out to be not separable under any chromatography conditions.

A solution of trans N-Cbz-O-mesylate (+)-3.30 (0.017 g, 0.039 mmol) in dry MeOH (0.2 mL) was treated at room temperature with t-BuOK (0.024 g, 0.21 mmol).

After approximately 30% conversion (about 2 h,

H NMR), dilution with Et

O and evaporation of the organic solution afforded a crude reaction product consisting of a

BnO O

NHCbz MsO

3.30

90:10 mixture of a- and -anomers 3.36 and 3.36.

Treatment of N-Cbz-O-mesyl derivative 3.30 with t-BuOK in dry MeCN in the presence of MeOH (3 equiv) (protocol B)

A solution of trans N-Cbz-O-mesylate (+)-3.30 (0.016 g, 0.035 mmol) in dry MeCN (2.2 mL) in the presence of MeOH (3 equiv) was treated at room temperature with t-BuOK (0.016 g, 0.14 mmol) and the reaction mixture was stirred at the same temperature for 1 h. Usual work-up afforded a crude product (0.013 g) consisting of practically pure (2S,5S,6S)-2-methoxy-5-(N-benzyloxycarbonyl)amino-6-O-Benzyl- 2H-5,6-dihydropyran [3.36a]:

α

D

+58.7 (c 0.33, CHCl

); R

= 0.11 (7:3 hexane/AcOEt, 2 runs);

H NMR (CDCl

) δ 7.41 – 7.28 (m, 10H), 5.83 (s, 2H), 5.09 (s, 2H), 4.92 (s, 1H), 4.58 (s, 3H), 4.39 (t, 1H, J = 9.6 Hz), 3.84 – 3.73 (m, 1H), 3.72 – 3.56 (m, 2H), 3.44 (s, 3H).

C NMR (CDCl

) δ 156.11, 139.05, 138.84, 138.34, 131.61, 128.72, 128.47, 128.40, 128.30, 127.82, 127.70, 95.23, 73.70, 70.21, 55.93, 46.58, 40.60, 29.85.

Synthesis of trans N-TFA-O-mesylate 3.32a

6-O-Benzyl-3-deoxy-3-N-(trifluoromethyl)acetamido- D -gulal [(+)-3.35a]. A solution of trans amino alcohol 2.45a (0.100 g, 0.46 mmol) in anhydrous MeOH (0.9 mL) was treated with Et

N (0.12 mL, 0.85 mmol) and ETFA (0.06 mL, 0.53 mmol) and the reaction mixture was stirred 17 h at room temperature.

Dilution with Et

O (30 mL), and evaporation of the filtered organic solution afforded a crude product which was subjected to flash chromatography. Elution with a 7:3 hexane/AcOEt mixture yielded N-TFA derivative (+)-3.35a (0.031 g, 25% yield), pure as a white solid, mp 117-118°C:

α

D

+68 (c 1.07, CHCl

); R

= 0.38 (1:1 hexane/AcOEt);

H NMR (CDCl

) δ 7.38 – 7.29 (m, 5H), 6.67 (d, 1H, J = 6.1 Hz), 6.44 (d, 1H, J = 6.4 Hz), 4.81 – 4.74 (m, 1H), 4.62 (d, 1H, J = 12.1 Hz), 4.56 (d, 1H, J = 12.0 Hz), 4.23 (t, 1H, J = 6.0 Hz), 3.98 (s, 1H), 3.82 (s, 3H), 3.38 (s, 1H).

C NMR (CDCl

) δ 156.48 (q, J = 37.5 Hz), 148.22, 137.15, 128.70, 128.22, 128.04, 115.64 (q, J = 287.9 Hz), 95.92, 74.08, 72.45, 70.45, 67.53, 46.85.

O OMe BnO

CbzHN

3.36

BnO O

NHCOCF

HO

3.35

6-O-Benzyl-3-deoxy-3-N-(trifluoromethyl)acetamido-4-O- mesyl- D -gulal [(+)-3.32]. A solution of the N-TFA derivative (+)- 3.35a (0.018 g, 0.05 mmol) in anhydrous pyridine (0.3 mL) was treated at 0°C with MsCl (24 L, 0.33 mmol) and the reaction mixture was stirred 18 h at 0°C. Dilution with CH

Cl

(40 mL) and evaporation of the washed (brine, 3 mL) organic solution afforded a crude residue (0.022 g) consisting of pure trans N-TFA-O-mesyl derivative (+)-3.32:

α

D

+36.6 (c 1.8, CHCl

); R

= 0.52 (1:1 hexane/AcOEt);

H NMR (CDCl

) δ 7.39 – 7.27 (m, 5H), 6.95 (bs, 1H), 6.66 (d, 1H, J = 5.8 Hz), 4.86 – 4.76 (m, 2H), 4.59 (d, 1H, J = 11.9 Hz), 4.54 (d, 1H, J = 11.9 Hz), 4.46 – 4.34 (m, 1H), 4.10 (t, 1H, J = 5.8 Hz), 3.85 – 3.69 (m, 2H), 3.19 (s, 3H).

C NMR (CDCl

) δ 156.96 (q, J = 38.3 Hz), 148.42, 137.46, 128.63, 128.26, 128.14, 115.52 (q, J = 287.8 Hz), 94.96, 73.98, 73.43, 71.80, 68.49, 45.13, 38.43.

Treatment of N-TFA-O-mesyl derivative 3.32 with t-BuOK and MeOH in anhydrous MeCN

A solution of trans N-TFA-O-mesylate (+) -3.32 (0.027 g, 0.067 mmol) in MeCN (0.2 mL) was treated at room temperature with t- BuOK (0.050 g, 0.44 mmol, 2.5 equiv) and MeOH. After 3 h stirring at the same temperature, the reaction mixture was partitioned between Et

O (20 mL) and brine (5 mL). Evaporation of the combined organic extracts afforded a crude reaction product mostly consisting of cis hydroxy trifluoroacetylamino glycal derivative 3.41 (0.013g) which was subjected to flash chromatography. Elution with a 7:3 hexane/AcOEt mixture yielded 6-O-Benzyl-3-deoxy- 3-N-(trifluoromethyl)acetamido- D -allal [3.41]: pure as solid, m.p. 94-96°C;

H NMR (CDCl

) δ 7.44 – 7.28 (m, 5H), 6.62 – 6.45 (bs, 1H, NH), 6.49 (dd, 1H, J = 6.0, 1.2 Hz), 4.83 (dd, 1H, J = 6.0, 4.7 Hz), 4.63 (d, 1H, J = 12.0 Hz), 4.57 (d, 1H, J = 12.0 Hz), 4.58 – 4.48 (m, 1H), 4.18 – 4.06 (m, 1H), 3.96 – 3.87 (m, 1H), 3.85 – 3.70 (m, 2H), 2.77 (bs, 1H).

C NMR (CDCl

) δ 156.48 (q, J = 37.5 Hz), 146.53, 137.45, 128.72, 128.20, 128.02, 115.64 (q, J = 287.9 Hz), 97.17, 74.06, 73.97, 68.88, 66.50, 44.92.

BnO O

NHCOCF

MsO

3.32

BnO O

NHCOCF

HO

3.41