Supporting Information

© Copyright Wiley-VCH Verlag GmbH & Co. KGaA, 69451 Weinheim, 2008

Tuning the Acyclic Ether Moiety of Anticancer Agent AA005 with

Conformation-Constrained Fragments

Hai-Xia Liu, Fei Shao, Gang-Qin Li, Guo-Liang Xun, Zhu-Jun Yao*

State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Road, Shanghai 200032, China

E-mail: yaoz@mail.sioc.ac.cn

S-1

I. Experimental procedures and characterizations of new compounds

General methods: Optical rotations were measured by a Perkin-Elmer 341MC

polarimeter at room temperature. Infrared (IR) spectra were obtained using a Fourier

transform infrared spectrometer (FTIR). 1H NMR spectra were recorded with Varian

EM and Bruker AMX machines at 300 MHz, 400 MHz or 500 MHz and are reported

in ppm (δ) downfield relative to TMS as internal standard, and 13C NMR spectra were

recorded at 100 and 150 MHz and assigned in ppm (δ). HRMS spectra were recorded

by using either a Kratos Concept instrument, a Q-Tof micro instrument or an APEXIII

7.0 TESLA FTMS. Elemental analysis was preformed by using an Elemental VARIO

EL apparatus. All melting points were uncorrected. Flash column chromatography

was performed on silica gel (10 - 40 μm).

(2S)-Methoxymethoxydodecane-1-ol (8). To a stirred suspension of diol 7 (0.2 g, 1.0

mmol) and D-camphorsulfonic acid (2.3 mg, 0.01 mmol) in dry

CH2Cl2 (12 mL) was added CH(OMe)3 (0.2 mL, 2.0 mmol) under

N2. The resulting reaction mixture was stirred at rt. The reaction process was

monitored by TLC. After complete conversion of the diol, the reaction mixture was

cooled down to -78 oC, and DIBAL-H (6 mL, 1.0 M in toluene, 6.0 mmol) was added.

After 2 hours of stirring, the reaction was quenched by slow addition of 1N HCl at -78

oC. The reaction mixture was extracted with CH2Cl2 (3 x 10 mL).The combined

organic layers were dried over anhydrous Na2SO4, filtered, and concentrated. The

residue was purified by column chromatography on silica gel to afford 8 (0.22 g, 90%)

as a colorless oil. [α]D25 = +44.4 (c 1.1, CHCl3); 1H NMR (300 MHz, CDCl3) δ: 0.89

(3H, t, J = 6.6 Hz), 1.26 - 1.44 (18H, m), 3.02 (1H, m), 3.44 (3H, s), 3.53 - 3.61 (2H,

s), 4.73 (2H, dd, J = 9.3, 6.9 Hz) ppm.

OHOMOM8

7

(2S)-Methanesulfonic acid 2-methoxymethoxydodecyl ester (9). To a solution of

alcohol 8 (1.90 g, 7.9 mmol) and Et3N (1.3 ml, 9.5 mmol) in

CH2Cl2 (25 mL) was added MsCl (0.73 g, 9.5 mmol) in OMs

OMOM7

( )

9

S-2

CH2Cl2 (15 mL) at 0 oC. The reaction mixture was stirred at 0 oC for 2 hrs and

quenched by adding H2O (5 mL). The mixture was extracted with CH2Cl2 (3 x 50 mL).

The combined organic layers were washed with 1N HCl and brine, dried over Na2SO4,

and filtered. The solvent was removed under reduced pressure. The residue was

purified by flash column chromatography (hexanes/EtOAc = 5:1) to afford 9 (2.56 g,

100%) as a white solid. mp: 34 - 36 oC; [α]D25 = +3.02 (c 1.03, CHCl3); 1H NMR (300

MHz, CDCl3) δ: 0.88 (3H, t, J = 6.6 Hz), 1.20 - 1.43 (16H, m), 1.57 (2H, m), 3.04

(3H, s), 3.40 (3H, s), 3.80 (1H, m), 4.18 (1H, dd, J = 6.0, 10.8 Hz), 4.29 (1H, dd, J =

3.6, 10.8 Hz), 4.70 (2H, dd, J = 6.9, 13.7 Hz) ppm.

General procedure for compounds 10-15: To a suspension of NaH (4 mmol) in

anhydrous DMF (10 mL) was added a solution of diol 1-6 (5 mmol) in anhydrous

DMF (15 mL) at -20 oC. The resulting mixture was stirred at -20 oC for 0.5 h, and the

solution of 9 (2 mmol) in anhydrous DMF (10 mL) was added slowly. The reaction

mixture was then heated to 100 oC and stirred for 24 hrs. The reaction mixture was

cooled to rt, and quenched with aq. NH4Cl. The mixture was extracted with ether (3 x

40 mL). The combined organic layers were washed successively with 1N HCl, H2O

and brine, dried over Na2SO4, and concentrated. Purification of the residue by column

chromatography on silica gel afforded 10-15, respectively.

Data for 10: yellowish oil (yield: 82%). [α]D25 = +3.6 (c 3.1, CHCl3); 1H NMR (400

MHz, CDCl3) δ: 0.88 (3H, t, J = 7.0 Hz), 1.23 (16H,

m), 1.52 (2H, m), 3.37 (3H, s), 3.38 (3H, s), 3.39 (3H,

s), 3.53-3.78 (8H, m), 3.87 (1H, dd, J = 5.5, 10.0 Hz),

4.64 (5H, m), 4.75 (1H, d, J = 6.8 Hz) ppm; 13C

NMR (100 MHz, CDCl3) δ: 97.0, 96.8, 96.0, 79.7, 77.0, 73.7, 70.8, 69.0, 67.1, 55.5,

55.47, 55.43, 32.1, 32.0, 29.8, 29.7, 29.4, 25.5, 22.7, 14.1 ppm; IR (film): 3479, 2925,

2854, 1464, 1378, 1213, 1152, 1111, 1038, 918 cm-1; MS (ESI, m/z): 461 (M+ + Na);

HRMS (ESI) calcd for C22H46O8Na 461.3084, Found 461

OOMOM

7 OH

OMOMMOMO

10

( )

.3095.

Data for 11: yellowish oil (yield: 82%). [α]D25 = +9.6 (c 0.94, CHCl3); 1H NMR (400

S-3

MHz, CDCl3) δ: 0.88 (3H, t, J = 7.0 Hz), 1.26 (16H, m), 1.50 (2H, m), 3.37 (3H, s),

3.38 (3H, s), 3.39 (3H, s), 3.51-3.80 (8H, m), 3.88

(1H, dd, J = 5.5, 10.1 Hz), 4.63 (2H, s), 4.66 (2H, s),

4.72 (2H, dd, J = 6.8, 8.9 Hz) ppm; 13C NMR (100

MHz, CDCl3) δ: 96.8, 96.6, 96.2, 79.6, 77.3, 74.2,

70.7, 68.8, 66.8, 55.5, 55.27, 55.25, 31.9, 31.8, 29.6, 29.5, 29.4, 29.23, 29.28, 22.5,

14.0 ppm; IR (film): 3479, 2925, 2854, 2822, 1464, 1403, 1378, 1213, 1152, 1111,

1037, 918 cm-1; MS (ESI, m/z): 461 (M+ + Na); HRMS (ESI) calcd for C22H46O8Na

461.3084, F

OOMOM

7 OH

OMOMMOMO

11

ound 461.3095.

4.

55.2458.

Data for 12: yellowish oil (yield: 80%). [α]D25 = +1.5 (c 2.45, CHCl3); 1H NMR (500

MHz, CDCl3) δ: 0.88 (3H, t, J = 7.1 Hz), 1.26 (16H, m),

1.50 (2H, m), 3.38 (3H, s), 3.52 (2H, m), 3.70 (3H, m),

3.88 (1H, m), 3.93 (1H, m), 4.04 (1H, m), 4.28 (1H, m),

4.65 (1H, d, J = 6.8 Hz), 4.74 (1H, d, J = 6.8 Hz) ppm; 13C

NMR (100 MHz, CDCl3) δ: 95.9, 85.8, 76.3, 75.2, 73.6, 72.3, 71.3, 55.4, 31.9, 31.8,

31.5, 29.6, 29.58, 29.54, 29.51, 25.3, 22.6, 14.0 ppm; IR (film): 3418, 2925, 2854,

1464, 1216, 1104, 1038, 918cm-1; MS (ESI, m/z): 355(M+ + Na); HRMS (ESI) calcd

for C18H36O5Na 355.2455, Found 355.247

OOMOM

7 OH

12

O

Data for 13: yellowish oil (yield: 80%). [α]D25 = -8.8 (c 2.7, CHCl3); 1H NMR (500

MHz, CDCl3) δ: 0.88 (3H, t, J = 7.1 Hz), 1.26 (16H, m),

1.49 (2H, m), 3.38 (3H, s), 3.51 (2H, m), 3.92 (2H, m),

4.04 (1H, dd, J = 4.9, 10.0 Hz), 4.28 (1H, m), 4.65 (1H, d,

J = 6.7 Hz), 4.73 (1H, d, J = 6.7 Hz) ppm; 13C NMR (100

MHz, CDCl3) δ: 96.0, 85.8, 76.4, 75.1, 73.6, 72.4, 71.3, 55.4, 31.9, 31.8, 29.6, 29.54,

29.51, 29.2, 25.3, 22.6, 14.0 ppm; IR (film): 3419, 2925, 2854, 1466, 1104, 1038, 978,

918 cm-1; MS (ESI, m/z): 355(M+ + Na); HRMS (ESI) calcd for C18H36O5Na

355.2455, Found 3

OOMOM

7 OH

13

O

S-4

Data for 14: yellowish oil (yield: 79%). [α]D25 = +22.8 (c 2.2, CHCl3); 1H NMR (500

MHz, CDCl3) δ: 0.88 (3H, t, J = 7.0 Hz), 1.26 (15H, m),

1.37 (1H, m), 1.48 (2H, m), 2.71 (1OH, d, J = 2.5 Hz), 2.74

(1H, dd, J = 4.4, 11.2 Hz), 2.80 (1H, dd, J = 4.2, 11.3 Hz),

3.02 (1H, dd, J = 5.4, 11.3 Hz), 3.06 (1H, dd, J = 5.0, 11.2

Hz), 3.39 (3H, s), 3.48 (1H, dd, J = 3.6, 10.4 Hz), 3.58 (1H, dd, J = 6.0, 10.4 Hz),

3.67 (1H, m), 3.92 (1H, m), 4.30 (1H, m), 4.64 (1H, d, J = 6.7 Hz), 4.75 (1H, d, J =

6.9 Hz) ppm; 13C NMR (100 MHz, CDCl3) δ: 96.0, 86.2, 76.5, 76.2, 72.6, 55.4, 34.7,

31.8, 31.6, 29.6, 29.5, 29.3, 25.4, 22.6, 14.0 ppm; IR (film): 3437, 2925, 2854, 1465,

1152, 1103, 1036, 919 cm-1; MS (ESI, m/z): 371 (M+ + Na); Anal. calcd for C18H36O4

S (%): C, 62.03; H, 10.41. Found C, 62.23; H, 10.70.

OOMOM

7 OH

14

S

Data for 15: yellowish oil (yield: 79%). [α]D25 = -23.9 (c 2.95, CHCl3); 1H NMR

(500 MHz, CDCl3) δ: 0.88 (3H, t, J = 7.0 Hz), 1.26 (15H,

m), 1.37 (1H, m), 1.48 (2H, m), 2.69 (1OH, d, J = 2.5 Hz),

2.74 (1H, dd, J = 4.3, 11.1 Hz), 2.80 (1H, dd, J = 4.2, 11.3

Hz), 3.02 (1H, dd, J = 5.3, 11.3 Hz), 3.06 (1H, dd, J = 5.1,

11.2 Hz), 3.39 (3H, s), 3.46 (1H, dd, J = 6.5, 10.0 Hz), 3.58 (1H, dd, J = 3.7, 10.0Hz),

3.67 (1H, m), 3.92 (1H, m), 4.30 (1H, m), 4.68 (1H, d, J = 6.9 Hz), 4.73 (1H, d, J =

6.8 Hz) ppm; 13C NMR (100 MHz, CDCl3) δ: 96.2, 86.3, 77.0, 76.3, 72.9, 55.5, 34.8,

31.9, 31.8, 31.6, 29.6, 29.5, 29.3, 25.3, 22.6, 14.0 ppm; IR (film): 3438, 2925, 2854,

1466, 1216, 1153, 1104, 1037, 919 cm-1; MS (ESI, m/z): 371 (M+ + Na); Anal. calcd

for C18H36O4 S (%): C, 62.03; H, 10.41. Found C, 61.95; H, 10.61.

OOMOM

7 OH

15

S

General procedure for 16-21: A mixture of (R)-(-)-epichlorohydrin (10 mmol),

10-15 (5 mmol) and n-Bu4NHSO4 (0.5 mmol) in cyclohexane (40 mL) was treated

with aq. NaOH (50%, 10 mL) at rt for 10 hrs. The mixture was extracted with ethyl

ether (3 x 50 mL). The combined organic layers were washed with brine, dried over

Na2SO4, filtered and concentrated. The residue was purified by flash chromatography

on silica gel afforded 16-21, respectively.

S-5

Data for 16: yellowish oil (yield: 60%). [α]D25 = -15.5 (c 2.1, CHCl3); 1H NMR (500

MHz, CDCl3) δ: 0.88 (3H, t, J = 7.0 Hz), 1.26 (16H,

m), 1.55 (2H, m), 2.60 (1H, m), 2.77 (1H, dd, J = 4.2,

5.0 Hz), 3.15 (1H, m), 3.36 (6H, m), 3.37 (3H, s),

3.54-3.76 (10H, m), 3.84 (1H, m), 4.63 (5H, m), 4.77

(1H, d, J = 6.7 Hz) ppm; 13C NMR (100 MHz, CDCl3) δ: 96.7, 96.6, 95.9, 79.38,

79.32, 76.4, 73.8, 72.2, 72.0, 67.1, 66.8, 55.3, 55.2, 50.8

O O

OMOMMOMO

OMOM7 O

16

, 44.2, 32.0, 31.8, 29.6, 29.5,

918cm-1; MS (ESI, m/z): 517 +

5.3, 22.5, 13.9 -1

m/z): 517 (M+ + Na); HRMS (ES

,

50.6, 44.1, 31.9, 31.8, 29.6, 29.5, 29.2, 25.3, 22.6, 14.0

29.2, 25.3, 22.5, 13.9 ppm; IR (film): 2926, 2855, 1458, 1214, 1152, 1111, 1039,

(M + Na); HRMS (ESI) calcd for C25H50O9Na

: 60%). [α]D25 = -9.8 (c 2.0, CHCl3); 1H NMR (500

MHz, CDCl3) δ: 0.88 (3H, t, J = 7.0 Hz), 1.26

(16H, m), 1.52 (2H, m), 2.56 (1H, m), 2.77 (1H, dd,

J = 4.6, 4.6 Hz), 3.15 (1H, m), 3.36 (6H, s), 3.37

(3H, s), 3.54-3.76 (10H, m), 3.92 (1H, dd, J = 3.1,

11.6 Hz), 4.62 (2H, s), 4.63 (2H, s), 4.65 (1H, d, J = 6.7 Hz), 4.77 (1H, d, J = 6.7 Hz)

ppm; 13C NMR (100 MHz, CDCl3) δ: 96.7, 96.6, 96.0, 79.3, 79.2, 76.7, 74.0, 72.2,

67.0, 66.9, 55.3, 55.2, 55.1, 50.8, 44.3, 32.1, 31.8, 29.6, 29.5, 29.2, 2

517.3347, Found 517.3365.

Data for 17: yellowish oil (yield

O O

OMOMMOMO

OMOM7 O

17

ppm; IR (film): 2926, 2854, 1457, 1362, 1214, 1152, 1111, 1039, 918 cm ; MS (ESI,

I) calcd for C25H50O9Na 517.3347, Found 517.3361;

60.70; H, 10.19. Found C, 61.00; H, 10.51.

ld: 70%). [α]D25 = -4.85 (c 1.95, CHCl3); 1H NMR

(500 MHz, CDCl3) δ: 0.88 (3H, t, J = 7.1 Hz), 1.26

(16H, m), 1.51 (2H, m), 2.62 (1H, dd, J = 2.6, 5.1

Hz), 2.80 (1H, dd, J = 4.2, 4.2 Hz), 3.13 (1H, m),

3.37 (3H, s), 3.48 (3H, m), 3.67 (1H, m), 3.80 (3H,

m), 3.94 (3H, m), 4.03 (1H, m), 4.64 (1H, d, J = 6.8

Hz), 4.74 (1H, d, J = 6.8 Hz) ppm; 13C NMR (100 MHz, CDCl3) δ: 96.0, 83.58, 83.55,

76.2, 72.2, 71.4, 69.9, 55.4,

Anal. calcd for C25H50O9 (%): C

Data for 18: yellowish oil (yie

O

O OOMOM

7 O

18

S-6

ppm; IR (film): 2925, 2854, 1466, 1378, 1338, 1310, 1252, 1214, 1104, 1039, 916,

1 (M+ + Na); HRMS (ESI) calcd for C21H40O6Na

: 70%). [α] 25 = -8.8 (c 2.7, CHCl ); 1H NMR (500

MHz, CDCl ) δ: 0.88 (3H, t, J = 7.1 Hz), 1.26 (16H,

m), 1.49 (2H, m), 3.38 (3H, s), 3.51 (2H, m), 3.92

(2H, m), 4.04 (1H, dd, J = 4.9, 10.0 Hz), 4.28 (1H, m),

4.65 (1H, d, J = 6.7 Hz), 4.73 (1H, d, J = 6.7 Hz) ppm; 13C NMR (100 MHz, CDCl ) δ: 96.1, 83

852 cm-1; MS (ESI, m/z): 4

411.2717, Found 411.2735.

Data for 19: yellowish oil (yield

1

D 3

3

3 .6, 83.5, 76.3, 72.2, 71.4, 71.2, 70.2, 55.4,

un

i D 3

3

5.5, 50.8, 44.3, 33.0, 32.6, 31.9, 29.7, 29.6, 29.5, 29.3, 25.4, 22.7,

2

D 3

3

O

O OOMOM

7 O

19

50.6, 44.2, 31.9, 31.8, 29.6, 29.2, 25.3, 22.6, 14.0 ppm; IR (film): 3419, 2925, 2854, -1; MS (ESI, m/z): 355(M+ + Na); HRMS (ESI) calcd

d 355.2458.

eld: 65%). [α] 25 = +17.8 (c 1.30, CHCl ); 1H NMR

(500 MHz, CDCl ) δ: 0.88 (3H, t, J = 7.0 Hz), 1.26

(16H, m), 1.48 (2H, m), 2.63 (1H, dd, J = 2.7, 4.5 Hz),

2.80 (1H, dd, J = 4.5, 5.1 Hz), 2.83 (1H, dd, J = 3.3,

5.7 Hz), 2.87 (1H, dd, J = 3.3, 5.4 Hz), 3.00 (1H, dd,

J = 4.8, 7.8 Hz), 3.04 (1H, dd, J = 4.5, 7.8 Hz), 3.14 (1H, m), 3.38 (3H, s), 3.52 (3H,

m), 3.67 (1H, m), 3.81 (1H, dd, J = 3.3, 11.7 Hz), 4.11 (2H, m), 4.65 (1H, d, J = 6.6

Hz), 4.75 (1H, d, J = 6.6 Hz) ppm; 13C NMR (100 MHz, CDCl3) δ: 96.0, 84.6, 84.4,

76.2, 72.3, 70.0, 5

1466, 1104, 1038, 978, 918 cm

for C18H36O5Na 355.2455, Fo

Data for 20: yellowish oil (y

S

O OOMOM

7 O

20

14.1 ppm; IR (film): 2925, 2854, 1466, 1362, 1316, 1252, 1221, 1152, 1091, 1039,

7 (M+ + Na); HRMS (ESI) calcd for C21H40O5SNa

ld: 65%). [α] 25 = -55.0 (c 1.70, CHCl ); 1H NMR

(500 MHz, CDCl ) δ: 0.87 (3H, t, J = 7.0 Hz), 1.25

(16H, m), 1.47 (2H, m), 2.60 (1H, dd, J = 3.0, 5.4 Hz),

2.79 (1H, dd, J = 5.4, 5.4 Hz), 2.81 (1H, dd, J = 3.0,

917 cm-1; MS (ESI, m/z): 4

427.2488, Found 427.2485.

Data for 21: yellowish oil (yie

O OOMOM

7 O

21

S

( )

S-7

5.1 Hz), 2.85 (1H, dd, J = 3.0, 4.5 Hz), 3.00 (1H, dd, J = 4.5, 8.1 Hz), 3.04 (1H, dd, J

= 4.8, 8.7 Hz), 3.12 (1H, m), 3.38 (3H, s), 3.50 (3H, m), 3.66 (1H, m), 3.85 (1H, dd, J

= 2.7, 11.4 Hz), 4.11 (2H, m), 4.64 (1H, d, J = 6.6 Hz), 4.74 (1H, d, J = 6.6 Hz) ppm; 13C NMR (100 MHz, CDCl3) δ: 96.1, 84.6, 84.5, 76.3, 72.3, 70.3, 55.5, 50.8, 44.2,

-1 +

for 30 min at rt. The reaction

was separated, washed with brine,

2

:

32.9, 32.8, 32.0, 31.9, 29.7, 29.5, 29.3, 25.3, 22.7, 14.1 ppm; IR (film): 2925, 2854,

1466, 1362, 1316, 1252, 1221, 1154, 1091, 1039, 917 cm ; MS (ESI, m/z): 427 (M +

Na); HRMS (ESI) calcd for C21H40O5SNa 427.2488, Found 427.2485.

General procedure for 22-27: To a solution of trimethylsilyl acetylene (6 mmol) in

THF (6 mL) was added n-BuLi (1.6 M in hexanes, 6 mmol) at -78 oC. After 20 min,

BF3·Et2O (6 mmol) was added at -78 oC. After additional 30 min of stirring, a solution

of 16-21 (2 mmol) in THF (5 mL) was added slowly. After 2 hrs, the reaction mixture

was quenched by adding aq. NH4Cl solution. The mixture was extracted with ethyl

ether for three times. The combined organic layers were washed with brine, dried over

Na2SO4, concentrated. The crude product was used directly in the next step without

further purification. This crude product was dissolved in CH2Cl2 (10 mL) and treated

with MOMCl (10 mmol) and iPr2NEt (15 mmol) at 0 oC. After being stirred at rt for 8

hrs, the mixture was diluted with ethyl ether, washed with water and brine, dried over

Na2SO4, and concentrated. Purification on silica gel column chromatography to yield

a yellowish oil. To the solution of this newly prepared crude product in THF (10 mL)

was treated with TBAF (1.0 M in THF, 2.2 mmol)

mixture was diluted with ethyl ether (100 mL) and H2O (20 mL). The organic phase

dried over Na2SO4, and concentrated. Purification

-27, respectively.

88%). [α]D25 = -18.1 (c 2.95, CHCl3); 1H NMR

(500 MHz, CDCl3) δ: 0.88 (3H, t, J = 7.0 Hz),

1.26 (14H, m), 1.40 (2H, m), 1.55 (2H, m), 1.99

(1H, dd, J = 2.6, 2.6 Hz), 2.52 (2H, m), 3.36 (6H,

s), 3.37 (3H, s), 3.39 (3H, s), 3.55-3.76 (9H, m),

3.79 (1H, m), 3.85 (1H, m), 4.62 (5H, m), 4.74 (3H, m) ppm; 13C NMR (100 MHz,

by column chromatography gave 2

Data for 22: yellowish oil (yield

MOMO OMOM

O OOMOM

7OMOM

22

S-8

CDCl3) δ: 96.7, 96.0, 95.9, 80.7, 79.5, 79.2, 76.5, 74.3, 73.9, 72.0, 69.9, 67.0, 66.9,

55.4, 55.3, 55.2, 32.1, 31.8, 29.7, 29.5, 29.2, 25.4, 22.6, 21.9, 14.0 ppm; IR (film): -1

(M+ + Na); HRMS (ESI) calcd fo

H

8

.9, 14.0 ppm; IR (film):

1 -1

+ o

H

8

ppm; IR

106, 1040, 918 cm-1; MS (ESI, +

46O7Na 481.3159, Found 481.3158;

Found C, 65.65; H, 10.10.

-7.3 (c 2.05, CHCl3); 1H NMR (400

3274, 2928, 2858, 2824, 1467, 1214, 1153, 1110, 1039, 919cm ; MS (ESI, m/z): 587

r C29H56O10Na 587.3765, Found 587.3778; Anal.

, 9.99. Found C, 61.85; H, 10.25.

8%). [α]D25 = -9.9 (c 2.0, CHCl3); 1H NMR (500

MHz, CDCl3) δ: 0.88 (3H, t, J = 7.0 Hz), 1.26

(14H, m), 1.40 (2H, m), 1.55 (2H, m), 1.99 (1H,

dd, J = 2.6, 2.6 Hz), 2.51 (2H, m), 3.36 (6H, s),

3.37 (3H, s), 3.39 (3H, s), 3.55-3.76 (9H, m),

3.78 (1H, m), 3.85 (1H, m), 4.63 (5H, m), 4.74 (3H, m) ppm; 13C NMR (100 MHz,

CDCl3) δ: 96.7, 96.1, 96.0, 80.6, 79.4, 79.2, 76.5, 74.4, 74.0, 72.2, 69.9, 67.06, 67.00,

55.4, 55.3, 55.2, 32.1, 31.8, 29.7, 29.5, 29.2, 25.3, 22.6, 21

calcd for C29H56O10 (%): C, 61.68;

Data for 23: yellowish oil (yield:

OMOMMOMO

O OOMOM

7OMOM

23

3272, 2926, 2854, 2822, 1464, 1362, 1214, 1 10, 1038, 918cm ; MS (ESI, m/z): 587

r C29H56O10Na 587.3765, Found 587.3768; Anal.

, 9.99. Found C, 61.86; H, 10.33.

5%). [α]D25 = -2.9 (c 1.6, CHCl3); 1H NMR (400

MHz, CDCl3) δ: 0.88 (3H, t, J = 6.6 Hz), 1.27

(16H, m), 1.53 (2H, m), 2.02 (1H, dd, J = 2.7,

2.7 Hz), 2.51 (2H, m), 3.39 (3H, s), 3.41 (3H, s),

3.51 (2H, m), 3.66 (3H, m), 3.82 (3H, m), 3.97

(4H, m), 4.64 (1H, d, J = 6.6 Hz), 4.72 (2H, s), 4.74 (1H, d, J = 6.6 Hz) ppm; 13C

NMR (100 MHz, CDCl3) δ: 96.0, 95.9, 83.7, 83.5, 80.2, 76.2, 74.0, 72.1, 71.36, 71.34,

70.2, 70.1, 55.5, 55.3, 31.9, 31.8, 29.6, 29.5, 29.4, 29.2, 25.3, 22.5, 21.7, 14.0

(M + Na); HRMS (ESI) calcd f

calcd for C29H56O10 (%): C, 61.68;

Data for 24: yellowish oil (yield:

O

(film): 3311, 2926, 2855, 1466, 1377, 1308, 1216, 1

m/z): 481 (M + Na); HRMS (ESI) calcd for C25H

Anal. calcd for C25H46O7 (%): C, 65.47; H, 10.11.

Data for 25: yellowish oil (yield: 85%). [α]D25 =

MHz, CDCl3) δ: 0.89 (3H, t, J = 6.6 Hz), 1.27 (16H, m), 1.53 (2H, m), 2.02 (1H, dd, J

O OOMOM

7OMOM

24

S-9

= 2.7, 2.7 Hz), 2.52 (2H, m), 3.39 (3H, s), 3.41

(3H, s), 3.51 (2H, m), 3.66 (3H, m), 3.82 (3H,

m), 3.97 (4H, m), 4.66 (1H, d, J = 6.6 Hz), 4.73

(2H, s), 4.76 (1H, d, J = 6.6 Hz) ppm; 13C NMR

(100 MHz, CDCl3) δ: 96.0, 95.9, 83.7, 83.5,

80.3, 76.2, 74.2, 72.2, 71.4, 70.3, 70.1, 55.5, 55.4, 32.0, 31.8, 29.6, 29

O

O O

.5, 29.2, 25.4,

1039, 919cm-1; MS (ESI, m/z): 481 +

4 l

.2, 55.6, 55.5, 32.9, 32.8, 31.9, 29.7, 29.6,

1314, 1216, 1153, 1106, 1039, 918 -1 +

F

:

22.6, 21.78, 21.73, 14.0 ppm; IR (film): 3311, 2925, 2855, 1466, 1215, 1152, 1106,

(M + Na); HRMS (ESI) calcd for C25H46O7Na

cd for C25H46O7 (%): C, 65.47; H, 10.11. Found

8%). [α]D25 = -38.1 (c 3.30, CHCl3); 1H NMR

(500 MHz, CDCl3) δ: 0.87 (3H, t, J = 7.0 Hz),

1.25 (16H, m), 1.47 (2H, m), 2.00 (1H, dd, J =

2.7, 2.7 Hz), 2.48 (1H, m), 2.81 (1H, dd, J =

3.0, 4.8 Hz), 2.85 (1H, dd, J = 3.0, 4.8 Hz),

2.98 (1H, dd, J = 3.3, 4.5 Hz), 3.02 (1H, dd, J = 2.7, 4.5 Hz), 3.37 (3H, s), 3.38 (3H,

s), 3.47 (2H, m), 3.64 (3H, m), 3.83 (1H, m), 4.06 (2H, m), 4.63 (1H, d, J = 6.6 Hz),

4.71 (2H, s), 4.73 (1H, d, J = 6.6 Hz) ppm; 13C NMR (100 MHz, CDCl3) δ: 96.1, 96.0,

84.6, 84.4, 80.4, 76.3, 74.2, 72.3, 70.4, 70

81.3159, Found 481.3152; Anal. ca

C, 65.91; H, 10.16.

Data for 26: yellowish oil (yield: 8

29.3, 25.3, 22.6, 21.8, 14.1 ppm; IR (film): 3311, 2926, 2854, 2823, 2121, 1465, 1361,

cm ; MS (ESI, m/z): 497 (M + Na); HRMS (ESI)

ound 497.2927; Anal. calcd for C25H46O6S (%): C,

10.05.

88%). [α]D25 = +21.6 (c 4.15, CHCl3); 1H NMR

(500 MHz, CDCl3) δ: 0.87 (3H, t, J = 7.0 Hz),

1.25 (16H, m), 1.47 (2H, m), 2.00 (1H, dd, J =

2.7, 2.7 Hz), 2.48 (1H, m), 2.83 (2H, m), 2.98

(2H, m), 3.37 (3H, s), 3.38 (3H, s), 3.50 (2H, m),

3.64 (3H, m), 3.83 (1H, m), 4.07 (2H, m), 4.64 (1H, d, J = 6.6 Hz), 4.72 (H, m) ppm;

calcd for C25H46O6SNa 497.2907,

63.25; H, 9.77. Found C, 63.58; H,

Data for 27: yellowish oil (yield

O OOMOM

7OMOM

S

26

O OOMOM

7OMOM

S

27

OMOM7

OMOM

25

S-10

13C NMR (100 MHz, CDCl3) δ: 96.07, 96.01, 84.7, 84.4, 80.4, 76.2, 74.1, 72.2, 70.4,

70.1, 55.6, 32.9, 32.7, 31.9, 29.7, 29.6, 29.3, 25.4, 22.7, 21.8, 14.1 ppm; IR (film):

311, 2926, 2854, 2823, 2121, 1465, 1359, 1314, 1216, 1153, 1105, 1039, 918 cm-1;

MS (ESI, m/z): 497 (M+ + Na); HRMS (ESI) calcd for C25H46O6SNa 497.2907,

25 46 6

1.23, CHCl3); 1HNMR δ (500 MHz, CDCl3) : 1.26 (16H,

), 1.80 (2H, m), 3.40 (3H, s), 4.15 (1H, t, J = 5.7 Hz), 4.70 (2H, m) ppm; IR (film):

2918, 2850, 1737, 1475, 1464, 1264, 1205, 1164, 1118, 1083, 1028, 945, 900, 828,

14 28 4

10.84. Found: C, 64.87; H, 10.56.

3

Found 497.2920; Anal. calcd for C H O S (%): C, 63.25; H, 9.77. Found C, 63.58;

a stirred solution of alcohol 8 (2.00 g, 4.06 mmol) in CH2Cl2 (50

mL) was added Dess-Martin periodinane (4.14 g, 4.87 mmol) at

rt. The reaction was stirred for 1 h and then quenched by

saturated aq. Na2SO3. The mixture was extracted with ethyl

acetate (60 mL x 3). The combined organic layers were washed

with sat. NaHCO3 and brine, dried over Na2SO4, and concentrated. The crude product

was used in next step without further purification. To a stirred solution of the crude

aldehyde in t-BuOH (40 mL) at rt was added 2-methyl-2-butene (9.6 mL, 81.9 mmol).

The resulting solution was cooled down to 0 oC, and a solution of NaClO2 (2.22 g,

24.6 mmol) and KH2PO4 (3.35 g, 24.6 mmol) in H2O (10 mL) was added. The

resulting solution was stirred at this temperature for 10 min and then allowed to warm

to rt. The solution was stirred at rt for 10 h, and t-BuOH was then removed under

reduced pressure. The residue was extracted with ethyl acetate (3 x 50 mL). The

combined organic layers were washed with brine, dried over Na2SO4, concentrated.

Purification by flash column chromatography gave compound 47 (1.90 g, 81%) as a

white solid. [α]D25 = -39.3 (c

H, 10.01.

Compound 47. To

OHOMOM

7

47

O

m

727, 669 cm-1; MS (ESI, m/z): 283 (M+ + Na); Anal. calcd for C H O : C, 64.58; H,

S-11

Compound 49. To a stirred solution of diol 48 (100 mg, 0.33 mmol) and imidazole

(50 mg, 0.73 mmol) in CH2Cl2 (5 mL) was

added TBDPSCl (102mg, 0.37 mmol) in

CH2Cl2 (3 mL) slowly at 0 oC. After being

stirred for 2 h, i-Pr2NEt (0.58 mL, 3.33 mol)

and MOMCl (0.12 mL, 1.67 mmol) were added successively at 0 oC. The mixture was

stirred overnight at rt. The reaction was quenched with saturated NH4Cl, and extracted

with ether. The extracts were washed with brine, dried over Na2SO4, filtered, and

concentrated under reduced pressure. The crude product was purified by column

chromatography on silica gel to afford 49 (175 mg, 90%) as a colorless oil. [α]D25 =

-15.30 (c 1.70, CHCl3); 1H NMR (400 MHz, CDCl3) δ: 1.05 (9H, s), 1.29 (20H, m),

1.62 (4H, m), 2.30 (2H, t, J = 7.5 Hz), 3.34 (3H, s), 3.64 (6H, m), 4.64 (1H, d, J = 6.7

Hz), 4.77 (1H, d, J = 6.8 Hz), 7.39 (6H, m), 7.68 (4H, m) ppm

OMeOMOM

TBDPSO

O8

49

; 13C NMR (100 MHz,

3 6

2 , -1

M

CDCl3) δ: 174.2, 135.6, 133.5, 135.5, 129.5, 127.6, 96.1, 77.9, 66.4, 55.3, 51.3, 34.0,

.8, 25.3, 24.4, 19.1ppm; IR (film): 3070, 3049,

1142, 1113, 918, 823, 741, 702, 613, 505 cm ;

S (MALDI) calcd for C35H56SiO5Na 607.3789,

Found 607.3790.

Compound 50. To a solution of diisopropylamine ( 0.12 mL, 0.821 mmol) in THF (3

mL) was added n-BuLi (1.6 M in hexane, 0.34

mL, 0.548 mmol) at -78 oC. After being stirred

for 30 min, the ester 49 (0.16 g, 0.274 mmol)

in dry THF (5 mL) was added. After additional 30 min, O-THP-(S)-lactaldehyde

(0.087 g, 0.548 mmol) in THF (3 mL) was added. The reaction mixture was stirred for

2 h and then quenched with saturated aqueous NH4Cl. The aqueous layer was

extracted with diethyl ether three times and the combined extracts were washed with

brine, dried over Na2SO4, and concentrated under reduced pressure. 10% H2SO4 (1.0

mL) was added to the resultant residue and the mixture was stirred at rt for 24 h. The

reaction was quenched with saturated NaHCO3 and extracted with ether. The extracts

1.7, 19.6, 29.5, 29.4, 29.2, 29.1, 2

928, 2854, 1741, 1464, 1429, 1362

MS (ESI, m/z): 607 (M+ + Na); HR

OMOMTBDPSO

O8

50

O

S-12

were washed with brine, dried over Na2SO4, and concentrated under reduced pressure.

(CF3CO)2O (0.45 mL, 6.2 mmol) was added to the solution of the above crude

product in dry CH2Cl2 and Et3N (2.16 mL, 12.4 mmol) at 0 oC. The reaction was

stirred at room temperature for 6 h, and quenched with saturated NaHCO3. The

mixture was extracted with diethyl ether. The extracts were washed with brine, dried

over Na2SO4, and concentrated under reduced pressure. Purification by column

chromatography on silica gel afforded 50 (0.100 g, 60%) as a yellowish oil. [α]D25 =

-3.37 (c 2.70, CHCl3); 1HNMR (500 MHz, CDCl3) δ: 1.05 (9H, s), 1.31 (20H, m),

1.40 (3H, d, J = 6.8 Hz), 1.55 (4H, m), 2.26 (2H, t, J = 7.4 Hz), 3.35 (3H, s), 3.64 (3H,

m), 4.64 (1H, d, J = 6.7 Hz), 4.77 (1H, d, 6.8 Hz), 4.99 (1H, dq, J = 1.6, 6.8 Hz), 6.97

(1H, d, J = 1.4 Hz), 7.39 (6H, m), 7.68 (4H, m) ppm; 13C NMR (125 MHz, CDCl3) δ:

2

8

M+

631.3793, Found 631.3784.

z), 7.00 (1H, d, J = 1.5 Hz) ppm; 13C NMR (100 MHz,

29.0, 27.3, 25.4, 25.0, 19.1 ppm

173.8, 148.7, 135.6, 135.5, 134.3, 133.5, 129.6, 127.6, 96.1, 77.9, 76.7, 66.4, 55.4,

9.1, 27.4, 26.8, 25.3, 25.1, 19.2ppm; IR (film): 3071,

, 1318, 1196, 1112, 1036, 919, 824, 741, 703, 614, 505

+ Na); HRMS (MALDI) calcd for C37H56SiO5Na

Compound 51. To a stirred solution of 50 (190 mg, 0.312 mmol) in THF (3 mL) and

pyridine (0.8 mL) was added 40% HF (0.5 mL) at 0 oC.

The reaction mixture was stirred for 48 h at rt, and

finally quenched with saturated NH4Cl. The mixture

was extracted with ethyl acetate. The extracts were

washed with 1 N HCl and brine, dried over Na2SO4 and concentrated under reduced

pressure. The residue was purified by column chromatography afforded compound 51

(90 mg, 78%) as a white solid. [α]D25 = +45.8 (c 3.0, CHCl3); 1H NMR (400 MHz,

CDCl3) δ: 1.26 (20H, m), 1.40 (3H, d, J = 6.8 Hz), 1.53 (4H, m), 2.26 (2H, t, J = 7.6

Hz), 3.42 (3H, s), 3.55 (3H, m), 4.68 (1H, d, J = 6.9 Hz), 4.74 (1H, d, J = 6.9 Hz),

4.99 (1H, dq, J = 1.6, 6.8 H

31.7, 29.7, 29.6, 29.5, 29.3,

2928, 2855, 1759, 1464, 142

cm-1; MS (ESI, m/z): 631 (

OMOMHO

O8

51

O

CDCl3) δ: 173.3, 148.8, 134.1, 96.8, 81.8, 77.3, 65.5, 55.4, 31.5, 29.5, 29.4, 29.3, 29.1,

; IR (film): 3074, 2914, 2851, 1749, 1653, 1473, 1437,

S-13

1374, 1328, 1218, 1164, 1133, 1084, 1054, 1028, 974, 888, 869, 810, 765, 717,

637cm-1; MS (ESI, m/z): 393 (M+ + Na); HRMS (MALDI) calcd for C31H38O5Na

393.2611, Found 393.2623.

ompound 52. Using the same procedure as the preparation of 47, compound 52 was

afforded as a colorless oil. [α] 25 = +45.8 (c 3.0,

CHCl ); 1H NMR (400 MHz, CDCl ) δ: 1.26 (20H, m),

1.40 (3H, d, J = 6.8 Hz), 1.53 (4H, m), 2.26 (2H, t, J =

7.6 Hz), 3.42

C

D

3 3

(3H, s), 3.55 (3H, m), 4.68 (1H, d, J =

7 (0.26 g, 1.0 mmol), HOBt

Na2SO4, concentrated under r

D 3

s), 7.34 (5H, m) ppm; 13C NMR (125 MHz, CDCl3) δ:

32.9, 31.9, 29.5, 29.4, 29.3, 24.7,

1695, 1656, 1542, 1455, 1267, 1232, 1160, 1105, 1024, 921, 732 cm-1; MS (ESI, m/z):

OMOMHO

O8

52

O

O

6.9 Hz), 4.74 (1H, d, J = 6.9 Hz), 4.99 (1H, dq, J = 1.6, 6.8 Hz), 7.00 (1H, d, J = 1.5

Hz) ppm; 13C NMR (100 MHz, CDCl3) δ: 173.3, 148.8, 134.1, 96.8, 81.8, 77.3, 65.5,

55.4, 31.5, 29.5, 29.4, 29.3, 29.1, 29.0, 27.3, 25.4, 25.0, 19.1 ppm; IR (film): 3074,

2914, 2851, 1749, 1653, 1473, 1437, 1374, 1328, 1218, 1164, 1133, 1084, 1054, 1028,

974, 888, 869, 810, 765, 717, 637cm-1; MS (ESI, m/z): 393 (M+ + Na); HRMS

(MALDI) calcd for C31H38O5Na 393.2611, Found 393.2623.

General procedure for 53-58: To a mixture of acid 4

(0.27 g, 2.0 mmol) and the mono-N-Cbz protected diamine (1.2 mmol) in CH2Cl2 (20

2.0 mmol) at 0 oC. The reaction was stirred for 5 h at rt,

rated NH4Cl. The mixture was extracted with ethyl

ashed with saturated NaHCO3 and brine, dried over

educed pressure. The residue was purified by column

chromatography to give compound 53-58, respectively.

Data for 53: white solid (yield: 90%). [α] 25 = -35.8 (c 0.65, CHCl ); 1H NMR (500

MHz, CDCl3) δ: 0.88 (3H, t, J = 7.0 Hz), 1.25 ( 16H,

m), 1.74 (2H, m), 3.39 (7H, m), 4.02 (1H, t, J = 5.5

Hz), 4.63 (2H, m), 5.11 (2H, s), 5.22 (1H, s), 6.91 (1H,

mL) was added EDCI (0.38 g,

and then quenched with satu

acetate. The extracts were w

O

173.4, 169.0, 156.8, 136.4, 128.5, 128.1, 128.0, 96.4, 78.3, 66.7, 56.0, 41.3, 41.1, 39.3,

22.6, 15.6, 14.0 ppm; IR (KBr): 3325, 2920, 2851,

OMOM7 N

HNHCbz

53

S-14

437 (M+ +H); HRMS (MALDI) calcd for C24H40 N2O5Na 459.2829, Found 459.2834;

Anal. calcd for C24H40 N2O5: C, 66.03; H, 9.23; N, 6.42. Found: C, 66.42; H, 9.33; N

6.26.

Data for 54: white solid (yield: 90%). [α] 25 = -34.6 (c 2.30, CHCl ); 1H NMR (500

MHz, CDCl ) δ: 0.88 (3H, t, J = 7.1 Hz), 1.25

(16H, m), 1.67 (2H, m), 1.76 (2H, m), 3.21 (2H, m),

3.34 (2H, m), 3.39 (3H, s), 4.04 (1H, t, J = 5.5 Hz),

4.65 (2H, s), 5.09 (2H, s), 5.41 (1H, s), 6.

D 3

3

90 (1H, s),

0

9

(M+ + Na); HRMS (MALD

D 3

3 .24 (16H,

,

31.8, 29.4, 29.2, 25.6, 25.5,

D 3

3

1.64 (2H, m), 3.33 (3H, s), 3.52 (8H, m), 4.33 (1H, t, J =

7.34 (5H, m) ppm; 13C NMR (125 MHz, CDCl3) δ: 173.1, 156.7, 136.6, 128.4, 128.0,

, 37.6, 35.5, 32.9, 31.8, 30.1, 29.5, 29.4, 29.3, 29.2, 24.7,

3327, 2921, 2852, 1687, 1652, 1546, 1458, 1438, 1276,

, 916, 751, 707, 695, 620, 574 cm-1; MS (ESI, m/z): 473

I) calcd for C25H42 N2O5Na 473.2985, Found 473.2990.

Anal. calcd for C25H42 N2O5: C, 66.64; H, 9.39; N, 6.22. Found: C, 66.53; H, 9.41; N

5.99.

Data for 55: yellowish oil (yield: 85%). [α] 25 = -31.4 (c 1.25, CHCl ); 1H NMR

(500 MHz, CDCl ) δ: 0.88 (3H, t, J = 7.1 Hz), 1

127.9, 96.2, 78.0, 66.5, 56.

22.6, 14.0 ppm; IR (KBr):

1217, 1143, 1103, 1039, 98

m), 1.69 (2H, m), 2.96 (6H, m), 3.31-3.80 (7H, m), 4.37

(1H, m), 4.58 (2H, m), 5.12 (2H, s), 7.32 (5H, m) ppm; 13C NMR (125 MHz, CDCl3) δ: 172.2, 156.4, 136.6,

95.5, 73.7, 66.9, 55.7, 45.9, 45.2, 35.0, 34.2, 34.1, 32.1,

22.5, 14.0 ppm; IR (film): 3327, 2926, 2856, 1705, 1528,

1404, 1361, 1278, 1216, 1157, 1033, 921, 768, 697 cm-1; MS (ESI, m/z): 487 (M+ +

Na); HRMS (MALDI) calcd for C26H44 N2O5Na 487.3142, Found 487.3148.

Data for 56: white solid (yield: 90%). [α] 25 = -26.9 (c 0.92, CHCl ); 1H NMR (500

MHz, CDCl ) δ: 0.84 (3H, t, J = 7.0 Hz), 1.22 (16H, m),

128.3, 128.0, 127.8, 127.6

5.5 Hz), 4.59 (2H, s), 5.11 (2H, s), 7.30 (5H, m) ppm;

NHOMOM

O

NHCbz

54

7

O

OMOM7

N NCbz

55

ON NCbz

OMOM7

56

S-15

13C NMR (125 MHz, CDCl3) δ: 170.6, 154.9, 136.2, 128.3, 128.0, 127.8, 95.6, 75.3,

67.2, 55.7, 44.8, 43.7, 43.6, 41.7, 32.6, 31.7, 29.5, 29.4, 29.3, 29.2, 29.1, 25.4, 22.4,

13.9 ppm; IR (film): 3489, 2925, 2854, 1706, 1651, 1498, 1463, 1428, 1360, 1286,

1230, 1152, 1125, 1040, 984, 919, 764, 698, 604, 557 cm-1; MS (ESI, m/z): 485 (M+ +

Na); HRMS (MALDI) calcd for C26H42 N2O5Na 485.2985, Found 485.2980.

Data for 57: white solid (yield: 85%). [α] 25 = -59.09 (c 0.58, CHCl ); 1H NMR

(500 MHz, CDCl3) δ: 0.80 (3H, t, J = 7.1 Hz), 1.18

( 20H, m), 1.63 (4H, m), 1.95 (2H, m), 3.23 (3H, s),

3.36 (1H, m), 3.60 (1H

D 3

, m), 3.90 (1H, t, J = 5.3 Hz),

d

J 1

128

29. ,

D 3

3

(3H, s),

3.31 (1H, m), 3.62 (1H, m), 3.93 (1H, m), 4.56 (2H,

s), 4.89 (1H, d, J = 12.5 Hz), 5.06 (1H, d, J = 12.5

Hz), 5.18 (1H, d, J = 8.1 Hz), 6.65 (1H, d, J = 8.6 Hz), 7.23 (5H, m) ppm; 13C NMR

(125 MHz, CDCl3) δ: 173.2, 156.4, 136.4, 128.3, 127.8, 127.6, 96.1, 77.2, 66.4, 56.0,

55.5, 52.5, 32.9, 32.7, 32.4, 31.8, 29.5, 29.4, 29.3, 29.2, 24.8, 24.6, 22.5, 14.0 ppm; IR

(film): 3308, 2922, 2853, 1687, 1649, 1543, 1467, 1364, 1320, 1281, 1239, 1149,

1133, 1108, 1042, 918, 856, 775, 722, 695, 654, 574 cm-1; MS (ESI, m/z): 513 (M+ +

Na); HRMS (MALDI) calcd for C28H46 N2O5Na 513.3298, Found 513.3282.

4.39 (1H, d, J = 6.7 Hz), 4.47 (1H, d, J = 6.7 Hz), 4.91

, J = 12.4 Hz), 5.23 (1H, d, J = 8.5 Hz), 6.71 (1H, d, 3C NMR (125 MHz, CDCl3) δ: 172.8, 156.4, 136.4,

66.2, 55.7, 54.8, 52.9, 32.8, 32.7, 32.4, 31.7, 29.4,

13.9 ppm; IR (film): 3314, 2924, 2854, 1686, 1647,

1540, 1454, 1322, 1282, 1256, 1239, 1150, 1132, 1043, 919, 750, 696 cm-1; MS (ESI,

m/z): 513 (M+ + Na); HRMS (MALDI) calcd for C28H46 N2O5Na 513.3298, Found

513.3288.

Data for 58: white solid (yield: 70%). [α] 25 = -9.66 (c 0.58, CHCl ); 1H NMR (500

MHz, CDCl ) δ: 0.80 (3H, t, J = 7.1 Hz), 1.14

( 20H, m), 1.57 (4H, m), 1.96 (2H, m), 3.31

(1H, d, J = 12.4 Hz), 5.00 (1H,

= 8.6 Hz), 7.23 (5H, m) ppm;

.3, 127.8, 127.7, 95.8, 77.2,

3, 29.2, 29.1, 24.7, 24.5, 22.5

OMOM7

O

NH

NHCbz

57

O

OMOM7

NH

NHCbz

58

S-16

II. Copies of NMR spectra of new compounds

S-17

S-18

53

53

54

54

55

55

56

56

57

57

58

58

59

59

60

60

61

61

62

62

63

64

64

65

65

66

66

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70