M. Quintiliani et al. / Tetrahedron 69 (2013) 9111e9119
9117
4.1.1.21. 2,5-Anhydro-4,6-di-O-benzyl-1,3-dideoxy-1-phenoxy-
(cyclohexyloxy- -alaninyl) phosphinyl- -altritol and -allitol
(24c). Prepared as described above, from 22 (1.0 g, 2.13 mmol),
6%) (mixture of four diastereoisomers in
(CDCl3, 202 MHz):
500 MHz): 7.40e7.07 (m, 15H, OPh, OCH2Ph), 4.64e4.40 (m, 5H,
a
and
b
forms). 31P NMR
L
D
d
27.37, 27.35, 27.23, 27.19. 1H NMR (CDCl3,
L-
d
Ala-cHex ester (0.89 g, 4.27 mmol), anhydrous TEA (0.87 mL,
6.24 mmol), anhydrous pyridine (13 mL), aldrithiol-2 (1.66 g,
7.55 mmol) and PPh3 (1.96 g, 7.47 mmol) in anhydrous pyridine
(8.5 mL). The residue was purified by flash chromatography (pe-
troleum ether/ethyl acetate 1:1) to give a colourless oil (0.35 g, 26%)
H-2, CH2Ph), 4.29e4.03 (m, 4H, H-4, H-5, OCH2), 3.63e3.45 (m, 2H,
H-6), 2.66e1.72 (m, 4H, H-1, H-3), 1.53, 1.50 (2s, 6H, CH3-DiMeGly),
1.33e1.19 (m, 3H, CH2CH3). 13C NMR (CDCl3, 126 MHz):
d 14.10
(CH2CH3), 24.55, 25.62, 25.72 (CH3-DiMeGly), 34.98, 35.98 (C-1),
38.38, 38.45, 38.94, 39.04, 39.69, 39.80 (C-3), 55.96, 57.45, 57.53
(OCH2), 70.85, 71.01, 71.09 (C-4), 71.12, 71.48, 71.57, 73.41, 73.43,
73.46, 73.49 (CH2Ph), 73.77, 73.96, 74.00, 74.12, 74.44 (C-2), 80.77,
80.91, 80.94 (C-4), 82.61, 82.68, 83.67, 83.96 (C-5), 120.89, 120.92,
121.00, 121.03, 121.10, 121.74, 124.31, 124.41, 125.89, 126.51, 127.57,
127.59, 127.65, 128.38, 128.41, 129.23, 129.43, 129.49 (OPh, OCH2Ph),
138.00, 138.13 (‘ipso’ OCH2Ph), 156.66, 156.90 (‘ipso’ OPh), 174.34,
175.74 (C]O ester). MS (ESþ) m/z: 582 (MþH)þ, 604 (MþNa)þ.
HRMS (ESþ): C32H41NO7P [MþH]þ requires 582.2621, found
582.2627.
(mixture of four diastereoisomers in
(CDCl3, 202 MHz):
28.66, 28.30, 27.69, 27.66. 1H NMR (CDCl3,
500 MHz): 7.48e7.02 (m, 15H, OPh, OCH2Ph), 4.83e4.35 (2m, 6H,
a and b
forms). 31P NMR
d
d
CH-cHex, H-2, CH2Ph), 4.33e4.01 (3m, 3H, H-5, H-4, CH-Ala),
3.67e3.40 (m, 2H, H-6), 2.58e1.05 (m, 17H, H-1, H-3, (CH2)5-
cHex, CH3-Ala). 13C NMR (CDCl3, 126 MHz):
d 21.48, 21.61, 21.78
(CH3-Ala), 23.49, 23.53 (CH2-cHex), 25.29 (CH2-cHex), 31.27, 31.32,
31.39, 31.41 (CH2-cHex), 33.59, 34.15, 34.55, 34.62, 35.17, 35.57,
35.63 (C-1), 38.36, 38.43, 38.75, 38.84, 39.08, 39.14, 39.53, 39.62 (C-
3), 49.26, 49.40, 49.47, 49.51 (CH-Ala), 70.86, 70.89, 71.00 (C-6),
71.05, 71.13, 71.39, 71.49, 73.37, 73.39, 73.41, 73.45 (CH2Ph), 73.61
(CH-cHex), 73.87, 74.04, 74.28, 74.31 (C-2), 80.85, 81.04, 81.07, 81.10
(C-4), 82.69, 82.76, 83.63, 83.93 (C-5),120.78,120.81,120.94, 120.97,
121.10, 121.13, 124.42, 124.52, 127.58, 127.61, 127.65, 128.37, 128.41,
129.49, 129.52, 129.55, 129.59 (OPh, OCH2Ph), 138.01, 138.09, 138.14,
138.17, 138.20, 138.24 (‘ipso’ OCH2Ph), 150.59, 150.67, 150.74, 150.76,
150.81, 150.88 (‘ipso’ OPh), 173.08, 173.13, 173.43, 173.49, 173.53,
173.59 (C]O ester). MS (ESþ) m/z: 622 (MþH)þ. HRMS (ESþ):
4.1.1.24. 2,5-Anhydro-4,6-di-O-benzyl-1,3-dideoxy-1-phenoxy-
(methoxy-valininyl)phosphinyl-D-altritol and -allitol (24g). Prepared
as described above, from 22 (0.7940 g, 1.69 mmol),
L
-Val-Me ester
(0.5682 g, 3.39 mmol), anhydrous TEA (0.71 mL, 5.07 mmol),
anhydrous pyridine (10 mL), aldrithiol-2 (1.3 g, 5.91 mmol) and
PPh3 (1.55 g, 5.91 mmol) in anhydrous pyridine (7.0 mL). The
residue was purified by flash chromatography (petroleum ether/
ethyl acetate 1:1) to give a colourless oil (0.0840 g, 8%) (mixture
C
35H45NO7P [MþH]þ requires 622.2934, found 622.2943.
of four diastereoisomers in
202 MHz):
29.12, 28.42, 28.40. 1H NMR (CDCl3, 500 MHz):
7.49e7.07 (m, 15H, OPh, OCH2Ph), 4.71e4.45 (m, 5H, H-2,
a and b
forms). 31P NMR (CDCl3,
d
4.1.1.22. 2,5-Anhydro-4,6-di-O-benzyl-1,3-dideoxy-1-phenoxy-
d
(ethoxy-
L
-prolininyl)phosphinyl-
D
-altritol and -allitol (24e). Prepared
CH2Ph), 4.34e4.05 (m, 2H, H-4, H-5), 3.99e3.90 (m, 1H, CH-Val),
3.66e3.45 (m, 5H, H-6, OCH3), 2.55e1.83 (m, 5H, H-1, H-3,
CH(CH3)2), 1.01e0.72 (m, 6H, CH(CH3)2). 13C NMR (CDCl3,
as described above, from 22 (0.7278 g, 1.55 mmol),
L-Pro-Et ester
(0.6876 g, 3.84 mmol), anhydrous TEA (0.80 mL, 5.76 mmol), anhy-
drous pyridine (11.5 mL), aldrithiol-2 (1.48 g, 6.72 mmol) and PPh3
(1.76 g, 6.72 mmol) in anhydrous pyridine (8.0 mL). The residue was
purified by flash chromatography (petroleum ether/ethyl acetate
1:1) to give a colourless oil (0.2467 g, 27%) (mixture of four di-
126 MHz): d 17.27, 17.46, 17.52, 18.69, 18.86, 18.95 (CH3-Val), 32.18,
32.22, 32.42, 32.47 (CH(CH3)2), 33.39, 34.42, 34.47, 34.58, 35.50,
35.58 (C-1), 38.42, 38.50, 38.87, 38.97, 39.04 (C-3), 51.69, 51.84,
51.91 (OCH3), 58.39, 58.59, 58.86, 58.99 (CH-Val), 70.74, 70.82,
70.85, 71.08 (C-6), 71.47, 71.57, 73.40, 73.45, 73.51 (CH2Ph), 73.57,
74.01, 74.46, 74.50 (C-2), 80.79, 80.93, 81.09 (C-4), 82.70, 83.00,
83.72 (C-5), 120.79, 120.84, 120.88, 120.95, 120.99, 124.35, 124.50,
124.60, 127.59, 127.63, 127.65, 127.66, 127.73, 128.40, 128.43,
129.48, 129.53 (OPh, OCH2Ph), 137.90, 138.04, 138.10, 138.16 (‘ipso’
OCH2Ph), 150.57, 150.64, 150.79, 150.87 (‘ipso’ OPh), 173.21, 173.23,
173.65, 173.68 (C]O ester). MS (ESþ) m/z: 582 (MþH)þ, 604
(MþNa)þ; HRMS (ESþ): C32H41NO7P [MþH]þ requires 582.2621,
found 582.2632.
astereoisomers in
a
and
b
forms). 31P NMR (CDCl3, 202 MHz):
7.50e7.07
d
27.59, 27.41, 27.22, 27.20. 1H NMR (CDCl3, 500 MHz):
d
(m, 15H, OPh, OCH2Ph), 4.77e4.44 (m, 5H, H-2, CH2Ph), 4.44e4.33
(m,1H, CH-Pro), 4.33e4.00 (m, 4H, H-5, H-4, CH2CH3), 3.61e3.44 (m,
2H, H-6), 3.37e3.11 (m, 2H, CH2-Pro), 2.75e1.59 (m, 8H, H-1, H-3,
(CH2)2-Pro), 1.33e1.13 (m, 3H, CH2CH3). 13C NMR (CDCl3, 126 MHz):
d
14.13, 14.18 (CH2CH3), 24.83, 24.89, 24.98, 25.04, 25.21, 25.26 (CH2-
Pro), 30.71, 30.76, 30.83, 30.86, 30.89, 30.91, 31.26, 31.31, 31.40, 31.45
(CH2-Pro), 32.03, 32.98, 33.06, 33.47, 33.63, 33.83, 34.02, 34.49,
34.67, 34.85 (C-1), 37.97, 38.00, 38.11, 38.14, 38.83, 38.99, 39.03,
39.08, 39.48, 39.55 (C-3), 46.25, 46.29, 46.32, 46.47, 46.51, 46.56,
46.91, 46.95, 47.09 (CH2-Pro), 59.52, 59.56, 59.87, 59.92, 60.04, 60.08,
60.12, 60.19, 60.23, 60.29, 60.33 (CH-Pro), 60.83, 60.94, 60.96, 61.01
(CH2CH3), 70.95, 71.02 (C-6), 71.07, 71.10, 71.36, 71.38, 71.46, 73.41
(CH2Ph), 73.53, 73.77, 73.90, 73.94, 74.18 (C-2), 81.05, 81.08, 81.13,
81.25, 81.28, 81.35 (C-4), 82.44, 82.52, 82.63, 83.38, 83.44, 83.50,
83.60 (C-5), 120.27, 120.31, 120.53, 121.14, 124.85, 128.13, 128.70,
129.35, 129.71 (OPh, OCH2Ph), 138.17, 138.22, 138.26 (‘ipso’ OCH2Ph),
150.85, 150.88, 150.93 (‘ipso’ OPh), 173.44, 173.61, 173.70, 173.76 (C]
O ester). MS (ESþ) m/z: 594 (MþH)þ, 616 (MþNa)þ. HRMS (ESþ):
4.1.1.25. 2,5-Anhydro-1,3-dideoxy-1-phenoxy-(methoxy-
L-ala-
ninyl)phosphinyl- -altritol and -allitol (2a). A solution of 24a
D
(0.1244 mg, 0.22 mmol) in ethanol (20 mL) and 10% Pd/C (0.36 g)
was shaken under H2 at 4.5 bar for 8 h. The solution was filtered
through Celite and evaporated and the residue was subjected to
flash chromatography (DCM/MeOH 90:10) to give a colourless oil
(0.1904 g 19%) (mixture of four diastereoisomers in
31P NMR (MeOD, 202 MHz): 30.70, 30.66, 29.66, 29.60. 1H NMR
(MeOD, 500 MHz): 7.41e7.11 (m, 5H, Ph), 4.59e4.46 (m, 1H, H-2),
a and b forms).
d
d
4.31e4.21 (m, 1H, H-4), 4.08e3.97 (m, 1H, CH-Ala), 3.94e3.78 (m,
1H, H-5), 3.73e3.50 (m, 5H, H-6, OCH3), 2.56e1.81 (m, 4H, H-1, H-
C
33H41NO7P [MþH]þ requires 594.2621, found 594.2628.
3),1.39e1.16 (2m, 3H, CH3-Ala). 13C NMR (MeOD,126 MHz):
d 20.69,
4.1.1.23. 2,5-Anhydro-4,6-di-O-benzyl-1,3-dideoxy-1-phenoxy-
20.73, 20.99, 21.04, 21.17, 21.21 (CH3-Ala), 34.83, 35.79, 35.86, 35.91,
36.82, 36.94 (C-1), 42.52, 42.54, 42.59, 42.61, 43.26, 43.33 (C-3),
50.48, 50.59, 50.64 (CH-Ala), 52.64, 52.66, 52.70 (OCH3), 63.40,
63.46, 63.84 (C-6), 73.67, 74.06 (C-4), 74.61, 74.71, 74.74 (C-2), 87.27,
87.40, 88.82 (C-5), 122.06, 122.10, 122.22, 122.26, 125.89, 125.99,
130.69 (Ph), 151.74, 151.82, 151.88, 151.94, 152.01 (‘ipso’ Ph), 175.57,
175.60, 175.96, 176.00 (C]O ester). MS (ESþ) m/z: 374 (MþH)þ, 396
(MþNa)þ, 412 (MþK)þ; HRMS (ESþ): C16H25NO7P [MþH]þ requires
(ethoxy-dimethylglycininyl)
(24f). Prepared as described above, from 22 (0.8946 g, 1.91 mmol),
-DiMeGly-Et ester (0.6402 g, 3.82 mmol), anhydrous TEA (0.80 mL,
phosphinyl-
D
-altritol
and
-allitol
L
5.76 mmol), anhydrous pyridine (11.5 mL), aldrithiol-2 (1.47 g,
6.68 mmol) and PPh3 (1.75 g, 6.68 mmol) in anhydrous pyridine
(7.6 mL). The residue was purified by flash chromatography (pe-
troleum ether/ethyl acetate 1:1) to give a colourless oil (0.0677 g,