1704
I. Cumpstey et al.
LETTER
(17) The stereochemistry of the bromides (7 and 8) and
pseudodisaccharides (9, 10 and 12) was assigned using the
J1,2 and J1,5a coupling constants from the 1H NMR spectra, in
comparison with reported data.28 In a-xylo compounds, J1,5a
was in the range 4.4–5.8 Hz; J1,2 was in the range 3.5–4.4 Hz.
In b-xylo compounds, H-5a appeared as a singlet; J1,2 was
between 7.1–9.2 Hz (not determined for 9). These J1,2 values
are consistent with the 2H3 half-chair conformation expected
for both diastereomers. For the nosylated
pseudodisaccharide 9, many of the NMR resonances were
broad, possibly resulting from steric crowding and
conformational change, which weakens an argument for
configurational assignment of this compound based on
coupling constants, but its configuration was confirmed by
its deprotection (PhSH, K2CO3, DMF, 83%) to give 12.
(18) Kok, S. H. L.; Shing, T. K. M. Tetrahedron Lett. 2000, 41,
6865.
(25) Representative Data:
2,3,4,6-Tetra-O-benzyl-5a-carba-b-D-xylo-hex-5(5a)-
enopyranosyl Trichloroacetimidate (6): colourless oil;
[a]D21 –53.9 (c = 1.0, CHCl3). IR (film): 1662 (C=N) cm–1.
1H NMR (500 MHz, CDCl3): d = 3.91–4.00 (m, 3 H, H-2, H-
3, H-6), 4.23 (d, J6,6¢ = 12.2 Hz, 1 H, H-6¢), 4.37 (d, J3,4 = 7.5
Hz, 1 H, H-4), 4.49, 4.53 (2 × d, J = 11.9 Hz, 2 H, PhCH2),
4.73 (d, J = 10.9 Hz, 1 H, PhCHH¢), 4.82, 5.00 (2 × d, J =
11.0 Hz, 2 H, PhCH2), 4.85–4.91 (m, 3 H, PhCH2, PhCHH¢),
5.75 (d, J1,2 = 7.1 Hz, 1 H, H-1), 5.82 (s, 1 H, H-5a), 7.26–
7.35 (m, 20 H, ArH), 8.48 (s, 1 H, NH). 13C NMR (125 MHz,
CDCl3): d = 69.7, 72.5, 74.8, 75.3, 75.5, 79.5, 79.6, 81.7,
83.9, 91.4, 122.1, 127.6, 127.7, 127.7, 127.8, 127.9, 127.9,
128.3, 128.4, 128.4, 137.9, 138.2, 138.3, 138.4, 138.6,
162.1. HRMS–ESI: m/z [M + Na]+ calcd for
C37H36O5NCl3Na: 702.1551; found: 702.1521.
2,3,4,6-Tetra-O-benzyl-5a-carba-b-D-xylo-hex-5(5a)-
enopyranosyl Bromide (8): colourless oil; [a]D23 –73.3 (c =
1.0, CHCl3). 1H NMR (500 MHz, CDCl3): d = 3.75 (dd,
J2,3 = 10.2 Hz, J3,4 = 8.0 Hz, 1 H, H-3), 3.94–3.98 (m, 2 H,
(19) Kinzy, W.; Schmidt, R. R. Adv. Carbohydr. Chem. Biochem.
1994, 50, 21.
(20) Palladium-Catalysed Coupling: b-Imidate 6 (94 mg, 0.14
mmol), trimethylolpropane phosphite (TMPP; 5 mg, 0.028
mmol) and Pd2(dba)3 (7 mg, 0.014 mmol) were placed in a
round-bottomed flask with a magnetic stirrer bar. The flask
was evacuated, then placed under Ar. Amine 3 (194 mg, 0.42
mmol) was suspended in MeCN (it was partially soluble),
the solvent was degassed and the mixture was placed under
Ar. The amine suspension was transferred to the reaction
vessel by syringe. Et3N (0.09 mL, 0.63 mmol) was added,
and the mixture colour changed from a purple/brown
suspension to a pale yellow solution. The reaction mixture
was stirred at r.t. under Ar. After 15 h, TLC (pentane–
EtOAc, 3:1) showed complete consumption of the imidate
(Rf 0.8), amine remaining (Rf 0), and the formation of a major
product (Rf 0.1). The mixture was concentrated in vacuo and
the residue was purified by flash column chromatography to
give the b-linked pseudodisaccharide 12 (115 mg, 85%).
(21) (a) Ogawa, S.; Toyokuni, T.; Suami, T. Chem. Lett. 1981,
10, 947. (b) Toyokuni, T.; Ogawa, S.; Suami, T. Bull. Chem.
Soc. Jpn. 1983, 2999. (c) Sakairi, N.; Kuzuhara, H.
Tetrahedron Lett. 1982, 23, 5327.
(22) Appel, R. Angew. Chem., Int. Ed. Engl. 1975, 14, 801.
(23) Coupling with C-1 Bromides: b-Bromide 8 (42 mg, 0.070
mmol) and amine 3 (80 mg, 0.17 mmol) were dissolved in
MeCN (1 mL) under Ar. N,N¢-Diisopropylethylamine (35
mL, 0.20 mmol) was added and the reaction mixture was
heated to 50 °C. After 24 h, TLC (pentane–EtOAc, 2:1)
indicated the formation of a major product (Rf 0.3). The
mixture was concentrated in vacuo, and the residue was
purified by flash column chromatography to give the a-
linked pseudodisaccharide 10 (46 mg, 67%).
H-2, H-6), 4.23 (d, J6,6¢ = 12.7 Hz, 1 H, H-6¢), 4.37 (d, J3,4
8.0 Hz, 1 H, H-4), 4.51, 4.54 (2 × d, J = 11.8 Hz, 2 H,
PhCH2), 4.73 (d, J = 10.8 Hz, 1 H, PhCHH¢), 4.76 (d, J1,2
=
=
7.9 Hz, 1 H, H-1), 4.82 (d, J = 11.0 Hz, 1 H, PhCHH¢), 4.86
(d, J = 10.9 Hz, 1 H, PhCHH¢), 4.93–4.98 (m, 3 H, PhCH2,
PhCHH¢), 5.91 (s, 1 H, H-5a), 7.25–7.41 (m, 20 H, ArH). 13
C
NMR (125 MHz, CDCl3): d = 51.7, 69.5, 72.6, 75.4, 75.7,
76.2, 79.8, 85.0, 85.5, 125.9, 127.9, 127.9, 127.9, 127.9,
128.0, 128.0, 128.3, 128.5, 128.5, 128.6, 137.7, 138.1,
138.1, 138.3, 138.4. HRMS–ESI: m/z [M + Na]+ calcd for
C35H35O4BrNa: 621.1611; found: 621.1610.
Methyl 6-[2,3,4,6-Tetra-O-benzyl-5a-carba-b-D-xylo-
hex-5(5a)-enopyranosylamino]-2,3,4-tri-O-benzyl-6-
deoxy-a-D-glucopyranoside (12): white solid; [a]D25 –21.2
(c = 1.0, CHCl3). 1H NMR (500 MHz, CDCl3): d = 2.60 (dd,
J5,6 = 6.4 Hz, J6,6¢ = 11.7 Hz, 1 H, H-6I), 3.01 (dd, J5,6¢ = 2.5
Hz, J6,6¢ = 11.7 Hz, 1 H, H-6¢I), 3.29 (s, 3 H, OMe), 3.36 (m,
1 H, H-1II), 3.46–3.51 (m, 2 H, H-2I, H-4I), 3.59 (at J = 9.2
Hz, 1 H, H-2II), 3.73 (m, 1 H, H-5I), 3.87–3.90 (m, 2 H, H-
3II, H-6II), 3.99 (at, J = 9.3 Hz, 1 H, H-3I), 4.26 (d, J6,6¢ = 12.0
Hz, 1 H, H-6¢II), 4.33 (d, J3,4 = 7.1 Hz, 1 H, H-4II), 4.41–5.00
(m, 15 H, 7 × PhCH2, H-1I), 5.67 (s, 1 H, H-5aII), 7.23–7.40
(m, 35 H, ArH). 13C NMR (125 MHz, CDCl3): d = 47.1,
55.3, 60.0, 70.3, 70.5, 72.3, 73.5, 74.7, 75.1, 75.2, 75.4, 75.9,
79.3, 80.2, 80.4, 82.0, 82.1, 85.2, 98.1, 127.2, 127.7, 127.8,
127.9, 127.9, 128.0, 128.1, 128.3, 128.5, 128.5, 128.5,
128.6, 135.6, 138.4, 138.4, 138.6. HRMS–ESI: m/z [M +
Na]+ calcd for C63H67NO9Na: 1004.4708; found: 1004.4626.
(26) Acarbose is used as a diabetes type 2 drug; Validamycin A
is used as an agrochemical fungicide against rice sheath
blight.
(24) The b-bromide 8 does react at a higher rate with the amine 3
(reacting slowly at r.t.) than does its a epimer 7 (which
needed heating for any reaction to take place).
(27) Errey, J. C.; Lee, S. S.; Gibson, R. P.; Martinez Fleites, C.;
Barry, C. S.; Jung, P. M. J.; O’Sullivan, A. C.; Davis, B. G.;
Davies, G. J. Angew. Chem. Int. Ed. 2010, 49, 1234.
(28) Hayashida, M.; Sakairi, N.; Kuzuhara, H. Carbohydr. Res.
1986, 154, 115.
Synlett 2011, No. 12, 1701–1704 © Thieme Stuttgart · New York