Novel Carbasugar Amino Acid Dipeptide Isostere
53
1
0.194 mmol) in quantitative yield. H NMR (400 MHz, MeOD): d 7.33–7.26
(m, 15H, CHarom), 4.63 (d, 1H, J ¼12.0 Hz, CH Bn), 4.57 (d, 1H, J ¼ 12.0 Hz,
CH Bn), 4.53 (d, 1H, J ¼ 11.9 Hz, CH Bn), 4.43 (d, 1H, J ¼ 11.9 Hz, CH Bn),
4.40 (d, 1H, J ¼ 11.8 Hz, CH Bn), 4.27 (d, 1H, J ¼ 11.8 Hz, CH Bn),
3.85–3.82 (ddd, 1H, J ¼ 1.3 Hz, J ¼ 2.9 Hz, J2,1 ¼ 4.3 Hz, H-2), 3.76 (dd, 1H,
J ¼ 3.1 Hz, J1,2 ¼ 4.3 Hz, H-1), 3.76 (m, 1H, H-3), 3.70 (dd, 1H, J ¼ 3.6 Hz,
J ¼ 7.3 Hz, H-6), 2.51 (m, 1H, H-4), 2.42 (dd, 1H, JCHH,4 ¼ 7.2 Hz,
JCHH,CHH ¼ 16.0 Hz, CHH), 2.29 (1H, dd, JCHH,4 ¼ 6.6 Hz, JCHH,CHH ¼ 16.0
Hz, CHH), 1.99-1.92 (dddd, 1H, J ¼ 1.2 Hz, J ¼ 3.1 Hz, J ¼ 4.1 Hz,
J5a,5b ¼ 14.8 Hz, H-5a), 1.86–1.77 (dd, 1H, J ¼ 3.8 Hz, J5b,5a ¼ 14.8 Hz,
H-5b). MS (ESI): m/z ¼ 476.2 [M þ H]þ.
(1S,2R,3S,4R,6S)-N-(9-Fluorenylmethoxycarbonyl)-
6-amino-1,2,3-tris-benzyloxy-4-carboxymethyl-
cyclohexane (15)
To a suspension of amino acid 14 (0.194 mmol) in dioxane (0.5 mL) and sat.
aq. NaHCO3 (2.0 mL) was added Fmoc-OSu (85 mg, 0.252 mmol, 1.3 equiv.).
After stirring for 17 h, TLC analysis (MeOH/DCM 1:19) revealed complete con-
sumption of starting material into a higher running spot. Water and dioxane
were added to the suspension and the resulting solution was acidified with
1.0 M aq. HCl to pH 5. The mixture was diluted with EtOAc, the organic
layer was separated, and the aqueous layer was extracted twice with EtOAc.
All organic layers were combined, dried (MgSO4), filtered, and concentrated.
After purification by silica gel column chromatography (EtOAc/PE
1:1 þ 1.0% HOAc), carbamate 15 was obtained (0.124 g, 0.178 mmol, 92%).
[a]2D0 þ 25.5 (c 1.0, CHCl3). H NMR (600 MHz, C6D6): d 7.56–7.54 (m, 4H,
1
CHarom Fmoc), 7.37–7.30 (m, 4H, CHarom Fmoc), 7.22–7.06 (m, 15H, CHarom
Bn), 6.79 (bs, 1H, NH), 4.64 (d, 1H, J ¼ 11.8 Hz, CH Bn), 4.60 (d, 1H,
J ¼ 11.8 Hz, CH Bn), 4.58 (m, 1H, H-6), 4.54 (d, 1H, J ¼ 11.8 Hz, CH Bn),
4.50 (dd, 1H, J ¼ 10.6 Hz, J ¼ 7.3 Hz, CHH, CH2Fmoc), 4.27 (dd, 1H,
J ¼ 10.6 Hz, J ¼ 7.3 Hz, CHH CH2Fmoc), 4.22 (m, 1H, CH Bn), 4.16 (m, 3H,
CH2 Bn, CH Fmoc), 3.84 (m, 1H, H-2), 3.74 (m, 1H, H-3), 3.71 (m, 1H, H-1),
2.69 (m, 1H, H-4), 2.40 (m, 1H, CHH CH2CO2H), 2.11 (m, 1H, CHH
CH2CO2H), 1.92 (m, 1H, H-5a), 1.60 (m, 1H, H-5b). 13C-NMR (100 MHz,
CDCl3): d 177.6 (C55O CO2H), 156.5 (C55O Fmoc), 144.1, 141.2 (2 ꢀ Cq
Fmoc), 138.3, 137.9, 137.8 (3 ꢀ Cq Bn), 129.0, 128.5, 128.4, 128.4, 127.9,
127.8, 127.6, 127.5, 127.0 (CHarom Bn), 125.3, 119.8 (CHarom Fmoc), 77.3 77.0,
76.7 (C-1, C-2, C-3), 73.8, 72.6, 70.4 (3 ꢀ CH2 Bn), 66.8 (CH2 Fmoc), 47.8
(C-6), 47.2 (CH Fmoc), 30.7 (CH2CO2), 29.7 (C-4), 28.2 (C-5). IR (thin film):
3032, 2924, 2870, 2363, 2341, 1705, 1514, 1452, 1248, 1055, 739, 698 cm21
.
MS (ESI): m/z ¼ 698.5 [M þ H]þ, 1395.6 [2M þ H]þ. HRMS (ESI): calcd for
[C44H43NO7 þ NH4]þ 715.3383. Found 715.3370.