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Synlett 2008(19): 2985-2988  
DOI: 10.1055/s-0028-1083629
LETTER
© Georg Thieme Verlag Stuttgart ˙ New York

A Concise Synthesis of (+)-Polyoxamic Acid and (+)-5-O-Carbamoyl Polyoxamic Acid

In Su Kim, Qing Ri Li, Guang Ri Dong, Seol Hee Woo, Hyun-ju Park, Ok Pyo Zee, Young Hoon Jung*
College of Pharmacy, Sungkyunkwan University, Suwon 440-746, Korea
Fax: +82(31)2907773; e-Mail: yhjung@skku.ac.kr;
Further Information

Publication History

Received 12 August 2008
Publication Date:
12 November 2008 (online)

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Abstract

We report the concise synthesis of (+)-polyoxamic acid and (+)-5-O-carbamoyl polyoxamic acid from l-xylose in seven or six steps, respectively. The key steps include a diastereoselective amination of syn-1,2-polybenzyl ethers using chlorosulfonyl isocyanate (CSI) and the one-pot introduction of carbamates into the allylic benzyl ether and primary hydroxyl moieties.

Key words

polyoxamic acid - polyoxin - chlorosulfonyl isocyanate - amination - sugar

8

Characterization data for 5: [α]D ²5 -25.8 (c 1.0, CHCl3). IR (CH2Cl2): 3450, 3011, 2866, 1513, 1494, 1055 cm-¹. cis-Isomer: ¹H NMR (500 MHz, CDCl3): δ = 2.22-2.24 (br, 1 H), 3.45 (dd, J = 12.5, 3.5 Hz, 1 H), 3.68 (dd, J = 11.5, 3.5 Hz, 1 H), 3.78-3.83 (m, 2 H), 4.19 (d, J = 12.0 Hz, 1 H), 4.57-4.82 (m, 6 H), 5.88 (dd, J = 12.0, 10.0 Hz, 1 H), 6.78 (d, J = 12.0 Hz, 1 H), 7.07-7.40 (m, 20 H). ¹³C NMR (125 MHz, CDCl3): δ = 61.63, 70.40, 73.15, 73.21, 75.38, 80.27, 82.47, 126.85, 127.54, 127.88, 127.98, 128.13, 128.31, 128.55, 128.56, 128.61, 128.77, 129.12, 133.99, 136.66, 137.82, 138.48. trans-Isomer: ¹H NMR (500 MHz, CDCl3): δ = 2.22-2.24 (br, 1 H), 3.61 (dd, J = 11.5, 3.5 Hz, 1 H), 3.72-3.77 (m, 3 H), 4.30 (dd, J = 7.5, 4.0 Hz, 1 H), 4.45 (d, J = 11.5 Hz, 1 H), 4.60-4.82 (m, 5 H), 6.22 (d, J = 16.0, 7.5 Hz, 1 H), 6.59 (d, J = 16.0 Hz, 1 H), 7.07-7.40 (m, 20 H). ¹³C NMR (125 MHz, CDCl3): δ = 61.78, 71.03, 72.96, 75.15, 79.70, 80.49, 82.22, 126.84, 127.53, 127.87, 127.94, 127.97, 128.04, 128.17, 128.42, 128.56, 128.60, 128.65, 128.77, 128.83, 129.94, 133.82, 133.99, 138.68. HRMS (FAB): m/z [M + H+] calcd for C33H35O4: 495.2535; found: 495.2525.

9

Characterization data for 6: [α]D ²5 -33.8 (c 0.5, CHCl3). IR (CH2Cl2): 2864, 2360, 1541, 1496, 1454, 1395, 1352, 1027, 1089, 1028, 914, 806, 736 cm-¹. cis-Isomer: ¹H NMR (500 MHz, CDCl3): δ = 3.23 (d, J = 9.0 Hz, 1 H), 3.57-3.59 (m, 1 H), 3.92 (br s, 2 H), 4.12 (d, J = 12.0 Hz, 1 H), 4.25 (d, J = 12.0 Hz, 1 H), 4.41-4.88 (m, 7 H), 5.89 (t, J = 10.0 Hz, 1 H), 6.77 (d, J = 10.0 Hz, 1 H), 7.01-7.39 (m, 25 H). ¹³C NMR (125 MHz, CDCl3): δ = 69.59, 70.16, 73.17, 73.47, 75.74, 78.90, 82.51, 126.85, 127.43, 127.72, 127.75, 127.89, 128.03, 128.31, 128.43, 128.52, 128.59, 128.62, 128.78, 129.22, 130.48, 133.55, 136.78, 138.10, 138.95. trans-Isomer: ¹H NMR (500 MHz, CDCl3): δ = 3.60-3.66 (m, 2 H), 3.64 (dd, J = 10.0, 4.5 Hz, 1 H), 3.76 (dd, J = 6.0, 4.5 Hz, 1 H), 4.29-4.39 (m, 1 H), 4.41-4.88 (m, 8 H), 6.16 (dd, J = 12.5, 7.5 Hz, 1 H), 6.52 (d, J = 12.5 Hz, 1 H), 7.01-7.39 (m, 25 H). ¹³C NMR (125 MHz, CDCl3): δ = 70.36, 70.95, 73.34, 73.56, 75.43, 80.14, 81.21, 81.97, 116.53, 127.30, 127.56, 127.76, 127.84, 127.99, 128.20, 128.42, 128.50, 128.55, 128.61, 128.72, 128.96, 130.47, 133.71, 136.84, 138.51, 139.12. HRMS (FAB): m/z [M + H+] calcd for C40H41O4: 585.3005; found: 585.3010.

10

Characterization data for 7: [α]D ²5 +25.8 (c 1.0, CHCl3). IR (CH2Cl2): 3030, 2867, 1719, 1491, 1454, 1214, 1090, 1027, 967, 737, 697 cm-¹. cis-Isomer: ¹H NMR (500 MHz, CDCl3): δ = 3.53-3.73 (m, 3 H), 3.85 (dd, J = 7.0, 2.0 Hz, 1 H), 4.35 (d, J = 12.0 Hz, 1 H), 4.48-6.63 (m, 4 H), 4.82 (d, J = 11.0 Hz, 1 H), 5.06 (br m, 3 H), 5.37 (d, J = 8.0 Hz, 1 H), 5.72 (dd, J = 12.0, 9.5 Hz, 1 H), 6.52 (d, J = 12.0 Hz, 1 H), 7.18-7.44 (m, 25 H). ¹³C NMR (125 MHz, CDCl3): δ = 49.83, 66.97, 69.39, 73.27, 73.59, 75.64, 80.25, 82.21, 127.38, 127.74, 127.83, 128.01, 128.08, 128.29, 128.51, 128.54, 128.59, 128.72, 128.97, 130.85, 131.02, 136.61, 138.48, 138.71, 155.86. trans-Isomer: ¹H NMR (500 MHz, CDCl3): δ = 3.68 (br, 1 H), 3.78 (br m, 2 H), 3.86 (br, 1 H), 4.54-4.66 (m, 5 H), 4.72 (d, J = 12.0 Hz, 1 H), 4.79 (d, J = 12.0 Hz, 1 H), 5.11 (s, 2 H), 5.44 (br, 1 H), 6.15 (dd, J = 16.0, 5.5 Hz, 1 H), 6.50 (d, J = 16.0 Hz, 1 H), 7.25-7.36 (m, 25 H). ¹³C NMR (125 MHz, CDCl3 ): δ = 53.79, 67.07, 69.79, 73.40, 73.75, 75.22, 80.24, 81.30, 126.73, 127.78, 127.83, 127.90, 128.00, 128.04, 128.11, 128.36, 128.43, 128.58, 128.61, 128.63, 128.71, 128.75, 131.00, 136.75, 136.95, 138.38, 138.75, 156.04. HRMS (FAB): m/z [M + H+] calcd for C41H42NO5: 628.3063; found: 628.3062.

11

Characterization data for 8: [α]D ²5 -7.5 (c 1.0, CHCl3). IR (CH2Cl2): 3060, 1717, 1541, 1508, 1456, 1091, 697 cm-¹. ¹H NMR (300 MHz, CDCl3): δ = 3.58-3.66 (m, 3 H), 3.72-3.78 (m, 1 H), 4.34 (br, 1 H), 4.44 (d, J = 11.7 Hz, 1 H), 4.46 (s, 2 H), 4.59 (d, J = 11.7 Hz, 1 H), 4.73 (s, 2 H), 5.12 (d, J = 15.6 Hz, 1 H), 5.16 (d, J = 15.6 Hz, 1 H), 5.62 (br d, J = 5.7 Hz, 1 H), 7.27-7.41 (m, 20 H), 9.73 (s, 1 H). ¹³C NMR (125 MHz, CDCl3): δ = 60.19, 67.41, 69.67, 73.05, 73.71, 74.23, 76.69, 78.59, 128.01, 128.14, 128.36, 128.52, 128.59, 128.67, 128.72, 128.75, 128.81, 136.29, 137.62, 137.70, 138.10, 156.38, 197.629. HRMS (FAB): m/z [M + H+] calcd for C34H36NO6: 554.2543; found: 554.2543.

13

Characterization data for 9: [α]D ²5 -12.5 (c 0.5, CHCl3). IR (CH2Cl2): 3421, 3031, 2870, 2360, 1716, 1507, 1455, 1397, 1214, 1092, 737, 698 cm-¹. ¹H NMR (300 MHz, CDCl3): δ = 3.60-3.86 (m, 4 H), 4.40-4.78 (m, 7 H), 5.14 (s, 2 H), 5.61 (br, 1 H), 7.30-7.36 (m, 20 H). ¹³C NMR (125 MHz, CDCl3): δ = 54.21, 67.49, 69.18, 73.32, 73.70, 75.13, 76.68, 78.31, 78.69, 127.95, 128.30, 128.43, 128.59, 128.63, 128.70, 128.76, 132.36, 136.29, 137.34, 138.14, 156.65, 174.37. HRMS (FAB): m/z [M + H+] calcd for C34H36NO7: 570.2498; found: 570.2492.

14

Characterization data for 1: [α]D ²5 +2.2 (c 1.0, H2O); mp 170-174 ˚C (dec.). ¹H NMR (300 MHz, D2O): δ = 4.21 (dd, J = 3.3, 2.7 Hz, 1 H), 3.93-3.87 (m, 2 H), 3.72-3.60 (m, 2 H). ¹³C NMR (125 MHz, D2O): δ = 172.83, 73.33, 68.26, 62.63, 58.16. HRMS (CI): m/z [M + H+] calcd for C5H12NO5: 166.0715; found: 166.0716.

15

Characterization data for 10: [α]D ²5 +35.6 (c 0.5, CHCl3). IR (CH2Cl2): 3425, 2939, 2865, 2360, 1716, 1507, 1456, 1339, 1067, 697 cm-¹. cis-Isomer: ¹H NMR (300 MHz, CDCl3): δ = 3.64-3.72 (m, 2 H), 4.17 (br s, 2 H), 4.55 (d, J = 11.1 Hz, 1 H), 4.61 (d, J = 11.1 Hz, 1 H), 4.65 (d, J = 11.1 Hz, 1 H), 4.85 (d, J = 11.1 Hz, 1 H), 5.10 (s, 2 H), 5.18 (t, J = 8.4 Hz, 1 H), 5.47 (d, J = 7.2 Hz, 1 H), 5.75 (dd, J = 11.4, 9.3 Hz, 1 H), 6.54 (d, J = 11.4 Hz, 1 H), 7.23-7.42 (m, 20 H). ¹³C NMR (125 MHz, CDCl3): δ = 49.43, 62.86, 67.22, 73.43, 75.95, 78.70, 83.19, 126.78, 127.48, 127.91, 128.09, 128.21, 128.36, 128.53, 128.77, 130.84, 131.64, 136.74, 136.86, 138.07, 138.13, 138.25, 156.15, 156.52. trans-Isomer: ¹H NMR (300 MHz, CDCl3): δ = 3.80-3.90 (m, 2 H), 4.32-4.37 (m, 2 H), 4.61-4.85 (m, 5 H), 5.13 (s, 2 H), 5.48-5.50 (m, 1 H), 6.15 (dd, J = 15.6, 6.0 Hz, 1 H), 6.58 (d, J = 15.6 Hz, 1 H), 7.23-7.42 (m, 20 H). ¹³C NMR (125 MHz, CDCl3): δ = 53.43, 63.13, 66.84, 73.07, 75.47, 77.71, 78.59, 82.01, 126.08, 126.85, 127.90, 128.03, 128.17, 128.29, 128.30, 128.67, 128.81, 131.24, 136.76, 136.85, 137.61, 138.07, 156.26, 156.68. HRMS (FAB): m/z [M + H+] calcd for C35H37N2O6: 581.2652; found: 581.2655.

16

Characterization data for 11: [α]D ²5 -7.5 (c 1.0, CHCl3). IR (CH2Cl2): 3444, 2972, 2360, 1716, 1508, 1456, 1418, 1339, 1067, 739, 698 cm-¹. ¹H NMR (300 MHz, CDCl3): δ = 3.72-3.73 (m 1 H), 4.17-4.74 (m, 9 H), 5.10-5.15 (m, 2 H), 5.64 (d, J = 6.5 Hz, 1 H), 7.27-7.42 (m, 15 H), 9.67 (s, 1 H). ¹³C NMR (125 MHz, CDCl3): δ = 60.03, 62.83, 67.53, 73.10, 74.33, 75.79, 77.91, 128.30, 128.34, 128.47, 128.55, 128.65, 128.69, 128.77, 128.84, 136.24, 137.32, 137.39, 156.39, 156.61, 198.01. HRMS (FAB): m/z [M + H+] calcd for C28H31N2O7: 507.2131; found: 507.2142.

17

Characterization data for 12: [α]D ²5 -10.4 (c 1.0, CHCl3). IR (CH2Cl2): 3365, 3032, 2965, 2360, 1716, 1508, 1456, 1339, 1220, 1066, 740, 698 cm-¹. ¹H NMR (500 MHz, CD3OD): δ = 3.79 (br, 1 H), 4.08 (dd, J = 12.0, 5.0 Hz, 1 H), 4.30 (d, J = 7.0 Hz, 1 H), 4.41 (br d, J = 12.0 Hz, 1 H), 4.51 (s, 1 H), 4.57-4.73 (m, 4 H), 5.08-5.14 (m, 2 H), 7.24-7.37 (m, 15 H). ¹³C NMR (125 MHz, CD3OD): δ = 63.26, 66.68, 72.88, 74.66, 78.79, 79.33, 127.50, 127.64, 127.80, 127.96, 128.06, 128.13, 128.29, 136.98, 138.29, 138.47, 157.75, 158.39, 176.12. HRMS (FAB): m/z [M + Na+] calcd for C28H30N2O8Na: 545.1900; found: 545.1903.

18

Characterization data for 2: [α]D ²5 +1.2 (c 1.0, H2O); mp 215-220 ˚C (dec.). ¹H NMR (500 MHz, D2O): δ = 4.17 (br m, 1 H), 4.09-4.04 (m, 3 H), 3.82 (br m, 1 H). ¹³C NMR (125 MHz, D2O): δ = 172.95, 159.35, 71.07, 68.28, 65.76, 58.13. HRMS (FAB): m/z [M + H+] calcd for C6H13N2O6: 209.0774; found: 209.0776.