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Synlett 2007(11): 1711-1714  
DOI: 10.1055/s-2007-984518
LETTER
© Georg Thieme Verlag Stuttgart · New York

An Efficient Synthesis of Aminocyclopentitols via the Stereoselective Amination of Polybenzyl Ethers Using Chlorosulfonyl Isocyanate

In Su Kim, Qing Ri Li, Jae Koo Lee, Sang Hwi Lee, Jae Kyung Lim, 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;
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Publikationsverlauf

Received 4 April 2007
Publikationsdatum:
25. Juni 2007 (online)

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Abstract

An efficient stereoselective route for the preparation of stereoisomeric aminocyclopentitols 3-5 was achieved using a six-step sequence starting from the corresponding d-sugars. Key steps of the synthesis of the title compounds involved the regioselective and diastereoselective amination of cinnamylic 1,2-anti- or 1,2-syn-tribenzyl ethers using chlorosulfonyl isocyanate (CSI), intramolecular olefin metathesis, and diastereoselective dihydroxylation.

Key words

aminocyclopentitol - chlorosulfonyl isocyanate - amination - mannostatin - dihydroxylation

13

Characterization data for 7a-c:
7a: (Z:E = 2.5:1, anti:syn = 24:1); [α]D 30 -14.9 (c = 1.0, CHCl3). 1H NMR (500 MHz, CDCl3): δ = 3.50-3.53 (t, J = 4.5 Hz, 0.71 H), 3.60-3.61 (br, 0.29 H), 3.91-4.01 (m, 1 H), 4.32 (d, J = 11.5 Hz, 0.29 H), 4.33 (d, J = 12.0 Hz, 0.71 H), 4.60-4.77 (m, 3.29 H), 5.01-5.15 (m, 4.13 H), 5.29 (d, J = 17.0 Hz, 0.29 H), 5.38 (d, J = 10.0 Hz, 0.29 H), 5.53 (t, J = 10.0, 12.0 Hz, 0.71 H), 5.70-5.84 (m, 1.71 H), 5.90-5.99 (m, 0.29 H),6.00 (dd, J = 7.5, 15.5 Hz, 0.29 H), 6.52 (d, J = 15.5 Hz, 0.29 H), 6.53 (d, J = 15.5 Hz, 0.71 H), 7.23-7.36 (m, 20 H). 13C NMR (125 MHz, CDCl3): δ = 49.69, 66.67, 70.64, 73.65, 81.66, 81.94, 119.76, 120.06, 126.80, 127.51, 127.94, 127.99, 128.09, 128.17, 128.40, 128.55, 128.66, 128.69, 132.55, 132.85, 134.88, 135.12, 136.58, 137.05, 138.14, 138.33, 155.99. HRMS (FAB): m/z [M + H+] calcd for C35H36NO4: 534.2644; found: 534.2639.
7b: (Z:E = 2.6:1, anti:syn = 18:1); [α]D 25 -79.6 (c = 0.1, CHCl3). 1H NMR (500 MHz, CDCl3): δ = 3.68-3.73 (br, 0.56 H), 3.80 (t, J = 7.0 Hz, 0.72 H), 3.88-3.92 (m, 0.72 H), 4.29 (d, J = 11.5 Hz, 0.28 H), 3.39 (d, J = 11.5 Hz, 0.72 H), 4.47 (d, J = 11.5 Hz, 0.28 H), 4.54 (d, J = 11.5 Hz, 0.72 H), 4.57 (d, J = 11.5 Hz, 0.28 H), 4.61 (d, J = 11.5 Hz, 0.72 H), 4.63 (d, J = 11.5 Hz, 0.28 H), 4.67 (d, J = 11.5 Hz, 0.72 H), 4.89 (br, 0.28 H), 5.06-5.16 (m, 2 H), 5.25 (t, J = 8.0 Hz, 0.72 H), 5.35-5.44 (m, 3 H), 5.76 (dd, J = 10.0, 10.5 Hz, 0.72 H), 5.85-5.94 (m, 1 H), 6.17 (dd, J = 8.0, 15.5 Hz, 0.28 H), 6.49 (d, J = 15.5 Hz, 0.28 H), 6.63 (d, J = 10.5 Hz, 0.72 H), 7.03-7.46 (m, 20 H). 13C NMR (125 MHz, CDCl3): δ = 50.32, 66.87, 70.47, 70.53, 74.49, 81.12, 81.34, 83.20, 83.50, 119.70, 120.25, 126.78, 127.53, 127.60, 127.85, 128.01, 128.15, 128.23, 128.37, 128.58, 128.65, 128.68, 128.76, 128.90, 132.74, 132.82, 136.18, 136.58, 138.25, 155.60. HRMS (FAB): m/z [M + H+] calcd for C35H36NO4: 534.2644; found: 534.2640.
7c: (Z:E = 2.8:1, anti:syn = 1:5); [a]D 25 +1.2 (c = 1.0, CHCl3). 1H NMR (500 MHz, CDCl3): δ = 3.56 (t, J = 7.5 Hz, 0.74 H), 3.71 (dd, J = 3.5, 6.5 Hz, 0.26 H), 3.88-3.93 (m, 1 H), 4.30 (d, J = 11.5 Hz, 0.26 H), 4.45-4.64 (m, 3.46 H), 4.76 (d, J = 11.5 Hz, 0.26 H), 4.91-4.93 (br, 0.26 H), 5.09-5.14 (m, 2.74 H), 5.31-5.64 (m, 3 H), 5.84 (dd, J = 10.0, 11.0 Hz, 0.74 H), 5.84-5.87 (m, 1 H), 6.18 (dd, J = 8.0, 16.0 Hz, 0.26 H), 6.53 (d, J = 11.0 Hz, 0.74 H), 6.56 (d, J = 16.0 Hz, 0.26 H), 7.06-7.49 (m, 20 H). 13C NMR (125 MHz, CDCl3): δ = 54.78, 66.88, 70.52, 74.50, 74.66, 81.11, 83.47, 120.33, 126.06, 126.81, 127.82, 127.87, 127.97, 128.14, 128.17, 128.27, 128.35, 128.53, 128.67, 128.69, 128.72, 128.79, 132.76, 136.18, 136.86, 137.01, 138.30, 155.80. HRMS (FAB): m/z [M + H+] calcd for C35H36NO4: 534.2644; found: 534.2654.

15

Characterization data for 10a-c:
10a: [α]D 29 -32.9 (c = 1.0, CHCl3). 1H NMR (500 MHz, CDCl3): δ = 4.09 (br t, J = 5.5 Hz, 1 H), 4.52-4.61 (m, 5 H), 4.90-4.93 (br, 1 H), 5.12 (s, 2 H), 5.19 (d, J = 7.5 Hz, 1 H), 5.95 (d, J = 6.0 Hz, 1 H), 6.03 (d, J = 5.5 Hz, 1 H), 7.27-7.40 (m, 15 H). 13C NMR (125 MHz, CDCl3): δ = 55.67, 66.99, 71.92, 72.79, 82.56, 86.81, 128.00, 128.09, 128.17, 128.22, 128.34, 128.61, 128.67, 128.72, 128.74, 132.89, 134.65, 136.76, 137.77, 138.37, 156.37. HRMS (FAB): m/z [M + H+] calcd for C27H28NO4: 430.2018; found: 430.2020.
10b: [α]D 25 -79.6 (c = 0.1, CHCl3). 1H NMR (500 MHz, CDCl3): δ = 4.02 (t, J = 5.5 Hz, 1 H), 4.30 (dd, J = 2.5, 5.0 Hz, 1 H), 4.64 (d, J = 12.0 Hz, 1 H), 4.65 (d, J = 12.0 Hz, 1 H), 4.69-4.71 (br, 1 H), 4.72 (d, J = 12.0 Hz, 1 H), 4.79 (d, J = 12.0 Hz, 1 H), 5.12 (s, 2 H), 5.29 (d, J = 9.0 Hz, 1 H), 6.05 (dd, J = 2.0, 6.0 Hz, 1 H), 6.09 (dd, J = 3.0, 6.0 Hz, 1 H), 7.27-7.38 (m, 15 H). 13C NMR (125 MHz, CDCl3): δ = 54.65, 66.88, 72.31, 72.58, 78.42, 80.03, 127.86, 127.90, 128.02, 128.05, 128.22, 128.61, 128.69, 133.06, 135.08, 136.90, 138.30, 138.79, 156.36. HRMS (FAB): m/z [M + H+] calcd for C27H28NO4: 430.2018; found: 430.2013.
10c: [α]D 29 +6.2 (c = 1.0, CHCl3). 1H NMR (500 MHz, CDCl3): δ = 4.02 (t, J = 5.5 Hz, 1 H), 4.30 (dd, J = 2.5, 5.0 Hz, 1 H), 4.64 (d, J = 12.0 Hz, 1 H), 4.65 (d, J = 12.0 Hz, 1 H), 4.70-4.73 (br m, 2 H), 4.79 (d, J = 12.0 Hz, 1 H), 5.12 (s, 2 H), 5.28 (d, J = 9.0 Hz, 1 H), 6.05 (dd, J = 1.5, 6.0 Hz, 1 H), 6.08 (dd, J = 2.5, 6.5 Hz, 1 H), 7.27-7.41 (m, 15 H). 13C NMR (125 MHz, CDCl3): δ = 54.65, 66.87, 72.31, 72.58, 78.44, 80.03, 127.84, 127.90, 128.01, 128.03, 128.21, 128.60, 128.69, 133.05, 135.08, 136.91, 138.30, 143.67, 156.35. HRMS (FAB): m/z [M + H+] calcd for C27H28NO4: 430.2018; found: 430.2019.

17

Characterization data for 11a-13a and 11b:
11a: [α]D 23 +1.0 (c = 0.22, CHCl3). 1H NMR (500 MHz, CDCl3): δ = 3.92-4.25 (m, 5 H), 4.46 (d, J = 11.0 Hz, 1 H), 4.53 (d, J = 12.0 Hz, 1 H), 4.57 (d, J = 11.0 Hz, 1 H), 4.65 (d, J = 12.0 Hz, 1 H), 5.11 (d, J = 12.5 Hz, 1 H), 5.16 (d, J = 12.5 Hz, 1 H), 5.54-5.59 (br, 1 H), 7.22-7.36 (m, 15 H). 13C NMR (125 MHz, CDCl3): δ = 53.83, 67.33, 72.06, 72.71, 73.41, 80.22, 82.63, 88.40, 128.04, 128.09, 128.24, 128.39, 128.45, 128.71, 128.78, 128.81, 136.52, 137.20, 137.92, 154.56. HRMS (FAB): m/z [M + H+] calcd for C27H30NO6: 464.2073; found: 464.2068.
11b: [α]D 22 -18.2 (c = 0.08, CHCl3). 1H NMR (500 MHz, CDCl3): δ = 1.58-1.64 (br, 1 H), 2.84-2.88 (br, 1 H), 3.86 (dd, J = 4.0, 4.5 Hz, 1 H), 3.93 (t, J = 6.5 Hz, 1 H), 4.01-4.21 (m, 3 H), 4.78 (d, J = 11.5 Hz, 1 H), 4.52-4.60 (m, 2 H), 4.71 (d, J = 11.5 Hz, 1 H), 5.12 (s, 2 H), 5.52 (br s, 1 H), 7.24-7.48 (m, 15 H). 13C NMR (125 MHz, CDCl3): δ = 57.16, 67.41, 69.13, 72.46, 73.06, 77.49, 80.21, 82.78, 128.22, 128.28, 128.33, 128.42, 128.49, 128.79, 136.41, 137.42, 137.57, 157.66. HRMS (FAB): m/z [M + Na+] calcd for C27H29NO6Na: 486.1893; found: 486.1896.
12a: [α]D 23 +7.3 (c = 0.44, CHCl3). 1H NMR (500 MHz, CDCl3): δ = 1.82 (br s, 1 H), 3.09 (br s, 1 H), 3.91-3.99 (m, 3 H), 4.17 (dd, J = 4.5, 5.5 Hz, 1 H), 4.23 (br d, J = 3.0 Hz, 1 H), 4.52 (d, J = 12.0 Hz, 1 H), 4.68 (d, J = 12.0 Hz, 1 H), 4.76 (d, J = 12.0 Hz, 1 H), 4.79 (d, J = 12.0 Hz, 1 H), 5.14 (d, J = 12.5 Hz, 1 H), 5.10 (d, J = 12.5 Hz, 1 H), 5.62 (d, J = 6.0 Hz, 1 H), 7.27-7.40 (m, 15 H). 13C NMR (125 MHz, CDCl3): δ = 58.34, 67.35, 72.63, 73.27, 73.59, 76.42, 77.58, 84.59, 127.94, 128.01, 128.21, 128.37, 128.50, 128.69, 128.76, 128.82, 136.45, 138.04, 138.29, 157.59. HRMS (FAB): m/z [M + H+] calcd for C27H30NO6: 464.2073; found: 464.2083.
13a: [α]D 29 -2.5 (c = 1.0, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 2.98-3.22 (br, 2 H), 3.90-3.98 (br m, 2 H), 4.21-4.26 (br m, 3 H), 4.51 (d, J = 11.7 Hz, 1 H), 4.71 (d, J = 12.0 Hz, 1 H), 4.79 (d, J = 12.0 Hz, 1 H), 4.82 (d, J = 11.7 Hz, 1 H), 5.17 (s, 2 H), 5.63 (br d, J = 5.7 Hz, 1 H), 7.23-7.65 (m, 15 H). 13C NMR (125 MHz, CDCl3): δ = 58.41, 67.34, 72.66, 73.31, 73.61, 76.46, 77.52, 84.55, 127.91, 127.98, 128.17, 128.34, 128.47, 128.66, 128.74, 128.80, 136.44, 138.00, 138.29, 157.69. HRMS (FAB): m/z
[M + H+] calcd for C27H30NO6: 464.2073; found: 464.2072.

20

Characterization data for 3-5:
3: [α]D 23 +6.3 (c = 0.79, MeOH). 1H NMR (500 MHz, D2O): δ = 3.22 (t, J = 3.0 Hz, 1 H), 3.73 (dd, J = 4.0, 7.5 Hz, 1 H), 3.80 (dd, J = 3.0, 7.5 Hz, 1 H), 3.91-3.94 (m, 2 H). 13C NMR (125 MHz, D2O): δ = 51.91, 73.32, 75.91, 76.01, 83.35. HRMS (FAB): m/z [M + H+] calcd for C5H12NO4: 150.0766; found: 150.0766.
4: [α]D 23 -11.9 (c = 0.23, MeOH). 1H NMR (500 MHz, D2O): δ = 3.35 (t, J = 8.0 Hz, 1 H), 3.86-3.92 (m, 2 H), 3.99 (t, J = 4.5 Hz, 1 H), 4.07 (dd, J = 6.0, 8.0 Hz, 1 H). 13C NMR (125 MHz, D2O): δ = 56.37, 71.18, 73.37, 74.80, 76.84. HRMS (FAB): m/z [M + H+] calcd for C5H12NO4: 150.0766; found: 150.0767.
5: [α]D 22 -2.3 (c = 1.0, MeOH). 1H NMR (500 MHz, D2O): δ = 3.46 (t, J = 6.0 Hz, 1 H), 3.96 (t, J = 5.0 Hz, 1 H), 4.00 (dd, J = 6.0, 6.5 Hz, 1 H), 4.19 (t, J = 7.0 Hz, 1 H), 4.22 (dd, J = 4.5, 5.5 Hz, 1 H). 13C NMR (125 MHz, D2O): δ = 57.19, 67.83, 71.83, 73.85, 76.39. HRMS (FAB): m/z [M + H+] calcd for C5H12NO4: 150.0766; found: 150.0767.