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

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

References and Notes

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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.