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Synlett 2014; 25(5): 661-664
DOI: 10.1055/s-0033-1340181
letter
© Georg Thieme Verlag Stuttgart · New York

Stereoselective Total Synthesis of Rhoiptelol B via Prins Cyclization

Jhillu S. Yadav*
a   Centre for Semio Chemicals, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India   Fax: +91(40)27160512   Email: yadavpub@gmail.com
b   Engineer Abdullah Bagshan for Bee Research, King Saud University, Saudi Arabia
,
Md. Ataur Rahman
a   Centre for Semio Chemicals, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India   Fax: +91(40)27160512   Email: yadavpub@gmail.com
,
N. Mallikarjuna Reddy
a   Centre for Semio Chemicals, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India   Fax: +91(40)27160512   Email: yadavpub@gmail.com
,
Attaluri R. Prasad
a   Centre for Semio Chemicals, CSIR-Indian Institute of Chemical Technology, Hyderabad 500007, India   Fax: +91(40)27160512   Email: yadavpub@gmail.com
,
Ahmad Al Khazim Al Ghamdi
b   Engineer Abdullah Bagshan for Bee Research, King Saud University, Saudi Arabia
› Author Affiliations
Further Information

Publication History

Received: 17 December 2013

Accepted after revision: 10 January 2014

Publication Date:
11 February 2014 (online)

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Abstract

The stereoselective total synthesis of rhoiptelol B, a diaryl­heptanoid isolated from Rhoiptelea chiliantha is described. The tetrahydropyran ring was constructed by using Prins cyclization. The key steps involved in this synthesis are Prins cyclization, Mistunobu inversion, cross metathesis, Sharpless asymmetric dihydroxylation, and hydrogenolysis.

Key words

rhoiptelol B - natural products - diarylheptanoid - Prins cyclization - Mitsunobu inversion
 

  • References and Notes

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  • 16 (2R,4S,6R)-2-[2-(Benzyloxy)ethyl]-6-(4-hydroxy-3-methoxyphenyl)tetrahydro-2H-pyran-4-ol (7) [α]D 25 +38.3 (c 1.01, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 7.20–7.17 (m, 5 H), 6.83–6.78 (m, 2 H), 6.77–6.71 (m, 1 H), 5.45 (br s, OH, 1 H), 4.47 (s, 2 H), 4.23 (dd, J = 1.3, 11.3 Hz, 1 H), 3.86 (s, 3 H), 3.70–3.50 (m, 4 H), 2.18–2.08 (m, 1 H), 2.04–1.94 (m, 1 H), 1.93–1.74 (m, 2 H), 1.34–1.20 (m, 2 H). 13C NMR (75 MHz, CDCl3): δ = 146.3, 144.9, 144.94, 138.4, 134.0, 128.3, 127.5, 127.5, 118.9, 114.0, 108.6, 77.1, 72.9, 68.4, 66.6, 55.8, 42.5, 40.9, 36.1. IR (neat): νmax = 3385, 2921, 2853, 1517, 1273, 1074, 1033, 747 cm–1. ESI-MS: m/z = 381 [M + Na]+. (2R,4R,6R)-2-[2-(Benzyloxy)ethyl]-6-(4-hydroxy-3-methoxyphenyl)tetrahydro-2H-pyran-4-ol (8) [α]D 25 +32.2 (c 0.83, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 7.34–7.29 (m, 5 H), 6.89–6.81 (m, 3 H), 4.77 (d, J = 10.6 Hz, 1 H), 4.51 (s, 2 H), 4.34–4.31 (m, 1 H), 4.17–4.09 (m, 1 H), 3.86 (s, 3 H), 3.69–3.59 (m, 2 H), 1.93–1.85 (m, 2 H), 1.84–1.76 (m, 1 H), 1.75–1.69 (m, 2 H), 1.64–1.57 (m, 1 H). 13C NMR (75 MHz, CDCl3): δ = 146.3, 144.7, 138.5, 135.0, 128.2, 127.5, 127.4, 118.7, 114.0, 108.7, 73.2, 72.8, 69.2, 66.8, 64.9, 55.8, 40.1, 38.5, 36.2; IR (neat): νmax = 3385, 2921, 2853, 1517, 1273, 1074, 1033, 747 cm–1. ESI-MS: m/z = 381 [M + Na]+. (2R,4R,6R)-2-[2-(Benzyloxy)ethyl]-6-[3-methoxy-4-(methoxymethoxy)phenyl]-4-(methoxymethoxy)-tetrahydro-2H-pyran (9) [α]D 25 +34.2 (c 1.04, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 7.29–7.16 (m, 5 H), 7.02 (d, J = 8.0 Hz, 1 H), 6.86–6.75 (m, 2 H), 5.13 (s, 2 H), 4.70–4.63 (m, 3 H), 4.43 (s, 2 H), 4.08–3.96 (m, 2 H), 3.78 (s, 2 H), 3.61–3.52 (m, 2 H), 3.43 (s, 3 H), 3.33 (s, 3 H), 1.99–1.88 (m, 1 H), 1.87–1.68 (m, 3 H), 1.67–1.57 (m, 1 H), 1.51–1.39 (m, 1 H). 13C NMR (75 MHz, CDCl3): δ = 149.6, 145.5, 138.6, 137.5, 128.2, 127.4, 127.3, 118.1, 116.2, 109.7, 95.4, 95.0, 73.7, 72.9, 70.1, 69.9, 66.8, 56.0, 55.7, 55.3, 38.4, 36.4, 36.2. IR (neat): νmax = 2927, 1513, 1267, 1153, 1037 cm–1. ESI-HRMS: m/z [M + H]+ calcd for C25H34O7Na: 469.21792; found: 469.21967. 2-{(2R,4R,6R)-6-[3-Methoxy-4-(methoxymethoxy)-phenyl]-4-(methoxymethoxy)tetrahydro-2H-pyran-2-yl}ethanol (10) [α]D 25 +34.0 (c 0.65, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 7.03 (d, J = 8.3 Hz, 1 H), 6.84–6.74 (m, 2 H), 5.14 (s, 2 H), 4.72 (dd, J = 1.1, 11.3 Hz, 1 H), 4.67 (s, 2 H), 4.17–4.02 (m, 2 H), 3.81 (s, 3 H), 3.79–3.72 (m, 2 H), 3.44 (s, 3 H), 3.35 (s, 3 H), 2.03–1.94 (m, 1 H), 1.85–1.56 (m, 5 H). 13C NMR (75 MHz, CDCl3): δ = 149.7, 145.7, 136.9, 118.0, 109.4, 95.4, 95.1, 74.2, 73.6, 69.9, 61.6, 56.0, 55.8, 55.4, 38.3, 37.8, 36.1. IR (neat): νmax = 3417, 2924, 1516, 1036 cm–1. ESI-HRMS: m/z [M + H]+ calcd for C18H28O7Na: 379.17191; found: 379.17272. (2S,4R,6R)-2-(2-Iodoethyl)-6-[3-methoxy-4-(methoxymethoxy)phenyl]-4-(methoxymethoxy)-tetrahydro-2H-pyran (11) [α]D 25 +28.4 (c 0.34, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 7.10 (d, J = 8.2 Hz, 1 H), 6.97 (d, J = 1.9 Hz, 1 H), 6.88 (dd, J = 1.6, 8.2 Hz, 1 H), 6.86–5.89 (m, 1 H), 5.31 (m, 1 H), 5.12 (m, 1 H), 5.20 (s, 2 H), 4.81 (dd, J = 1.8, 11.7 Hz, 1 H), 4.76 (d, J = 0.9 Hz, 2 H), 4.47–4.42 (m, 1 H), 4.16–4.13 (m, 2 H), 3.89 (s, 3 H), 3.50 (s, 3 H), 3.43 (s, 3 H), 2.04–1.98 (m, 1 H), 1.94–1.90 (m, 1 H), 1.75–1.69 (dtd, J = 2.7, 11.9, 14.3 Hz, 1 H), 1.64–1.58 (dtd, J = 2.7, 11.7, 14.3, 1 H). 13C NMR (75 MHz, CDCl3): δ = 149.6, 145.6, 139.0, 137.2, 118.2, 116.2, 4.8, 109.8, 95.5, 95.1, 73.9, 73.3, 70.0, 56.0, 55.8, 55.4, 38.2, 35.9. IR (neat): νmax = 2923, 2851, 1513, 1266, 1153, 1075, 1037 cm–1. ESI-HRMS: m/z [M + H]+ calcd for C18H26O6Na: 361.16163; found: 361.16216. (2R,4R,6S)-2-[3-Methoxy-4-(methoxymethoxy)phenyl]-4-(methoxymethoxy)-6-[(E)-4-(methoxymethoxy)styryl]-tetrahydro-2H-pyran (2) [α]D 25 +6.4 (c 0.74, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 7.34–7.28 (m, 2 H), 7.11 (d, J = 8.8 Hz, 1 H), 7.01–6.89 (m, 4 H), 6.59 (d, J = 16.0 Hz, 1 H), 6.15 (d, J = 6.2, 16.0 Hz, 1 H), 5.21 (s, 2 H), 5.16 (s, 2 H), 4.89–4.82 (m, 1 H), 4.78 (s, 2 H), 4.65–4.55 (m, 1 H), 4.22–4.15 (m, 1 H), 3.90 (s, 3 H), 3.50 (s, 3 H), 3.47 (s, 3 H), 3.45 (s, 3 H), 2.06–1.94 (m, 2 H), 1.83–1.65 (m, 2 H). 13C NMR (75 MHz, CDCl3): δ = 156.7, 149.6, 145.7, 137.1, 130.8, 129.6, 128.7, 127.5, 118.4, 116.3, 116.1, 109.9, 95.5, 95.1, 94.3, 74.1, 73.4, 70.1, 56.0, 55.9, 55.8, 55.4, 38.1, 36.3. IR (neat): νmax = 2925, 2852, 1511, 1266, 1235, 1152, 1077, 1037, 999 cm–1. ESI-HRMS: m/z [M + H]+ calcd for C26H34O8Na: 497.21229; found: 497.21459. (1S,2R)-1-{(2S,4S,6R)-6-[3-Methoxy-4-(methoxymethoxy)-phenyl]-4-(methoxymethoxy)tetrahydro-2H-pyran-2-yl}-2-[4-(methoxymethoxy)phenyl]ethane-1,2-diol (12) [α]D 25 +24.6 (c 0.44, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 7.32–7.28 (m, 2 H), 7.13 (d, J = 3.2 Hz, 1 H), 7.03–7.00 (m, 2 H), 6.91–6.86 (m, 2 H), 5.23 (s, 3 H), 5.16 (s, 3 H), 4.84 (d, J = 5.0 Hz, 1 H), 4.77 (dd, J = 1.6, 11.7 Hz, 1 H), 4.69 (s, 3 H), 4.17–3.69 (m, 1 H), 3.90 (s, 3 H), 3.52 (s, 3 H), 3.47 (s, 3 H), 3.32 (s, 3 H), 2.50–2.48 (m, 1 H), 2.02–1.94 (m, 1 H), 1.77–1.67 (m, 1 H), 1.63 (br s, OH, 1 H), 1.37–1.23 (m, 2 H). 13C NMR (75 MHz, CDCl3): δ = 156.7, 149.7, 16.4, 134.2, 127.7, 118.2, 116.1, 109.7, 95.4, 95.1, 94.4, 74.7, 74.3, 73.6, 70.0, 56.1, 55.9, 55.4, 43.3, 37.9, 32.1, 29.6, 25.6. IR (neat): νmax = 3449, 2925, 2852, 1512, 1266, 1153, 1076, 1036, 1000 cm–1. ESI-HRMS: m/z [M + H]+ calcd for C26H36O10Na: 531.21809; found: 531.22007. (S)-1-{(2S,4S,6R)-6-[3-Methoxy-4-(methoxymethoxy)-phenyl]-4-(methoxymethoxy)tetrahydro-2H-pyran-2-yl}-2-[4-(methoxymethoxy)phenyl]ethanol (13) [α]D 25 +11.20 (c 0.87, CHCl3). 1H NMR (300 MHz, CDCl3): δ = 7.19–7.09 (m, 3 H), 7.02–6.82 (m, 4 H), 5.23 (s, 2 H), 5.16 (s, 3 H), 4.81–4.64 (m, 3 H), 4.36–4.24 (m, 1 H), 4.25–4.19 (m, 1 H), 3.89 (s, 3 H), 3.78–3.60 (m, 1 H), 3.51 (s, 3 H), 3.46 (s, 3 H), 3.37 (s, 3 H), 2.90–2.70 (m, 2 H), 2.51 (br s, OH, 1 H), 2.08–1.87 (m, 2 H), 1.79–1.64 (m, 2 H). 13C NMR (75 MHz, CDCl3): δ = 155.7, 149.6, 137.0, 131.8, 130.7, 130.3, 128.7, 118.2, 116.2, 114.1, 109.7, 95.5, 95.1, 94.5, 77.0, 74.4, 74.0, 70.1, 56.1, 55.8, 55.4, 38.6, 38.3, 31.9. IR (neat): νmax = 3450, 2925, 2854, 1636 cm–1. ESI-MS: m/z = 515 [M + Na]+. Rhoiptelol B (1): Mp 65–67 °C; [α]D 25 +87.4 (c 0.3, MeOH). 1H NMR (300 MHz, CD3OD): δ = 7.05 (br s, 1 H), 7.04 (d, J = 8.4 Hz, 2 H), 6.82 (dd, J = 8.4, 2.0 Hz, 1 H), 6.74 (d, J = 8.4 Hz, 1 H), 6.67 (d, J = 8.4 Hz, 2 H), 4.67 (dd, J = 10.7, 3.2 Hz, 1 H), 4.26 (t, J = 3.2 Hz, 1 H), 3.85 (s, 3 H), 3.80 (dt, J = 12.7, 2.9 Hz, 1 H), 3.59 (dt, J = 7.4, 3.2 Hz, 1 H), 2.84 (dd, J = 13.0, 6.6 Hz, 1 H), 2.67 (dd, J = 13.0, 7.4 Hz, 1 H), 1.91 (dd, J = 13.3, 3.0 Hz, 1 H), 1.82 (dd, J = 14.3, 2.9 Hz, 1 H), 1.73 (ddd, J = 13.6, 10.9, 2.8 Hz, 1 H), 1.57 (dd, J = 13.6, 2.0 Hz, 1 H). 13C NMR (75 MHz, CD3OD): δ = 156.7, 148.8, 146.8, 136.2, 131.4, 131.3, 131.1, 119.8, 116.0, 115.8, 115.7, 111.1, 76.4, 75.2, 74.3, 65.7, 56.4, 41.2, 39.7, 35.0; IR (neat): νmax = 3392, 2953, 2928, 1595, 1502, 1365, 1174, 1083, 854, 716 cm–1. ESI-HRMS: m/z [M + Na]+ calcd for C20H24O6Na: 383.1470; found: 383.1461.