Formal Total Synthesis of (–)-5,6-Dihydrocineromycine B

G. Venkateswar Reddy; R. Sateesh Chandra Kumar; B. Siva; K. Suresh Babu; J. Madhusudana Rao

doi:10.1055/s-0032-1317346

Synlett, Inhaltsverzeichnis

Synlett 2012; 23(18): 2677-2681
DOI: 10.1055/s-0032-1317346

letter

Formal Total Synthesis of (–)-5,6-Dihydrocineromycine B

G. Venkateswar Reddy

Division of Natural Product Chemistry, CSIR - Indian Institute of Chemical Technology, Hyderabad – 500007, India Fax: +91(40)27160512 eMail: suresh@iict.res.in

,

R. Sateesh Chandra Kumar

Division of Natural Product Chemistry, CSIR - Indian Institute of Chemical Technology, Hyderabad – 500007, India Fax: +91(40)27160512 eMail: suresh@iict.res.in

,

B. Siva

Division of Natural Product Chemistry, CSIR - Indian Institute of Chemical Technology, Hyderabad – 500007, India Fax: +91(40)27160512 eMail: suresh@iict.res.in

,

K. Suresh Babu

Division of Natural Product Chemistry, CSIR - Indian Institute of Chemical Technology, Hyderabad – 500007, India Fax: +91(40)27160512 eMail: suresh@iict.res.in

,

J. Madhusudana Rao*

Division of Natural Product Chemistry, CSIR - Indian Institute of Chemical Technology, Hyderabad – 500007, India Fax: +91(40)27160512 eMail: suresh@iict.res.in

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Abstract

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Abstract

An efficient and highly convergent formal total synthesis of the 14-membered macrolide (–)-5,6-dihydrocineromycine B is achieved. Key reaction sequences include a Sharpless asymmetric epoxidation followed by esterification for the formation of a fully functionalized acyclic precursor, Corey–Bakshi–Shibata reduction, and ring-closing metathesis, respectively.

Key words

antibiotic macrolide - (–)-5,6-dihydrocineromycine B - Sharpless asymmetric epoxidation - CBS reduction - ring-closing metathesis

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Referenzen

References and Notes

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25 Spectral Data for Representative New Compounds Compound 9: colorless oil; [α]_D ²⁵ –5.5 (c 1, CHCl₃). IR (KBr): 3399, 2933, 1612, 1513, 1248, 1035, 772 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 7.17 (d, 2 H, J = 8.30 Hz), 6.80 (d, 2 H, J = 9.00 Hz), 4.38 (s, 2 H), 3.74 (s, 3 H), 3.40 (t, 2 H, J = 5.20 Hz), 3.35–3.21 (m, 2 H), 1.70–1.39 (m, 4 H), 1.06 (s, 3 H). ¹³C NMR (75 MHz, CDCl₃): δ = 159.1, 129.2, 113.6, 72.5, 72.4, 70.4, 69.5, 54.8, 35.2, 24.0, 23.1. ESI-MS: m/z = 277 [M + Na]⁺. ESI-HRMS: m/z calcd for C₁₄H₂₂NaO₄: 277.1416; found: 277.1410. Compound 16: colorless oil; [α]_D ²⁵ +13.7 (c 1, CHCl₃). IR (KBr): 3446, 2926, 1722, 1655, 1513, 1219, 1035, 772 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 7.19 (d, 2 H, J = 8.49 Hz), 6.92–6.77 (m, 3 H), 5.97 (d, 1 H, J = 15.67 Hz), 4.40 (s, 2 H), 4.16 (q, 2 H, J = 7.17, 14.16 Hz), 3.77 (s, 3 H), 3.47–3.32 (m, 3 H), 1.75–1.56 (m, 4 H), 1.33–1.22 (m, 6 H). ¹³C NMR (75 MHz, CDCl₃): δ = 166.3, 159.1, 154.4, 129.7, 129.1, 118.9, 113.6, 72.6, 72.1, 70.0, 59.9, 54.8, 39.5, 28.1, 24.3, 14.3. ESI-MS: m/z = 345 [M + Na]⁺. ESI-HRMS: m/z calcd for C₁₈H₂₆NaO₅: 345.1678; found: 345.1667. Compound 17: colorless oil; [α]_D ²⁵ +10.6 (c 1, CHCl₃). IR (KBr): 3424, 2955, 1720, 1656, 1459, 1299, 1061, 772 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 6.83 (d, 1 H, J = 15.1 Hz), 5.88 (d, 1 H, J = 15.1 Hz), 4.18 (q, 2 H, J = 6.79, 14.35 Hz), 3.59 (t, 2 H, J = 6.04 Hz), 1.67–1.52 (m, 4 H), 1.39 (s, 3 H), 1.31 (t, 3 H, J = 6.79 Hz) 0.97 (t, 9 H, J = 8.30, 15.86 Hz), 0.61 (q, 6 H, J = 7.55, 15.86 Hz). ¹³C NMR (75 MHz, CDCl₃): δ = 166.4, 154.4, 119.0, 75.1, 62.9, 60.2, 39.8, 27.9, 27.4, 14.4, 7.2, 6.8. ESI-MS: m/z = 339 [M + Na]⁺. ESI-HRMS: m/z calcd for C₁₆H₃₂NaO₄Si: 339.1968; found: 339.1961. Compound 6: colorless oil; [α]_D ²⁵ –13.5 (c 1, CHCl₃). IR (KBr): 3414, 2924, 1706, 1454, 1219, 1018, 770 cm^–1. ¹H NMR (300 MHz, CDCl₃): δ = 6.92 (d, 1 H, J = 15.86 Hz), 5.95 (d, 1 H, J = 15.10 Hz), 5.91 (s, 1 H), 5.73 (s, 1 H), 2.83–2.69 (m, 1 H), 2.66–2.52 (m, 1 H), 1.95–1.81 (m, 5 H), 1.43 (s, 3 H), 0.97 (t, 9 H, J = 8.30 Hz), 0.61 (q, 6 H, J = 7.55, 15.86 Hz). ¹³C NMR (75 MHz, CDCl₃): δ = 200.6, 172.0, 156.7, 144.6, 124.1, 118.8, 74.8, 37.0, 31.9, 28.2, 17.8, 7.2, 6.7. ESI-MS: m/z = 349 [M + Na]⁺. ESI-HRMS: m/z calcd for C₁₇H₃₀NaO₄Si: 349.1811; found: 349.1820. Compound 11: colorless oil, [α]_D ²⁵ –2.5 (c 1, CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 7.79 (d, 2 H, J = 7.90 Hz), 7.34 (d, J = 7.90 Hz), 4.19–4.13 (m, 1 H), 4.03–3.96 (m, 2 H), 3.84 (q, 1 H, J = 6.30, 14.30 Hz), 3.58 (t, 1 H, J = 7.10 Hz), 2.45 (s, 3 H), 1.96–1.87 (m, 1 H), 1.31 (s, 3 H), 1.27 (s, 3 H), 0.90 (d, 3 H, J = 7.10 Hz). ¹³C NMR (75 MHz, CDCl₃): δ = 144.6, 132.9, 129.7, 127.8, 109.0, 76.3, 72.2, 67.6, 37.0, 26.5, 25.3, 21.5, 12.8. ESI-MS: m/z = 337 [M + Na]⁺. ESI-HRMS: m/z calcd for C₁₅H₂₂NaO₅S: 337.1086; found: 337.1091. Compound 7: colorless oil; [α]_D ²⁵ –12.8 (c 1, CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 5.85–5.65 (m, 1 H), 5.05–4.85 (m, 2 H), 3.62 (pent, 1 H, J = 6.04, 12.08, 18.12 Hz), 2.27–2.06 (m, 1 H), 2.05–1.86 (m, 2 H), 1.66–1.42 (m, 1 H), 1.23–1.13 (m, 1 H), 1.10 (d, 3 H, J = 6.04 Hz), 0.87 (d, 3 H, J = 6.79 Hz). ¹³C NMR (75 MHz, CDCl₃): δ = 138.73, 114.53, 71.26, 39.41, 31.73, 31.50, 19.39, 14.50. Compound 31: colorless oil; [α]_D ²⁵ –17.2 (c 1, CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 6.78 (d, 1 H, J = 15.70 Hz), 5.93–5.84 (m, 2 H), 5.77–5.69 (m, 2 H), 5.02–4.38 (m, 3 H), 2.80–2.69 (m, 1 H), 2.67–2.58 (m, 1 H), 2.21–2.09 (m, 1 H), 2.06–1.97 (m, 1 H), 1.91–1.83 (m, 5 H), 1.79–1.69 (m, 1 H), 1.56–1.45 (m, 1 H), 1.41 (s, 3 H), 1.27–1.23 (m, 1 H), 1.20 (d, 3 H, J = 6.87 Hz), 0.96 (t, 9 H, J = 7.85 Hz), 0.92 (d, 3 H, J = 6.87 Hz), 0.61 (q, 6 H, J = 7.85, 15.70 Hz). ¹³C NMR (75 MHz, CDCl₃): δ = 201.47, 166.14, 153.78, 144.47, 138.58, 124.34, 119.72, 114.63, 74.67, 74.17, 37.26, 36.80, 32.09, 31.78, 31.29, 28.09, 17.73, 16.07, 14.60, 7.12, 6.71. ESI-MS: m/z = 459 [M + Na]⁺. ESI-HRMS: m/z calcd for C₂₅H₄₄NaO₄Si: 459.2907; found: 459.2910. Compound 5: colorless oil; [α]_D ²⁵ –21.7 (c 1, CHCl₃). ¹H NMR (300 MHz, CDCl₃): δ = 6.86 (d, 1 H, J = 15.48 Hz), 5.93–5.84 (m, 2 H), 5.91 (d, 1 H, J = 15.48 Hz), 5.87–5.69 (m, 1 H), 5.07–4.81 (m, 5 H), 4.02 (t, 1 H, J = 5.28 Hz), 2.30–2.30 (m, 1 H), 2.23–1.93(m, 2 H), 1.69 (s, 3 H), 1.64–1.44 (m, 4 H), 1.38 (s, 3 H), 1.30–1.23 (m, 2 H), 1.19 (d, 3 H, J = 6.7 Hz), 0.96 (t, 9 H, J = 7.55 Hz), 0.92 (d, 3 H, J = 6.79 Hz), 0.61 (q, 6 H, J = 7.55, 15.86 Hz). ¹³C NMR (75 MHz, CDCl₃): δ = 166.17, 154.27, 147.27, 128.58, 127.58, 126.56, 114.75, 111.27, 75.81, 74.96, 74.10, 39.02 36.83, 31.81, 31.34, 29.79, 29.11, 27.71, 17.64, 16.12, 14.68, 7.16, 6.79. ESI-MS: m/z 461 [M + Na]⁺. ESI-HRMS: m/z calcd for C₂₅H₄₆NaO₄Si: 461.3063; found: 461.3044.