First Enantioselective Total Synthesis of the Angucyclinone-Type Antibiotic YM-181741

Krishna P. Kaliappan; Velayutham Ravikumar

doi:10.1055/s-2007-973863

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Synlett 2007(6): 0977-0979
DOI: 10.1055/s-2007-973863

LETTER

First Enantioselective Total Synthesis of the Angucyclinone-Type Antibiotic YM-181741

Krishna P. Kaliappan*, Velayutham Ravikumar
Department of Chemistry, Indian Institute of Technology-Bombay, Powai, Mumbai 400076, India
Fax: +91(22)25723480; e-Mail: kpk@chem.iitb.ac.in;

Further Information

Publication History

Received 19 December 2006
Publication Date:
26 March 2007 (online)

Abstract
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Abstract

A simple and efficient strategy for angucyclinone antibiotics is described with the disclosure of first total synthesis of YM-181741.

Key words

Grubbs’ catalyst - enyne metathesis - Diels-Alder reaction - quinones - angucyclinone antibiotic

References and Notes

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11

HPLC conditions: YMC Pack Pro-C18, 4.6 × 250 mm, eluents H₂O-MeCN (10:90), flow 1.0 mL/min, UV detector at 254 nm; t _R = 2.928 min.

16

Spectral Data for Selected Compounds
Diene 15: R _f = 0.9 (EtOAc-PE, 3:7); [α]_D ²⁰ +99.1 (c 1.35, CHCl₃). IR (neat): 3454, 2930, 1655, 1465, 1257, 1104 cm^-1. ¹H NMR (400 MHz, CDCl₃): δ = 6.37 (2 H, dd, J = 17.6, 10.8 Hz), 5.75 (1 H, br s), 5.07 (1 H, d, J = 17.7 Hz), 4.9 (1 H, d, J = 10.8 Hz), 3.59-3.49 (2 H, m), 2.30-2.18 (2 H, m), 2.30-2.18 (1 H, m), 1.80-1.76 (2 H, m), 1.29-1.20 (1 H, m), 0.89 (9 H, s), 0.06 (6 H, s). ¹³C NMR (75 MHz, CDCl₃): δ = 140.0, 135.3, 129.6, 109.8, 67.9, 36.3, 26.9, 26.0, 25.3, 18.4, -5.4, -5.3. Compound 18: R _f = 0.4 (EtOAc-PE, 1:19); mp 86-88 °C; [α]_D ²⁰ +130.0 (c 0.9, CHCl₃). IR (KBr): 3444, 2896, 2930, 1667, 1634, 1454, 1284, 1256, 1107 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 12.55 (1 H, s), 8.14 (1 H, d, J = 8.4 Hz), 7.72 (1 H, dd, J = 7.6, 1.2 Hz), 7.64 (1 H, t, J = 7.8 Hz), 7.50 (1 H, d, J = 7.6 Hz), 7.24 (1 H, dd, J = 8.4, 1.2 Hz), 3.68-3.29 (2 H, m), 3.28-3.20 (1 H, m), 3.00 (1 H, dd, J = 17.2, 2.8 Hz), 2.67 (1 H, dd, J = 17.2, 10.8 Hz), 2.09-2.0 (2 H, m), 1.47-1.25 (1 H, m), 3.05-2.81 (2 H, m), 0.92 (9 H, s), 0.07 (6 H, s). ¹³C NMR (100 MHz, CDCl₃): δ = 188.8, 161.9, 146.2, 141.7, 136.6, 136.5, 135.1, 135.0, 132.8, 131.2, 124.8, 123.1, 119.4, 115.7, 67.5, 35.7, 34.5, 28.9, 26.1, 18.5, -5.1, -5.2; HRMS (EI): m/z calcd for C₂₅H₃₁O₄Si: 423.1992; found: 423.1981.
Ketone 19: R _f = 0.33 (EtOAc-PE, 1:9); mp 91-93 °C; [α]_D ²⁰ +56.5 (c 0.52, CHCl₃). IR (KBr): 3425, 2927, 1706, 1672, 1592, 1457, 1363, 1284, 1099 cm^-1. ¹H NMR (300 MHz, CDCl₃): δ = 12.30 (1 H, s), 8.30 (1 H, d, J = 7.8 Hz), 7.69 (1 H, dd, J = 5.4, 1.8 Hz), 7.65 (1 H, d, J = 7.8 Hz), 7.58 (1 H, d, J = 8.1 Hz), 7.28 (1 H, dd, J = 8.1, 2.1 Hz), 3.71 (1 H, dd, J = 9.9, 5.1 Hz), 3.62 (1 H, dd, J = 10.2, 6.3 Hz), 3.05-2.81 (2 H, m), 2.73 (2 H, dd, J = 16.2, 10.8 Hz), 2.56-2.49 (1 H, m), 0.91 (9 H, s), 0.07 (6 H, s). ¹³C NMR (100 MHz, CDCl₃): δ = 199.3, 187.6, 183.0, 162.2, 150.4, 137.2, 136.9, 135.8, 135.1, 133.5, 133.4, 129.1, 123.8, 119.8, 115.5, 66.2, 42.3, 38.0, 33.0, 26.0, 18.4, -5.3. HRMS (EI): m/z calcd for C₂₅H₂₉O₅Si: 437.1784; found: 437.1779.
Natural product YM 181741 (1): 68% yield (0.05 g); R _f = 0.3 (EtOAc-PE, 6:4); mp 192 °C; [α]_D ²⁵ +27.2 (c 0.367, CHCl₃). IR (KBr): 3433, 2927, 1702, 1671, 1588, 1453, 1362, 1276, 1588, 1453, 1362, 1276, 1215 cm^-1. UV (MeOH): λ_max (ε) = 276, 402 nm. ¹H NMR (400 MHz, CDCl₃): δ = 12.30 (1 H, s), 8.30 (1 H, d, J = 7.6 Hz), 7.68 (1 H, dd, J = 7.6, 2.4 Hz), 7.65 (1 H, d, J = 7.2 Hz), 7.58 (1 H, d, J = 8 Hz), 7.28 (1 H, dd, J = 8.0, 2.4 Hz), 3.77 (1 H, dd, J = 10.4, 4.8 Hz), 3.70 (1 H, dd, J = 7.2, 10.4 Hz), 3.10 (1 H, dd, J = 16.8, 4.8 Hz), 3.03 (1 H, dd, J = 16, 6.4 Hz), 2.85 (1 H, dd, J = 16.4, 10.4 Hz), 2.69 (1 H, dd, J = 16.0, 10.4 Hz), 2.61-2.54 (1 H, m), 1.86 (1 H, br s). ¹³C NMR (100 MHz, CDCl₃): δ = 198.8, 187.4, 182.9, 162.0, 149.8, 137.0, 136.7, 135.6, 134.9, 133.5, 133.2, 129.1, 123.8, 119.6, 115.4, 65.8, 42.0, 37.6, 32.7. HRMS (EI): m/z calcd for C₁₉H₁₅O₅: 323.0919; found: 323.0910.