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Synlett 2005(3): 433-436  
DOI: 10.1055/s-2004-837223
LETTER
© Georg Thieme Verlag Stuttgart · New York

Synthesis of Functionalized Cyclopentane for Pactamycin, a Potent Antitumor Antibiotic

Takashi Tsujimotoa, Toshio Nishikawa*a,b, Daisuke Urabeb, Minoru Isobe*b
a PRESTO of Japan Science and Technology Agency (JST), 4-1-8 Honcho, Kawaguchi, Saitama, 332-0012, Japan
b Graduate School of Bioagricultural Sciences, Nagoya University, Chikusa, Nagoya 464-8601, Japan
Fax: +81(52)7894111; e-Mail: nisikawa@agr.nagoya-u.ac.jp;
Further Information

Publication History

Received 11 November 2004
Publication Date:
22 December 2004 (online)

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Abstract

A tricyclic compound including a cyclopentane structure for pactamycin, an antitumor antibiotic, was constructed by Overman rearrangement and Pauson-Khand cyclization as key steps starting from diacetone-d-glucose.

Key words

pactamycin - natural products - antibiotics - Overman ­rearrangement - Pauson-Khand reaction

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Duchamp, D. J. American Crystallographic Association Winter Meeting, Albuquerque, N. M. 1972, Abstracts, p. 23.

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Spectral data of 6: colorless crystalline solids, mp 116-118 °C; [α]D 26 +41.4 (c 1.05, CHCl3). IR (NaCl, film): νmax = 3312, 2990, 1720, 1507, 1375, 1248, 1216, 1164, 1081, 1007, 872, 844, 822 cm-1. 1H NMR (300 MHz, CDCl3): δ = 1.35, 1.37, 1.49, 1.57 (each 3 H, s, acetonide), 3.96 (1 H, t, J = 8 Hz, H-6), 4.06 (1 H, dd, J = 8.0, 6.5 Hz, H6), 4.18 (1 H, d, J = 3.5 Hz, H-4), 4.56 (1 H, ddd, J = 8.0, 6.5, 3.5 Hz, H-5), 5.28 (1 H, d, J = 3.5 Hz, H-2), 5.43 (1 H, d, J = 11.0 Hz, CH=CHH), 5.44 (1 H, d, J = 17.5 Hz, CH=CHH), 5.92 (1 H, d, J = 3.5 Hz, H-1), 6.04 (1 H, dd, J = 17.5, 11.0 Hz, CH=CH2), 8.54 (1 H, s, NH) ppm.
13C NMR (75 MHz, CDCl3): δ = 25.8, 26.0, 26.5, 26.6, 66.0, 69.8, 75.4, 78.5, 83.7, 92.9, 103.9, 110.5, 112.4, 117.5, 131.0, 161.5 ppm. Anal. Calcd for C16H22NO6Cl3: C, 44.62; H, 5.15; N, 3.25. Found: C, 44.63; H, 5.12; N, 3.23.

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All attempts to synthesize the desired diastereomer 10 failed.

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Spectral data of 16a: colorless oil; [α]D 26 +88.8 (c 0.16, CHCl3). IR (NaCl, film): νmax = 3413, 2960, 2175, 1724, 1414, 1250, 1075, 845 cm-1. 1H NMR (300 MHz, CDCl3): δ = 0.13 (9 H, s, TMS), 1.52 (3 H, d, J = 7.0 Hz, CH 3), 2.49 (1 H, br, -OH), 2.85 (1 H, br, -OH), 4.58 (2 H, s, CH 2-Ph), 4.68 (1 H, br d, J = 5.0 Hz, CH2=CH-CH-OH), 4.94 (1 H, s, C≡C-CH-OH), 4.97 (1 H, q, J = 7.0 Hz, CHCH3), 5.37 (1 H, dt, J = 10.5, 1.5 Hz, CH AHB=CH), 5.52 (1 H, dt, J = 17.0, 1.5 Hz, CHA H B=CH), 5.99 (1 H, ddd, J = 17.0, 10.5, 5.0 Hz, CH2=CH), 7.25-7.42 (5 H, m, Ph) ppm. 13C NMR (75 MHz, CDCl3): δ = -0.5, 15.9, 46.6, 65.0, 69.9, 72.3, 75.8, 94.9, 101.8, 119.6, 127.6, 128.5, 128.7, 135.1, 137.9, 159.0 ppm. Anal. Calcd for C20H27NO4Si: C, 64.31; H, 7.29; N, 3.75. Found: C, 64.28; H, 7.13; N, 3.71.

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Spectral data of 19: [α]D 26 +26.7 (c 0.55, CHCl3). IR (NaCl, film): νmax = 2956, 1755, 1705, 1621, 1497, 1386, 1212, 1086, 976, 887 cm-1. 1H NMR (400 MHz, CDCl3): δ = 0.21 (9 H, s, TMS), 1.37 (3 H, d, J = 6.0 Hz, CH 3), 1.77 (1 H, dd, J = 17.5, 4.5 Hz, CH AHB-C=O), 1.97 (3 H, s, Ac), 2.13 (3 H, s, Ac), 2.33 (1 H, dd, J = 17.6, 6.8 Hz, CHA H B-C=O), 3.54 (1 H, m, CHCH2), 4.08 (1 H, d, J = 17.2 Hz, -CH AHB-Ph), 4.70 (1 H, q, J = 6.0 Hz, CHCH3), 5.24 (1 H, d, J = 5.6 Hz, CH-CHOAc), 5.24 (1 H, d, J = 17.2 Hz, CHA H B-Ph), 6.04 (1 H, d, J = 1.6 Hz, C=C-CH-OAc), 7.41-7.24 (5 H, m, Ph) ppm. 13C NMR (75 MHz, CDCl3): δ = -1.6, 17.5, 20.3, 20.4, 38.9, 47.2, 48.5, 73.4, 74.9, 76.8, 77.8, 126.2, 128.1, 129.2, 137.1, 144.7, 158.2, 168.9, 169.1, 181.7, 211.2 ppm. HRMS (FAB+): m/z calcd for C25H32NO7Si [M + H]: 486.1948; found: 486.1930.

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Another fraction contained an inseparable mixture of two minor products, whose structures have not been elucidated.