Synthesis of Functionalized Cyclopentane for Pactamycin, a Potent Antitumor Antibiotic

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.

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

References

1a Bhuyan BK. Dietz A. Smith CG. Antimicrob. Agents Chemother.  1962,  184 

1b Argoudelis AD. Jahnke HK. Fox JA. Antimicrob. Agents Chemother.  1962,  191 

2 Weller DD. Rinehart KL. J. Am. Chem. Soc.  1978,  100:  6757 

3 Wiley PF. Jahnke HK. MacKellar F. Kelly RB. Argoudelis A. J. Org. Chem.  1970,  35:  1420 

4

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

5 Adama ES. Rinehart KL. J. Antibiot.  1994,  47:  1456 

6 Cohen LB. Goldberg IH. Herner AE. Biochemistry  1969,  8:  1327 

The crystal structure of the complex of pactamycin with a ribosomal 30S subunit was reported. See:

7a Brodersen DE. Clemons WM. Carter AP. Morgan-Warren RJ. Wimberly BT. Ramakrishnan V. Cell  2000,  103:  1143 

7b Dinos G. Wilson DN. Teraoka Y. Szaflarski W. Fucini P. Kalpaxis D. Nierhaus KH. Mol. Cell  2004,  13:  113 

For reviews of Pauson-Khand reaction, see:

8a Pauson PL. Tetrahedron  1985,  41:  5855 

8b Shore NE. Org. React.  1991,  40:  1 

For reviews of the Overman rearrangement, see:

9a Overman LE. Acc. Chem. Res.  1980,  13:  218 

9b Ritter K. Stereoselective Synthesis, In Houben-Weyl   Vol. E21:  Helmchen G. Hoffmann RW. Mulzer J. Schaumann E. Thieme; Stuttgart: 1996.  p.5677 

9c Sato H. Oishi T. Chida N. J. Synth. Org. Jpn.  2004,  62:  693 

10 Tadano K.-I. Idogaki Y. Yamada H. Suami T. J. Org. Chem.  1987,  52:  1201 

11 We have synthesized 6 according to the procedure described by Tadano and co-workers except for oxidation of diacetone-d-glucose(7); TPAP was employed instead of PCC because of environmental consideration. See: Ley SV. Norman J. Griffith WP. Marsden SP. Synthesis  1994,  639 

12 Nishikawa T. Asai M. Ohyabu N. Isobe M. J. Org. Chem.  1998,  63:  188 

13

Spectral data of 6: colorless crystalline solids, mp 116-118 °C; [α]_D ²⁶ +41.4 (c 1.05, CHCl₃). IR (NaCl, film): ν_max = 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.

14a Gonda J. Bednárikova M. Tetrahedron Lett.  1997,  38:  5569 

14b Eguchi T. Kakinuma K. J. Synth. Org. Jpn.  1997,  55:  814 

15 Iio H. Isobe M. Kawai T. Goto T. Tetrahedron  1979,  35:  941 

16

All attempts to synthesize the desired diastereomer 10 failed.

17 Gemal AL. Luche J.-L. J. Am. Chem. Soc.  1981,  103:  5454 

18 Oishi T. Ando K. Inomiya K. Sato H. Iida M. Chida N. Bull. Chem. Soc. Jpn.  2002,  75:  1927 

19 Tipson RS. Cohen A. Carbohydr. Res.  1965,  1:  338 

20

Spectral data of 16a: colorless oil; [α]_D ²⁶ +88.8 (c 0.16, CHCl₃). IR (NaCl, film): ν_max = 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 _AH_B=CH), 5.52 (1 H, dt, J = 17.0, 1.5 Hz, CH_A 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.

21 Mukai C. Kim JS. Uchiyama M. Sakamoto S. Hanaoka M. J. Chem. Soc., Perkin Trans. 1  1998,  2903 

22

Spectral data of 19: [α]_D ²⁶ +26.7 (c 0.55, CHCl₃). IR (NaCl, film): ν_max = 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 _AH_B-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, CH_A H _B-C=O), 3.54 (1 H, m, CHCH₂), 4.08 (1 H, d, J = 17.2 Hz, -CH _AH_B-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, CH_A 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.

23

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