@article{67f5c9ba6eb044f797f55440f5b57019,
title = "A synthesis of (-)-indolactam V",
abstract = "(-)-Indolactam V (1) was synthesized in 14 steps from 2,6-dinitrotoluene in 15% overall yield via enantiospecific SN2 displacement of a chiral triflate with the 4-amino group of a 4-aminoindole and coupling of 3-bromomethyl indole with Sch{\"o}llkopf's asymmetric bislactim ether.",
author = "Semmelhack, {M. F.} and Hakjune Rhee",
note = "Funding Information: References 1. Indolactam V (1) is the central structure of a family of tumor promoters including the t&&dins (e.g., 2), olivoretin6, and lyngbyatoxins. For a review, see: Fujiki, H.; Sugimura, T. Adv. Cancer. Res., 1987,49,223. 2. Indolactam V (l), a likely biogenetic precursor of the teleocidins, was isolated from Strepromyces mediocidicus: (a) Irie, K.; Hirota, M.; Hagiwara, N.; Hayashi, H.; Murao, S.; Tokuda, H.; Ito, Y. Agric. Biol. Chem. 1984,48, 1269. It has been the subject of several successful synthesis efforts; for a recent example and leading references, see: (b) Kogan, T. P.; Somers, T. C.; Venuti, M. C. Terruhedron1 990,46,6623. 3. Semmelhack, M. F.; Wulff, W.; Garcia, J. L. J. Organomet.C hem. 1982,240, C5. 4. For a recent review, see: Semmelhack, M. F., in “Comprehensive Org. Synthesis,” Vol 4, M. F. Semmelhack, ed., Pergamon, NY (1992). 5. Keller, L.; Times-Marshall, K.; Behar, S.; Richards, K. TerruhedronL en. 1989,30, 3373. 6. Beswick, P. J.; Greenwood, C. S.; Mowlem, T. J.; Neuchatel, G.; Widdowson, D. A. Tetrahedron, 1988,44, 7325. 7. Clark, R. B.; Repke, V. B. Heterocycles1 984,22, 195. 8. Complexation was attempted with a various group6 attached to the indole nitrogen, including H, Me, SiR3, MgMe, Na, Cu, and ZnBr. Only in the case of Zn reagents was a yield in excess of 15% obtained. 9. Kruse, L. I. Heterocycles, 1981,16, 1119. 10. In our hands, using a 4-(N,N-diall@mino)indole substrate, formylation leads to reaction at C-3 and C-5 in a ratio of 23. For related earlier results see: (a) Clementi, S.; Linda, P.; Marino, G. J. Chem. Sot., Chem. Commun. 1972, 427. (b) Anthony, W. C. .I. Org. Chem. 1960,25, 2049. (c) Nogrady, T.; Morris, L. Can. J. Chem. 1969,47, 1999. (d) Smith, G. F. J. Chem. Sot. 1954, 3842. (e) Tyson, F. T.; Shaw, J. T. J. Am. Chem. Sot. 1952,74, 2273. 11. (a) Weygand, F.; Frauendorfer, E. Chem. Ber. 1970,103, 2437. (b) Planner, P. A.; Vogler, K.; Studer, R. 0.; Quitt, P.; Keller-Schierlein, W. Helv. Chim. Acru 1963,46, 927. 12. Schollkopf, U.; Lonsky, R.; Lehr, P. Liebigs Ann. Gem. 1985,413. 13. An analyticals ample was obtained by recrystallization from dichloromethane and hexane: mp 43-45 “C; [a]u = -35.5 (c = 0.08, CH2C12, 20 “C); IR (Thin film) 2973, 2943, 1732, 1694, 1460, 1426, 1369, 1288, 1236, 1159,1118, 1013,735 cm-1; 1H NMR (270 MHz, CDCl3, at 53 “C) 8 7.95 (dd, lH, J = 7.4, 1.5 Hz, H at C-7), 7.68 (6, lH, H at C-2), 7.15 (t, lH, J = 7.8 Hz, H at C-6), 7.11 (dd, lH, J = 7.8, 1.7 Hz, H at C-S), 4.32 (m, IH, H at C-9), 4.01 (dd, lH, J = 15.3, 3.6 Hz, H at C-8 Hs/Hh), 3.98 (d, lH, J = 6.9 Hz, H at C-12), 3.69 (6, 6I-I, H{\textquoteright}s at C-11 and C-16), 3.53 (d, lH, J = 7.3 Hz, H at C-18), 3.07 (dd, lH, J = 15.8, 8.9 Hz, Hat C-8 Ha/I-It)), 2.81 (6, 3H, H at C-17), 2.26 (m, 2H, H{\textquoteright}s at C-13 and C-19), 1.64 (6, 9H, H at C-26), 1.28 (6, 9H, H at C-23), 1.09 (d, 3H, J = 6.9 Hz, H at C-20/20{\textquoteright}), 1.07 (d, 3H, J = 6.9 Hz, H at C-14/14{\textquoteright}), 1.00 (d, 3H, J = 6.6 Hz, H at C-20/20{\textquoteright}), 0.75 (d, 3H, J = 6.6 Hz, H at C-14114{\textquoteright}); *3C NMR (67.9 MHz, CDC13) 8 171.57 (6, C-21), 163.90 (6, C-10/15), 163.29 (6, C-10/15), 149.71 (6, C-24), 147.37 (6, C-7a), 136.63 (6, C-4), 126.55 (d, C-2), 124.06 (d, C-7), 123.47 (6, C-3), 118.22 (6, C-3a), 116.74 (d, C-6), 111.62 (d, C-5), 82.85 (6, C-25), 80.48 (6, C-22), 73.24 (d, C-18), 60.80 (q, C-11/16), 55.94 (d, C-9), 52.37 (d, C-12), 52.21 (q, C-11/16), 31.81 (q, C-17), 30.88 (t, C-8), 28.55 (d, C-19/13), 28.19 (q, C-26), 27.89 (q, C-23), 20.14 (d, C-13/19), 19.08 (q, C-20 and C-20{\textquoteright}), 16.77 (q, C-14 and C-14{\textquoteright}); MS (EI) m/e (rel intensity) 598 &I+, 8.3), 555 (20.4), 497 (38.4), 441 (26.5), 397 (60.2), 259 (15.0), 213 (96.5), 184 (22.1), 171 (19.0), 141 (31.4), 78 (100.0). 14. Castro, B.; Dormoy, J. R.; Evin, G.; and Selve, C. TetrahedronL eft., 1975, 1219. 15. Webb II, R. R.; Venuti, M. C.; Eigenbrot, C. J. Org. Chem. 1991,56, 4706. 16. (a) Endo, Y.; Shudo, K.; Itai, A.; Hasegawa, M.; Sakai, S. Tetrahedron, 1986,42,5905. (b) tie, K.; Koshimizu, K. Mem. CON. Agric., Kyoto Univ. 1988,132, 1. 17. Soai, K.; Okawa, A. J. Org. Chem. 1986,51,4000. lg. We wish to &nowledge support from the National Institutes of Health (GM 31352) and a generous gift of synthetic (-)-indolactam V from Dr. T. P. Kogan (Genentech).",
year = "1993",
month = feb,
day = "26",
doi = "10.1016/S0040-4039(00)60300-3",
language = "English (US)",
volume = "34",
pages = "1395--1398",
journal = "Tetrahedron Letters",
issn = "0040-4039",
publisher = "Elsevier Limited",
number = "9",
}