Design and implementation of an efficient synthetic approach to furanosylated indolocarbazoles: Total synthesis of (+)- and (-)-K252a

Journal of the American Chemical Society

Volumn 119, Issue 41, 1997, Pages 9641-9651

  Wood, John L ^a   Stoltz, Brian M ^a   Dietrich, Hans Jürgen ^a   Pflum, Derek A ^a   Petsch, Dejah T ^a  

^a YALE UNIVERSITY   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

K 252A;

DIASTEREOISOMER; DRUG SYNTHESIS; NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY; REACTION ANALYSIS; REVIEW; STEREOCHEMISTRY;

EID: 0030670394     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja9713035     Document Type: Review

References (104)

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45. Recently, we reported the synthesis of (+)- and (-)-K252a in a communication; see: Wood, J. L.; Stoltz, B. M.; Dietrich, H.-J. J. Am. Chem. Soc. 1995, 117, 10413.
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58. In terms of substrates, this approach is similar to attempted Diels Alder reactions between maleimides and biindole 20. These efforts have met with limited success; see: (a) Kaneko, T.; Wong, H.; Okamoto, K. T.; Clardy, J. Tetrahedron Lett. 1985, 26, 4015.
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67. See following paper in this issue.
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70. Details regarding the crystallographic analyses have been deposited in the Cambridge Crystallographic database and are included as Supporting Information.
71. In the actual course of events, these studies paralleled our efforts to optimize the preparation of 4a-e.
72. 1H NMR between a and β ester signals in 8b.
73. Ultimately, the regio- and stereochemical outcome of the cyclogly-cosidation was deduced from the fact that the major isomer produces the natural product.
74. 1H NMR.
75. Initially, attempts to cycloglycosidate 4c with acetates (±)-30a,b failed. This result was clarified upon isolation of furan i in 53% yield following reaction of carbazole (16) with (±)-30a,b.
76. 32
77. Aglycons 4b,d, and e could be cycloglycosidated with similar results; however, only the products arising from 4d were successfully deprotected.
78. Weygand, F.; Steglich, W.; Bjarnason, J.; Akhtar, R.; Khan, N. M. Tetrahedron Lett. 1966, 29, 3483.
79. More recently, substituted benzyl amides have been utilized in the tirandamycin area and the 3,4-DMB group was successfully used in a synthesis of the tetrapyrrole pigment precursor porphobilinogen; see: (a) Schlessinger, R. H.; Bebernitz, G. R.; Lin, P.; Poss, A. J. J. Am. Chem. Soc. 1985, 107, 1777.
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82. The well-known tendency of indolocarbazoles to undergo Friedel - Crafts reactions necessitated using a large excess of scavenger. For examples of this Friedel-Crafts reactivity, see: (a) Nakanishi, S.; Yamada, K.; Iwahashi, K.; Kuroda, K.; Kase, H. Mol. Pharmacol. 1990, 37, 482.
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84. In the absence of a cation scavenger, an appreciable amount of iii is formed along with (±)-2.
85. We thank the Bayer Corp. for a sample of nat-(+)-K252a.
86. For a recent example describing the use of RAMP and SAMP hydrazones in the alkylation of β-keto esters, see: Enders, D.; Zamponi, A.; Schäfer, T.; Nübling, C.; Eichenauer, H.; Demir, A. S.; Raabe, G. Chem. Ber. 1994, 127, 1707.
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90. The Sharpless kinetic resolution protocol provides a convenient means of accessing a variety of allylic alcohols of very high optical purity; see: Gao, Y.; Hanson, R. M.; Klunder, J. M.; Ko, S. Y.; Masamune, H.; Sharpless, K. B. J. Am. Chem. Soc. 1987, 109, 5765.
91. (a) Koreeda, M.; Luengo, J. I. J. Am. Chem. Soc. 1985, 107, 5572.
92. (b) Examples of both [2,3] and [3,3] rearrangements of α-allyloxy ketones have been reported; see: Ziegler, F. E. Chem. Rev. 1988, 88, 1423 and references therein.
93. For a leading reference to the Lewis acid-catalyzed α-ketol rearrangement, see: Crout, D. H. G.; Rathbone, D. L. J. Chem. Soc., Chem. Commun. 1987, 290.
94. 1H NMR) of the derived allylic alcohol established an optical purity of 98% ee.
95. The dramatic increase in yield over the two-step procedure is attributed to the difficulties of isolating the somewhat volatile products (+)-40 and (-)-41b.
96. These studies were performed simultaneously in the racemic series.
97. Compound 42 has been prepared previously from citramalic acid and is of known absolute configuration; see: Gill, M.; Smrdel, A. F. Tetrahedron Asymmetry 1990, 1, 453.
98. In the absence of rhodium, one would likely attribute the observed stereochemistry to reaction via a chair transition structure possessing a (Z)-enol and an equatorial methyl substituent (i.e., iv). However, unpublished results from these laboratories suggest the apparent involvement of rhodium, hence this rationalization may eventually require refinement.
99. Compound 45 has been prepared previously and is of known absolute stereochemistry; see: Spencer, H. K.; Khatri, H. N.; Hill. R. K. Bioorg. Chem. 1976, 5, 177.
100. 2 is unable to form a chelate its role, if any, in enforcing this transition structure is not obvious.
101. 34
102. 13C chemical shifts are reported as δ values relative to tetramethylsilane. High-resolution mass spectra were performed at The University of Illinois Mass Spectrometry Center. Microanalyses were performed by Atlantic Microlab (Norcross, GA). Single-crystal X-ray analyses were performed by Dr. Susan DeGala of Yale University.
103. The material obtained proved identical to a sample purchased from Aldrich Chemical Co.
104. Due to space limitations, spectral data pertaining to the b, d, and e analogs are provided as Supporting Information.