Skip to main content
SpringerLink
Log in
Book cover

Progress in the Chemistry of Organic Natural Products pp 1–80Cite as

Cephalostatin Analogues — Synthesis and Biological Activity

  • Chapter

Part of the book series: Progress in the Chemistry of Organic Natural Products ((FORTCHEMIE (closed),volume 87))

Abstract

The cephalostatin field started off with the seminal publication of Pettitet al.in 1988 describing structure and biological activity of cephalostatin 1 (1) (84).Since then several reviews have covered the activities regarding isolation, structure elucidation, biological activities, and synthetic efforts up to 1995 (1,2,34–36,54,111). This account will focus on the synthesis and biological activity of cephalostatin analogues as published until early 2002. The authors understand the purpose of this review to provide a complete overview of the cephalostatin/ritterazine analogue field. However, this article will in parts be biased to describe some work of the Winterfeldt group in more detail, based on the personal experience of the authors.

This is a preview of subscription content, log in via an institution.

Chapter
USD   29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD   84.99
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD   109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD   109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Learn about institutional subscriptions

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. Atta-ur-Rahmann, Choudary MI (1997) Diterpenoid and steroidal alkaloids. Nat Prod Rep14:191

    Google Scholar 

  2. Atta-ur-Rahmann, Choudary MI (1999) Chemistry and biology of steroidal alkaloids from marine organisms. Alkaloids52:233

    Google Scholar 

  3. Adam W, Bialas J, Hadjiarapoglou L (1991) A convenient preparation of acetone solutions of dimethyldioxirane. Chem Ber124:2377

    CAS  Google Scholar 

  4. Baesler S, Brunck A, Jautelat R, Winterfeldt E (2000) Synthesis of cytostatic tetradecacyclic pyrazines and a novel reduction-oxidation sequence for spiroketal opening in sapogenins. Helv Chim Acta83:1854

    Google Scholar 

  5. Banert K, Köhler F (2001) Synthesis of 1,4-Diazidobuta-l,3-dienes by Electrocyclic Ring Opening: Precursors for Bi-2H-azirin-2-yls and Their Valence Isomerization to Diazabenzenes. Angew Chem Int Ed40:174, and references therein

    CAS  Google Scholar 

  6. Banert K (1993) In: Houben Weyl, Methoden der Organischen Chemie, 4th ed, volE15p 818

    Google Scholar 

  7. Bhandaru S, Fuchs PL (1995) Cephalostatin chemistry. 7. Synthesis of C14’,15’ dihydro derivative of the south hexacyclic steroid unit of cephalostatin 1. Part I. Regiospecific Rh[II]-mediated intermolecular oxygen alkylation of a primary neopentyl alcohol. Tetrahedron Lett36:8347

    CAS  Google Scholar 

  8. Bladon P, McMeekin W, Williams IA (1963) Steroids derived form hecogenin. Part III. The Photochemistry of hecogenin acetate. J Chem Soc: 5727

    Google Scholar 

  9. Bovicelli P, Lupattelli P, Fracassi D, Minocione E (1994) Sapogenins and dimethyldioxirane: A new entry to cholestanes functionalized at the side chain. Tetrahedron Lett35:935

    CAS  Google Scholar 

  10. Boyd MR, Paull KD (1995) Some practical consideration and applications of the NCIin vitrodrug discover screen. Drug Dev Res34:91

    CAS  Google Scholar 

  11. Boyd MR (1997) In: B. Teicher B (ed) Anticancer Drug Development Guide; Humana Press, Totowas, NJ, p 23

    Google Scholar 

  12. Breslow R, Corcoran RJ, Snider BB, Doll RJ, Khanna PL, Kaleya R (1977) Selective halogenation of steroids using attached aryl iodide templates. J Am Chem Soc99:905

    CAS  Google Scholar 

  13. Breslow R (1995) Biomimetic chemistry and artificial enzymes: catalysis by design. Acc Chem Res28:146

    CAS  Google Scholar 

  14. Campbell MM, Craig RC, Boyd AC, Gilbert IM, Logan RT, Redpath J, Roy RG, Savage DS, Sleigh T (1979) Amino-steroids. Part 6. Stereospecific synthesis of eight, isomeric, steroidal vincinal 2,3-amino-alcohols. J Chem Soc, Perkin Trans I: 2235

    Google Scholar 

  15. Cerny I, Pouzar V, Budesinsky M, Drasar P (2000) Synthesis of symmetrical bis-steroid pyrazines connected via D-rings. Collect Czech Chem Commun65:1597

    CAS  Google Scholar 

  16. Chinn LJ (1967) Oxidation and solvaolysis of lumi-and photohecogenin and their derivatives. J Org Chem32:687

    CAS  Google Scholar 

  17. Dauben WG, Wight HG, Boswell GA (1958) An Ozonide of Cholestenone. J Org Chem23:1787

    CAS  Google Scholar 

  18. Djerassi C, Voelter W (1968) Katalytische Hydrierungen and Deuterierungen von Steroiden in homogener Phase. Chem Ber101:58

    Google Scholar 

  19. Drögemüller M, Jautelat R, Winterfeldt E (1996) Directed synthesis of nonsymmetrical bis-steroidal pyrazines and the first biologically active cephalostatin analogs. Angew Chem Int Ed35: 1572

    Google Scholar 

  20. Drögemüller M, Flessner T, Jautelat R, Scholz U, Winterfeldt E (1998) Synthesis of cephalostatin analogs by symmetrical and non-symmetrical routes. Eur J Org Chem 2811

    Google Scholar 

  21. Eder U, Sauer G, Wiechert R (1971) Neuartige asymmetrische Cyclisierung zu optisch aktiven Steroid-CD-Teilstücken. Angew Chem83:492

    Google Scholar 

  22. Fieser LF, Fieser M (1959) Steroids, Rheinhold: New York, and references therein.

    Google Scholar 

  23. Flessner T (1999) Beiträge zur chemischen Diversität der Cephalostatine, Dissertation, University of Hannover

    Google Scholar 

  24. Flessner T, Doye S (1999) Cesium carbonate: A powerful inorganic base in organic synthesis. J Prakt Chem341:186

    CAS  Google Scholar 

  25. Flessner T, Ludwig V, Siebeneicher H, Winterfeldt E (2003) A practical route to a complex bis-steroidal diene-intermediate using a microwave-assisted Heck reaction. Synthesis: 1373

    Google Scholar 

  26. Fürst A, Plattner A (1949) Über Steroide and Sexualhormone. 2α,3α-and 2,β,3βOxido-cholestane; Konfiguration der 2-Oxy-cholestane. Helv Chim Acta32:275

    Google Scholar 

  27. Fukuzawa S, Matsunaga S, Fusetani N (1994) Ritterazine A, a highly cytotoxic dimeric steroidal alkaloid, from the tunicate Ritterella tokioka. J Org Chem59:6164

    CAS  Google Scholar 

  28. Fukuzawa S, Matsunaga S, Fusetani N (1994) Ritterazines, highly cytotoxic dimeric steroidal alkaloids, from the tunicate Ritterella tokioka. Tennen Yuki Kogabutsu Toronkai Koen Yoshisbu36:81

    Google Scholar 

  29. Fukuzawa S, Matsunaga S, Fusetani N (1995) Bioactive marine metabolites. 71. Ten more ritterazines, cytotoxic steroidal alkaloids from the tunicate Ritterella tokioka. Tetrahedron51:6707

    CAS  Google Scholar 

  30. Fukuzawa S, Matsunaga S, Fusetani N (1995) Isolation and structure elucidation of ritterazines B and C, highly cytotoxic dimeric steroidal alkaloids, from the tunicate Ritterella tokioka. J Org Chem60:608

    CAS  Google Scholar 

  31. Fukuzawa S, Matsunaga S, Fusetani N (1996) Bioactive marine metabolites series. 74. Use of 15N-HMBC NMR techniques to determine the orientation of the steroidal units in ritterazine A. Tetrahedron Lett 37: 1447

    CAS  Google Scholar 

  32. Fukuzawa S, Matsunaga S, Fusetani N (1996) Structure-activity relationships for the ritterazines, highly cytotoxic dimeric steroidal alkaloids of the tunicate ritterella tokioka. Tennen Yuki Kogabutsu Toronkai Koen Yoshisbu38:73

    Google Scholar 

  33. Fukuzawa S, Matsunaga S, Fusetani N (1997) Isolation of 13 new ritterazines from the tunicate Ritterella tokioka and chemical transformation of ritterazine B. J Org Chem62:4484

    CAS  Google Scholar 

  34. Ganesan A, Heathcock CH (1988) Isolation and structure of the powerful cell growth inhibitor cephalostatin 1. Chemtracts: Org Chem1:311

    CAS  Google Scholar 

  35. Ganesan A (1996) The dimeric steroid-pyrazine marine alkaloids: challenges for isolation, synthesis, and biological studies. Angew Chem Int Ed35:611

    CAS  Google Scholar 

  36. Ganesan A (1996) When two steroids are better than one: The dimeric steroidpyrazine marine alkaloids. Stud Nat Prod Chem18:875

    CAS  Google Scholar 

  37. Garai S, Mahato SB (1997) Novel reduction and hydroxylation products formed by Aspergillus fumigatus from Reichstein’s Substance S. Steroids62:253

    CAS  Google Scholar 

  38. Grieco PA, Masaki Y, Boyler D (1975) Sesterterpenes. I. Stereospecific total synthesis of moenocinol. J Am Chem Soc97:1597

    CAS  Google Scholar 

  39. Guo C, Bhandaru S, Fuchs PL (1996) An Efficient Protocol for the Synthesis of Unsymmetrical Pyrazines. Total Synthesis of Dihydrocephalostatin 1. J Am Chem Soc118:10672

    CAS  Google Scholar 

  40. Guo C, LaCour TG, Fuchs PL (1999) Cephalostatin support studies. 15. On the relationship of OSW-1 to the cephalostatins. Bioorg Med Chem Lett9:419

    CAS  Google Scholar 

  41. Gutknecht H (1879) Chem Ber12:2292

    Google Scholar 

  42. Haase-Held M, Hatzis M, Mann J (1992) The synthesis of 4-cyanoprogesterone: a potent inhibitor of the enzyme 5-a-reductase. J Chem Soc Perkin Trans I, 2999

    Google Scholar 

  43. Hajos ZG, Parrish DR (1974) Asymmetric synthesis of bicyclic intermediates of natural product chemistry. J Org Chem39:1615

    CAS  Google Scholar 

  44. Hajos ZG, Parrish DR (1985) Tetrahydro-7a-methyl-1H-indenedione. Org Synth63:26

    CAS  Google Scholar 

  45. Hamann PE, Habermehl GG (1987) Synthesis of apocholic acid derivatives by photochemical rearrangement of 12-oxo-steroids. Z Naturforsch42b:781

    Google Scholar 

  46. Hanson JR, Uyanik C (1998) Simple routes to keto-norsteroids. J Chem Research (Synopsis)5:221

    Google Scholar 

  47. Hassner A, Fowler FW (1968) Synthesis and reactions of lazirines. J Am Chem Soc90:2869

    CAS  Google Scholar 

  48. Hassner A (1971) Regiospecific and stereospecific introduction of azide functions into organic molecules. Acc Chem Res4:9, and references cited therein

    CAS  Google Scholar 

  49. Heathcock CH, Smith SC (1994) Synthesis and Biological Activity Of Unsymmetrical Bis-Steroidal Pyrazines Related to the Cytotoxic Marine Natural Product Cephalostatin 1. J Org Chem59:6828

    CAS  Google Scholar 

  50. Honda H, Mimaki Y, Sashida Y, Kogo H (1997) Influence of OSW-1, a steroidal saponin, on endothelium dependent relaxation caused by acetylcholine in rat aorta. Biol Pharm Bull20:428

    CAS  Google Scholar 

  51. Holland HL, Dore S, Xu W, Brown FM (1994) Formation of 5a steroids by biotransformation involving the 5a-reductase activity ofpenicillium decumbens.Steroids59:642

    CAS  Google Scholar 

  52. Holland HL, Nguyen H, Pearson NM (1995) Biotransformation of corticosteroids bypenicillium decumbensATCC 10436. Steroids60:646

    CAS  Google Scholar 

  53. Hotopp T (1996) Die erste stereoselective Totalsynthese von (—)-Myltaylenol. Dissertation, University of Hannover

    Google Scholar 

  54. Jacobs MF, Kitching W (1998) Spiroacetals of marine origin. Curr Org Chem2:395

    CAS  Google Scholar 

  55. Jautelat R, Müller-Fahrnow A, Winterfeldt E (1996) Photochemistry of Hecogenine Acetate Revisited. J Prakt Chem338:695

    CAS  Google Scholar 

  56. Jautelat R, Winterfeldt E, Kramer A (1997) Preparation of symmetrical and asymmetrical cephalostatins, cephalostatin analogs and pharmaceutical preparations containing them, as well as the application of these drugs. Ger Offen (patent) DE 19620146 Al (CA 128:23056)

    Google Scholar 

  57. Jautelat R, Müller-Fahmow A, Winterfeldt E (1999) A Novel Oxidative Cleavage of the Steroidal Skeleton. Chem Eur J5:1226

    CAS  Google Scholar 

  58. Jeffery T (1984) Palladium-catalysed vinylation of organic halides under solid-liquid phase transfer conditions. J Chem Soc Chem Commun: 1287

    Google Scholar 

  59. Jeffery T (1985) Highly stereospecific palladium-catalysed vinylation of vinylic halides under solid-liquid phase transfer conditions. Tetrahedron Lett26:2667

    CAS  Google Scholar 

  60. Jeong JU, Fuchs PL (1994) Synthesis of a 17-Deoxy, C-14,15-Dihydro Derivative of the North Spiroketal Moiety of the Cephalostatins. Conversion to a (+)-Trisdecacyclic C2 Symmetrical Pyrazine. J Am Chem Soc116:773

    CAS  Google Scholar 

  61. Jeong JU, Sutton SC, Kim SH, Fuchs PL (1995) Biomimetic Total Syntheses of (+)Cephalostatin 7, (+)-Cephalostatin 12, and (+)-Ritterazine K. JAm Chem Soc117:10157

    CAS  Google Scholar 

  62. Kamano Y, Inoue M, Pettit GR, Dufresne C, Christie N, Herald DL (1988) Chemistry of the powerful cell growth inhibitors cephalostatins, isolated from the South African marine worm Cephalodiscus gilchristi. Tennen Yuki Kogabutsu Toronkai Koen Yoshisbu30:220

    CAS  Google Scholar 

  63. Kim SH, Jin Z, Fuchs PL (1995) Synthesis of beta-substituted cyclopentenones via carbon alkylation of metalated gamma-methoxycyclopentenyl phenylsulfonyl anion. Tetrahedron Lett36:4537

    CAS  Google Scholar 

  64. Kimura M, Kawata M, Thoma M, Fujino A, Yamazaki K, Sawaya T (1972) Metal ion catalysed oxidation of steroids. I. 15a-hydroxylation of deoxycholic acid in aqueous solution by ferrous ion-molecular oxygen system. Chem Pharm Bull20:1883

    CAS  Google Scholar 

  65. Kramer A, Ullmann U, Winterfeldt E (1993) A short route to cephalostatin analogs. J Chem Soc, Perkin Trans I: 2865

    Google Scholar 

  66. Kubo A, Nakagawa K, Varma RK, Conrad NK, Cheng JQ, Lee WC, Testa JR, Johnson BE, Kaye FJ, Kelley MJ (1999) The p16 status of tumor cell lines identifies small molecule inhibitors specific for cyclin-dependent kinase 4. Clin Canc Res5:4279

    CAS  Google Scholar 

  67. LaCour TG, Guo C, Bhandaru S, Boyd MR, Fuchs PL (1998) Interphylal Product Splicing: The First Total Syntheses of Cephalostatin 1, the North Hemisphere of Ritterazine G, and the Highly Active Hybrid Analog, Ritterostatin GN1N. J Am Chem Soc120:692

    CAS  Google Scholar 

  68. LaCour TG, Tong Z, Fuchs PL (1999) Consequences of Acid Catalysis in Concurrent Ring Opening and Halogenation of Spiroketals. Org Lett1:1815

    CAS  Google Scholar 

  69. LaCour TG, Fuchs PL (1999) Cephalostatin synthesis. 17. Concurrent ring opening and halogenation of spiroketals. Tetrahedron Lett40:4655

    CAS  Google Scholar 

  70. LaCour TG, Guo C, Boyd MR, Fuchs PL (2000) Outer-Ring stereochemical modulation of cytotoxicity in cephalostatins. Org Lett2:33

    CAS  Google Scholar 

  71. Laurent H, Schulz G, Wiechert R (1969) Darstellung und Reaktionen von 6,7disubstituierten 3-oxo-1α,2α-methylen-△4-steroiden. Chem Ber102:2570

    CAS  Google Scholar 

  72. Liotta D (1987) Organoselenium ChemistryJ.Wiley & Sons, p 209

    Google Scholar 

  73. Lotowski Z, Dubis EN, Morzycki JW (2000) Functionalization of dimeric cholestanopyrazines at the quasi-benzylic position. Monatsh Chem131:65

    CAS  Google Scholar 

  74. Mimaki Y, Kuroda M, Kameyama A, Sashida Y, Hirano T, Oka K, Maekawa R, Wada T, Sugita K, Beutler JA (1997) Cholestane glycosides with potent cytostatic activities on various tumor cells from ornithogalum saundersiae bulbs. Bioorg Med Chem Lett7:633

    CAS  Google Scholar 

  75. Miyamoto K, Kubodera N, Murayama E, Ochi K, Mori T, Matsunaga I (1986) Synth Commun16: 513

    Google Scholar 

  76. Moriarty RM, Hu H, Gupta SC (1981) Direct a-hydroxylation of ketones using iodosobenzene. Tetrahedron Lett22:1283

    CAS  Google Scholar 

  77. Moriarty RM, Gupta SC, Hu H, Berenschot DR, White KB (1981) Oxygen-atom transfer form iodosobenzene to ketenes, α-ketocarboxylic acids, and ketones. J Am Chem Soc103:686

    CAS  Google Scholar 

  78. Moriarty RM, Hou K (1984) α-hydroxylation of ketones using o-iodosylbenzoic acid. Tetrahedron Lett25:691

    CAS  Google Scholar 

  79. Nakada F, Osawa R, Yamasaki K (1961) Dehydration of bile acid and their derivatives. VIII. Synthesis of 3α-hydroxy-△8(14)-cholenic and a-hydroxy-A14cholenic acids. Bull Chem Soc Jpn34:538

    CAS  Google Scholar 

  80. Nawasreh M (2000) Stereoselective synthesis of cephalostatin analogs asanti-canceragents. Dissertation, University of Hannover

    Google Scholar 

  81. Nowak P, Blaszczyk K, Paryzek Z (1994) The preparation of △2steroids. An improved procedure. Org Prep Proced Int3:374

    Google Scholar 

  82. Pan Y, Merriman RL, Tanzer LR, Fuchs PL (1992) Synthesis and pharmacological evaluation of nonacyclic and trisdecacyclic pyrazines related to cephalostatin. Bioorg Med Chem Lett 2: 967

    CAS  Google Scholar 

  83. Papa AJ (1966) J Org Chem31:1545

    Google Scholar 

  84. Pettit GR, Inoue M, Kamano Y, Herald DL, Arm C, Dufresne C, Christie ND, Schmidt JM, Doubek DL, Krupa TS (1988) Antineoplastic agents. 147. Isolation and structure of the powerful cell growth inhibitor cephalostatin 1 J Am Chem Soc110:2006

    CAS  Google Scholar 

  85. Pettit GR, Inoue M, Kamano Y, Dufresne C, Christie N, Niven ML, Herald DL (1988) Isolation and structure of the hemichordate cell growth inhibitors cephalostatins 2, 3, and 4. J Chem Soc Chem Comm 865

    Google Scholar 

  86. Pettit GR, Inoue M, Kamano Y, Dufresne C, Christie N, Niven ML, Herald DL (1988) Isolation and structure of the hemichordate cell growth inhibitors cephalostatins 2, 3, and 4 [Erratum to document cited in CA109(13):107868k1. J Chem Soc Chem Comm 1440

    Google Scholar 

  87. Pettit GR, Inoue M, Kamano Y, Dufresne C, Christie N, Schmidt JM, Herald DL (1989) Antineoplastic agents. 165. Isolation and structure of the unusual Indian Ocean Cephalodiscus gilchristi components, cephalostatins 5 and 6. Can J Chem67:1509

    CAS  Google Scholar 

  88. Pettit GR, Kamano Y (1989) Isolation and structural elucidation of antitumor cephalostatins 1–4 from Cephalodiscus gilchristi. PCT Int Appl, WO 8908655 Al 19890921 (CA 113:84818)

    Google Scholar 

  89. Pettit GR, Kamano Y (1989) Isolation and structural elucidation of cephalostatins 1–4. US Pat Appl, US 4873245 A 19891010 (CA 112:62611)

    Google Scholar 

  90. Pettit GR, Kamano Y (1991) Isolation and elucidation of antitumor Cephalostatins 5 and 6. US Pat Appl, US 5047532 A 19910910 (CA 115:248095)

    Google Scholar 

  91. Pettit GR, Kamano Y, Inoue M, Dufresne C, Boyd MR, Herald DL, Christie ND, Schmidt JM, Doubek DL (1992) Antineoplastic agents. 214. Isolation and structure of cephalostatins 7–9. J Org Chem57:429

    CAS  Google Scholar 

  92. Pettit GR, Xu J-P, Williams MD, Christie ND, Schmidt JM, Doubek DL, Boyd MR (1994) Antineoplastic agents. 271. Isolation and structure of cephalostatins 10 and 11. J Nat Prod57:52

    CAS  Google Scholar 

  93. Pettit GR, Ichihara Y, Xu J-P, Williams MD, Boyd MR (1994) Antineoplastic agents. 284. Isolation and structure of the symmetrical disteroidal alkaloids cephalostatin 12 and cephalostatin 13. Bioorg Med Chem Lett4:1507

    CAS  Google Scholar 

  94. Pettit GR, Ichihara Y, Xu J-P, Williams MD, Boyd MR (1994) Antineoplastic agents. 285. Isolation and structures of cephalostatins 14 and 15. Can J Chem72:2260

    CAS  Google Scholar 

  95. Pettit GR, Kamano Y (1994) Isolation and structural elucidation of cephalostatins 7, 8, and 9 and their use as antitumor agents. Eur Pat Appl, EP 608109 Al 19940727 (CA 121:221984)

    Google Scholar 

  96. Pettit GR, Xu JP, Schmidt JM (1995) Antineoplastic agents. Part 292. Isolation and structure of the exceptional pterobranchia human cancer inhibitors cephalostatins 16 and 17. Bioorg Med Chem Lett5:2027

    CAS  Google Scholar 

  97. Pettit GR (1996) Progress in the discovery of biosynthetic anticancer drugs. J Nat Prod59:812

    CAS  Google Scholar 

  98. Pettit GR, Tan R, Xu JP, Ichihara Y, Williams MD, Boyd MR (1998) Antineoplastic Agents. 398. Isolation and Structure Elucidation of Cephalostatins 18 and 19. J Nat Prod61:955

    CAS  Google Scholar 

  99. Polman J, Kasal A (1991) Preparation of antiadrogenic 17-hydroxy-3,6-cyclo-4-nor3,5-seco-6ß-androstan-3-one by deoxygenation of the corresponding 5-hydroxy dervatives. J Chem Soc Perkin Trans I, 127

    Google Scholar 

  100. Rose B, Schollmeyer D, Meier H (1997) Synthesis of a tetraazido-substituted 2-tetrazene from 1,5-cyclooctadiene and iodine azide. Liebigs Ann Org Bioorg Chem 2: 409

    Google Scholar 

  101. Rudloff V (1965) Can J Chem 4: 266

    Google Scholar 

  102. Sakurai M, Nogushi K, Isomura K, Tanaka R, Tanigucki H (1992) Intermolecular trapping of vinyl nitrene equilibrated with azirine. Heterocycles 33: 519

    CAS  Google Scholar 

  103. Schweng J, Zbiral E (1978) Synthese von cyclischen Vinylaziden. Liebigs Ann Chem 1089

    Google Scholar 

  104. Schwesinger R (1990)Nachr Chem Tech Lab 38:1214

    CAS  Google Scholar 

  105. Schwesinger R, Hasenfratz C, Schlemper H, Walz L, Peters EM, Peters K, von Schnering HG (1993) How strong and how hindered can uncharged phosphazene bases be. Angew Chem Int Ed Engl 32: 1361

    Google Scholar 

  106. Schwesinger R, Willaredt J, Schlemper H, Keller M, Schmitt D, Fritz H (1994) Novel, very strong, uncharged, auxiliary bases — design and synthesis of monomeric and polymer-bound triaminoiminophosphorane bases of broadly varied steric demand. Chem Ber127:2435

    CAS  Google Scholar 

  107. Sondheimer F, Mechoulam R (1957) Synthesis of steroidal methylene compounds by the wittig reaction. J Am Chem Soc79:5029

    CAS  Google Scholar 

  108. Tamura K, Honda H, Mimaki Y, Sashida Y, Kogo H (1997) Inhibitory effect of a new steroidal saponin, OSW-1, on ovarian functions in rats. Br J Pharmacol121:1796

    CAS  Google Scholar 

  109. Tietze LF, Krahnert WR (2001) Selective synthesis of bissteroidal compounds by multifold Heck reactions. Synlett 560

    Google Scholar 

  110. Ullmann U (1993) Selektivitäts-and Aktivitätsstudien an Cephalostatinanaloga. Dissertation, University of Hannover

    Google Scholar 

  111. Urban S, Hickford SJH, Blunt JW, Munro MHG (2000) Bioactive marine alkaloids. Curr Org Chem 4: 765

    CAS  Google Scholar 

  112. Weisenbom FL, Applegate HE (1959) Synthesis of a-norsteroids. J Am Chem Soc 81: 1960

    Google Scholar 

  113. Welzel P, Stein H (1981) 14β-hydroxy steroids — III. Synthesis of digoxigenin from deoxycholic acid. Tet Lett22:3385

    CAS  Google Scholar 

  114. Welzel P, Janssen B, Duddeck H (1981) Zur Prins-Reaktion von Lumihecogeninacetat. Liebigs Ann Chem 546

    Google Scholar 

  115. Welzel P, Stein H, Milkova T (1982) Synthese von Digoxigenin and Digitoxigenin aus Desoxycholsäure. Liebigs Ann Chem 2119

    Google Scholar 

  116. Winterfeldt E, Kramer A, Ullmann U, Laurent H (1994) Preparation of cephalostatin analogs as neoplasm inhibitors. Ger Offen (Patent) DE 4318924 Al (CA 122:265778)

    Google Scholar 

  117. http://dtp.nci.nih.gov/docs/dtp_search.html

  118. http://dtp.nci.nih.gov/docs/cancer/searches/standard_mechanism.html

  119. LaCour TG, Guo C, Ma S, Jeong JU, Boyd MR, Matsunaga S, Fusetani N, Fuchs PL (1999) On topography and functionality in the B-D rings of cephalostatin cytotoxins. Bioorg Med Chem Lett9:2587

    CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Pharma Research, Bayer HealthCare AG, Wuppertal, Germany

    Timo Flessner

  2. Medicinal Chemistry, Schering AG, Berlin, Germany

    Rolf Jautelat

  3. Central Research, Bayer Chemicals AG, Leverkusen, Germany

    Ulrich Scholz

  4. Institut für Organische Chemie der Universität Hannover, Hannover, Germany

    Ekkehard Winterfeldt

Authors
  1. Timo Flessner
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Rolf Jautelat
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Ulrich Scholz
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Ekkehard Winterfeldt
    View author publications

    You can also search for this author in PubMed Google Scholar

Editor information

Editors and Affiliations

  1. Department of Chemistry, The Florida State University, Tallahassee, Florida, USA

    W. Herz

  2. Institut für Chemie, Johannes-Kepler-Universität, Linz, Austria

    H. Falk

  3. Chemistry Department, The University of Glasgow, Glasgow, Scotland

    G. W. Kirby

Rights and permissions

Reprints and permissions

Copyright information

© 2004 Springer-Verlag Wien

About this chapter

Cite this chapter

Flessner, T., Jautelat, R., Scholz, U., Winterfeldt, E. (2004). Cephalostatin Analogues — Synthesis and Biological Activity. In: Herz, W., Falk, H., Kirby, G.W. (eds) Progress in the Chemistry of Organic Natural Products. Progress in the Chemistry of Organic Natural Products, vol 87. Springer, Vienna. https://doi.org/10.1007/978-3-7091-0581-8_1

Download citation

  • DOI: https://doi.org/10.1007/978-3-7091-0581-8_1

  • Publisher Name: Springer, Vienna

  • Print ISBN: 978-3-7091-7199-8

  • Online ISBN: 978-3-7091-0581-8

  • eBook Packages: Springer Book Archive

Publish with us

Policies and ethics

Search

Navigation