Toward the Total Synthesis ofDisorazole A₁: Asymmetric Synthesis of the MaskedNorthern Half

Abstract

The stereoselective synthesis of the masked northern half ofthe antimitotic natural product disorazole A₁ is describedinvol­ving as key step a Z-selectiveWittig olefination of a C1-C11 epoxy aldehyde with a C12-C19phosphonium iodide.

Key words

total synthesis - cell cycle modulation - polyketides - oxazoles - Wittig reactions

References

• 1 Jansen R. Irschik H. Reichenbach H. Wray V. Höfle G. LiebigsAnn.  1994,  759 
• 2a Elnakady YA. PhDThesis   TU Braunschweig; Germany: 2001. 
• 2b Irschik H. Jansen R. Gerth K. Höfle G. Reichenbach H. J. Antibiotics  1995,  48:  31 
• 3a Walsh CT. ChemBioChem  2002,  3:  124 
• 3b Staunton J. Weisman KJ. Nat. Prod. Rep.  2001,  18:  380 
• 3c Cane DE. Walsh CT. Khosla C. Science  1998,  282:  63 
• Independently, Meyers et al. pursueda similar approach in their pioneering work toward the southernsegment of disorazole A₁ and the C₂-symmetricdisorazole C₁:
• 4a Hillier MC. Price AT. Meyers AI. J. Org. Chem.  2001,  66:  6037 
• 4b Hillier MC. Park DH. Price AT. Ng R. Meyers AI. Tetrahedron Lett.  2000,  41:  2821 
• 5 Hartung IV. Niess B. Haustedt LO. Hoffmann HMR. Org. Lett.  2002,  4:  3239 
• 6 trans-Cinnamamidewas prepared on a large scale in 89% yield from inexpensive trans-cinnamic acid chloride with (Me₃Si)₂NH: Pellegata R. Italia A. Villa M. Palmisano G. Lesma G. Synthesis  1985,  517 
• 7 Ethyl lactate was converted into α-bromoethylpyruvate by reacting with NBS in CCl₄: Kruse PF. Geurkink N. Grist KL. J. Am. Chem. Soc.  1954,  76:  5796 
• 8 Panek JS. Beresis RT. J. Org. Chem.  1996,  61:  6496 
• 9 Evans DA. Fitch DM. Smith TE. Cee VJ. J. Am. Chem. Soc.  2000,  122:  10033 
• 10 Carlsen PHJ. Katsuki T. Martin VS. Sharpless KB. J.Org. Chem.  1981,  46:  3936 
• 11 Corey EJ. Fuchs PL. Tetrahedron Lett.  1972,  14:  3769 
• 12a Colvin EW. Hamill BJ. J. Chem. Soc., Perkin Trans. 1  1977,  869 
• 12b Colvin EW. Hamill BJ. J.Chem. Soc., Chem. Commun.  1973,  151 
• 13a Seyferth D. Marmor RS. Hilbert P. J. Org. Chem.  1971,  36:  1379 
• 13b Gilbert JC. Weerasooriya U. J.Org. Chem.  1979,  44:  4997 
• 13c Brown DG. Velthuisen EJ. Commerford JR. Brisbois RG. Hoye TR. J. Org. Chem.  1996,  61:  2540 
• 14a Ohira S. Synth. Commun.  1989,  19:  561 
• 14b Müller S. Liepold B. Roth GJ. Bestmann HJ. Synlett  1996,  521 
• Epoxy alcohol 13 wasprepared from cis-butene diol by monoPMB protection and Sharpless epoxidation (99% ee, 75% overallyield):
• 16a Zhi-min W. Wei-shan Z. Guo-giang L. TetrahedronLett.  1985,  26:  6221 
• 16b Gao Y. Hanson RM. Klunder JM. Ko SY. Masamune H. Sharpless KB. J.Am. Chem. Soc.  1987,  109:  5765 
• 17 Lu X. Huang X. Ma S. Tetrahedron Lett.  1992,  33:  2535 
• 18 Betzer J.-F. Delaloge F. Muller B. Pancrazi A. Prunet J. J.Org. Chem.  1997,  62:  7768 
• 19 Shen W. Wang L. J. Org. Chem.  1999,  64:  8873 
• 21 De Mico A. Margarita R. Parlanti L. Vescovi A. Piancatelli G. J.Org. Chem.  1997,  62:  6974 
• 23 Smith AB. Adams CM. Kozmin SA. Paone DV. J.Am. Chem. Soc.  2001,  123:  5925 
• 24 Smith AB. Qiu Y. Jones DR. Kobayashi K. J. Am. Chem.Soc.  1995,  117:  12011 
• 25 Bestmann HJ. Stransky W. Vostrowsky O. Chem.Ber.  1976,  109:  1694 
• 26a Corey EJ. Marfat A. Munroe J. Kim KS. Hopkins PB. Brion F. TetrahedronLett.  1981,  22:  1077 
• 26b Corey EJ. Clark DA. Goto G. Marfat A. Mioskowski C. Samuelsson B. Hammarström S. J. Am. Chem. Soc.  1980,  102:  1436 
• 26c Nicolaou KC. Rutjes FPJT. Theodorakis EA. Tiebes J. Sato M. Untersteller E. J.Am. Chem. Soc.  1995,  117:  1173 
• 27a Meyers AI. Lawson JP. Tetrahedron Lett.  1981,  22:  3163 
• 27b Evans DA. Cee VJ. Smith TE. Santiago KJ. Org.Lett.  1999,  1:  87 
• 27c Nicolaou KC. Bella M. Chen DY.-K. Huang X. Ling T. Snyder SA. Angew. Chem.Int. Ed.  2002,  41:  3495 
• 28 Williams DR. Brooks DA. Meyer KG. Pagel M. TetrahedronLett.  1998,  39:  8023 

15

The absolute configuration of disorazoleA₁ had not been assigned unambiguously until late 2000.Therefore, the non-natural C7/C11 fragment was used inour earlier studies.

20

Quantified by conversion to the Mosherester.

22

The corresponding C16 MOM and SEMethers were not sufficiently stable under standard halogenationconditions.