Formal Total Synthesis of Benzylpedamide: The Right Half of (+)-Pederin

Abstract

The right half of (+)-pederin was synthesized through a convenient and efficient asymmetric synthesis in 14 steps with 8.3% overall yield. The key step was an iodine-induced heterocyclization to construct the pyran ring. The chiral centers were constructed separately via asymmetric allylation, substrate-controlled diastereoselective reactions, and Sharpless asymmetric dihydroxylation.

Key words

synthesis - pedamide - pederin

References and Notes

• 1a Piel J. Butzke D. Fusetani D. Hui D. Platzer M. Wen G. Matsunaga S. J. Nat. Prod.  2005,  68:  472 
• 1b Cichewicz RH. Valeriote FA. Crews P. Org. Lett.  2004,  6:  1951 
• 2a Ueta A. J. Kurume Med. Coll., Kyushu  1949,  249 
• 2b Pavan M. Bo G. Physiol. Comput. Oecol.  1953,  3: 307; Chem. Abstr. 1954, 48, 57887
• 3a Narquizian R. Kocienski P. In The Role of Natural Products in Drug Discovery   Mulzer J. Bohlmann R. Springer; New York: 2000.  p.25-56  
• 3b Levine MR. Dancis J. Pavan M. Cox RP. Pediat. Res.  1974,  8:  606 
• 4 Green ME. Rech JC. Floreancig PE. Org. Lett.  2005,  7:  4117 
• For total synthesis of pederin compounds, see:
• 5a Hong CY. Kishi Y. J. Org. Chem.  1990,  55:  4242 
• 5b Hong CY. Kishi Y. J. Am. Chem. Soc.  1991,  113:  9693 
• 5c Roush WR. Pfeifer LA. Org. Lett.  2000,  2:  859 
• 5d Trost BM. Yang H. Probst GD. J. Am. Chem. Soc.  2004,  126:  48 
• 5e Jiang X. Garcia-Fortanet J. De Brabander JK. J. Am. Chem. Soc.  2005,  127:  11254 
• 5f For synthesis of the left halves, see: Huang X. Shao N. Palani A. Aslanian R. Buevich A. Org. Lett.  2007,  9:  2597 
• 5g Adams MA. Duggan AJ. Smolanoff J. Meinwald J. J. Am. Chem. Soc.  1979,  101:  5364 
• 5h Roush WR. Marron TG. Pfeifer LA. J. Org. Chem.  1997,  62:  474 
• 5i For synthesis of the right halves, see: Breitfelder S. Schuemacher AC. Rolle T. Kikuchi M. Hoffmann RW. Helv. Chim. Acta  2004,  87:  1202 
• 5j Hoffman RW. Schlapbach A. Tetrahedron  1992,  48:  1959 
• 5k Marron T. Roush WR. Tetrahedron Lett.  1995,  36:  1581 
• 5l Breitfelder S. Schlapbach A. Hoffmann RW. Synthesis  1998,  468 
• 5m Jiang X. Williams N. DeBrabander JK. Org. Lett.  2007,  9:  227 
• For total synthesis of pederin compounds, see:
• 6a Matsuda F. Tomiyoshi N. Yanagiya M. Matsumoto T. Tetrahedron  1988,  44:  7063 
• 6b For synthesis of the left halves, see: Tsuzuki K. Watanabe T. Yanagiya M. Matsumoto T. Tetrahedron Lett.  1976,  17:  4745 
• 6c Yanagiya M. Matsuda F. Hasegawa K. Matsumoto T. Tetrahedron Lett.  1982,  23:  4039 
• 6d Matsumoto T. Matsuda F. Hasagawa K. Yanagiya M. Tetrahedron  1984,  40:  2337 
• For total synthesis of pederin compounds, see:
• 7a Nakata T. Nagao S. Oishi T. Tetrahedron Lett.  1985,  26:  6465 
• 7b Nakata T. Fukui H. Nakagawa T. Matsukura H. Heterocycles  1996,  42:  159 
• 7c For synthesis of the left halves, see: Trotter NS. Nakata T. Org. Lett.  1999,  1:  957 
• 7d Nakata T. Nagao S. Mori N. Oishi T. Tetrahedron Lett.  1985,  26:  6461 
• 7e Nakata T. Matsukura H. Dunlong J. Nagashima H. Tetrahedron Lett.  1994,  35:  8229 
• 7f Takemura T. Nishii Y. Takahashi S. Kobayashi J. Nakata T. Tetrahedron  2002,  58:  6359 
• For total synthesis of pederin compounds, see:
• 8a Willson T. Kocienski P. Faller A. Campbell S. J. Chem. Soc., Chem. Commun.  1987,  106 
• 8b Willson TM. Kocienski P. Jarowicki K. Isaac K. Hitchcock PM. Faller A. Campbell SF. Tetrahedron  1990,  46:  1767 
• 8c Kocienski P. Jarowicki K. Marczak S. Synthesis  1991,  1191 
• 8d Kocienski P. Raubo P. Davis JK. Boyle FT. Davies DE. Richter A. J. Chem. Soc., Perkin Trans. 1  1996,  1797 
• 8e Kocienski P. Narquizian R. Raubo P. Smith C. Farrugia LJ. Muir K. Boyle FT. J. Chem. Soc., Perkin Trans. 1  2000,  2357 
• 8f For synthesis of the left halves, see: Willson TM. Kocienski P. Jarowicki K. Isaac K. Faller A. Campbell SF. Bordner J. Tetrahedron  1990,  46:  1757 
• 8g For synthesis of the right halves, see: Kocienski P. Willson TM. J. Chem. Soc., Chem. Commun.  1984,  1011 
• For total synthesis of pederin compounds, see:
• 9a Sohn J. Waizumi N. Zhong HM. Rawal VH. J. Am. Chem. Soc.  2005,  127:  7290 
• 9b John CJ. Rawal VH. Angew Chem. Int. Ed.  2007,  119:  6622 
• 9c For synthesis of the right halves, see: Zhong HM. Sohn JH. Rawal HV. J. Org. Chem.  2007,  72:  386 
• 10 Ihara M. Suzuki M. Fukunoto K. Kameani T. Kabuto C. J. Am. Chem. Soc.  1988,  110:  1963 
• 11 Jadhav PK. Bhat KS. Perumal PT. Brown HC.
  J. Org. Chem.  1986,  51:  432 
• 12 Heathcock CH. Kiyooka S. Blumenkopf TA. J. Org. Chem.  1984,  49:  4214 
• 14a Tietze LF. Schneider C. J. Org. Chem.  1991,  56:  2476 
• 14b Kan A. Kang SY. Choi HW. Kim CM. Jun HS. Younb JH. Synthesis  2004,  1102 
• 15 Carey FA. Sundberg RJ. Advanced Organic Chemistry: Reactions and Synthesis (Part B)   4th ed.:  Plenum; New York: 2002.  p.205 
• 16 Michael HKC. VanNieuwenhze S. Sharpless KB. Chem. Rev.  1994,  94:  2483 
• 18 Nakamura E. Inubushi T. Aoki S. Machii D. J. Am. Chem. Soc.  1991,  113:  8980 

13

Compound similar to 9 has been synthesized in different steps. See ref. 5e.

17

These attempts include oxidating 12 with MCPBA, or aerobic oxidation in the presence of Bu₃SnH, and hydrolyzation with H₂O either in strong polar solvents or in the presence of a base.