Synthesis of Onychine and Formal Synthesis of Eupolauridine via the Vinylogous Aza-Morita-Baylis-Hillman Reaction

Abstract

A concise and efficient synthesis of the antimycotic alkaloid onychine was developed, based on the vinylogous aza-Morita-Baylis-Hillman reaction of N-(benzylidene)benzenesulfonamide with methyl 2,4-pentadienoate, followed by intramolecular conjugate addition, Friedel-Crafts acylation, methyl cuprate addition, and aromatization.

Key Words

alkaloids - onychine - aza-Morita-Baylis-Hillman ­reaction - cyclization - cuprates

References and Notes

• 1 Goulart MOF. Santana AEG. De Oliveira AB. De Oliveria GG. Maia JGS. Phytochemistry  1986,  25:  1691 
• 2 De Almeida MEL. Braz FR. von Bülow MV. Gottlieb OR. Maia JGS. Phytochemistry  1976,  15:  1186 
• 3a Koyama J. Sugita T. Suzuta Y. Heterocycles  1979,  12:  1017 
• 3b Okatani T. Koyama J. Suzuta Y. Tagahara K. Heterocycles  1988,  27:  2213 
• 3c Tadic D. Cassels BK. Cavé A. Goulart MOF. De Oliveira AB. Phytochemistry  1987,  26:  1551 
• 3d Tadic D. Cassels BK. Leboeuf M. Cavé A. Phytochemistry  1987,  26:  537 
• 3e Zhang J. El-Shabrawy A.-RO. El-Shanawany MA. Schiff PL. Slatkin DJ. J. Nat. Prod.  1987,  50:  800 
• 4 Bowden BF. Picker K. Ritchie E. Taylor WC. Aust. J. Chem.  1975,  28:  2681 
• 5a Hufford CD. Liu S. Clark AM. J. Nat. Prod.  1987,  50:  961 
• 5b Bracher F. Arch. Pharm. (Weinheim)  1994,  327:  371 
• 6 Koyama J. Morita I. Kobayashi N. Osakai T. Usuki Y. Taniguchi M. Bioorg. Med. Chem. Lett.  2005,  15:  1079 
• 7 Aoyagi S. Ohata S. Shimada K. Takikawa Y. Synlett  2007,  615 
• 8 Padwa A. Heidelbaugh TM. Kuethe JT. J. Org. Chem.  2000,  65:  2368 
• 9 Tong TH. Wong HNC. Synth. Commun.  1992,  22:  1773 
• 10 Sreekumar R. Rugmini P. Padmakumar R. Synth. Commun.  1998,  28:  2071 
• 11 Bracher F. Arch. Pharm. (Weinheim)  1989,  322:  293 
• 12 Alves T. de Oliveira AB. Snieckus V. Tetrahedron Lett.  1988,  29:  2135 
• 13 Rebstock A.-S. Mongin F. Trécourt F. Quéguiner G. Tetrahedron  2004,  60:  2181 
• 14 Nitta M. Ohnuma M. Iino Y. J. Chem. Soc., Perkin Trans. 1  1991,  1115 
• 15a Back TG. Rankic DA. Sorbetti JM. Wulff JE. Org. Lett.  2005,  7:  2377 
• 15b Sorbetti JM. Clary KN. Rankic DA. Wulff JE. Parvez M. Back TG. J. Org. Chem.  2007,  72:  3326 
• 15c Clary KN. Back TG. Synlett  2007,  2995 
• 15d Clary KN. Parvez M. Back TG. Org. Biomol. Chem.  2009,  7:  1226 
• 15e Clary KN. Parvez M. Back TG. J. Org. Chem.  2010,  75:  3751 
• 16 For the accelerating and trapping effects of trimethylsilyl chloride on the conjugate additions of organocopper reagents to α,β-unsaturated carbonyl compounds, see: Nakamura E. In Organocopper Reagents - A Practical Approach   Taylor RJK. Oxford University Press; Oxford: 1994.  Chap. 6.
• 17a For C-desulfonylation with Mg/MeOH, see: Brown AC. Carpino LA. J. Org. Chem.  1985,  50:  1749 
• 17b For N-desulfonylation with this reagent, see: Tichenor MS. Trzupek JD. Kastrinsky DB. Shiga F. Hwang I. Boger DL. J. Am. Chem. Soc.  2006,  128:  15683 

18

For experimental procedures and characterization data for new compounds and the final product 1, see the Supporting Information.