Preparation of an Advanced Phenylglycine-Derived Intermediate en route to the Southern Hemisphere Tetraene of Viridenomycin

Abstract

A high-yielding synthesis of a phenylglycine derived (E,Z)-dienylboronate en route to the C16-C23 tetraene of the polyene macrolide viridenomycin is described. Crucial to this synthesis was the development of conditions enabling ready access to synthetically useful amino acid derivatives that should be widely applicable to other amino acids. These conditions confer advantages of increased yield and reliability over many of the existing literature alternatives, and also circumvent several of the problems encountered when dealing with such derivatives. The synthesis features a highly selective Heck coupling between an N-protected (Z)-alkenyl iodide and a hexylene glycol derived vinylboronate ester.

Key words

natural product - palladium - Heck reaction - asymmetric synthesis - amino alcohol

References

• 1 Thirsk C. Whiting A. J. Chem. Soc., Perkin Trans. 1  2002,  8:  999 
• 2a Nakagawa M. Furihata K. Hayakawa Y. Seto H. Tetrahedron Lett.  1991,  32:  659 
• 2b Hasegawa T. Kamiya T. Henmi T. Iwasaki H. Yamatodani S. Antibiotics  1975,  28:  167 
• 3a Hénaff N. Whiting A. Org. Lett.  1999,  1:  1137 
• 3b Hénaff N. Whiting A. Tetrahedron  2000,  56:  5193 
• 4a Stewart SK. Whiting A. Tetrahedron Lett.  1995,  36:  3925 
• 4b Stewart SK. Whiting A. Tetrahedron Lett.  1995,  36:  3929 
• 5 The macrocyclic polyene hitachimycin is a structurally similar polyene, which also contains this same phenylalanine derived moiety, and has the (S)-configuration at the related center. See: Smith AB. Pure Appl. Chem.  1989,  61:  405 
• 6 See for example: Caputo R. Cassano E. Longobardo L. Palumbo G. Tetrahedron  1995,  51:  12337 
• 7 See for example: Willis CL. Sutherland A. J. Org. Chem.  1998,  63:  7764 
• 8a Correa A. Denis J.-N. Greene A. Synth. Commun.  1991,  21:  1 
• 8b Cran GC. Gibson CL. Handa S. Tetrahedron: Asymmetry  1995,  6:  1553 
• 9 McKennon MJ. Meyers AI. J. Org. Chem.  1993,  58:  3568 
• 10 Wessig P. Schwartz J. Synlett  1997,  893 
• 11a Lee JW. Lee JH. Son HJ. Choi YK. Yoon GJ. Park MH. Synth. Commun.  1996,  26:  83 
• 11b Agami C. Couty F. Hamon L. Vernier O. Tetrahedron Lett.  1993,  34:  4509 
• 11c Agami C. Couty F. Hamon L. Vernier O. Bull. Chim. Soc. Fr.  1995,  132:  808 
• 12a Kaseda T. Kikuchi T. Kibayashi C. Tetrahedron Lett.  1989,  30:  4539 
• 12b Araldi G. Donati D. Oliosi B. Ursini A. van Amsterdam F. Farmaco  1996,  51:  471 
• 12c Cran GC. Gibson CL. Handa S. Tetrahedron: Asymmetry  1995,  6:  1553 
• 12d Marinzi C. Bark SJ. Offer J. Dawson PE. Bioorg. Med. Chem.  2001,  9:  2323 
• 12e Lazer ES. Miao CK. Wong H.-C. Sorcek R. Spero DM. J. Med. Chem.  1994,  37:  913 
• 12f O’Brien PM. Sliskovic DR. Blankley CJ. Roth BD. Wilson MW. J. Med. Chem.  1994,  37:  1810 
• 12g Higashiura K. Morino H. Matsuura H. Toyomaki Y. Ienaga K. J. Chem. Soc., Perkin Trans. 1  1989,  1479 
• 12h Giardina GAM. Raveglia LF. Grugni M. Sarau HM. Farina C. J. Med. Chem.  1999,  42:  1053 
• 13a

  Toujas, J. M.; Vaultier, M. unpublished results.

• 13b

  To a solution of mesylate (10 g, 31.7 mmol) in anhyd DMSO (150 mL) stirred under argon, was added NaCN (4.7 g, 3 equiv) in one portion. The suspension was stirred vigorously at 45 °C for 18 h, then cooled to 0 °C. To this mixture H₂O (250 mL) was added, and the DMSO-H₂O phase was washed with Et₂O (3 × 100 mL). The combined ether extracts were washed with sat. NaCl (3 × 100 mL), and dried over MgSO₄. Concentration in vacuo gave a white solid that was recrystallized from cold CH₂Cl₂-hexane to give white crystals of nitrile 8 (5.84 g, 74%); analytical data was consistent with that reported. [6]

• 14 Toujas J.-L. Jost E. Vaultier M. Bull. Chim. Soc. Fr.  1997,  134:  713 
• 15a Stork G. Zhao K. Tetrahedron Lett.  1989,  30:  2173 
• 15b Kruger AW. Meyers AI. Tetrahedron Lett.  2001,  42:  4301 
• 15c

  We thank Professor Meyers for the provision of experimental details and data for 5.

• 16 Lightfoot AP. Maw G. Thirsk C. Twiddle S. Whiting A. Tetrahedron Lett.  2003,  44:  7645 
• 17a Brown HC. Hamaoka T. Ravindran N. J. Am. Chem. Soc.  1973,  95:  5786 
• 17b Brown HC. Campbell JB. J. Org. Chem.  1980,  45:  389 
• 17c Brown HC. Somayaji V. Synthesis  1984,  6075