A Simple and Efficient Synthesis of 3′-Azido-3′-deoxythymidine (AZT) Employing a Convergent Route

Abstract

The syn-homoallyl alcohol 2a has been prepared with absolute stereoselectivity following PDC oxidation of the mixture of diastereomers 2a, 2b and subsequent K-selectride® reduction of the resulting ketone 3. Compound 2a has been efficiently utilized for a simple synthesis of AZT I in a convergent manner.

Key words

AIDS - convergent synthesis - (R)-2,3-O-cyclohexylideneglyceraldehyde - K-selectride - syn selective reduction - open chain model - flexibility

References

• 1a Huryn DM. Okabe M. Chem. Rev.  1992,  92:  1745 ; and references cited therein
• 1b Dueholm KL. Pedersen EB. Synthesis  1992,  1 ; and references cited therein
• 1c Lipshutz BH. Hayawaka H. Kato K. Lowe RF. Synthesis  1994,  1476 ; and references cited therein
• 1d Wilson LJ. Hager MW. El-Kattan YA. Liotta DC. Synthesis  1995,  1465 ; and references cited therein
• 1e Jung ME. Nichols CJ. J. Org. Chem.  1998,  63:  347 
• 1f Shuto S. Kanazaki M. Ichikawa S. Minakawa N. Matsuda A. J. Org. Chem.  1998,  63:  746 
• 1g Sorensen MD. Khalifa NM. Pedersen EB. Synthesis  1999,  1937 
• 2 DeClercq E. Collect. Czech. Chem. Commun.  1998,  63:  449 
• 3a Mitsua H. Yarchoan R. Broder S. Science  1990,  249:  1533 
• 3b DeClerq E. Nucleosides, Nucleotides  1994,  13:  1271 
• 3c DeClerq E. J. Med. Chem.  1995,  38:  2491 
• 3d Mansour TS. Storer R. Current Pharmac. Design  1997,  3:  227 
• 3e

  New medicines in Development of AIDS, available at http://www.pharma.org.

• 4a Fleet GWJ. Son JC. Derome AE. Tetrahedron  1988,  44:  625 
• 4b Gurjar MK. Pawar SM. Rama Rao AVJ. J. Carbohydr. Chem.  1988,  7:  271 
• 4c Chu CK. Beach WJ. Ullas GV. Kosugi Y. Tetrahedron Lett.  1988,  29:  5349 
• 4d Hansen P. Pedersen EB. Acta Chem. Scand.  1990,  44:  522 
• 4e Sugimura H. Osumi K. Yamazaki T. Yamaya T. Tetrahedron Lett.  1991,  32:  1813 
• 5a Hager MW. Liotta DC. J. Am. Chem. Soc.  1991,  113:  5117 
• 5b Jung ME. Gardiner JM. J. Org. Chem.  1991,  56:  2614 
• 5c Chen B. Quinlan SL. Read SG. Tetrahedron Lett.  1995,  36:  7691 
• 5d Mandal SB. Achari B. J. Chem. Res., Synop.  1993,  327 ; and references cited therein
• 5e Sigmund H. Pfleiderer W. Helv. Chim. Acta  1996,  79:  426 
• 6a Chattopadhyay A. Mamdapur VR. J. Org. Chem.  1995,  60:  585 
• 6b Chattopadhyay A. J. Org. Chem.  1996,  61:  6104 
• 6c Chattopadhyay A. Tetrahedron: Asymmetry  1997,  8:  2727 
• 7 Corey EJ. Schmidt G. Tetrahedron Lett.  1979,  399 
• 8a Sato F. Kobayashi O. Chiba T. Takeda Y. Kasakabe M. J. Chem. Soc., Chem. Commun.  1985,  1636 
• 8b Roush WR. Walts AE. Hong LK. J. Am. Chem. Soc.  1985,  107:  8186 
• 8c Dondoni A. Fantin G. Fogagnoto M. Medici A. Pedrini P. J. Org. Chem.  1989,  54:  702 
• 8d Dondoni A. Synthesis  1998,  1681 ; and references cited therein
• 8e Dehoux C. Mothien C. Baltas M. Gorricon L. Synthesis  2000,  1409 
• 9a Cherest M. Felkin H. Prudent N. Tetrahedron Lett.  1968,  2199 
• 9b Oishi T. Nakata T. Acc. Chem. Res.  1984,  17:  338 
• 9c Nakata T. Tanaka T. Oishi T. Tetrahedron Lett.  1983,  2653 
• 9d Mengel A. Reiser O. Chem. Rev.  1999,  99:  1191 ; and references cited therein
• 10 Grauert M. Schollkopf U. Liebigs Ann. Chem.  1985,  1817