Subscribe to RSS
Please copy the URL and add it into your RSS Feed Reader.
https://www.thieme-connect.de/rss/thieme/en/10.1055-s-00000084.xml
Synthesis 2004(17): 2869-2876
DOI: 10.1055/s-2004-834881
DOI: 10.1055/s-2004-834881
PAPER
© Georg Thieme Verlag Stuttgart · New York
Regioselectivity in Cross-Coupling Reactions of 2,6,8-Trichloro-9-(tetrahydropyran-2-yl)purine: Synthesis of 2,6,8-Trisubstituted Purine Bases
Further Information
Received
12 July 2004
Publication Date:
15 October 2004 (online)
Publication History
Publication Date:
15 October 2004 (online)
Abstract
The regioselectivity of cross-coupling reactions (Pd-catalyzed Suzuki-Miyaura reactions with phenylboronic acid and Fe-catalyzed reactions with methylmagnesium chloride) of 2,6,8-trichloro-9-(tetrahydropyran-2-yl)purine with varying amounts of the organometallic reagent was studied. In general, the regioselectivity of these reactions was quite low giving mixtures of isomers of mono-, di- and trisubstituted products. Nevertheless, 2,6-dichloro-8-methyl-9-THP-purine (1aab), 2-chloro-6,8-dimethyl-9-THP-purine (1abb) and 2,8-dichloro-6-phenyl-9-THP-purine (1aca) were isolated in acceptable yields and used as intermediates for further cross-coupling reactions giving a series of 2,6,8-trisubstituted 9-THP-purines that were deprotected to the corresponding purine bases. Characteristic 13C NMR shifts of CH3 or ipso-Ph carbons in different positions of the purine ring have been observed enabling rapid and facile identification of the particular isomer.
Key words
purines - nucleobases - cross-coupling reactions - iron - palladium
-
1a
Montgomery JA.Hewson K. J. Med. Chem. 1968, 11: 48 -
1b
Parker WB.King SA.Allan PW.Bennett LL.Secrist JA.Montgomery JA.Gilbert KS.Waud WR.Wells AH.Gillespie GY.Sorscher EJ. Hum. Gene Ther. 1997, 8: 1637 -
1c
Parker WB.Allan PW.Shaddix SC.Rose LM.Speegle HF.Gillespie GY.Bennett LL. Biochem. Pharmacol. 1998, 55: 1673 -
1d
Hassan AEA.Abou-Elkair RAI.Montgomery JA.Secrist JA. Nucleosides, Nucleotides, Nucleic Acids 2000, 19: 1123 -
2a
Hocek M.Hol A.Votruba I.Dvořáková H. J. Med. Chem. 2000, 43: 1817 -
2b
Hocek M.Hol A.Votruba I.Dvoøáková H. Collect. Czech. Chem. Commun. 2001, 66: 483 -
2c
Andresen G.Gundersen L.-L.Nissen-Meyer J.Rise F.Spilsberg B. Bioorg. Med. Chem. Lett. 2002, 12: 567 -
2d
Gundersen L.-L.Nissen-Meyer J.Spilsberg D. J. Med. Chem. 2002, 45: 1383 - 3
Hocek M. Eur. J. Org. Chem. 2003, 245 - 4
Hocek M.Hol A.Dvořáková H. Collect. Czech. Chem. Commun. 2002, 67: 325 - 5
Hocek M.Hocková D.tambask J. Collect. Czech. Chem. Commun. 2003, 68: 837 - 6
Hocek M.Dvořáková H. J. Org. Chem. 2003, 68: 5773 -
7a
Havelková M.Dvořák D.Hocek M. Synthesis 2001, 1704 -
7b
Hocek M.Votruba I.Dvořáková H. Tetrahedron 2003, 59: 607 - 8
Hocek M.Hocková D.Dvořáková D. Synthesis 2004, 889 -
9a
Havlíček L.Hanus J.Vesel J.Leclerc S.Meijer L.Shaw G.Strnad M. J. Med. Chem. 1997, 40: 408 -
9b
Legraverend M.Ludwig O.Bisagni E.Leclerc S.Meijer L. Bioorg. Med. Chem. Lett. 1998, 8: 793 -
9c
Legraverend M.Ludwig O.Bisagni E.Leclerc S.Meijer L.Giocanti N.Sadri R.Favaudon V. Bioorg. Med. Chem. 1999, 7: 1281 -
9d
Gray NS.Wodicka L.Thunnissen A.-MWH.Nornam TC.Kwon S.Espinoza FH.Morgan DO.Barnes G.LeClerc S.Meijer L.Kim S.-H.Lockhart DJ.Schultz PG. Science 1998, 281: 533 -
9e
Chang Y.-T.Gray NS.Rosania GR.Sutherlin DP.Kwon S.Norman TC.Sarohia R.Leost M.Meijer L.Schultz PG. Chem. Biol. 1999, 6: 361 - 10
Verdugo DE.Cancilla MT.Ge X.Gray NS.Chang Y.-T.Schultz PG.Negishi M.Leary JA.Bertozzi CR. J. Med. Chem. 2001, 44: 2683 -
11a
Rosania GR.Chang Y.-T.Perez O.Sutherlin D.Dong HL.Lockhart DJ.Schultz PG. Nature Biotechnol. 2000, 18: 304 -
11b
Chang Y.-T.Wignall SM.Rosania GR.Gray NS.Hanson SR.Su AI.Merlie J.Moon HS.Sangankar SB.Perez O.Heald R.Schultz PG. J. Med. Chem. 2001, 44: 4497 -
11c
Franěk F.Siglerová V.Havlíček L.Strnad M.Eckschlager T.Weigl E. Collect. Czech. Chem. Commun. 2002, 67: 257 - 12
Cocuzza AJ.Chidester DR.Culp S.Fitzgerald L.Gilligan P. Bioorg. Med. Chem. Lett. 1999, 9: 1063 -
13a
Brill WK.-D.Riva-Toniolo C.Müller S. Synlett 2001, 1097 -
13b
Brill WK.-D.Riva-Toniolo C. Tetrahedron Lett. 2001, 42: 6515 -
13c
Ding S.Gray NS.Ding Q.Schultz PG. Tetrahedron Lett. 2001, 42: 8751 -
13d
Ding S.Gray NS.Wu X.Ding Q.Schultz PG. J. Am. Chem. Soc. 2002, 124: 1594 -
13e
Brun V.Legraverend M.Grierson DS. Tetrahedron 2002, 58: 7911 -
13f
Bork JT.Lee JW.Chang Y.-T. QSAR Comb. Sci. 2004, 23: 245 -
14a
Langli G.Gundersen L.-L.Rise F. Tetrahedron 1996, 52: 5625 -
14b
Nolsoe JMJ.Gundersen L.-L.Rise F. Acta Chem. Scand. 1999, 53: 366 -
15a
Fischer E. Ber. Dtsch. Chem. Ges. 1897, 30: 2220 -
15b
Davoll J.Lowry BA. J. Am. Chem. Soc. 1951, 73: 2926 - 16
Nolsøe JMJ.Gundersen L.-L.Rise F. Synth. Commun. 1998, 28: 4303 -
17a
Fürstner A.Leitner A. Angew. Chem. Int. Ed. 2002, 41: 609 -
17b
Fürstner A.Leitner A.Mendez M.Krause H. J. Am. Chem. Soc. 2002, 124: 13856 -
17c
Fürstner A.Leitner A. Angew. Chem. Int. Ed. 2003, 42: 308 -
18a
Havelková M.Hocek M.Česnek M.Dvořák D. Synlett 1999, 1145 -
18b
Lakshman MK. J. Organomet. Chem. 2002, 653: 234 -
18c
Lakshman MK.Hilmer JH.Martin JQ.Keeler JC.Dinh YQV.Ngassa FN.Russon LM. J. Am. Chem. Soc. 2001, 123: 7779 -
19a
Hirota K.Kitade Y.Kanbe Y.Maki Y. J. Org. Chem. 1992, 57: 5268 -
19b
Česnek M.Hocek M.Hol A. Collect. Czech. Chem. Commun. 2000, 65: 1357 - 20
Hocek M.Hol A. Collect. Czech. Chem. Commun. 1995, 60: 1386 -
21a
Sečkářová P.Marek R.Maliňáková K.Kolehmainen E.Hocková D.Hocek M.Sklenář V. Tetrahedron Lett. 2004, 45: 6259 -
21b
poner J.Hobza P. Collect. Czech. Chem. Commun. 2003, 68: 2231 - 22
Sutcliffe EY.Robins RK. J. Org. Chem. 1963, 28: 1662 - 23
Oh C.-H.Kim H.-K.Lee S.-C.Oh C.Yang B.-S.Rhee HJ.Cho J.-H. Arch. Pharm. (Weinheim) 2001, 334: 345 - 24
Brown DJ.Jones RL.Angyal AM.Grigg GW. J. Chem. Soc., Perkin Trans. 1 1972, 1819