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DOI: 10.1055/s-2005-918439
Asymmetric Synthesis of 4′-epi-Trachycladines A and B
Publication History
Publication Date:
25 October 2005 (online)

Abstract
The first asymmetric synthesis of 4′-epi-trachycladines A and B is reported. Starting from 2,2-dimethyl-1,3-dioxan-5-one the title nucleosides were synthesised in 14 steps employing the SAMP-/RAMP-hydrazone methodology. The dioxanone-SAMP-hydrazone was first transformed into a trisubstituted derivative by a triple α-/α′-alkylation. Removal of the chiral auxiliary and subsequent reduction gave the corresponding alcohol, which could be transformed over four steps into TBS-protected 2′-C-methyl-5′-deoxy-l-lyxose. The trachycladines were then obtained via the corresponding triacetate using standard Vorbrüggen and silyl-Hilbert-Johnson conditions in an overall yield of 18-21%. Such 2′-C-branched ribonucleosides are potential agonists for adenosine receptors and play an important role in drug discovery.
Key words
nucleosides - asymmetric synthesis - hydrazones - quaternary stereocenters - Vorbrüggen coupling
-
1a
Rachakonda S.Cartee L. Curr. Med. Chem. 2004, 11: 775 -
1b
Newman DJ.Cragg GM. Curr. Med. Chem. 2004, 11: 1693 - Reviews:
-
2a
Knapp S. Chem. Rev. 1995, 95: 1859 -
2b
Zhang D.Miller MJ. Curr. Pharm. Des. 1999, 5: 73 -
2c
Isono K. J. Antibiot. 1988, 41: 1711 -
2d
Isono K. Pharmacol. Ther. 1991, 52: 269 - 3
Searle PA.Molinski TF. J. Org. Chem. 1995, 60: 4296 -
4a
Ichiba T.Nakao Y.Scheuer PJ. Tetrahedron Lett. 1995, 36: 3977 -
4b
Erdogan I.Higa T. J. Fac. Pharm., Ankara 2000, 29: 1 - 5
Jaiyesimi IA.Kantarjian HM.Estey EH. Cancer 1993, 72: 5 -
6a
Bio MM.Xu F.Waters M.Williams JM.Savary KA.Cowden CJ.Yang C.Buck E.Song ZJ.Tschaen DM.Volante RP.Reamer RA.Grabowski EJJ. J. Org. Chem. 2004, 69: 6257 -
6b
Eldrup AB.Allerson CR.Bennett CF.Bera S.Bhat B.Bhat N.Bosserman MR.Brooks J.Burlein C.Carroll SS.Cook PD.Getty KL.MacCoss M.McMasters DR.Olsen DB.Prakash TP.Prhavc M.Song Q.Tomassini JE.Xia J. J. Med. Chem. 2004, 47: 2283 -
7a
Franchetti P.Cappellacci L.Marchetti S.Trincavelli L.Martini C.Mazzoni MR.Lucacchini A.Grifantini M. J. Med. Chem. 1998, 41: 1708 -
7b
van Tilburg EW.van der Klein PAM.von Frijtag Drabbe Künzel J.de Groote M.Stannek C.Lorenzen A.Ijzerman AP. J. Med. Chem. 2001, 44: 2966 - 8
Vorbrüggen H.Ruh-Pohlenz C. Org. React. (N.Y.) 2000, 55: 1 -
9a
Hilbert GE.Johnson TB. J. Am. Chem. Soc. 1930, 52: 4489 -
9b
Birkofer L.Ritter A.Kühltau H.-P. Chem. Ber. 1964, 97: 934 -
10a
Enders D.Nühring A.Runsink J.Raabe G. Synthesis 2001, 1406 -
10b
Nühring A. PhD Dissertation RWTH Aachen; Germany: 2001. - Reviews:
-
11a
Enders D.Voith M.Lenzen A. Angew. Chem. Int. Ed. 2005, 44: 1304 ; Angew. Chem. 2005, 117, 1330 -
11b
Job A.Janeck CF.Bettray W.Peters R.Enders D. Tetrahedron 2002, 58: 2253 - 12
Enders D.Breuer I.Raabe G. Synthesis 2005, in press - 13
Jegelka U. PhD Dissertation RWTH Aachen; Germany: 1992. - 14
Moore CM.Chiaramonte M.Higgins T.Kuchta RD. Biochemistry 2002, 41: 14066 -
15a
Chenon M.-T.Pugmire RJ.Grant DM.Panzica RP.Townsend LB. J. Am. Chem. Soc. 1975, 97: 4636 -
15b
Chenon M.-T.Pugmire RJ.Grant DM.Panzica RP.Townsend LB. J. Am. Chem. Soc. 1975, 97: 4627