Download PDF
Synthesis 2010(8): 1303-1310  
DOI: 10.1055/s-0029-1218677
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

A Synthetic Route to Fully Substituted Chiral Cyclopentylamine Derivatives: Precursors of Carbanucleosides

Ramprasad Ghosha, Joy Krishna Maitya, Michael G. B. Drewb, Basudeb Acharia, Sukhendu B. Mandal*a
a Chemistry Division, Indian Institute of Chemical Biology (a unit of CSIR), Jadavpur, Kolkata 700 032, India
Fax: +91(33)24735197; e-Mail: sbmandal@iicb.res.in;
b Department of Chemistry, University of Reading, Whiteknights, Reading, RG6 6AD, UK
Further Information

Publication History

Received 21 December 2009
Publication Date:
11 February 2010 (online)

    Permissions and Reprints All articles of this category

Abstract

Removal of silyl protection from d-glucose derived substrate 6 afforded 7, which upon acetonide deprotection followed by reaction with N-benzylhydroxylamine furnished two isomeric isoxazolidinocyclopentane derivatives via spontaneous cyclization of an in situ generated nitrone. The methyl xanthate derivative of the tertiary hydroxyl group of one isomer was isolated and subjected to radical deoxygenation reaction to form epimeric products, while with the other isomer it underwent spontaneous 1,2-elimination to form a mixture of the two possible endocyclic olefins. Hydrogenolytic cleavage of the isoxazolidine rings of the purified products followed by insertion of 5-amino-4-chloropyrimidine moiety and purine ring construction smoothly afforded structurally unique carbanucleoside analogues. Various spectroscopic methods on the synthesized compounds and X-ray analysis on one important intermediate were used to assign the structures and stereochemistry of the products.

Key words

cyclopentylamine - INC reaction - carbanucleosides - d-glucose

    References

  • 1a Jenkins GN. Turner NJ. Chem. Soc. Rev.  1995,  169 
    Google Scholar
  • 1b Wachtmeister J. Classon B. Samuelsson B. Kvarnstrõm I. Tetrahedron  1995,  51:  2029 
    Google Scholar
  • 2 Altona C. Sunderalingam M. J. Am. Chem. Soc.  1972,  94:  8205 
    CrossrefGoogle Scholar
  • 3a Mandal SB. Sahabuddin Sk. Singha K. Roy A. Roy BG. Maity JK. Achari B. Proc. Indian Natl. Sci. Acad.  2005,  71A:  283 ; and references cited therein
    Google Scholar
  • 3b Crimmins MT. King BW. Zuercher WJ. Choy AL. J. Org. Chem.  2000,  65:  8499 ; and references cited therein
    Google Scholar
  • 3c Gurjar MK. Maheswar K. J. Org. Chem.  2001,  66:  7552 
    Google Scholar
  • 3d Ono M. Nishimura K. Tsubouchi H. Nagaoka Y. Tomoika K. J. Org. Chem.  2001,  66:  8199 
    Google Scholar
  • 4a Jin YH. Liu P. Wang J. Baker R. Huggins J. Chu CK. J. Org. Chem.  2003,  68:  9012 
    Google Scholar
  • 4b Seley KL. Mosley SL. Zeng F. Org. Lett.  2003,  5:  4401 
    Google Scholar
  • 4c Li F. Brogan JB. Gage JL. Zhang D. Miller MJ. J. Org. Chem.  2004,  69:  4538 
    Google Scholar
  • 5a Khan FA. Rout B. J. Org. Chem.  2007,  72:  7011 
    Google Scholar
  • 5b Arjona O. Gómez AM. López C. Plumet J. Chem. Rev.  2007,  107:  1919 
    Google Scholar
  • 6a Marcé P. Djaz Y. Matheu MI. Castillón S. Org. Lett.  2008,  10:  4735 
    Google Scholar
  • 6b Yoshimura Y. Ohta M. Imahori T. Imamichi T. Org. Lett.  2008,  10:  3449 
    Google Scholar
  • 6c Leung LMH. Gibson V. Linclau B. J. Org. Chem.  2008,  73:  9197 
    Google Scholar
  • 6d Besada P. Gonzalezmoa MJ. Teran C. Synthesis  2008,  2363 
    Google Scholar
  • 6e Quadrelli P. Piccanello A. Mella M. Corsaro A. Pistara V. Tetrahedron  2008,  64:  3541 
    Google Scholar
  • 7a Cesario C. Miller MJ. J. Org. Chem.  2009,  74:  5730 
    Google Scholar
  • 7b Jessel S. Meier C. Nucleic Acids Symp. Ser.  2008,  52:  615 
    Google Scholar
  • 8a Wang J. Jin Y. Rapp KL. Schinazi RF. Chu CK. J. Med. Chem.  2007,  50:  1828 
    Google Scholar
  • 8b Migliore MD. Zontra N. McGuigan C. Henson G. Andrei G. Resnoeck R. Balzarini J. J. Med. Chem.  2007,  50:  6485 
    Google Scholar
  • 8c Ahn H. Choi TH. De Castro K. Lee KC. Kim B. Moon BS. Hong SH. Lee JC. Chun KS. Cheon GJ. Lim SM. An GI. Rhee H. J. Med. Chem.  2007,  50:  6032 
    Google Scholar
  • 8d Kim H.-J. Sharon A. Bal C. Wang J. Allu M. Huang Z. Murray MG. Bassit L. Schinazi RF. Korba B. Chu CK. J. Med. Chem.  2009,  52:  206 
    Google Scholar
  • 8e Boyer PL. Vu BC. Ambrose Z. Julias JG. Warnecke S. Liao C. Meier C. Marquez VE. Hughes SH. J. Med. Chem.  2009,  52:  5356 
    Google Scholar
  • 9a Nicolaou KC. Dai W.-M. Angew. Chem., Int. Ed. Engl.  1991,  30:  1387 
    Google Scholar
  • 9b Pratbiel G. Bernadou J. Meunier B. Angew. Chem., Int. Ed. Engl.  1995,  34:  746 
    Google Scholar
  • 10 Kusuka T. Yamamoto H. Shibata M. Muroi M. Kishi T. Mizuno K. J. Antibiot.  1968,  21:  255 
    CrossrefGoogle Scholar
  • 11 Yaginuma S. Muto N. Tsujino M. Sudate Y. Hayashi M. Otani M. J. Antibiot.  1981,  34:  359 
    CrossrefGoogle Scholar
  • 12 Vince R. Hua M. J. Med. Chem.  1990,  33:  17 
    CrossrefPubMedGoogle Scholar
  • 13 Daluge SM. Good SS. Faletto MB. Miller WH. St. Clair MH. Boone LR. Tisdale M. Parry NR. Reardon JE. Dornsife RE. Averette DR. Krenitsky TA. Antimicrob. Agents Chemother.  1997,  41:  1082 
    Google Scholar
  • 14 Katagiri N. Nomura N. Sato H. Kaneko C. Tusa K. Tsuruo T. J. Med. Chem.  1992,  35:  1882 
    CrossrefGoogle Scholar
  • 15 Balzarini J. Baumgartner H. Bodenteich M. De Clercq E. Griengl H. J. Med. Chem.  1989,  32:  1861 
    CrossrefGoogle Scholar
  • 16 Borthwick AD. Butt S. Biggadike K. Exall AM. Roberts SM. Youds PM. Kirk BE. Booth BR. Cameron JM. Cox SW. Marr CLP. Shill MD.
    J. Chem. Soc., Chem. Commun.  1988,  656 
    CrossrefGoogle Scholar
  • 17a Ando O. Nakajima M. Hamano K. Itoi K. Takahasi S. Takamatsu Y. Sato A. Enokita R. Okazaki T. Haruyama H. Kinoshita T. J. Antibiot.  1993,  46:  1116 
    Google Scholar
  • 17b Wen X. Norling H. Hegedus LS. J. Org. Chem.  2000,  65:  2096 
    Google Scholar
  • 18 Elbein AD. Annu. Rev. Biochem.  1987,  56:  497 
    CrossrefGoogle Scholar
  • 19a Singha K. Roy A. Dutta PK. Tripathi S. Sahabuddin Sk. Achari B. Mandal SB. J. Org. Chem.  2004,  69:  6507 
    Google Scholar
  • 19b Sahabuddin Sk. Drew MGB. Roy A. Achari B. Mandal SB. J. Org. Chem.  2006,  71:  5980 
    Google Scholar
  • 19c Roy BG. Maiti JK. Drew MGB. Achari B. Mandal SB. Tetrahedron Lett.  2006,  47:  8821 
    Google Scholar
  • 19d Tripathi S. Roy BG. Drew MGB. Achari B. Mandal SB. J. Org. Chem.  2007,  72:  7427 
    Google Scholar
  • 20a Gothelf KV. Jørgensen KA. Chem. Rev.  1998,  98:  863 
    Google Scholar
  • 20b Shing TKM. Elsley DA. Gillhouley JG. J. Chem. Soc., Chem. Commun.  1989,  1280 
    Google Scholar
  • 20c Gallos JK. Stathakis CI. Kotoulas SS. Koumbis AE. J. Org. Chem.  2005,  70:  6884 
    Google Scholar
  • 21 Maity JK. Ghosh R. Drew MGB. Achari B. Mandal SB. J. Org. Chem.  2008,  73:  4305 
    CrossrefGoogle Scholar
  • 23a Anantharamaiah GM. Sivanandaiah KM. J. Chem. Soc., Perkin Trans. 1  1977,  490 
    Google Scholar
  • 23b Hanessian S. Liak TJ. Vanasse B. Synthesis  1981,  396 
    Google Scholar
  • 23c Collins PM. Ashwood MS. Eder H. Wright SHB. Kennedy DJ. Tetrahedron Lett.  1990,  31:  2055 
    Google Scholar
  • 25a CrysAlis   Oxford Diffraction Ltd.; Abingdon UK: 2006. 
    Google Scholar
  • 25b Sheldrick GM. Acta Crystallogr., Sect. A  2008,  64:  112 
    Google Scholar
22

We tried several times to cleave the isoxazolidine ring in addition to reducing the double bond of 19 by hydrogenation reaction, but every time only the double bond was reduced. In contrast, successful isoxazolidine ring cleavage occurred in the cases of 9 and 10. We do not have an explanation for this.

24

Crystal data for 9 have been deposited at the Cambridge Crystallographic Data Centre with reference number CCDC 750271. Data can be obtained via www.ccdc.cam.ac.uk/data_request/cif.