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Synthesis 2011(22): 3669-3674  
DOI: 10.1055/s-0030-1260223
PAPER
© Georg Thieme Verlag Stuttgart ˙ New York

A Library of Conformationally Restricted Saturated Heterocyclic Sulfonyl Chlorides

Sergey Zhersha,b, Volodymyr V. Buryanova,b, Oleksandr V. Karpenkoa, Oleksandr O. Grygorenko*a,b, Andrey A. Tolmacheva,b
a Enamine Ltd., Alexandra Matrosova Street, 23, Kyiv 01103, Ukraine
b Department of Chemistry, Kyiv National Taras Shevchenko University, Volodymyrska St. 64, Kyiv 01033, Ukraine
Fax: +380(44)5024832; e-Mail: gregor@univ.kiev.ua;
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Publication History

Received 14 July 2011
Publication Date:
14 September 2011 (online)

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Abstract

An approach to the synthesis of conformationally restricted saturated heterocyclic sulfonyl chlorides is described. Being guided by the principle of diversity-oriented conformational restriction, a mini-library of saturated heterocyclic sulfonyl chlorides was designed and synthesized. The library consists of nine members that are derivatives of azetidine, pyrrolidine, and piperidine. These compounds were prepared in 19-88% total yields on multigram scale starting from the corresponding Cbz-protected amino alcohols.

Key words

sulfonyl chlorides - nitrogen heterocycles - molecular rigidity - libraries - conformational restriction

    References

  • 2a Lovering F. Bikker J. Humblet C. J. Med. Chem.  2009,  52:  6752 
    Google Scholar
  • 2b Kingwell K. Nature Rev. Drug Discovery  2009,  8:  931 
    Google Scholar
  • 2c Nicholls A. McGaughey GB. Sheridan RP. Good AC. Warren G. Mathieu M. Muchmore SW. Brown SP. Grant JA. Haigh JA. Nevins N. Jain AN. Kelley B. J. Med. Chem.  2010,  53:  3862 
    Google Scholar
  • 2d Feher M. Schmidt JM. J. Chem. Inf. Comput. Sci.  2003,  43:  218 
    Google Scholar
  • 3 Mann A. In Practice of Medicinal Chemistry   3rd ed.:  Wermuth CG. Academic Press/Elsevier; Amsterdam: 2008.  p.363-379  
    Google Scholar
  • 4 Watanabe M. Kazuta Y. Hayashi H. Yamada S. Matsuda A. Shuto S. J. Med. Chem.  2006,  49:  5587 
    CrossrefGoogle Scholar
  • 5a Cowell SM. Lee YS. Cain JP. Hruby VJ. Curr. Med. Chem.  2004,  11:  2785 
    Google Scholar
  • 5b Hruby VJ. Al-Obeidi F. Kazmierski W. Biochem. J.  1990,  268:  249 
    Google Scholar
  • 5c Shemyakin MM. Ovchinnikov YA. Ivanov VT. Angew. Chem., Int. Ed. Engl.  1969,  8:  492 
    Google Scholar
  • 5d Komarov IV. Grigorenko AO. Turov AV. Khilya VP. Russ. Chem. Rev.  2004,  73:  785 
    Google Scholar
  • 5e Soloshonok VA. Curr. Org. Chem.  2002,  6:  341 
    Google Scholar
  • 5f Cativiela C. Ordóñez M. Tetrahedron: Asymmetry  2009,  20:  1 
    Google Scholar
  • 5g Trabocchi A. Scarpi D. Guarna A. Amino Acids  2008,  34:  1 
    Google Scholar
  • 5h Grygorenko OO. Artamonov OS. Palamarchuk GV. Zubatyuk RI. Shishkin OV. Komarov IV. Tetrahedron: Asymmetry  2006,  17:  252 
    Google Scholar
  • 5i Radchenko DS. Kopylova N. Grygorenko OO. Komarov IV. J. Org. Chem.  2009,  74:  5541 
    Google Scholar
  • 5j Kotti SRSS. Timmons C. Li G. Chem. Biol. Drug Des.  2006,  67:  101 
    Google Scholar
  • 5k Lucet D. Le Gall T. Mioskowski C. Angew. Chem. Int. Ed.  1998,  37:  2580 
    Google Scholar
  • 5l Radchenko DS. Pavlenko SO. Grygorenko OO. Volochnyuk DM. Shishkina SV. Shishkin OV. Komarov IV. J. Org. Chem.  2010,  75:  5941 
    Google Scholar
  • 5m Mityuk AP. Denisenko AV. Dacenko OP. Grygorenko OO. Mykhailiuk PK. Volochnyuk DM. Tolmachev AA. Tetrahedron Lett.  2010,  51:  1790 
    Google Scholar
  • 5n The Quinolones   Andriole VT. Academic Press; San Diego: 2000.  p.655 
    Google Scholar
  • 5o Grygorenko OO. Radchenko DS. Volochnyuk DM. Tolmachev AA. Komarov IV. Chem. Rev.  2011,  in press
    Google Scholar
  • 6a Bogen SL. Arasappan A. Velazquez F. Blackman M. Huelgas R. Pan W. Siegel E. Nair LG. Venkatraman S. Doll R. Shih N.-Y. George Njoroge F. Guo Z. Bioorg. Med. Chem.  2010,  18:  1854 
    Google Scholar
  • 6b Wels B. Kruijtzer JAW. Garner KM. Adan RAH. Liskamp RMJ. Bioorg. Med. Chem. Lett.  2005,  15:  287 
    Google Scholar
  • 6c Giordano C. Nalli M. Paradisi MP. Sansone A. Lucente G. Spisani S. Farmaco  2004,  59:  953 
    Google Scholar
  • 6d de Bont DBA. Sliedregt-Bol KM. Hofmeyer LJF. Liskamp RMJ. Bioorg. Med. Chem.  1999,  7:  1043 
    Google Scholar
  • 6e Lowik DWPM. Liskamp RMJ. Eur. J. Org. Chem.  2000,  7:  1219 
    Google Scholar
  • 6f Carson KG. Schwender CF. Shroff HN. Cochran NA. Gallant DL. Briskin MJ. Bioorg. Med. Chem. Lett.  1997,  7:  711 
    Google Scholar
  • 6g Moree WJ. van der Marel GA. Liskamp RMJ. J. Org. Chem.  1995,  60:  5157 
    Google Scholar
  • 6h Moree WJ. van Gent LC. van der Marel GA. Liskamp RMJ. Tetrahedron  1993,  49:  1133 
    Google Scholar
  • 7a Giordano C. Sansone A. Masi A. Lucente G. Punzi P. Mollica A. Pinnen F. Feliciani F. Cacciatore I. Davis P. Lai J. Ma S.-W. Porreca F. Hruby V. Eur. J. Med. Chem.  2010,  45:  4594 
    Google Scholar
  • 7b Giordano C. Masi A. Pizzini A. Sansone A. Lucente G. Consalvi V. Chiaraluce R. Eur. J. Med. Chem.  2009,  44:  179 
    Google Scholar
  • Synthesis of 1a was also described in the patents, see:
  • 8a Miner JN, Chapman MS, Quart B, Adjei A, and Yu C. inventors; PCT Int. Pat. WO  2009/38974. 
    Google Scholar
  • 8b Carlson S. inventors; PCT Int. Pat. WO  2008/75070. 
    Google Scholar
  • Synthesis of 1c was described in the patents, see:
  • 9a Ting PC, Aslanian RG, Berlin MY, Boyce CW, Cao J, Mangiaracina P, McCormick KD, Mutahi MW, Rosenblum SB, Shih N.-Y, Solomon DM, Tom WC, and Zeng Q. inventors; PCT Int. Pat. WO  2003/103669. 
    Google Scholar
  • 9b Imazaki N, Kitano M, Ohashi N, and Matsui K. inventors; Eur. Pat.  EP 1403255. 
    Google Scholar
  • 10 Bull DJ, Maguire RJ, Palmer MJ, and Wythes MJ. inventors; U.S. Patent  6610707. Syntheses of 1e and 1g were described in a patent, see:
  • 11 Genari C. Ceccarelli S. Piarulli U. Montalbetti CAGN. Jackson RFW. J. Org. Chem.  1998,  63:  5312 
    CrossrefGoogle Scholar
  • 12 Gruetter C. Alonso E. Chougnet A. Woggon W.-D. Angew. Chem. Int. Ed.  2006,  45:  1126 
    CrossrefGoogle Scholar
  • 14 Michael FE. Sibbald PA. Cochran BM. Org. Lett.  2008,  10:  793 
    CrossrefGoogle Scholar
  • Isolated yields are given in Scheme 3. In the case of 3b, the alkenes 8 and 9 were obtained as a mixture that was not separated. For spectral and physical data of 7-9, see:
  • 15a Beaulieu F. Beauregard L.-P. Courchesne G. Couturier M. Laflamme F. L’Heureux A. Org. Lett.  2009,  11:  5050 
    Google Scholar
  • 15b Schramm H. Pavlova M. Christoffers J. Hoenke C. Synthesis  2009,  1659 
    Google Scholar
  • 15c Kim S. Yoon J.-Y. Synthesis  2000,  1622 
    Google Scholar
  • 16a Brown HC. Prasad JVNV. Zee S.-H. J. Org. Chem.  1985,  50:  1582 
    Google Scholar
  • 16b Tomori H. Shibatani K. Ogura K. Bull. Chem. Soc. Jpn.  1996,  69:  207 
    Google Scholar
  • 16c Chang D. Feiten H.-J. Engesser K.-H. van Beilen JB. Witholt B. Li Z. Org. Lett.  2002,  4:  1859 
    Google Scholar
  • 16d Takeda K. Tsuboyama K. Hoshino M. Kishino M. Ogura H. Synthesis  1987,  557 
    Google Scholar
  • 16e Mazzini C. Lebreton J. Alphand V. Furstoss R. J. Org. Chem.  1997,  62:  5215 
    Google Scholar
  • 16f Sanchez-Sancho F. Herradon B. Tetrahedron: Asymmetry  1998,  9:  1951 
    Google Scholar
  • 16g Abreu AR. Costa I. Rosa C. Ferreira LM. Lourenco A. Santos PP. Tetrahedron  2005,  61:  11986 
    Google Scholar
  • 16h Boyer N. Jubault P. Quirion J.-C. Gloanec P. De Nanteuil G. Eur. J. Org. Chem.  2008,  4277 
    Google Scholar
  • 16i Hanselmann R. Johnson G. Reeve MM. Huang S.-T. Org. Process Res. Dev.  2009,  13:  54 
    Google Scholar
  • 17a Back TG. Nakajima K. Org. Lett.  1999,  1:  261 
    Google Scholar
  • 17b Norton TR. Seibert RA. Benson AA. Bergstrom FW. J. Am. Chem. Soc.  1946,  68:  1572 
    Google Scholar
  • 18 Sanchez JP. Domagala JM. Heifetz CL. Priebe SR. Sesnie JA. Trehan AK. J. Med. Chem.  1992,  35:  1764 
    CrossrefGoogle Scholar
  • 19 Jones CA. Jones IG. Mulla M. North M. Sartori L. J. Chem. Soc., Perkin Trans. 1  1997,  2891 
    Google Scholar
  • 20 Rosenberg SH. Spina KP. Condon SL. Polakowski J. Yao Z. Kovar P. Stein HH. Cohen J. Barlow JL. Klinghofer V. Egan DA. Tricarico KA. Perun TJ. Baker WR. Kleinert HD. J. Med. Chem.  1993,  36:  460 
    CrossrefGoogle Scholar
  • 21 Nicolaides ED. Tinney FJ. Kaltenbronn JS. Repine JT. DeJohn DA. Lunney EA. Roark WH. Marriott JG. Davis RE. Voigtman RE. J. Med. Chem.  1986,  29:  959 
    CrossrefGoogle Scholar
1

MDL Drug Data Report; Elsevier MDL, version
2010.2/32.08.

13

A method analogous to that reported herein was disclosed in the patents; in particular, the syntheses of 1a and 1c on a gram scale were described (see ref. 8 and 9b).