Proline Methanologues: Design, Synthesis, Structural Properties, and Applications in Medicinal Chemistry

Part of the Topics in Heterocyclic Chemistry book series (TOPICS, volume 48)


In this review, we discuss methanoprolines, which are analogues of proline that contain a bridged methylene group at different positions, which we designate herein as proline methanologues. Particular emphasis is placed on naturally occurring members, general methods for the stereocontrolled synthesis of different diastereoisomers, functionalized analogues, conformational and stereoelectronic features, as well as their utility as proline congeners in medicinally relevant compounds.


Conformational analysis Constrained amino acids Drug prototypes Natural products 



We thank CONACyT for a fellowship to Miguel Vilchis and to NSERC for financial support.


  1. 1.
    Avan I, Hall CD, Katritzky AR (2014) Chem Soc Rev 43:3575CrossRefGoogle Scholar
  2. 2.
    Liskamp RMJ, Rijkers DTS, Kruijtzer JAW, Kemmink J (2011) ChemBioChem 12:1626CrossRefGoogle Scholar
  3. 3.
    Reichelt A, Martin SF (2006) Acc Chem Res 39:433CrossRefGoogle Scholar
  4. 4.
    Hanessian S, McNaughton-Smith G, Lombart H-G, Lubell WD (1997) Tetrahedron 53:12789CrossRefGoogle Scholar
  5. 5.
    Trabocchi A, Scarpi D, Guarna A (2008) Amino Acids 34:1CrossRefGoogle Scholar
  6. 6.
    Hanessian S, Auzzas L (2008) Acc Chem Res 41:1241CrossRefGoogle Scholar
  7. 7.
    Komarov IV, Grigorenko AO, Turov AV, Khilya VP (2004) Russ Chem Rev 73:785CrossRefGoogle Scholar
  8. 8.
    Grygorenko OO, Artamonov OS, Komarov IV, Mykhailiuk PK (2011) Tetrahedron 67:803CrossRefGoogle Scholar
  9. 9.
    Brackmann F, de Meijere A (2007) Chem Rev 107:4493CrossRefGoogle Scholar
  10. 10.
    Salaün J (2000) Cyclopropane derivatives and their diverse biological activities. In: de Meijere A (ed) Small ring compounds in organic synthesis VI, vol 207, Topics in current chemistry. Springer, Berlin/Heidelberg, pp 1CrossRefGoogle Scholar
  11. 11.
    Milewska MJ (2000) Pol J Chem 74:447Google Scholar
  12. 12.
    Stammer CH (1990) Tetrahedron 46:2231CrossRefGoogle Scholar
  13. 13.
    Adams DO, Yang SF (1979) Proc Natl Acad Sci U S A 76:170CrossRefGoogle Scholar
  14. 14.
    Pirrung MC (1987) J Org Chem 52:4179CrossRefGoogle Scholar
  15. 15.
    Wheeler TN, Ray J (1987) J Org Chem 52:4875CrossRefGoogle Scholar
  16. 16.
    Pirrung MC, McGeehan GM (1986) J Org Chem 51:2103CrossRefGoogle Scholar
  17. 17.
    Hoffman NE, Yang SF, Ichihara A, Sakamura S (1982) Plant Physiol 70:195CrossRefGoogle Scholar
  18. 18.
    Switzer FL, Van Halbeek H, Holt EM, Stammer CH, Saltveit ME Jr (1989) Tetrahedron 45:6091CrossRefGoogle Scholar
  19. 19.
    Häusler J (1981) Liebigs Ann Chem 1981:1073CrossRefGoogle Scholar
  20. 20.
    Matsui S, Srivastava VP, Holt EM, Taylor EW, Stammer CH (1991) Int J Pept Protein Res 37:306CrossRefGoogle Scholar
  21. 21.
    Hercouet A, Bessières B, Le Corre M (1996) Tetrahedron Asymmetry 7:1267CrossRefGoogle Scholar
  22. 22.
    Le Corre M, Hercouet A, Bessieres B (1995) Tetrahedron Asymmetry 6:683CrossRefGoogle Scholar
  23. 23.
    Hercouet A, Bessières B, Le Corre M (1996) Tetrahedron Asymmetry 7:283CrossRefGoogle Scholar
  24. 24.
    Gao Y, Sharpless KB (1988) J Am Chem Soc 110:7538CrossRefGoogle Scholar
  25. 25.
    Stork G, Leong AYW, Touzin AM (1976) J Org Chem 41:3491CrossRefGoogle Scholar
  26. 26.
    Beak P, Wu S, Yum EK, Jun YM (1994) J Org Chem 59:276CrossRefGoogle Scholar
  27. 27.
    Kodama H, Yamamoto H, Miyazaki M, Kondo M (1994) Synthesis and beta-turn stabilizing of cyclopropaneproline analogues. In: Okada K (ed) Peptide chemistry 1993, vol 31. Protein Research Foundation, Osaka, pp 61Google Scholar
  28. 28.
    Barluenga J, Aznar F, Gutiérrez I, García-Granda S, Llorca-Baragaño MA (2002) Org Lett 4:4273CrossRefGoogle Scholar
  29. 29.
    Kodama H, Matsui S, Kondo M, Stammer CH (1992) Bull Chem Soc Jpn 65:2668CrossRefGoogle Scholar
  30. 30.
    Mapelli C, Elrod LF, Holt EM, Stammer CH (1989) Tetrahedron 45:4377CrossRefGoogle Scholar
  31. 31.
    Elrod LF, Holt EM, Mapelli C, Stammer CH (1988) J Chem Soc Chem Commun 252Google Scholar
  32. 32.
    Bateson JH, Southgate R, Tyler JW, Fell SCM (1986) J Chem Soc Perkin Trans 1:973Google Scholar
  33. 33.
    Ezquerra J, Escribano A, Rubio A, Remuiñán MJ, Vaquero JJ (1996) Tetrahedron Asymmetry 7:2613CrossRefGoogle Scholar
  34. 34.
    Gnad F, Poleschak M, Reiser O (2004) Tetrahedron Lett 45:4277CrossRefGoogle Scholar
  35. 35.
    Adamovskyi MI, Artamonov OS, Tymtsunik AV, Grygorenko OO (2014) Tetrahedron Lett 55:5970CrossRefGoogle Scholar
  36. 36.
    Bell EA, Qureshi MY, Pryce RJ, Janzen DH, Lemke P, Clardy J (1980) J Am Chem Soc 102:1409CrossRefGoogle Scholar
  37. 37.
    Kite GC, Ireland H (2002) Phytochemistry 59:163CrossRefGoogle Scholar
  38. 38.
    Stevens CV, Smagghe G, Rammeloo T, De Kimpe N (2005) J Agric Food Chem 53:1945CrossRefGoogle Scholar
  39. 39.
    Chung HH, Benson DR, Cornish VW, Schultz PG (1993) Proc Natl Acad Sci U S A 90:10145CrossRefGoogle Scholar
  40. 40.
    Hughes P, Martin M, Clardy J (1980) Tetrahedron Lett 21:4579CrossRefGoogle Scholar
  41. 41.
    Hughes P, Clardy J (1988) J Org Chem 53:4793CrossRefGoogle Scholar
  42. 42.
    Liu RSH, Hammond GS (1964) J Am Chem Soc 86:1892CrossRefGoogle Scholar
  43. 43.
    Varnes JG, Scott Lehr G, Moore GL, Hulsizer JM, Albert JS (2010) Tetrahedron Lett 51:3756CrossRefGoogle Scholar
  44. 44.
    Pirrung MC (1980) Tetrahedron Lett 21:4577CrossRefGoogle Scholar
  45. 45.
    Rammeloo T, Stevens CV, De Kimpe N (2002) J Org Chem 67:6509CrossRefGoogle Scholar
  46. 46.
    Rammeloo T, Stevens CV (2002) Chem Commun 250Google Scholar
  47. 47.
    Montelione GT, Hughes P, Clardy J, Scheraga HA (1986) J Am Chem Soc 108:6765CrossRefGoogle Scholar
  48. 48.
    Talluri S, Montelione GT, Van Duyne G, Piela L, Clardy J, Scheraga HA (1987) J Am Chem Soc 109:4473CrossRefGoogle Scholar
  49. 49.
    Piela L, Nemethy G, Scheraga HA (1987) J Am Chem Soc 109:4477CrossRefGoogle Scholar
  50. 50.
    Mapelli C, Halbeek HV, Stammer CH (1990) Biopolymers 29:407CrossRefGoogle Scholar
  51. 51.
    Esslinger SC, Koch HP, Kavanaugh MP, Philips DP, Chamberlin RA, Thompson CM, Bridges RJ (1998) Bioorg Med Chem Lett 8:3101CrossRefGoogle Scholar
  52. 52.
    Malpass JR, Patel AB, Davies JW, Fulford SY (2003) J Org Chem 68:9348CrossRefGoogle Scholar
  53. 53.
    Patel AB, Malpass JR (2008) J Med Chem 51:7005CrossRefGoogle Scholar
  54. 54.
    Grygorenko OO, Artamonov OS, Palamarchuk GV, Zubatyuk RI, Shishkin OV, Komarov IV (2006) Tetrahedron Asymmetry 17:252CrossRefGoogle Scholar
  55. 55.
    Tkachenko AN, Radchenko DS, Mykhailiuk PK, Grygorenko OO, Komarov IV (2009) Org Lett 11:5674CrossRefGoogle Scholar
  56. 56.
    Vasiuta RI, Gorichko MV (2014) Tetrahedron Lett 55:466CrossRefGoogle Scholar
  57. 57.
    Fowden L, Smith A, Millington DS, Sheppard RC (1969) Phytochemistry 8:437CrossRefGoogle Scholar
  58. 58.
    Fowden L, Lea PJ, Worris RD (1972) Symp Biol Hung 13:137Google Scholar
  59. 59.
    Caveney S, Starratt A (1994) Nature 372:509CrossRefGoogle Scholar
  60. 60.
    Starratt AN, Caveney S (1995) Phytochemistry 40:479CrossRefGoogle Scholar
  61. 61.
    Norris RD, Fowden L (1972) Phytochemistry 11:2921CrossRefGoogle Scholar
  62. 62.
    Rowland I, Tristram H (1972) Chem Biol Interact 4:377CrossRefGoogle Scholar
  63. 63.
    Kerr MW (1984) Rational design of a pollen suppressant for small-grained cereals. In: British Plant Growth Regulator Group (ed) Biochemical aspects of synthetic and naturally occurring plant growth regulators, vol 11. The Group, Wantage, pp 59Google Scholar
  64. 64.
    Macháčková I, Zmrhal Z (1983) Biol Plant 25:394CrossRefGoogle Scholar
  65. 65.
    Thondorf I, Voigt V, Schäfer S, Gebauer S, Zebisch K, Laug L, Brandsch M (2011) Bioorg Med Chem 19:6409CrossRefGoogle Scholar
  66. 66.
    Abraham S, Hadd MJ, Tran L, Vickers T, Sindac J, Milanov ZV, Holladay MW, Bhagwat SS, Hua H, Ford Pulido JM, Cramer MD, Gitnick D, James J, Dao A, Belli B, Armstrong RC, Treiber DK, Liu G (2011) Bioorg Med Chem Lett 21:5296CrossRefGoogle Scholar
  67. 67.
    Wood DA, Mason RF, Day JA, Searle RJG (1980) EP 001 079 9B1Google Scholar
  68. 68.
    Kollmeyer WD (1980) US 4 183 857Google Scholar
  69. 69.
    Day JA, Devlin BRJ, Searle RJG (1981) US 4 279 821Google Scholar
  70. 70.
    Scholes G, Baardman F (1981) US 4 262 124Google Scholar
  71. 71.
    Levy OE, Madison EL, Semple JE, Tamiz AP, Weinhouse MI (2002) WO 02/14349Google Scholar
  72. 72.
    Witkop B, Fujimoto Y, Irreverre F, Karle JM, Karle IL (1971) J Am Chem Soc 93:3471CrossRefGoogle Scholar
  73. 73.
    Fowler FW (1971) Angew Chem 83:147CrossRefGoogle Scholar
  74. 74.
    Sagnard I, Sasaki NA, Chiaroni A, Riche C, Potier P (1995) Tetrahedron Lett 36:3149CrossRefGoogle Scholar
  75. 75.
    Pellicciari R, Natalini B, Marinozzi M, Monahan JB, Snyder JP (1990) Tetrahedron Lett 31:139CrossRefGoogle Scholar
  76. 76.
    Tverezovsky VV, Baird MS, Bolesov IG (1997) Tetrahedron 53:14773CrossRefGoogle Scholar
  77. 77.
    Oba M, Nishiyama N, Nishiyama K (2005) Tetrahedron 61:8456CrossRefGoogle Scholar
  78. 78.
    Barton DHR, Hervé Y, Potier P, Thierry J (1988) Tetrahedron 44:5479CrossRefGoogle Scholar
  79. 79.
    Barton DHR, Crich D, Motherwell WB (1983) J Chem Soc Chem Commun 939Google Scholar
  80. 80.
    Bakonyi B, Furegati M, Kramer C, La Vecchia L, Ossola F (2013) J Org Chem 78:9328CrossRefGoogle Scholar
  81. 81.
    Tufariello JJ, Milowsky AS, Al-Nuri M, Goldstein S (1987) Tetrahedron Lett 28:267CrossRefGoogle Scholar
  82. 82.
    Heiser U, Niestroj AJ, Gaertner UT, Demuth HU (2008) US 029 3618 A1Google Scholar
  83. 83.
    Kerrick ST, Beak P (1991) J Am Chem Soc 113:9708CrossRefGoogle Scholar
  84. 84.
    Genet C, McGrath MJ, O’Brien P (2006) Org Biomol Chem 4:1376CrossRefGoogle Scholar
  85. 85.
    O’Brien P, Wiberg KB, Bailey WF, Hermet J-PR, McGrath MJ (2004) J Am Chem Soc 126:15480CrossRefGoogle Scholar
  86. 86.
    Gallagher DJ, Wu S, Nikolic NA, Beak P (1995) J Org Chem 60:8148CrossRefGoogle Scholar
  87. 87.
    Abraham RJ, Gatti G (1970) Org Magn Reson 2:173CrossRefGoogle Scholar
  88. 88.
    Zhang R, Mamai A, Madalengoitia JS (1998) J Org Chem 64:547CrossRefGoogle Scholar
  89. 89.
    Zhang R, Madalengoitia JS (1998) J Org Chem 64:330CrossRefGoogle Scholar
  90. 90.
    Mamai A, Zhang R, Natarajan A, Madalengoitia JS (2001) J Org Chem 66:455CrossRefGoogle Scholar
  91. 91.
    Venkatraman S, Bogen SL, Arasappan A, Bennett F, Chen K, Jao E, Liu Y-T, Lovey R, Hendrata S, Huang Y, Pan W, Parekh T, Pinto P, Popov V, Pike R, Ruan S, Santhanam B, Vibulbhan B, Wu W, Yang W, Kong J, Liang X, Wong J, Liu R, Butkiewicz N, Chase R, Hart A, Agrawal S, Ingravallo P, Pichardo J, Kong R, Baroudy B, Malcolm B, Guo Z, Prongay A, Madison V, Broske L, Cui X, Cheng K-C, Hsieh Y, Brisson J-M, Prelusky D, Korfmacher W, White R, Bogdanowich-Knipp S, Pavlovsky A, Bradley P, Saksena AK, Ganguly A, Piwinski J, Girijavallabhan V, Njoroge FG (2006) J Med Chem 49:6074CrossRefGoogle Scholar
  92. 92.
    de Meijere A, Williams CM, Kourdioukov A, Sviridov SV, Chaplinski V, Kordes M, Savchenko AI, Stratmann C, Noltemeyer M (2002) Chem Eur J 8:3789CrossRefGoogle Scholar
  93. 93.
    de Meijere A, Kozhushkov SI, Savchenko AI (2004) J Organomet Chem 689:2033CrossRefGoogle Scholar
  94. 94.
    Brackmann F, Colombo N, Cabrele C, de Meijere A (2006) Eur J Org Chem 2006:4440CrossRefGoogle Scholar
  95. 95.
    Mykhailiuk PK, Afonin S, Palamarchuk GV, Shishkin OV, Ulrich AS, Komarov IV (2008) Angew Chem Int Ed 47:5765CrossRefGoogle Scholar
  96. 96.
    Reiersen H, Rees AR (2001) Trends Biochem Sci 26:679CrossRefGoogle Scholar
  97. 97.
    MacArthur MW, Thornton JM (1991) J Mol Biol 218:397CrossRefGoogle Scholar
  98. 98.
    Nimni ME (ed) (1988) Collagen, vol 1–4. CRC, Boca RatonGoogle Scholar
  99. 99.
    Gorres KL, Edupuganti R, Krow GR, Raines RT (2008) Biochemistry 47:9447CrossRefGoogle Scholar
  100. 100.
    Eberhardt ES, Panasik N, Raines RT (1996) J Am Chem Soc 118:12261CrossRefGoogle Scholar
  101. 101.
    Bretscher LE, Jenkins CL, Taylor KM, DeRider ML, Raines RT (2001) J Am Chem Soc 123:777CrossRefGoogle Scholar
  102. 102.
    Renner C, Alefelder S, Bae JH, Budisa N, Huber R, Moroder L (2001) Angew Chem Int Ed 40:923CrossRefGoogle Scholar
  103. 103.
    Jenkins CL, Lin G, Duo J, Rapolu D, Guzei IA, Raines RT, Krow GR (2004) J Org Chem 69:8565CrossRefGoogle Scholar
  104. 104.
    Krow GR, Shoulders MD, Edupuganti R, Gandla D, Yu F, Sonnet PE, Sender M, Choudhary A, DeBrosse C, Ross CW, Carroll P, Raines RT (2012) J Org Chem 77:5331CrossRefGoogle Scholar
  105. 105.
    O’Hagan D, Bilton C, Howard JAK, Knight L, Tozer DJ (2000) J Chem Soc Perkin Trans 2:605Google Scholar
  106. 106.
    Holmgren SK, Taylor KM, Bretscher LE, Raines RT (1998) Nature 392:666CrossRefGoogle Scholar
  107. 107.
    Holmgren SK, Bretscher LE, Taylor KM, Raines RT (1999) Chem Biol 6:63CrossRefGoogle Scholar
  108. 108.
    Jenkins CL, Raines RT (2002) Nat Prod Rep 19:49CrossRefGoogle Scholar
  109. 109.
    Krow GR, Yuan J, Fang Y, Meyer MD, Anderson DJ, Campbell JE, Carroll PJ (2000) Tetrahedron 56:9227CrossRefGoogle Scholar
  110. 110.
    Krow GR, Lin G, Yu F (2004) J Org Chem 70:590CrossRefGoogle Scholar
  111. 111.
    Hommel U, Lorthiois ELJ, Maibaum JK, Ostermann N, Randl SA, Vulpetti A (2014) WO 2014002057 A1Google Scholar
  112. 112.
    Giannis A, Kolter T (1993) Angew Chem 105:1303CrossRefGoogle Scholar
  113. 113.
    Giannis A, Kolter T (1993) Angew Chem Int Ed 32:1244CrossRefGoogle Scholar
  114. 114.
    Gardner B, Nakanishi H, Kahn M (1993) Tetrahedron 49:3433CrossRefGoogle Scholar
  115. 115.
    Gante J (1994) Angew Chem 106:1780CrossRefGoogle Scholar
  116. 116.
    Gante J (1994) Angew Chem Int Ed 33:1699CrossRefGoogle Scholar
  117. 117.
    Adang AEP, Hermkens PHH, Linders JTM, Ottenheijm HCJ, van Staveren CJ (1994) Recl Trav Chim Pays-Bas 113:63CrossRefGoogle Scholar
  118. 118.
    Curran TP, McEnaney PM (1995) Tetrahedron Lett 36:191CrossRefGoogle Scholar
  119. 119.
    Müller G, Gurrath M, Kurz M, Kessler H (1993) Proteins Struct Funct Bioinf 15:235CrossRefGoogle Scholar
  120. 120.
    Hanessian S, Reinhold U, Gentile G (1997) Angew Chem Int Ed 36:1881CrossRefGoogle Scholar
  121. 121.
    Duez H, Cariou B, Staels B (2012) Biochem Pharmacol 83:823CrossRefGoogle Scholar
  122. 122.
    Robl JA, Hamann LG (2011) The discovery of the dipeptidyl peptidase-4 (DPP4) inhibitor OnglyzaTM: from concept to market. In: Accounts in drug discovery: case studies in medicinal chemistry. The Royal Society of Chemistry, Cambridge, pp 1Google Scholar
  123. 123.
    Augeri DJ, Robl JA, Betebenner DA, Magnin DR, Khanna A, Robertson JG, Wang A, Simpkins LM, Taunk P, Huang Q, Han S-P, Abboa-Offei B, Cap M, Xin L, Tao L, Tozzo E, Welzel GE, Egan DM, Marcinkeviciene J, Chang SY, Biller SA, Kirby MS, Parker RA, Hamann LG (2005) J Med Chem 48:5025CrossRefGoogle Scholar
  124. 124.
    Baggio LL, Drucker DJ (2007) Gastroenterology 132:2131CrossRefGoogle Scholar
  125. 125.
    Mentlein R (1999) Regul Pept 85:9CrossRefGoogle Scholar
  126. 126.
    Nauck M, Stöckmann F, Ebert R, Creutzfeldt W (1986) Diabetologia 29:46CrossRefGoogle Scholar
  127. 127.
    Neumiller JJ (2015) Med Clin North Am 99:107CrossRefGoogle Scholar
  128. 128.
    Magnin DR, Robl JA, Sulsky RB, Augeri DJ, Huang Y, Simpkins LM, Taunk PC, Betebenner DA, Robertson JG, Abboa-Offei BE, Wang A, Cap M, Xin L, Tao L, Sitkoff DF, Malley MF, Gougoutas JZ, Khanna A, Huang Q, Han S-P, Parker RA, Hamann LG (2004) J Med Chem 47:2587CrossRefGoogle Scholar
  129. 129.
    Urbach HD, Henning RD, Becker RD (1985) DE 3324263 A1Google Scholar
  130. 130.
    Urbach H, Henning R, Becker R (1986) US 4 591 598Google Scholar
  131. 131.
    Woo K-C, Jones K (1991) Tetrahedron Lett 32:6949CrossRefGoogle Scholar
  132. 132.
    Pickering L, Malhi BS, Coe PL, Walker RT (1994) Nucleosides Nucleotides 13:1493CrossRefGoogle Scholar
  133. 133.
    Shin C, Nakamura Y, Yamada Y, Yonezawa Y, Umemura K, Yoshimura J (1995) Bull Chem Soc Jpn 68:3151CrossRefGoogle Scholar
  134. 134.
    Arndt H-D, Polborn K, Koert U (1997) Tetrahedron Lett 38:3879CrossRefGoogle Scholar
  135. 135.
    Rassu G, Carta P, Pinna L, Battistini L, Zanardi F, Acquotti D, Casiraghi G (1999) Eur J Org Chem 1395Google Scholar
  136. 136.
    Bunch L, Norrby PO, Frydenvang K, Krogsgaard-Larsen P, Madsen U (2001) Org Lett 3:433CrossRefGoogle Scholar
  137. 137.
    Arndt H-D, Welz R, Mueller S, Ziemer B, Koert U (2004) Chem Eur J 10:3945CrossRefGoogle Scholar
  138. 138.
    Shinada T, Hamada M, Kawasaki M, Ohfune Y (2005) Heterocycles 66:511CrossRefGoogle Scholar
  139. 139.
    Zanardi F, Sartori A, Curti C, Battistini L, Rassu G, Nicastro G, Casiraghi G (2007) J Org Chem 72:1814CrossRefGoogle Scholar
  140. 140.
    Zaminer J, Brockmann C, Huy P, Opitz R, Reuter C, Beyermann M, Freund C, Mueller M, Oschkinat H, Schmalz H-G, Kuehne R (2010) Angew Chem Int Ed 49:7111CrossRefGoogle Scholar
  141. 141.
    Vu H-D, Renault J, Roisnel T, Gouault N, Uriac P (2014) Eur J Org Chem 2014:4506CrossRefGoogle Scholar
  142. 142.
    Charette AB, Beauchemin A (2004) Org React 58:1Google Scholar
  143. 143.
    Hanessian S, Reinhold U, Saulnier M, Claridge S (1998) Bioorg Med Chem Lett 8:2123CrossRefGoogle Scholar
  144. 144.
    Shono T, Matsumura Y, Tsubata K, Sugihara Y, Yamane S, Kanazawa T, Aoki T (1982) J Am Chem Soc 104:6697CrossRefGoogle Scholar
  145. 145.
    Charette AB, Marcoux J-F (1995) Synlett 1995:1197CrossRefGoogle Scholar
  146. 146.
    Yu J, Truc V, Riebel P, Hierl E, Mudryk B (2005) Tetrahedron Lett 46:4011CrossRefGoogle Scholar
  147. 147.
    Wang G, James CA, Meanwell NA, Hamann LG, Belema M (2013) Tetrahedron Lett 54:6722CrossRefGoogle Scholar
  148. 148.
    Ramirez A, Truc VC, Lawler M, Ye YK, Wang J, Wang C, Chen S, Laporte T, Liu N, Kolotuchin S, Jones S, Bordawekar S, Tummala S, Waltermire RE, Kronenthal D (2014) J Org Chem 79:6233CrossRefGoogle Scholar
  149. 149.
    Gill I, Patel R (2006) Bioorg Med Chem Lett 16:705CrossRefGoogle Scholar
  150. 150.
    Dong J, Gong Y, Liu J, Chen X, Wen X, Sun H (2014) Bioorg Med Chem 22:1383CrossRefGoogle Scholar
  151. 151.
    Politino M, Cadin MM, Skonezny PM, Chen JG (2006) WO 2005106011Google Scholar
  152. 152.
    Rayner PJ, O’Brien P, Horan RAJ (2013) J Am Chem Soc 135:8071CrossRefGoogle Scholar
  153. 153.
    Villhauer EB, Brinkman JA, Naderi GB, Burkey BF, Dunning BE, Prasad K, Mangold BL, Russell ME, Hughes TE (2003) J Med Chem 46:2774CrossRefGoogle Scholar
  154. 154.
    Gwaltney SL, Stafford JA (2005) Inhibitors of dipeptidyl peptidase 4. In: Doherty AM, Bock MG, Desai MC, Overington J, Plattner JJ, Stamford A, Wustrow D (eds) Annual reports in medicinal chemistry, vol 40. Academic, San Diego, p 149Google Scholar
  155. 155.
    Traynor K (2009) Am J Health Syst Pharm 66:1513Google Scholar
  156. 156.
    Rasmussen HB, Branner S, Wiberg FC, Wagtmann N (2003) Nat Struct Mol Biol 10:19CrossRefGoogle Scholar
  157. 157.
    Engel M, Hoffmann T, Wagner L, Wermann M, Heiser U, Kiefersauer R, Huber R, Bode W, Demuth H-U, Brandstetter H (2003) Proc Natl Acad Sci U S A 100:5063CrossRefGoogle Scholar
  158. 158.
    Thoma R, Löffler B, Stihle M, Huber W, Ruf A, Hennig M (2003) Structure 11:947CrossRefGoogle Scholar
  159. 159.
    Oefner C, D’Arcy A, Mac Sweeney A, Pierau S, Gardiner R, Dale GE (2003) Acta Crystallogr Sect D 59:1206CrossRefGoogle Scholar
  160. 160.
    Hiramatsu H, Kyono K, Higashiyama Y, Fukushima C, Shima H, Sugiyama S, Inaka K, Yamamoto A, Shimizu R (2003) Biochem Biophys Res Commun 302:849CrossRefGoogle Scholar
  161. 161.
    Zhao G, Taunk PC, Magnin DR, Simpkins LM, Robl JA, Wang A, Robertson JG, Marcinkeviciene J, Sitkoff DF, Parker RA, Kirby MS, Hamann LG (2005) Bioorg Med Chem Lett 15:3992CrossRefGoogle Scholar
  162. 162.
    Arenare L, De Caprariis P, Marinozzi M, Natalini B, Pellicciari R (1994) Tetrahedron Lett 35:1425CrossRefGoogle Scholar
  163. 163.
    Pellicciari R, Arenare L, De Caprariis P, Natalini B, Marinozzi M, Galli A (1995) J Chem Soc Perkin Trans 1:1251Google Scholar
  164. 164.
    Hanessian S, Ninkovic S, Reinhold U (1996) Tetrahedron Lett 37:8971CrossRefGoogle Scholar
  165. 165.
    Smith CG, Vane JR (2003) FASEB J 17:788CrossRefGoogle Scholar
  166. 166.
    Akif M, Masuyer G, Schwager SLU, Bhuyan BJ, Mugesh G, Isaac RE, Sturrock ED, Acharya KR (2011) FEBS J 278:3644CrossRefGoogle Scholar
  167. 167.
    Altmann E, Hommel U, Lorthiois ELJ, Maibaum JK, Ostermann N, Quancard J, Randl SA, Vulpetti A (2014) WO 2014002054 A1Google Scholar
  168. 168.
    Bachand C, Belema M, Deon DH, Good AC, Goodrich J, James CA, Lavoie R, Lopez OD, Martel A, Meanwell NA (2009) US 20090068140 A1Google Scholar
  169. 169.
    Kim S, Gao Q, Yang F (2010) US 20100158862Google Scholar
  170. 170.
    Pack SK, Tymonko S, Patel BP, Natalie JKJ, Belema M (2012) US 20110269956Google Scholar
  171. 171.
    Kozlowski JA, Rosenblum SB, Coburn CA, Shankar BB, Anilkumar GN, Chen L, Dwyer MP, Jiang Y, Keertikar KM, Lavey BJ, Selyutin OB, Tong L, Wong M, Yang D-Y, Yu W, Zhou G, Wu H, Hu B, Zhong B, Sun F, Ji T, Shen C, Rizvi R, Zeng Q (2012) WO 2012041014 A1Google Scholar
  172. 172.
    Yu W, Tong L, Kozlowski JA, Selyutin O, Chen L, Kim J-H, Sha D, Rizvi R, Shankar B, Hu B, Zhong B, Wai D, Hao J, Wei W, Ji T, Zan S (2014) WO 2014110705 A1Google Scholar
  173. 173.
    Or YS, Peng X, Wang C, Ying L, Qiu YL (2011) WO 2011031904 A1Google Scholar
  174. 174.
    Qiu YL, Wang C, Cao H, Peng X, Ying L, Gao X, Or YS (2013) WO 2013052362 A1Google Scholar
  175. 175.
    Qiu YL, Cao H, Peng X, Chen Z, Or YS (2013) WO 2013059278 A2Google Scholar
  176. 176.
    Or YS, Kim IJ, Wang G, Long J (2011) US 8623814 B2Google Scholar
  177. 177.
    Altmann E, Hommel U, Lorthiois ELJ, Maibaum JK, Ostermann N, Quancard J, Randl SA, Simic O, Vulpetti A, Rogel O (2012) WO 2012093101Google Scholar
  178. 178.
    Altmann E, Hommel U, Lorthiois ELJ, Maibaum JK, Ostermann N, Quancard J, Randl SA, Vulpetti A, Rogel O (2014) WO 2014002051 A2Google Scholar
  179. 179.
    Kobayashi K, Suzuki T, Okuzumi T (2014) WO 2014098098 A1Google Scholar
  180. 180.
    Hajos ZG, Parrish DR (1976) US 3975440 AGoogle Scholar
  181. 181.
    Hajos ZG, Parrish DR (1971) DE 2102623 A1Google Scholar
  182. 182.
    Hajos ZG, Parrish DR (1974) J Org Chem 39:1615CrossRefGoogle Scholar
  183. 183.
    Eder U, Sauer G, Wiechert R (1971) DE 2 014 757Google Scholar
  184. 184.
    Eder U, Sauer G, Wiechert R (1971) Angew Chem Int Ed 10:496CrossRefGoogle Scholar
  185. 185.
    Cheong PH-Y, Legault CY, Um JM, Çelebi-Ölçüm N, Houk KN (2011) Chem Rev 111:5042CrossRefGoogle Scholar
  186. 186.
    Armstrong A, Boto RA, Dingwall P, Contreras-Garcia J, Harvey MJ, Mason NJ, Rzepa HS (2014) Chem Sci 5:2057CrossRefGoogle Scholar
  187. 187.
    Cheong PH-Y, Houk KN, Warrier JS, Hanessian S (2004) Adv Synth Catal 346:1111CrossRefGoogle Scholar
  188. 188.
    Bahmanyar S, Houk KN (2001) J Am Chem Soc 123:11273CrossRefGoogle Scholar
  189. 189.
    Hanessian S, Pham V (2000) Org Lett 2:2975CrossRefGoogle Scholar
  190. 190.
    Hanessian S, Shao Z, Warrier JS (2006) Org Lett 8:4787CrossRefGoogle Scholar
  191. 191.
    Hanessian S, Govindan S, Warrier JS (2005) Chirality 17:540CrossRefGoogle Scholar
  192. 192.
    Yamaguchi M, Igarashi Y, Reddy RS, Shiraishi T, Hirama M (1997) Tetrahedron 53:11223CrossRefGoogle Scholar
  193. 193.
    Yamaguchi M, Shiraishi T, Igarashi Y, Hirama M (1994) Tetrahedron Lett 35:8233CrossRefGoogle Scholar
  194. 194.
    Hanessian S, Shao Z, Betschart C, Rondeau J-M, Neumann U, Tintelnot-Blomley M (2010) Bioorg Med Chem Lett 20:1924CrossRefGoogle Scholar
  195. 195.
    Hanessian S, Maji DK, Govindan S, Matera R, Tintelnot-Blomley M (2010) J Org Chem 75:2861CrossRefGoogle Scholar
  196. 196.
    Yu H, Liu M, Han S (2014) Tetrahedron 70:8380CrossRefGoogle Scholar
  197. 197.
    Shimura M, Iwata M, Omoto S, Sekizawa Y (1979) Agric Biol Chem 43:2279Google Scholar
  198. 198.
    Kodama Y, Ito T (1980) Agric Biol Chem 44:73Google Scholar

Copyright information

© Springer International Publishing Switzerland 2015

Authors and Affiliations

  1. 1.Department of ChemistryUniversité de MontréalStation Centre-ville, MontréalCanada

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