RSS-Feed abonnieren
Bitte kopieren Sie die angezeigte URL und fügen sie dann in Ihren RSS-Reader ein.
https://www.thieme-connect.de/rss/thieme/de/10.1055-s-00000084.xml
Synthesis 2007(21): 3261-3285
DOI: 10.1055/s-2007-990831
DOI: 10.1055/s-2007-990831
REVIEW
© Georg Thieme Verlag Stuttgart · New York
Synthetic Approaches to Naturally Occurring Ten-Membered-Ring Lactones
Weitere Informationen
Received
27 June 2007
Publikationsdatum:
16. Oktober 2007 (online)
Publikationsverlauf
Publikationsdatum:
16. Oktober 2007 (online)
Abstract
The strategies for the synthesis of naturally occurring ten-membered-ring lactones, which are the most abundant of the medium-ring lactones, are discussed. According to their structures and/or biosynthesis, the molecules are classified in monocyclic polyketides, monocyclic oxylipins, aliphatic bicyclic and aromatic bicyclic lactones. In each subsection, the lactones are presented in chronological order of their isolation. Representative complex systems bearing multiple functionalities in addition to the lactone moiety, as well as a selection of recent synthetic approaches to non-natural medium-ring lactones, are briefly presented.
1 Introduction
2 Monocyclic Ten-Membered-Ring Lactones
2.1 Polyketides
2.2 Oxylipins
3 Bicyclic Ten-Membered-Ring Lactones
3.1 Aliphatic
3.2 Aromatic
4 Complex Ten-Membered-Ring Lactones
5 Non-natural Lactones: Selected Synthetic Approaches
6 Conclusion
Key words
natural products - medium-sized-ring systems - ten-membered-ring lactones - monocyclic lactones - bicyclic lactones
- 1
Back TG. Tetrahedron 1977, 33: 3041 - 2
Roxburgh CJ. Tetrahedron 1993, 49: 10749 - 3
Illuminati G.Mandolini L. Acc. Chem. Res. 1981, 14: 95 - 4
Wiberg KB.Waldron RF. J. Am. Chem. Soc. 1991, 113: 7697 - 5
Petasis NA.Patane MA. Tetrahedron 1992, 48: 5757 - 6
Mehta G.Singh V. Chem. Rev. 1999, 99: 881 - 7
Minnaard AJ.Wijnberg JBPA.de Groot A. Tetrahedron 1999, 55: 2115 - 8
Rousseau G. Tetrahedron 1995, 51: 2777 - 9
Dräger G.Kirschning A.Thiericke R.Zerlin M. Nat. Prod. Rep. 1996, 13: 365 - 10
Longo LS.Bombonato FI.Ferraz HMC. Quim. Nova 2007, 30: 415 - 11
Crimmins MT.Emmitte KA. J. Am. Chem. Soc. 2001, 123: 1533 ; and references cited therein - 12
Evans PA.Holmes AB. Tetrahedron 1991, 47: 9131 - 13
Nubbemeyer U. Top. Curr. Chem. 2001, 216: 125 - 14
Yet L. Chem. Rev. 2000, 100: 2963 - 15
Nubbemeyer U. Eur. J. Org. Chem. 2001, 1801 - 16
Parenty A.Moreau X.Campagne J.-M. Chem. Rev. 2006, 106: 911 - 17
Gradillas A.Perez-Castells J. Angew. Chem. Int. Ed. 2006, 45: 6086 - 18
van der Mee L.Helmich F.de Bruijn R.Vekemans JAJM.Palmans ARA.Meijer EW. Macromolecules 2006, 39: 5021 - 19
Shiina I. Chem. Rev. 2007, 107: 239 - 20
Ishida T.Wada K. J. Chem. Soc., Chem. Commun. 1975, 209 - 21
Wada K.Ishida T. J. Chem. Soc., Chem. Commun. 1976, 340 - 22
Wada K.Ishida T. J. Chem. Soc., Perkin Trans. 1 1979, 1154 - 23
Farooq A.Gordon J.Hanson JR.Takahashi JA. Phytochemistry 1995, 38: 557 - 24
Ackland MJ.Hanson JR.Hitchcock PB.Ratcliffe AH. J. Chem Soc., Perkin Trans. 1 1985, 843 -
25a
Ishida T.Wada K. J. Chem. Soc., Chem. Commun. 1977, 337 -
25b
Ishida T.Wada K. J. Chem. Soc., Perkin Trans. 1 1979, 323 -
26a
Wakamatsu T.Akasaka K.Ban Y. Tetrahedron Lett. 1977, 2755 -
26b
Wakamatsu T.Akasaka K.Ban Y. J. Org. Chem. 1979, 44: 2008 - 27
Anand RV.Baktharaman S.Singh VK. J. Org. Chem. 2003, 68: 3356 - 28
Ireland RE.Brown FR. J. Org. Chem. 1980, 45: 1868 - 29
Tsuji J.Mandai T. Tetrahedron Lett. 1978, 1817 - 30
Shenvi AB.Gerlach H. Helv. Chim. Acta 1980, 63: 2426 - 31
Boeckman RK.Pruitt JR. J. Am. Chem. Soc. 1989, 111: 8286 - 32
Sharma GVM.Reddy KL. Tetrahedron: Asymmetry 2006, 17: 3197 - 33
Moore BP.Brown WV. Aust. J. Chem. 1976, 29: 1365 - 34
Gerlach H.Künzler P.Oertle K. Helv. Chim. Acta 1978, 61: 1226 - 35
Cossy J.Pete JP. Tetrahedron Lett. 1986, 27: 2369 - 36
Bartra M. . J. Org. Chem. 1991, 56: 5132 - 37
Kitahara T.Koseki K.Mori K. Agric. Biol. Chem. 1983, 47: 389 - 38
Naoshima Y.Hasegawa H.Nishiyama T.Nakamura A. Bull. Chem. Soc. Jpn. 1989, 62: 608 - 39
Jones GB.Huber RS.Chapman BJ. Tetrahedron: Asymmetry 1997, 8: 1797 - 40
Petrzilka M. Helv. Chim. Acta 1978, 61: 3075 - 41
Takahashi T.Hashiguchi S.Kasuga K.Tsuji J. J. Am. Chem. Soc. 1978, 100: 7424 - 42
Trost BM.Verhoeven TR. J. Am. Chem. Soc. 1980, 102: 4743 - 43
Malherbe R.Rist G.Bellus D. J. Org. Chem. 1983, 48: 860 - 44
Vedejs E.Powell DW. J. Am. Chem. Soc. 1982, 104: 2046 - 45
Fouque E.Rousseau G. Synthesis 1989, 661 - 46
Ohnuma T.Hata N.Miyachi N.Wakamatsu T.Ban Y. Tetrahedron Lett. 1986, 27: 219 - 47
Ballini R.Marcantoni E.Petrini M. Liebigs Ann. 1995, 1381 - 48
Enders D.Plant A.Drechsel K.Prokopenko OF. Liebigs Ann. 1995, 1127 - 49
Saikia AK.Hazarika MJ.Barua NC.Bezbarua MS.Sharma RP.Ghosh AC. Synthesis 1996, 981 - 50
Mahajan JR.Silva CR. J. Braz. Chem. Soc. 1990, 1: 87 - 51
Mahajan JR.Araujo HC. Synthesis 1981, 49 - 52
Kostova K.Hesse M. Helv. Chim. Acta 1984, 67: 1713 - 53
Stanchev S.Hesse M. Helv. Chim. Acta 1990, 73: 460 - 54
Suginome H.Yamada S. Tetrahedron 1987, 43: 3371 - 55
Ono N.Miyake H.Kaji A. J. Org. Chem. 1984, 49: 4997 - 56
Posner GH.Asirvatham E.Webb KS.Jew S. Tetrahedron Lett. 1987, 28: 5071 - 57
Posner GH.Wang Q.Halford BA.Elias JS.Maxwell JP. Tetrahedron Lett. 2000, 41: 9655 - 58
Hatcher MA.Borstnik K.Posner GH. Tetrahedron Lett. 2003, 44: 5407 - 59
Posner GH.Hatcher MA.Maio WA. Org. Lett. 2005, 7: 4301 - 60
Nagumo S.Suemune H.Sakai K. Tetrahedron 1992, 48: 8667 - 61
Nukina M.Sassa T.Ikeda M. Tetrahedron Lett. 1980, 21: 301 - 62
Nukina M.Ikeda M.Sassa T. Agric. Biol. Chem. 1980, 44: 2761 - 63
Venkatasubbaiah P.Chilton WS. J. Nat. Prod. 1992, 55: 461 - 64
Asaoka M.Naito S.Takei H. Tetrahedron Lett. 1985, 26: 2103 - 65
Moricz A.Gassmann E.Bienz S.Hesse M. Helv. Chim. Acta 1995, 78: 663 - 66
Suzuki S.Tanaka A.Yamashita K. Agric. Biol. Chem. 1987, 51: 3095 - 67
Wasserman HH.Prowse KS. Tetrahedron 1992, 48: 8199 -
68a
Grabley S.Granzer E.Hutter K.Ludwig D.Mayer M.Thiericke R.Till G.Wink J.Phillips S.Zeeck A. J. Antibiot. 1992, 45: 56 -
68b
Gohrt A.Zeeck A.Hutter K.Kirsch R.Kluge H.Thiericke R. J. Antibiot. 1992, 45: 66 -
68c
Grabley S.Hammann P.Hutter K.Kirsch R.Kluge H.Thiericke R.Mayer M.Zeeck A. J. Antibiot. 1992, 45: 1176 - 69
Ayer WA.Sun M.Browne LM.Brinen LS.Clardy J. J. Nat. Prod. 1992, 55: 649 - 70
Rukachaisirikul V.Pramjit S.Pakawatchai C.Isaka M.Supothina S. J. Nat. Prod. 2004, 67: 1953 - 71
Boonphong S.Kittakoop P.Isaka M.Pittayakhajonwut D.Tanticharoen M.Thebtaranonth Y. J. Nat. Prod. 2001, 64: 965 - 72
Mayer M.Thiericke R. J. Antibiot. 1993, 46: 1372 - 73
Mayer M.Thiericke R. J. Chem. Soc., Perkin Trans. 1 1993, 495 - 74
Colle S.Taillefumier C.Chapleur Y.Liebl R.Schmidt A. Bioorg. Med. Chem. 1999, 7: 1049 - 75
Yamada S.Tanaka A.Oritani T. Biosci., Biotechnol., Biochem. 1995, 59: 1657 - 76
Arai M.Morita N.Aoyagi S.Kibayashi C. Tetrahedron Lett. 2000, 41: 1199 - 77
Andrus MB.Shih TL. J. Org. Chem. 1996, 61: 8780 -
78a
Kobayashi Y.Asano M.Yoshida S.Takeuchi A. Org. Lett. 2005, 7: 1533 -
78b
Kobayashi Y.Yoshida S.Asano M.Takeuchi A.Acharya HP. J. Org. Chem. 2007, 72: 1707 - 79
Krishna PR.Reddy PVN. Tetrahedron Lett. 2006, 47: 7473 -
80a
Pilli RA.Victor MM. Tetrahedron Lett. 1998, 39: 4421 -
80b
Pilli RA.Victor MM. J. Braz. Chem. Soc. 2001, 12: 373 -
81a
Okude Y.Hirano S.Hiyama T.Nozaki H. J. Am. Chem. Soc. 1977, 99: 3179 -
81b
Jin H.Uenishi J.Christ WJ.Kishi Y. J. Am. Chem. Soc. 1986, 108: 5644 - 82
Mohapatra DK.Ramesh DK.Giardello MA.Chorghade MS.Gurjar MK.Grubbs RH. Tetrahedron Lett. 2007, 48: 2621 - 83
Fuchser J.Zeeck A. Liebigs Ann./Recl. 1997, 87 - 84
Pilli RA.Victor MM.de Meijere A. J. Org. Chem. 2000, 65: 5910 - 85 For a review, see:
Katz L. Chem. Rev. 1997, 97: 2557 - 86
Evidente A.Lanzetta R.Capasso R.Vurro M.Bottalico A. Phytochemistry 1993, 34: 999 - 87
Evidente A.Capasso R.Abouzeid MA.Lanzetta R.Vurro M.Bottalico A. J. Nat. Prod. 1993, 56: 1937 - 88
Arnone A.Assante G.Montorsi M.Nasini G.Ragg E. Gazz. Chim. Ital. 1993, 123: 71 - 89
Garcia-Fortanet J.Murga J.Falomir E.Carda M.Marco JA. J. Org. Chem. 2005, 70: 9822 - 90 Evidente A., Lanzetta R., Capasso R., Andolfi A., Bottalico A., Vurro M., Zonno M. C.; Phytochemistry; 1995, 40: 1637
- 91
Evidente A.Lanzetta R.Capasso R.Andolfi A.Vurro M.Zonno MC. Phytochemistry 1997, 44: 1041 - 92
Evidente A.Capasso R.Andolfi A.Vurro M.Zonno MC. Phytochemistry 1998, 48: 941 - 93
de Napoli L.Messere A.Palomba D.Piccialli V.Evidente A.Piccialli G. J. Org. Chem. 2000, 65: 3432 - 94
Fürstner A.Radkowski K.Wirtz C.Goddard R.Lehmann CW.Mynott R. J. Am. Chem. Soc. 2002, 124: 7061 - 95
Liu D.Kozmin SA. Org. Lett. 2002, 4: 3005 - 96
Rivero-Cruz JF.Garcia-Aguirre G.Cerda-Garcia-Rojas CM.Mata R. Tetrahedron 2000, 56: 5337 - 97
Rivero-Cruz JF.Garcia-Aguirre G.Cerda-Garcia-Rojas CM.Mata R. J. Nat. Prod. 2003, 66: 511 - 98
Fürstner A.Radkowski K. Chem. Commun. 2001, 671 -
99a
Diez E.Dixon DJ.Ley SV.Polara A.Rodriguez F. Synlett 2003, 1186 -
99b
Diez E.Dixon DJ.Ley SV.Polara A.Rodriguez F. Helv. Chim. Acta 2003, 86: 3717 - 100
Sabino AA.Pilli RA. Tetrahedron Lett. 2002, 43: 2819 - 101
Gurjar MK.Karmakar S.Mohapatra DK. Tetrahedron Lett. 2004, 45: 4525 - 102
Salaskar A.Sharma A.Chattopadhyay S. Tetrahedron: Asymmetry 2006, 17: 325 - 103
Boruwa J.Gogoi N.Barua NC. Org. Biomol. Chem. 2006, 4: 3521 - 104
Nanda S. Tetrahedron Lett. 2005, 46: 3661 - 105
Ratnayake AS.Yoshida WY.Mooberry SL.Hemsheidt T. Org. Lett. 2001, 3: 3479 - 106
Bodo B.Molho L.Davoust D.Molho D. Phytochemistry 1983, 22: 447 - 107
Murga J.Falomir E.Garcia-Fortanet J.Carda M.Marco JA. Org. Lett. 2002, 4: 3447 - 108
Batty D.Crich D. J. Chem. Soc., Perkin Trans. 1 1992, 3193 - 109
Chavan SP.Praveen C. Tetrahedron Lett. 2005, 46: 1939 - 110
Fürstner A.Nagano T.Muller C.Seidel G.Muller O. Chem. Eur. J. 2007, 13: 1452 - 111
Gurjar MK.Nagaprasad R.Ramana CV. Tetrahedron Lett. 2003, 44: 2873 - 112
Ghosh S.Rao RV.Shashidhar J. Tetrahedron Lett. 2005, 46: 5479 -
113a
Davoli P.Spaggiari A.Castagnetti L.Prati F. Org. Biomol. Chem. 2004, 2: 38 -
113b
Davoli P.Fava R.Morandi S.Spaggiari A.Prati F. Tetrahedron 2005, 61: 4427 - 114
Sharma GVM.Cherukupalli GR. Tetrahedron: Asymmetry 2006, 17: 1981 -
115a
Ishigami K.Kitahara T. Heterocycles 2004, 63: 785 -
115b
Ishigami K.Watanabe H.Kitahara T. Tetrahedron 2005, 61: 7546 - 116
Kumar P.Naidu SVJ. J. Org. Chem. 2005, 70: 4207 - 117
Prasad KR.Penchalaiah K.Choudhary A.Anbarasan P. Tetrahedron Lett. 2007, 48: 309 - 118
Banwell MG.Loong DTJ. Heterocycles 2004, 62: 713 - For reviews about oxylipins, see:
-
119a
Gerwick WH. Chem. Rev. 1993, 93: 1807 -
119b
Noverr MC.Erb-Downward JR.Huffnagle GB. Clin. Microbiol. Rev. 2003, 16: 517 - 120
Seo Y.Cho KW.Rho JR.Shin J.Kwon BM.Bok SH.Song JI. Tetrahedron 1996, 52: 10583 - 121
Niwa H.Wakamatsu K.Yamada K. Tetrahedron Lett. 1989, 30: 4543 - 122
Luo X.Li F.Hong J.Lee C.-O.Sim CJ.Im KS.Jung JH. J. Nat. Prod. 2006, 69: 567 - 123
Niwa H.Inagaki H.Yamada K. Tetrahedron Lett. 1991, 32: 5127 - 124
Niwa H.Watanabe M.Inagaki H.Yamada K. Tetrahedron 1994, 50: 7385 - 125
Lindquist N.Fenical W. Tetrahedron Lett. 1989, 30: 2735 - 126
Congrève MS.Holmes AB.Hughes AB.Looney MG. J. Am. Chem. Soc. 1993, 115: 5815 - 127
Fürstner A.Schlede M. Adv. Synth. Catal. 2002, 344: 657 - 128
Papendorf O.Konig GM.Wright AD.Chorus I.Oberemm A. J. Nat. Prod. 1997, 60: 1298 - 129
Stierle DB.Stierle AA.Bugni T.Loewen G. J. Nat. Prod. 1998, 61: 251 -
130a
Ishigami K.Motoyoshi H.Kitahara T. Tetrahedron Lett. 2000, 41: 8897 -
130b
Motoyoshi H.Ishigami K.Kitahara T. Tetrahedron 2001, 57: 3899 - 131
Naves YR.Grampoloff AV. Helv. Chim. Acta 1942, 25: 1500 - 132
Demole E.Willhalm B.Stoll M. Helv. Chim. Acta 1964, 47: 1152 - 133
Gerlach H.Kunzler P. Helv. Chim. Acta 1978, 61: 2503 - 134
Fürstner A.Muller T. Synlett 1997, 1010 - 135
Kitahara T.Iwamoto M.Takagi Y.Mori K.Matsui M. Agric. Biol. Chem. 1984, 48: 1731 - 136
Shimizu I.Nakagawa H. Tetrahedron Lett. 1992, 33: 4957 - 137
Inoue M.Nishi T.Kitahara T. Biosci., Biotechnol., Biochem. 1999, 63: 1122 - 138
Chu M.Mierzwa R.Xu L.He L.Terracciano J.Patel M.Gullo V.Black T.Zhao W.Chan T.-M.McPhail AT. J. Nat. Prod. 2003, 66: 1527 - 139
Jayasuriya H.Zink DL.Polishook JD.Bills GF.Dombrowski AW.Genilloud O.Pelaez FF.Herranz L.Quamina D.Lingham RB.Danzeizen R.Graham PL.Tomassini JE.Singh SB. Chemistry & Biodiversity 2005, 2: 112 - 140
Mehta G.Shinde HM. Chem. Commun. 2005, 3703 - 141
Mehta G.Shinde HM. Tetrahedron Lett. 2005, 46: 6633 - 142
Wilson EM.Trauner D. Org. Lett. 2007, 9: 1327 - 143
Ishigami K.Katsuta R.Watanabe H. Tetrahedron 2006, 62: 2224 - 144
Snider BB.Zhou J. Org. Lett. 2006, 8: 1283 - 145
Kinoshita K.Sasaki T.Awata M.Takada M.Yaginuma S. J. Antibiot. 1997, 50: 961 - 146
Murakami Y.Ishii A.Mizuno S.Yaginuma S.Uehara Y. Anticancer Res. 1999, 19: 4145 - 147
Edrada RA.Heubes M.Brauers G.Wray V.Berg A.Grafe U.Wohlfarth M.Muhlbacher J.Schaumann K. .Bringmann G.Proksch P. J. Nat. Prod. 2002, 65: 1598 - 148
Bringmann G.Lang G.Michel M.Heubes M. Tetrahedron Lett. 2004, 45: 2829 - 149
Yoshino T.Ng F.Danishefsky SJ. J. Am. Chem. Soc. 2006, 128: 14185 - 150
Liang Q.Zhang J.Quan W.Sun Y.She X.Pan X. J. Org. Chem. 2007, 72: 2694 - 151
Jansen R.Kunze B.Reichenbach H.Höfle G. Eur. J. Org. Chem. 2000, 913 - 152
Bhattacharjee A.Seguil OR.De Brabander JK. Tetrahedron Lett. 2001, 42: 1217 -
153a
Nicolaou KC.Kim DW.Baati R. Angew. Chem. Int. Ed. 2002, 41: 3701 -
153b
Nicolaou KC.Kim DW.Baati R.O’Brate A.Giannakakou P. Chem. Eur. J. 2003, 9: 6177 - 154
Su Q.Panek JS. J. Am. Chem. Soc. 2004, 126: 2425 - 155
Petri AF.Bayer A.Maier ME. Angew. Chem. Int. Ed. 2004, 43: 5821 -
156a
Lewis A.Stefanuti I.Swain SA.Smith SA.Taylor RJK. Tetrahedron Lett. 2001, 42: 5549 -
156b
Lewis A.Stefanuti I.Swain SA.Smith SA.Taylor RJK. Org. Biomol. Chem. 2003, 1: 104 - 157
Hilli F.White JM.Rizzacasa MA. Tetrahedron Lett. 2002, 43: 8507 - 158
Kuhnert SM.Maier ME. Org. Lett. 2002, 4: 643 - 159
Graetz BR.Rychnovsky SD. Org. Lett. 2003, 5: 3357 - 160
Hilli F.White JM.Rizzacasa MA. Org. Lett. 2004, 6: 1289 - 161
Li M.O’Doherty GA. Org. Lett. 2006, 8: 6087 - 162
Yadav JS.Kumar NN.Prasad AR. Synthesis 2007, 1175 - 163
Aimi N.Uchida N.Ohya N.Hosokawa H.Takayama H.Sakai S.-i.Mendonza LA.Polz L.Stockigt J. Tetrahedron Lett. 1991, 32: 4949 -
164a
Takahashi S.Kakinuma N.Uchida K.Hashimoto R.Yanagishima T.Nakagawa A. J. Antibiot. 1998, 51: 596 -
164b
Takahashi S.Kakinuma N.Uchida K.Hashimoto R.Yanagishima T.Nakagawa A. J. Antibiot. 1998, 51: 1051 - 165
Irlapati NR.Baldwin JE.Adlington RM.Pritchard GJ.Cowley AR. Tetrahedron 2006, 62: 4603 - 166
Celmer WD.Chmurny GN.Moppett CE.Ware RS.Watts PC.Whipple EB. J. Am. Chem. Soc. 1980, 102: 4203 - 167
Whaley HA.Chidester CG.Mizsak SA.Wnuk RJ. Tetrahedron Lett. 1980, 21: 3659 -
168a
Rasmussen RR.Scherr MH.Whittern DN.Buko AM.McAlpine JB. J. Antibiot. 1987, 40: 1383 -
168b
McAlpine JB.Mitscher LA.Jackson M.Rasmussen RR.Velde DV.Veliz E. Tetrahedron 1996, 52: 10327 - 169
Roush WR.Koyama K.Curtin ML.Moriarty KJ. J. Am. Chem. Soc. 1996, 118: 7502 - 170
Gossinger E.Schwartz A.Sereinig N. Tetrahedron 2001, 57: 3045 ; and references cited therein - 171
Gossinger E.Schwartz A.Sereinig N. Tetrahedron 2000, 56: 2007 ; and references cited therein - 172
Ferraz HMC.Longo LS. Org. Lett. 2003, 5: 1337 - 173
Ferraz HMC.Longo LS. J. Org. Chem. 2007, 72: 2945 - 174
Hassner A.Pradhan TK. Tetrahedron Lett. 2006, 47: 5511 - 175
Métay E.Léonel E.Condon S.Nédélec JY. Tetrahedron 2006, 62: 8515 - 176
Ishihara K.Kubota M.Kurihara H.Yamamoto H. J. Org. Chem. 1996, 61: 4560 - 177
Abramite JA.Sammakia T. Org. Lett. 2007, 9: 2103 - 178
Corey EJ.Nicolaou KC. J. Am. Chem. Soc. 1974, 96: 5614 - 179
Inanaga J.Hirata K.Saeki H.Katsuki T.Yamaguchi M. Bull. Chem. Soc. Jpn. 1979, 52: 1989 - 180
Trnka TM.Grubbs RH. Acc. Chem. Res. 2001, 34: 18