Abstract
Recent accomplishments in the field of total synthesis of morphine
alkaloids are reviewed. Approaches to the skeleton of morphine are
included as are various efforts towards related medicinally important
agents. The literature coverage begins after the publication of
our last update in 2000 and continues mid-way through 2004.
1 Introduction
2 Total Syntheses of Morphine
2.1 Taber
2.2 Trost
2.3 Ogasawara
3 Approaches to the Morphine Skeleton
3.1 Vollhardt
3.2 Ogasawara
3.3 Cheng
3.4 Passarella
3.5 Hudlicky
3.6 Hudlicky
4 Unnatural Analogs and Mimics
4.1 Rice
4.2 Grauert
4.3 Trost
4.4 Ohno
4.5 Schmidhammer
5 Conclusions and Outlook
Key words
morphine - total synthesis - alkaloids - approaches
to morphine skeleton - morphine analogs and mimics
References
<A NAME="RA35604ST-1">1 </A>
Booth M.
Opium: A History
St. Martin’s
Press;
New York:
1998.
<A NAME="RA35604ST-2">2 </A>
Kappor LD.
Opium Poppy: Botany, Chemistry, and Pharmacology
Food
Products Press;
New York:
1995.
<A NAME="RA35604ST-3">3 </A>
Carr AS.
Holtby HM.
Hartley EJ.
Cox P.
Anesthesiology
1994,
81:
A1348
<A NAME="RA35604ST-4A">4a </A>
Hudlicky T.
Butora G.
Fearnley S.
Gum A.
Stabile M.
A Historical Perspective
of Morphine Syntheses , In Studies in
Natural Products Chemistry
Vol. 18:
.
Elsevier;
Amsterdam:
1996.
p.43
<A NAME="RA35604ST-4B">4b </A>
Waldman H.
Organic
Synthesis Highlights II
1995,
407
<A NAME="RA35604ST-4C">4c </A>
Maier M.
Organic
Synthesis Highlights II
1995,
357
<A NAME="RA35604ST-4D">4d </A>
Novak BH.
Hudlicky T.
Reed JW.
Mulzer J.
Trauner D.
Curr. Org. Chem.
2000,
4:
343
<A NAME="RA35604ST-4E">4e </A>
Blakemore PR.
White JD.
Chem.
Commun.
2002,
1159
<A NAME="RA35604ST-5A">5a </A>
Evans,
D. A. Consonant and Dissonant Relationships.
An Organizational Model for Organic Synthesis 1972 , unpublished
manuscript.
<A NAME="RA35604ST-5B">5b </A> For discussion of some
of these concepts see:
Wong HNC.
Hon MY.
Tse CW.
Yip YC.
Tanko J.
Hudlicky T.
Chem. Rev.
1989,
89:
165
<A NAME="RA35604ST-6A">6a </A>
Gates M.
Tschudi G.
J.
Am. Chem. Soc.
1952,
75:
1109 ; communication
<A NAME="RA35604ST-6B">6b </A>
Gates M.
Tschudi G.
J. Am. Chem. Soc.
1956,
78:
1380 ; full paper
<A NAME="RA35604ST-7A">7a </A>
Bergmann ED.
Pappo R.
Ginsberg D.
J. Chem. Soc.
1950,
1369
<A NAME="RA35604ST-7B">7b </A>
Ginsberg D.
Pappo R.
J. Chem. Soc.
1951,
516
<A NAME="RA35604ST-7C">7c </A>
Ginsberg D.
Pappo R.
J. Chem. Soc.
1951,
938
<A NAME="RA35604ST-7D">7d </A>
Ginsberg D.
Pappo R.
J. Chem. Soc.
1953,
1524
<A NAME="RA35604ST-7E">7e </A>
Ginsberg D.
Elad D.
J. Am. Chem. Soc.
1954,
77:
312
<A NAME="RA35604ST-8A">8a </A>
Grewe R.
Friedrichsen W.
Chem.
Ber.
1967,
100:
1550
<A NAME="RA35604ST-8B">8b </A>
Grewe R.
Fischer H.
Friedrichsen W.
Chem. Ber.
1967,
100:
1
<A NAME="RA35604ST-9">9 </A>
Rice KC.
J.
Org. Chem.
1980,
45:
3135
<A NAME="RA35604ST-10">10 </A>
Evans DA.
Mitch CH.
Tetrahedron Lett.
1982,
23:
285
<A NAME="RA35604ST-11">11 </A>
Moos WH.
Gless RD.
Rapoport H.
J.
Org. Chem.
1983,
48:
227
<A NAME="RA35604ST-12">12 </A>
Toth JE.
Hamann PR.
Fuchs PL.
J. Org. Chem.
1988,
53:
4694
<A NAME="RA35604ST-13">13 </A>
Tius M.
Kerr MA.
J. Am. Chem. Soc.
1992,
114:
312
<A NAME="RA35604ST-14">14 </A>
Parker KA.
Fokas D.
J. Am. Chem. Soc.
1992,
114:
9688
<A NAME="RA35604ST-15">15 </A>
Overman LE.
Hong CY.
Kado N.
J.
Am. Chem. Soc.
1993,
115:
11028
<A NAME="RA35604ST-16A">16a </A>
Trauner D.
Bats JW.
Werner A.
Mulzer J.
J.
Org. Chem.
1998,
63:
5908
<A NAME="RA35604ST-16B">16b </A>
Mulzer J.
Trauner D.
Chirality
1999,
11:
475 ; synthesis of (-)-morphine
<A NAME="RA35604ST-16C">16c </A>
Trauner D.
Porth S.
Opatz T.
Bats JW.
Giester G.
Mulzer J.
Synthesis
1998,
653
<A NAME="RA35604ST-16D">16d </A>
Mulzer J.
Bats JW.
List B.
Opatz T.
Trauner D.
Synlett
1997,
441
<A NAME="RA35604ST-16E">16e </A>
Mulzer J.
Duerner G.
Trauner D.
Angew.
Chem., Int. Ed. Engl.
1996,
35:
2835
<A NAME="RA35604ST-17">17 </A>
Parsons PJ.
Penkett CS.
Shell AJ.
Chem. Rev.
1996,
96:
195
<A NAME="RA35604ST-18">18 </A>
White JD.
Hrnciar P.
Stappenbeck F.
J.
Org. Chem.
1997,
62:
5250
<A NAME="RA35604ST-19">19 </A>
Butora G.
Hudlicky T.
Fearnley SP.
Stabile MR.
Gum AG.
Gonzales D.
Synthesis
1998,
665
<A NAME="RA35604ST-20">20 </A>
Liou J.-P.
Cheng C.-Y.
Tetrahedron Lett.
2000,
41:
915
<A NAME="RA35604ST-21">21 </A>
Yamada O.
Ogasawara K.
Org. Lett.
2000,
2:
2785
<A NAME="RA35604ST-22">22 </A>
Nagata H.
Miyazawa N.
Ogasawara K.
Chem.
Commun.
2001,
1094
<A NAME="RA35604ST-23">23 </A>
Taber DF.
Neuberth TD.
Rheingold AL.
J. Am. Chem. Soc.
2002,
124:
12416
<A NAME="RA35604ST-24">24 </A>
Trost BM.
Tang W.
J. Am. Chem. Soc.
2002,
124:
14542
<A NAME="RA35604ST-25A">25a </A>
Davis WA.
J. Chem. Soc.
1900,
33
<A NAME="RA35604ST-25B">25b </A>
Horn AS.
Grol CJ.
Dijkstra D.
Mulder AH.
J.
Med. Chem.
1978,
21:
825
<A NAME="RA35604ST-25C">25c </A>
McDermed JD.
McKenzie GM.
Phillips AP.
J. Med. Chem.
1975,
18:
362
<A NAME="RA35604ST-25D">25d </A>
Aristoff PA.
Johnson PD.
Harrison AW.
J. Am. Chem. Soc.
1985,
107:
7967
<A NAME="RA35604ST-26">26 </A>
Taber DF.
Sahli A.
Yu H.
Meagley RP.
J. Org. Chem.
1995,
60:
6571
<A NAME="RA35604ST-27">27 </A> For a review see:
Mitsunobu O.
Synthesis
1981,
1
<A NAME="RA35604ST-28">28 </A>
Rice KC.
J.
Med. Chem.
1977,
20:
164
<A NAME="RA35604ST-29">29 </A>
Amri H.
Rambaud M.
Villieras J.
Tetrahedron
1990,
46:
3535
<A NAME="RA35604ST-30A">30a </A>
Trost BM.
Tang W.
Angew.
Chem. Int. Ed.
2002,
41:
2795
<A NAME="RA35604ST-30B">30b </A> For the first report
see:
Trost BM.
Toste FD.
J. Am. Chem. Soc.
2000,
122:
11262
<A NAME="RA35604ST-31">31 </A>
Corey EJ.
Fuchs PL.
Tetrahedron Lett.
1972,
13:
3769
<A NAME="RA35604ST-32">32 </A>
Uenishi JI.
Kawahama R.
Shiga Y.
Yonemitsu O.
Tsuji J.
Tetrahedron
Lett.
1996,
37:
6759
<A NAME="RA35604ST-33">33 </A>
Hosomi A.
Sakurai H.
J. Am. Chem. Soc.
1977,
99:
1673
<A NAME="RA35604ST-34A">34a </A>
Nagata H.
Kawamura M.
Ogasawara K.
Synthesis
2000,
1825
<A NAME="RA35604ST-34B">34b </A>
Nagata H.
Miyazawa N.
Ogasawara K.
Org.
Lett.
2001,
3:
1737
<A NAME="RA35604ST-35">35 </A>
Miyazawa N.
Ogasawara K.
Synlett
2002,
7:
1065
<A NAME="RA35604ST-36">36 </A>
Hanada K.
Miyazawa N.
Ogasawara K.
Org.
Lett.
2002,
4:
4515
<A NAME="RA35604ST-37">37 </A>
Pérez D.
Siesel BA.
Malaska MJ.
David E.
Vollhardt KPC.
Synlett
2000,
306
<A NAME="RA35604ST-38">38 </A>
Kesten SJ.
Pattison IC.
Goel OP.
Org. Prep. Proced. Int.
1989,
21:
763
<A NAME="RA35604ST-39">39 </A>
Fukuyama T.
Lin S.-C.
Li L.
J.
Am. Chem. Soc.
1990,
112:
7050
<A NAME="RA35604ST-40">40 </A>
Yamada O.
Ogasawara K.
Tetrahedron Lett.
1998,
39:
7747
<A NAME="RA35604ST-41">41 </A>
Passarella D.
Consonni A.
Giardini A.
Lesma G.
Silvani A.
Bioorg.
Med. Chem. Lett.
2002,
12:
1981
<A NAME="RA35604ST-42A">42a </A>
Schmidhammer H.
Brossi A.
Can.
J. Chem.
1982,
60:
3055
<A NAME="RA35604ST-42B">42b </A>
Schmidhammer H.
Jacobsen AE.
Brossi A.
Heterocycles
1982,
17:
391
<A NAME="RA35604ST-43">43 </A>
Hussey BJ.
Johnstone RAW.
Entwistle ID.
Tetrahedron
1982,
38:
3775
<A NAME="RA35604ST-44">44 </A>
Kozikowski AP.
Park P.
J. Org. Chem.
1990,
55:
4668
<A NAME="RA35604ST-45">45 </A>
Botari P.
Endoma MA.
Hudlicky T.
Ghiviriga I.
Abboud KA.
Collect.
Czech. Chem. Commun.
1999,
64:
203 ;
and references therein
For recent reviews of the enzymatic
dihydroxylation of aromatics see:
<A NAME="RA35604ST-46A">46a </A>
Hudlicky T.
Gonzalez D.
Gibson DT.
Aldrichimica
Acta
1999,
32:
35
<A NAME="RA35604ST-46B">46b </A>
Boyd DR.
Sheldrake GN.
Nat.
Prod. Rep.
1998,
15:
309
<A NAME="RA35604ST-46C">46c </A>
Bugg TDH.
Tetrahedron
2003,
59:
7075
<A NAME="RA35604ST-46D">46d </A>
Johnson RA.
Org. React.
2004,
63:
117
<A NAME="RA35604ST-47">47 </A>
Zezula J.
PhD
Thesis
University;
Florida:
2003.
<A NAME="RA35604ST-48A">48a </A>
Kazmaier U.
Angew. Chem., Int. Ed. Engl.
1994,
33:
1998
<A NAME="RA35604ST-48B">48b </A>
Kazmaier U.
Schneider C.
Synlett
1996,
975
<A NAME="RA35604ST-48C">48c </A>
Wipf P. In
Comprehensive Organic Synthesis
Vol.
5:
Trost BM.
Pergamon
Press;
Oxford:
1991.
p.827
<A NAME="RA35604ST-48D">48d </A>
Ireland RE.
Wipf P.
J. Org. Chem.
1991,
5:
33572
<A NAME="RA35604ST-49">49 </A>
Zylstra GJ.
Gibson DT.
J. Biol. Chem.
1989,
264:
14940
<A NAME="RA35604ST-50A">50a </A>
Endoma MA.
Bui VP.
Hansen J.
Hudlicky T.
Org. Process
Res. Dev.
2002,
6:
525
<A NAME="RA35604ST-50B">50b </A>
Bui VP.
Hansen TV.
Stenstrøm Y.
Hudlicky T.
Green Chem.
2000,
2:
263
<A NAME="RA35604ST-51">51 </A>
Gonzales D.
Schapiro V.
Seoane G.
Hudlicky T.
Abboud KA.
J.
Org. Chem.
1997,
62:
1194
<A NAME="RA35604ST-52">52 </A>
Oppong KA.
PhD
Thesis
University;
Florida:
2001.
<A NAME="RA35604ST-53">53 </A>
Hudlicky T.
Oppong KA.
Duan C.
Stanton C.
Laufersweiler MJ.
Natchus MG.
Bioorg. Med. Chem. Lett.
2001,
11:
627
<A NAME="RA35604ST-54">54 </A>
Santos, L.; Finn, K.; Koroniak, L.;
Hudlicky, T. unpublished observations.
<A NAME="RA35604ST-55A">55a </A>
May EL.
Murphy JG.
J.
Org. Chem.
1955,
20:
257
<A NAME="RA35604ST-55B">55b </A>
May EL.
Murphy JG.
J.
Org. Chem.
1955,
20:
1197
<A NAME="RA35604ST-56">56 </A>
Yamada K.
Flippen-Anderson JL.
Jacobson AE.
Rice KC.
Synthesis
2002,
2359
<A NAME="RA35604ST-57">57 </A>
Evans DA.
Mitch CH.
Thomas RC.
Zimmerman DM.
Robbey RL.
J. Am. Chem. Soc.
1980,
102:
5955
<A NAME="RA35604ST-58">58 </A>
Gu XP.
Nishida N.
Ikeda I.
Okahara M.
J. Org. Chem.
1987,
52:
3192
<A NAME="RA35604ST-59">59 </A>
Linders JTM.
Mirsadeghi S.
Flippen-Anderson JL.
George C.
Jacobson AE.
Rice KC.
Helv.
Chim. Acta
2003,
86:
484
<A NAME="RA35604ST-60">60 </A>
Tadic D.
Linders JTM.
Flippen-Anderson JL.
Jacobson AE.
Rice KC.
Tetrahedron
2003,
59:
4603
<A NAME="RA35604ST-61">61 </A>
Kodato S.
Linders JTM.
Gu X.-H.
Yamada K.
Flippen-Anderson JL.
Deschamps JR.
Jacobson AE.
Rice KC.
Org.
Biomol. Chem.
2004,
2:
330
<A NAME="RA35604ST-62">62 </A>
Linders JTM.
Flippen-Anderson JM.
George CF.
Rice KC.
Tetrahedron
Lett.
1999,
40:
3905
<A NAME="RA35604ST-63">63 </A>
Grauert M.
Bechtel WD.
Weiser T.
Stransky W.
Nar H.
Carter AJ.
J. Med. Chem.
2002,
45:
3755
<A NAME="RA35604ST-64A">64a </A>
Kametani T.
Kigasawa K.
Hiiragi M.
Wagatsuma N.
Heterocycles
1974,
2:
79
<A NAME="RA35604ST-64B">64b </A>
Clarke EGC.
Nature
1959,
184:
451
<A NAME="RA35604ST-65">65 </A>
Trost BM.
Tang W.
J. Am. Chem. Soc.
2003,
125:
8744
<A NAME="RA35604ST-66">66 </A>
Kuehne ME.
J.
Am. Chem. Soc.
1961,
83:
1492
<A NAME="RA35604ST-67">67 </A>
Ohno H.
Kawamura K.
Otake A.
Nagase A.
Tanaka T.
Synlett
2002,
93
<A NAME="RA35604ST-68">68 </A>
Schütz J.
Brandt W.
Spetea M.
Wurst K.
Wunder G.
Schmidhammer H.
Helv. Chim. Acta
2003,
86:
2142