Recent Progress in the Synthesis
of Morphine Alkaloids

Josef Zezula; Tomas Hudlicky

doi:10.1055/s-2005-862383

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Synlett 2005(3): 388-405
DOI: 10.1055/s-2005-862383

ACCOUNT

Recent Progress in the Synthesis of Morphine Alkaloids

Josef Zezula^a, Tomas Hudlicky*^b
^a NIH/NIDDK, 9000 Rockville Pike, Bldg. 8/Rm. B1-25, Bethesda, MD 20892-0815, USA
^b Department of Chemistry, Brock University, 500 Glenridge Avenue, St. Catharines, Ontario L2S 3A1, Canada
Fax: +1(905)9844841; e-Mail: thudlicky@brocku.ca;

Further Information

Publication History

Received 15 June 2004
Publication Date:
04 February 2005 (online)

Abstract
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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

1 Booth M. Opium: A History St. Martin’s Press; New York: 1998.

Google Scholar
2 Kappor LD. Opium Poppy: Botany, Chemistry, and Pharmacology Food Products Press; New York: 1995.

Google Scholar
3 Carr AS. Holtby HM. Hartley EJ. Cox P. Anesthesiology 1994, 81: A1348

Google Scholar
4a 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

Crossref Google Scholar
4b Waldman H. Organic Synthesis Highlights II 1995, 407

Crossref Google Scholar
4c Maier M. Organic Synthesis Highlights II 1995, 357

Crossref Google Scholar
4d Novak BH. Hudlicky T. Reed JW. Mulzer J. Trauner D. Curr. Org. Chem. 2000, 4: 343

Crossref Google Scholar
4e Blakemore PR. White JD. Chem. Commun. 2002, 1159

Crossref Google Scholar
5a
Evans, D. A. Consonant and Dissonant Relationships. An Organizational Model for Organic Synthesis 1972, unpublished manuscript.

Crossref
5b 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

Crossref Google Scholar
6a Gates M. Tschudi G. J. Am. Chem. Soc. 1952, 75: 1109 ; communication

Crossref Google Scholar
6b Gates M. Tschudi G. J. Am. Chem. Soc. 1956, 78: 1380 ; full paper

Crossref Google Scholar
7a Bergmann ED. Pappo R. Ginsberg D. J. Chem. Soc. 1950, 1369

Google Scholar
7b Ginsberg D. Pappo R. J. Chem. Soc. 1951, 516

Google Scholar
7c Ginsberg D. Pappo R. J. Chem. Soc. 1951, 938

Google Scholar
7d Ginsberg D. Pappo R. J. Chem. Soc. 1953, 1524

Google Scholar
7e Ginsberg D. Elad D. J. Am. Chem. Soc. 1954, 77: 312

Google Scholar
8a Grewe R. Friedrichsen W. Chem. Ber. 1967, 100: 1550

Google Scholar
8b Grewe R. Fischer H. Friedrichsen W. Chem. Ber. 1967, 100: 1

Google Scholar
9 Rice KC. J. Org. Chem. 1980, 45: 3135

Crossref Google Scholar
10 Evans DA. Mitch CH. Tetrahedron Lett. 1982, 23: 285

Crossref Google Scholar
11 Moos WH. Gless RD. Rapoport H. J. Org. Chem. 1983, 48: 227

Google Scholar
12 Toth JE. Hamann PR. Fuchs PL. J. Org. Chem. 1988, 53: 4694

Crossref Google Scholar
13 Tius M. Kerr MA. J. Am. Chem. Soc. 1992, 114: 312

Google Scholar
14 Parker KA. Fokas D. J. Am. Chem. Soc. 1992, 114: 9688

Crossref Google Scholar
15 Overman LE. Hong CY. Kado N. J. Am. Chem. Soc. 1993, 115: 11028

Crossref Google Scholar
16a Trauner D. Bats JW. Werner A. Mulzer J. J. Org. Chem. 1998, 63: 5908

Google Scholar
16b Mulzer J. Trauner D. Chirality 1999, 11: 475 ; synthesis of (-)-morphine

Google Scholar
16c Trauner D. Porth S. Opatz T. Bats JW. Giester G. Mulzer J. Synthesis 1998, 653

Google Scholar
16d Mulzer J. Bats JW. List B. Opatz T. Trauner D. Synlett 1997, 441

Google Scholar
16e Mulzer J. Duerner G. Trauner D. Angew. Chem., Int. Ed. Engl. 1996, 35: 2835

Google Scholar
17 Parsons PJ. Penkett CS. Shell AJ. Chem. Rev. 1996, 96: 195

Crossref Google Scholar
18 White JD. Hrnciar P. Stappenbeck F. J. Org. Chem. 1997, 62: 5250

Crossref Google Scholar
19 Butora G. Hudlicky T. Fearnley SP. Stabile MR. Gum AG. Gonzales D. Synthesis 1998, 665

Article in Thieme Connect Google Scholar
20 Liou J.-P. Cheng C.-Y. Tetrahedron Lett. 2000, 41: 915

Crossref Google Scholar
21 Yamada O. Ogasawara K. Org. Lett. 2000, 2: 2785

Crossref Google Scholar
22 Nagata H. Miyazawa N. Ogasawara K. Chem. Commun. 2001, 1094

Crossref Google Scholar
23 Taber DF. Neuberth TD. Rheingold AL. J. Am. Chem. Soc. 2002, 124: 12416

Crossref Google Scholar
24 Trost BM. Tang W. J. Am. Chem. Soc. 2002, 124: 14542

Crossref PubMed Google Scholar
25a Davis WA. J. Chem. Soc. 1900, 33

Crossref Google Scholar
25b Horn AS. Grol CJ. Dijkstra D. Mulder AH. J. Med. Chem. 1978, 21: 825

Crossref Google Scholar
25c McDermed JD. McKenzie GM. Phillips AP. J. Med. Chem. 1975, 18: 362

Crossref Google Scholar
25d Aristoff PA. Johnson PD. Harrison AW. J. Am. Chem. Soc. 1985, 107: 7967

Crossref Google Scholar
26 Taber DF. Sahli A. Yu H. Meagley RP. J. Org. Chem. 1995, 60: 6571

Google Scholar
27 For a review see: Mitsunobu O. Synthesis 1981, 1

Article in Thieme Connect Google Scholar
28 Rice KC. J. Med. Chem. 1977, 20: 164

Crossref Google Scholar
29 Amri H. Rambaud M. Villieras J. Tetrahedron 1990, 46: 3535

Crossref Google Scholar
30a Trost BM. Tang W. Angew. Chem. Int. Ed. 2002, 41: 2795

Crossref Google Scholar
30b For the first report see: Trost BM. Toste FD. J. Am. Chem. Soc. 2000, 122: 11262

Crossref Google Scholar
31 Corey EJ. Fuchs PL. Tetrahedron Lett. 1972, 13: 3769

Crossref Google Scholar
32 Uenishi JI. Kawahama R. Shiga Y. Yonemitsu O. Tsuji J. Tetrahedron Lett. 1996, 37: 6759

Crossref Google Scholar
33 Hosomi A. Sakurai H. J. Am. Chem. Soc. 1977, 99: 1673

Crossref Google Scholar
34a Nagata H. Kawamura M. Ogasawara K. Synthesis 2000, 1825

Crossref Google Scholar
34b Nagata H. Miyazawa N. Ogasawara K. Org. Lett. 2001, 3: 1737

Crossref Google Scholar
35 Miyazawa N. Ogasawara K. Synlett 2002, 7: 1065

Article in Thieme Connect Google Scholar
36 Hanada K. Miyazawa N. Ogasawara K. Org. Lett. 2002, 4: 4515

Crossref Google Scholar
37 Pérez D. Siesel BA. Malaska MJ. David E. Vollhardt KPC. Synlett 2000, 306

Article in Thieme Connect Google Scholar
38 Kesten SJ. Pattison IC. Goel OP. Org. Prep. Proced. Int. 1989, 21: 763

Google Scholar
39 Fukuyama T. Lin S.-C. Li L. J. Am. Chem. Soc. 1990, 112: 7050

Crossref Google Scholar
40 Yamada O. Ogasawara K. Tetrahedron Lett. 1998, 39: 7747

Crossref Google Scholar
41 Passarella D. Consonni A. Giardini A. Lesma G. Silvani A. Bioorg. Med. Chem. Lett. 2002, 12: 1981

Crossref Google Scholar
42a Schmidhammer H. Brossi A. Can. J. Chem. 1982, 60: 3055

Google Scholar
42b Schmidhammer H. Jacobsen AE. Brossi A. Heterocycles 1982, 17: 391

Google Scholar
43 Hussey BJ. Johnstone RAW. Entwistle ID. Tetrahedron 1982, 38: 3775

Crossref Google Scholar
44 Kozikowski AP. Park P. J. Org. Chem. 1990, 55: 4668

Crossref Google Scholar
45 Botari P. Endoma MA. Hudlicky T. Ghiviriga I. Abboud KA. Collect. Czech. Chem. Commun. 1999, 64: 203 ; and references therein

Crossref Google Scholar
For recent reviews of the enzymatic dihydroxylation of aromatics see:
46a Hudlicky T. Gonzalez D. Gibson DT. Aldrichimica Acta 1999, 32: 35

Google Scholar
46b Boyd DR. Sheldrake GN. Nat. Prod. Rep. 1998, 15: 309

Google Scholar
46c Bugg TDH. Tetrahedron 2003, 59: 7075

Google Scholar
46d Johnson RA. Org. React. 2004, 63: 117

Google Scholar
47 Zezula J. PhD Thesis University; Florida: 2003.

Google Scholar
48a Kazmaier U. Angew. Chem., Int. Ed. Engl. 1994, 33: 1998

Google Scholar
48b Kazmaier U. Schneider C. Synlett 1996, 975

Google Scholar
48c Wipf P. In Comprehensive Organic Synthesis Vol. 5: Trost BM. Pergamon Press; Oxford: 1991. p.827

Google Scholar
48d Ireland RE. Wipf P. J. Org. Chem. 1991, 5: 33572

Google Scholar
49 Zylstra GJ. Gibson DT. J. Biol. Chem. 1989, 264: 14940

Google Scholar
50a Endoma MA. Bui VP. Hansen J. Hudlicky T. Org. Process Res. Dev. 2002, 6: 525

Crossref Google Scholar
50b Bui VP. Hansen TV. Stenstrøm Y. Hudlicky T. Green Chem. 2000, 2: 263

Crossref Google Scholar
51 Gonzales D. Schapiro V. Seoane G. Hudlicky T. Abboud KA. J. Org. Chem. 1997, 62: 1194

Crossref Google Scholar
52 Oppong KA. PhD Thesis University; Florida: 2001.

Google Scholar
53 Hudlicky T. Oppong KA. Duan C. Stanton C. Laufersweiler MJ. Natchus MG. Bioorg. Med. Chem. Lett. 2001, 11: 627

Crossref Google Scholar
55a May EL. Murphy JG. J. Org. Chem. 1955, 20: 257

Google Scholar
55b May EL. Murphy JG. J. Org. Chem. 1955, 20: 1197

Google Scholar
56 Yamada K. Flippen-Anderson JL. Jacobson AE. Rice KC. Synthesis 2002, 2359

Article in Thieme Connect Google Scholar
57 Evans DA. Mitch CH. Thomas RC. Zimmerman DM. Robbey RL. J. Am. Chem. Soc. 1980, 102: 5955

Crossref Google Scholar
58 Gu XP. Nishida N. Ikeda I. Okahara M. J. Org. Chem. 1987, 52: 3192

Google Scholar
59 Linders JTM. Mirsadeghi S. Flippen-Anderson JL. George C. Jacobson AE. Rice KC. Helv. Chim. Acta 2003, 86: 484

Crossref Google Scholar
60 Tadic D. Linders JTM. Flippen-Anderson JL. Jacobson AE. Rice KC. Tetrahedron 2003, 59: 4603

Crossref Google Scholar
61 Kodato S. Linders JTM. Gu X.-H. Yamada K. Flippen-Anderson JL. Deschamps JR. Jacobson AE. Rice KC. Org. Biomol. Chem. 2004, 2: 330

Crossref Google Scholar
62 Linders JTM. Flippen-Anderson JM. George CF. Rice KC. Tetrahedron Lett. 1999, 40: 3905

Crossref Google Scholar
63 Grauert M. Bechtel WD. Weiser T. Stransky W. Nar H. Carter AJ. J. Med. Chem. 2002, 45: 3755

Crossref Google Scholar
64a Kametani T. Kigasawa K. Hiiragi M. Wagatsuma N. Heterocycles 1974, 2: 79

Google Scholar
64b Clarke EGC. Nature 1959, 184: 451

Google Scholar
65 Trost BM. Tang W. J. Am. Chem. Soc. 2003, 125: 8744

Crossref PubMed Google Scholar
66 Kuehne ME. J. Am. Chem. Soc. 1961, 83: 1492

Crossref Google Scholar
67 Ohno H. Kawamura K. Otake A. Nagase A. Tanaka T. Synlett 2002, 93

Article in Thieme Connect Google Scholar
68 Schütz J. Brandt W. Spetea M. Wurst K. Wunder G. Schmidhammer H. Helv. Chim. Acta 2003, 86: 2142

Crossref Google Scholar

54

Santos, L.; Finn, K.; Koroniak, L.; Hudlicky, T. unpublished observations.