Abstract
Natural products play a dominant role in providing ligands that interfere with biopolymers such as receptors or enzymes. In many cases the exact mode of action or the targets are not known and synthesis of analogs provides a more detailed insight into the mode of action and helps to identify the protein target. We discuss the synthetic endeavors that led to the synthesis of members of the leptomycin family and will provide a picture of the mode of action.
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1 Introduction
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2 Synthetic Studies
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2.1 Syntheses of the Lactone Fragment (C1-C6)
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2.2 Syntheses of Callystatin A
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2.3 Syntheses of Ratjadone
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2.4 Synthesis of Leptomycin B
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3 Biological Evaluation
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4 Summary
Key words
natural products - anti-tumor - leptomycin B - callystatin A - ratjadone
References
1
Hung DT.
Jamison TF.
Schreiber SL.
Chem. Biol.
1996,
3:
623
2a
Hamamoto T.
Seto H.
Beppu T.
J. Antibiot.
1983,
36:
646
2b
Hamamoto T.
Uozumi T.
Beppu T.
J. Antibiot.
1985,
38:
1573
2c
Hurley TR.
Bunge RH.
Willmer NE.
Hokanson GC.
French JC.
J. Antibiot.
1986,
39:
1651
2d
Schaumberg JP.
Hokanson GC.
French JC.
J. Chem. Soc., Chem. Commun.
1984,
1450
2e
Yoshida M.
Nishikawa M.
Nishi K.
Abe K.
Horinouchi S.
Beppu T.
Exp. Cell Res.
1990,
187:
150
3a
Kobayashi M.
Higuchi K.
Murakami N.
Tajima H.
Aoki S.
Tetrahedron Lett.
1997,
38:
2859
3b
Murakami N.
Wang W.
Aoki S.
Kobayashi M.
Tetrahedron Lett.
1997,
38:
5533
4a
Gerth K.
Schummer D.
Höfle G.
Irschik H.
Reichenbach H.
J. Antibiot.
1995,
48:
973
4b
Schummer D.
Gerth K.
Reichenbach H.
Höfle G.
Liebigs Ann.
1995,
685
5a
Komiyama K.
Okada K.
Oka H.
Tomisaka S.
Miyano T.
Funayama S.
Umezawa I.
J. Antibiot.
1985,
38:
220
5b
Komiyama K.
Okada K.
Hirokawa Y.
Masuda K.
Tomisaka S.
Umezawa I.
J. Antibiot.
1985,
38:
224
6a
Hayakawa Y.
Adachi K.
Komeshima N.
J. Antibiot.
1987,
40:
1349
6b
Hayakawa Y.
Sohda K.
Shin-ya K.
Hidaka T.
Seto H.
J. Antibiot.
1995,
48:
954
7
Hayakawa Y.
Sohda K.
Seto H.
J. Antibiot.
1996,
49:
980
8a
Abe K.
Yoshida M.
Horinouchi S.
Beppu T.
J. Antibiot.
1993,
46:
728
8b
Abe K.
Yoshida M.
Naoki H.
Horinouchi S.
Beppu T.
J. Antibiot.
1993,
46:
735
9 (-)-Callystatin A was isolated from the marine sponge Callyspongia truncata collected from Goto Islands, Japan. Ratjadone was isolated from the myxobacteria Sorangium cellulosum collected at Cala Ratjada Mallorca, Spain. Leptolstatin was isolated from Streptomyces sp. SAM 1595 Leptomycin was isolated from Streptomyces sp. ATS1287.
10
Murakami N.
Wang W.
Aoki M.
Tsutsui Y.
Sugimoto M.
Kobayashi M.
Tetrahedron Lett.
1998,
39:
2349
11
Hayakawa Y.
Sohda K.-Y.
Shin-Ya K.
Hidaka T.
Seto H.
J. Antibiot.
1995,
48:
954
12
Nishi K.
Yoshida M.
Fujiwara D.
Nishikawa M.
Horinouchi S.
Beppu T.
J. Biol. Chem.
1994,
269:
6320
For example see: Fostriecin:
13a
Boger DL.
Ichikawa S.
Zhong W.
J. Am. Chem. Soc.
2001,
123:
4161
13b
Chavez DE.
Jacobsen EN.
Angew. Chem. Int. Ed.
2001,
40:
3667 ; Angew. Chem. 2001, 113, 3779
13c Pironetin: Yasui K.
Tamura Y.
Nakatani T.
Horibe I.
Kawada K.
Koizumi K.
Suzuki R.
Ohtani M.
J. Antibiot.
1996,
49:
173
13d See also: Keck GE.
Knutson CE.
Wiles S.
A. Org. Lett.
2001,
3:
707
14
Murakami N.
Wang W.
Aoki M.
Tsutsui Y.
Higuchi K.
Aoki S.
Kobayashi M.
Tetrahedron Lett.
1997,
38:
5533
15
Mancuso AJ.
Swern D.
Synthesis
1981,
165
For earlier approaches see:
16a
Carretero JC.
Ghosez L.
Tetrahedron Lett.
1988,
29:
2059
16b
Tsubuki M.
Kanai K.
Honda T.
Heterocycles
1993,
35:
281
16c
Boger DL.
Hikota M.
Lewis BM.
J. Org. Chem.
1997,
62:
1748
17
Murakami N.
Wang W.
Aoki M.
Tsutsui Y.
Sugimoto M.
Kobayashi M.
Tetrahedron Lett.
1998,
39:
2349
18
Williams DR.
Ihle DC.
Plummer SV.
Org. Lett.
2001,
3:
1883
19
Crimmins MT.
King BW.
J. Am. Chem. Soc.
1998,
120:
9084
20
Grubbs RH.
Miller SJ.
Fu GC.
Acc. Chem. Res.
1995,
28:
446
21
Bauer T.
Chapuis C.
Jezewski A.
Kozak J.
Jurczak J.
Tetrahedron: Asymmetry
1996,
7:
1391
22
Mikami K.
Motoyama Y.
Tereda M.
J. Am. Chem. Soc.
1994,
116:
2812
23
Smith AB.
Brandt BM.
Org. Lett.
2001,
3:
1685
24
Mitsunobu O.
Synthesis
1981,
1
25
Blakemore PR.
Cole WJ.
Kocienski PJ.
Morley A.
Synlett
1998,
26
26
Julia M.
Launay J.
Verpeaux S.
Verpeaux J.
Tetrahedron Lett.
1982,
23:
2465
27a
Jørgensen KA.
Angew. Chem. Int. Ed.
2000,
39:
3558 ; Angew. Chem. 2000, 112, 3702
27b
Dossetter AG.
Jamison TF.
Jacobsen EN.
Angew. Chem. Int. Ed.
1999,
38:
2398 ; Angew. Chem. 1999, 111, 2549
28
Quitschalle M.
Christmann M.
Bhatt U.
Kalesse M.
Tetrahedron Lett.
2001,
42:
1263
29a
Christmann M.
Bhatt U.
Quitschalle M.
Claus E.
Kalesse M.
Angew. Chem., Int. Ed.
2000,
39:
4364 ; Angew. Chem. 2000, 112, 4535
29b
Bhatt U.
Christmann M.
Quitschalle M.
Claus E.
Kalesse M.
J. Org. Chem.
2001,
66:
1885
30 Marshall, J. A.; Bourbeau, M. P. J. Org. Chem. 2002, ASAP article.
31
Vicario JL.
Job A.
Wolberg M.
Müller M.
Enders D.
Org. Lett.
2002,
4:
1023
32a
Wolberg M.
Hummel W.
Wandrey C.
Müller M.
Angew. Chem., Int. Ed. Engl.
2000,
39:
4306
32b
Wolberg M.
Hummel W.
Müller M.
Chem.- Eur. J.
2001,
7:
4562
33
Kalesse M.
Quitschalle M.
Chary KP.
Saeed A.
Org. Lett.
2001,
3:
3107
34a
Marshall JA.
Schaaf GM.
J. Org. Chem.
2001,
66:
7825
34b
Marshall JA.
Fitzgerald RN.
J. Org. Chem.
1999,
64:
4477
35a
Dias LC.
Meira PRR.
Tetrahedron Lett.
2002,
185
35b
Dias LC.
Meira PRR.
Tetrahedron Lett.
2002,
43:
1593
36
Tamura R.
Daegusa K.
Kakihana M.
Oda D.
J. Org. Chem.
1988,
53:
2723
37
Still WC.
Gennari C.
Tetrahedron Lett.
1983,
24:
4405
38
Ando K.
J. Org. Chem.
1997,
62:
1934
39
Crimmins MT.
King BW.
Tabet EA.
J. Am. Chem. Soc.
1997,
119:
7883
40
Evans DA.
Clark JS.
Metternich R.
Novak VJ.
Sheppard GS.
J. Am. Chem. Soc.
1990,
112:
866
41a
Enders D. In Asymmetric Synthesis
Vol. 3:
Morrison JD.
Academic Press;
Orlando:
1984.
p.275
41b
Enders D.
Klatt M. In Encyclopedia of Reagents for Organic Synthesis
Vol. 1:
Paquette LA.
Wiley;
Chichester:
1995.
p.178
42
White JD.
Bolton DL.
Dantanarayana AP.
Fox CMJ.
Hiner RN.
Jackson RW.
Sakuma K.
Warrier US.
J. Am. Chem. Soc.
1995,
117:
1908
43a
Overman LE.
Robinson LA.
Zablocki J.
J. Am. Chem. Soc.
1992,
114:
368
43b
Schinzer D.
Bauer A.
Schieber J.
Synlett
1998,
861
44a
Griffith WP.
Ley SV.
Aldrichimica Acta
1990,
23:
13
44b
Ley SL.
Norman J.
Griffith WP.
Marsden SP.
Synthesis
1994,
639
45
Corey EJ.
Fuchs PL.
Tetrahedron Lett.
1972,
36:
3769
46
Schwartz J.
Labinger JA.
Angew. Chem., Int. Ed. Engl.
1976,
15:
333 ; Angew. Chem. 1976, 88, 402
47a
Zimmerman HE.
Traxler MD.
J. Am. Chem. Soc.
1957,
79:
1920
47b
Li Y.
Paddon-Row MN.
Houk KN.
J. Am. Chem. Soc.
1988,
110:
3684
For similar stereodifferentiation see:
48a
Evans DA.
Rieger DL.
Bilodeau MT.
Urpi F.
J. Am. Chem. Soc.
1991,
113:
1047
48b
Roush WR.
J. Org. Chem.
1991,
56:
4151
48c
Evans DA.
Ng HP.
Rieger DL.
J. Am. Chem. Soc.
1993,
115:
11446
For more applications of allenylstannanes see:
49a
Marshall JA.
Lu Z.-H.
Johns BA.
J. Org. Chem.
1998,
63:
817
49b
Marshall JA.
Adams ND.
J. Org. Chem.
1998,
63:
3812
49c For the application in the total synthesis of discodermolide see: Marshall JA.
Jones BA.
J. Org. Chem.
1998,
63:
7885
50
Gilbert SC.
Weerasooriya U.
J. Org. Chem.
1979,
44:
4997
51 Attempts to selectively cleave the seemingly more labile TMS group at C17 at a later stage failed an afforded a triol.
52a
Dess DB.
Martin JC.
J. Org. Chem.
1983,
48:
4155
52b
Dess DB.
Martin JC.
J. Am. Chem. Soc.
1991,
113:
7277
52c
Meyer SD.
Schreiber SL.
J. Org. Chem.
1994,
59:
7549
53a
Saito S.
Itoh H.
Ono Y.
Nishioka K.
Moriwake T.
Tetrahedron: Asymmetry
1993,
4:
5
53b
Jorgensen KB.
Koshino H.
Nakata T.
Heterocycles
1998,
47:
679
54 For a different approach in the synthesis of lasonolid A see: Lee E.
Song HY.
Kang JW.
Kim D.-S.
Joo JM.
J. Am. Chem. Soc.
2002,
124:
384
55
Evans DA.
Rieger DL.
Jones TK.
Kaldor SW.
J. Org. Chem.
1990,
55:
6260
56a
Brown HC.
Jadhav PK.
J. Am. Chem. Soc.
1983,
105:
2092
56b
Brown HC.
Bhat KS.
Randad RS.
J. Org. Chem.
1989,
54:
1570
57a
Andrus MB.
Lepore SD.
Sclafani JA.
Tetrahedron Lett.
1997,
38:
4043
57b
Xu D.
Crispino GA.
Sharpless KB.
J. Am. Chem. Soc.
1992,
114:
7570
58 For an excellent review see: Casiraghi G.
Zanardi F.
Appendino G.
Rassu G.
Chem. Rev.
2000,
100:
1929
59a
Evans DA.
Black WC.
J. Am. Chem. Soc.
1993,
115:
4497
59b
Paterson I.
Smith JD.
Ward RA.
Tetrahedron
1995,
51:
9413
59c
Mutou T.
Suenaga K.
Fujita T.
Itoh T.
Takada N.
Hayamizu K.
Kigoshi H.
Yamada K.
Synlett
1997,
199
60
Christmann M.
Kalesse M.
Tetrahedron Lett.
1999,
40:
7201
61a
Christmann M.
Kalesse M.
Tetrahedron Lett.
2001,
42:
1269
61b
Hassfeld J.
Christmann M.
Kalesse M.
Org. Lett.
2001,
3:
3561
62
Gao Y.
Hanson RM.
Klunder JM.
Ko SY.
Masamune H.
Sharpless KB.
J. Am. Chem. Soc.
1987,
109:
5765
63
Tebbe FN.
Parshall GW.
Reddy GS.
J. Am. Chem. Soc.
1978,
100:
3611
64
Baker R.
Brimble MA.
Tetrahedron Lett.
1986,
27:
3311
65a
Negishi E.
Van Horn DE.
King AO.
Okukado N.
Synthesis
1979,
501
65b
Rand CL.
Van Horn DE.
Moore MW.
Negishi E.
J. Org. Chem.
1981,
46:
4093
65c
Negishi E.
Van Horn DE.
Yoshida T.
J. Am. Chem. Soc.
1985,
107:
6639
65d
Wender PA.
Tebbe MJ.
Synthesis
1991,
1089
66
Jeffery T.
J. Chem. Soc., Chem. Commun.
1984,
1287
67a
Plé PA.
Hamon A.
Jones G.
Tetrahedron
1997,
53:
3395
67b
Kobayashi M.
Wang W.
Tsutsui Y.
Sugimoto M.
Murakami M.
Tetrahedron Lett.
1998,
39:
8291
68
Evans DA.
Ennis MD.
Mathre DJ.
J. Am. Chem. Soc.
1982,
104:
1737
69a
Wipf P.
Xu W.
Tetrahedron Lett.
1994,
35:
5197
69b
Wipf P.
Ribe S.
J. Org. Chem.
1998,
63:
6454
70a
Terashima S.
Tanno N.
Koga K.
J. Chem. Soc., Chem. Commun.
1980,
1026
70b
Terashima S.
Tanno N.
Koga K.
Chem. Lett.
1980,
981
71a
Murakami N.
Sugimoto M.
Nakajima T.
Kawanishi M.
Tsutsui Y.
Kobayashi M.
Bioorg Med. Chem.
2000,
2651
71b
Murakami N.
Sugimoto M.
Kobayashi M.
Bioorg Med. Chem.
2001,
57
72
Kuhnt M.
Bitsch F.
Ponelle M.
Sanglier JJ.
Wang Y.
Wolff B.
Appl. Environ. Microbiol.
1998,
64:
714
73
Kudo N.
Wolff B.
Sekimoto T.
Schreiner EP.
Yoneda Y.
Yanagida M.
Horinouchi S.
Yoshida M.
Exp. Cell Res. 1
998,
242:
540
74a
Kudo N.
Matsumori N.
Taoka H.
Fujiwara D.
Schreiner EP.
Wolf B.
Yoshida M.
Horinouchi S.
Proc. Natl. Acad. Sci. U.S.A.
1999,
96:
9112
74b
Neville M.
Rosbash M.
EMBO J
1999,
18:
3746
74c
Yamaga M.
Fujii M.
Kamata H.
Hirata H.
Yagisawa H.
J. Biol. Chem.
1999,
274:
28537
For reviews on strain situations in organic chemistry see:
75a
Hoffmann RW.
Angew. Chem. Int. Ed. Engl.
1992,
31:
1124 ; Angew. Chem. 1992, 104: 1147
75b
Hoffmann RW.
Angew. Chem. Int. Ed.
2000,
39:
2054 ; Angew. Chem. 2000, 112, 2134
76 For the first synthetic example where an allylic strain situation governs the conformational changes and thereby induces the biological activity see: Hoffmann RW.
Ladner W.
Steinbach K.
Massa W.
Schmidt R.
Snatzke G.
Chem. Ber.
1981,
114:
2786
77
Kalesse M.
Christmann M.
Bhatt U.
Quitschalle M.
Claus E.
Saeed A.
Burzlaff A.
Kasper C.
Haustedt L.-O.
Hofer E.
Scheper T.
Beil W.
ChemBiochem
2001,
709
78 A similar conformation was reported by: Smith AB.
LaMarche MJ.
Falcone-Hindley M.
Org. Lett.
2001,
695
79
Lain S.
Midgley C.
Sparks A.
Lane EB.
Lane DP.
Exp. Cell Res.
1999,
457
