Abstract
The facile synthesis of a key intermediate for the total synthesis of the antiangiogenic compound fumagillin, its semisynthetic analogue TNP-470, and ovalicin is described. The methodology employs a Diels-Alder strategy and a zinc-mediated ring-opening reaction to realize the cyclohexane backbone.
Key words
angiogenesis inhibitors - Diels-Alder reaction -
syn reduction - dihydroxylation - HIV
References
1a
Hanahan D.
Folkman J.
Cell
1996,
86:
353
1b
Folkman J.
Nat. Med.
1995,
1:
27
1c
Folkman J.
Klagsbrun M.
Science
1987,
235:
442
1d
McCowen MC.
Callender ME.
Lawlis JF.
Science
1951,
113:
202
2a
Powell D.
Skotnicki J.
Upeslacis J.
Annu. Rep. Med. Chem.
1997,
32:
161
2b
Giannis A.
Rubsam F.
Angew. Chem., Int. Ed. Engl.
1997,
36:
588
2c
Auerbach W.
Auerbach R.
Pharmacol. Ther.
1994,
63:
265
2d
Folkman J.
N. Engl. J. Med.
1971,
285:
1182
3a
Killough JH.
Magill GB.
Smith RC.
Science
1952,
115:
71
3b
Katznelson H.
Jamieson CA.
Science
1952,
115:
70
3c See also ref. 1d.
3d
Eble TE.
Hanson FR.
Antibiot. Chemother. (Washington, D.C.)
1951,
1:
54
4a
Asami Y.
Kakeya H.
Onose R.
Chang Y.-H.
Toi M.
Osada H.
Tetrahedron
2004,
60:
7085
4b
Yamaguchi J.
Toyoshima M.
Shoji M.
Kakeya H.
Osada H.
Hayashi Y.
Angew. Chem. Int. Ed.
2006,
45:
789
5a
O’Reilly MS.
Boehm T.
Shing Y.
Fukai N.
Vasios G.
Lane WS.
Flynn E.
Birkhead JR.
Olsen BR.
Folkman J.
Cell
1997,
88:
277
5b
Oh SP.
Warman ML.
Seldin MF.
Cheng SD.
Knoll JHM.
Timmons S.
Olsen BR.
Genomics
1994,
19:
494
6a
O’Reilly MS.
Holmgren L.
Shing Y.
Chen C.
Rosenthal RA.
Moses M.
Lane WS.
Cao Y.
Sage EH.
Folkman J.
Cell
1994,
79:
315
6b
Gately S.
Twardowski P.
Stack MS.
Patrick M.
Boggio L.
Cundiff DL.
Schnaper HW.
Madison L.
Volpert O.
Bouck N.
Enghild J.
Kwaan HC.
Soff GA.
Cancer Res.
1996,
56:
4887
7a
Sigg HP.
Weber HP.
Helv. Chim. Acta
1968,
51:
1395
7b
Sassa T.
Kaise H.
Munata K.
Agric. Biol. Chem.
1970,
34:
649
7c
Corey EJ.
Dittami JP.
J. Am. Chem. Soc.
1985,
107:
256
7d
Tiefenbacher K.
Arion VB.
Mulzer J.
Angew. Chem. Int. Ed.
2007,
46:
1
8a
Ingber D.
Fujita T.
Kishimoto S.
Sudo K.
Kanamaru T.
Brem H.
Folkman J.
Nature
1990,
348:
555
8b
Figg WD.
Kruger EA.
Expert Opin. Invest. Drugs
2000,
9:
1383
8c
Kwon J.
Jeong H.
Kang K.
Hang Y.
Bae K.
Choi J.
Lee U.
Son K.
Kown B.
J. Antibiot.
2000,
53:
799
9a See also ref. 3b.
9b See also ref. 3a.
9c
Zhang P.
Nicholson DE.
Bujnicki JM.
Su X.
Brendle JJ.
Ferdig M.
Kyle DE.
Milhous WK.
Chiang PK.
J. Biomed. Sci.
2002,
9:
34
10a Molina JM, and Derouin F. inventors; PCT Int. Appl. WO 9630010.
; Chem. Abstr. 1996 , 125 , 309073
10b
Coyle C.
Kent M.
Tanowitz HB.
Wittner M.
Weiss LM.
J. Infect. Dis.
1998,
177:
515
10c
Molina JM.
Goguel J.
Sarfati C.
Michiels J.-F.
Desportes-Livage I.
Balkan S.
Chastang C.
Cotte L.
Maslo C.
Struxiano A.
Derouin F.
Decazes J.-M.
AIDS
2000,
14:
1341
11
Watanabe N.
Nishihara Y.
Yamaguchi T.
Koito A.
Miyoshi H.
Kakeya H.
Osada H.
FEBS Lett.
2006,
580:
2598
12
Corey EJ.
Snider BB.
J. Am. Chem. Soc.
1972,
94:
2549
For the total synthesis of fumagillin and the synthesis of its key intermediate fragments and some other analogues, see:
13a
Camara F.
Angarita J.
Mootoo DR.
J. Org. Chem.
2005,
70:
6870
13b
Ciampini M.
Perlmutter P.
Watson K.
Tetrahedron: Asymmetry
2007,
18:
243
13c
Bedel O.
Haudrechy A.
Pouilhes A.
Langlois Y.
Pure Appl. Chem.
2005,
77:
1139
13d
Manitschek R.
Huwe A.
Giannis A.
Org. Biomol. Chem.
2005,
3:
2150
13e
Vosburg DA.
Weiler S.
Sorensen E.
Chirality
2003,
15:
156
13f
Picoul W.
Bedel O.
Haudrechy A.
Langlois Y.
Pure Appl. Chem.
2003,
75:
235
13g
Fardis M.
Pyun HJ.
Tario J.
Jin HL.
Kim CU.
Ruckman J.
Lin Y.
Green L.
Hicke B.
Bioorg. Med. Chem.
2003,
11:
5051
13h
Picoul W.
Urchequi R.
Haudrechy A.
Langlois Y.
Tetrahedron Lett.
1999,
40:
4797
13i
Taber DF.
Christos TE.
Rheingold AL.
Guzei IA.
J. Am. Chem. Soc.
1999,
121:
5589
13j
Hutchings M.
Moffat D.
Simpkins NS.
Synlett
2001,
661
13k
Kim D.
Ahn SK.
Bae H.
Choi WJ.
Kim HS.
Tetrahedron Lett.
1997,
38:
4437
13l
Vosburg DA.
Weiler S.
Sorensen EJ.
Angew. Chem. Int. Ed.
1999,
38:
971
13m
Bedel O.
Haudrechy A.
Langlois Y.
Eur. J. Org. Chem.
2004,
3813
13n
Boiteau J.-G.
Van de Weghe P.
Eustache J.
Org. Lett.
2001,
3:
2737
14a
Yadav JS.
Sreedhar P.
Bhunia DC.
Srihari P.
Synlett
2007,
992
For our other contributions toward the synthesis of biologically active natural products, see:
14b
Yadav JS.
Chetia L.
Org. Lett.
2007,
9:
4587
14c
Yadav JS.
Pratap TV.
Rajender V.
J. Org. Chem.
2007,
72:
5882
14d
Srihari P.
Prem Kumar B.
Subbarayudu K.
Yadav JS.
Tetrahedron Lett.
2007,
48:
6977
14e
Yadav JS.
Prathap I.
Tadi BP.
Tetrahedron Lett.
2006,
47:
3773
14f
Yadav JS.
Srinivas R.
Sathaiah K.
Tetrahedron Lett.
2006,
47:
1603
14g
Yadav JS.
Raju AK.
Rao PP.
Rajaiah G.
Tetrahedron: Asymmetry
2005,
16:
3283
14h
Yadav JS.
Prakash SJ.
Gangadhar Y.
Tetrahedron: Asymmetry
2005,
16:
2722
14i
Yadav JS.
Reddy MS.
Prasad AR.
Tetrahedron Lett.
2005,
46:
2133
15
Leroy J.
Synth. Commun.
1992,
22:
567
16 Regiospecificity was determined by comparing the corresponding reactions of furfuryl alcohols with different protecting groups and studying their stereochemistry by NMR spectroscopic methods. When TBS protection was used, a mixture of isomers was formed; however, with a PMB protecting group, only one regioisomer was synthesized, see: Nelson WL.
Allen DR.
Heterocycl. Chem.
1972,
9:
561
17
Leroy J.
Tetrahedron Lett.
1992,
33:
2969
18 Initially, we isolated the double-bond-reduced product with the PMB group intact and then proceeded with PMB deprotection using DDQ in CH2 Cl2 /H2 O. However, a prolonged reaction time with Pd/C also resulted in the saturated PMB-deprotected product.
19a
Bernet B.
Vasella A.
Helv. Chim. Acta
1979,
62:
1990
For applications and modified procedures, see:
19b
Ferrier RJ.
Furneaux RH.
Prasit P.
Tyler PC.
Brown KL.
Gainsford GJ.
Diehl W.
J. Chem. Soc., Perkin Trans. 1
1983,
1621
19c
Ferrier RJ.
Prasit P.
J. Chem. Soc., Perkin Trans. 1
1983,
1645
19d
Ferrier RJ.
Schmidt P.
Tyler PC.
J. Chem. Soc., Perkin Trans. 1
1985,
301
19e
Nicolaou KC.
Duggan ME.
Ladduwahetty T.
Tetrahedron Lett.
1984,
25:
2069
19f
Yadav JS.
Reddy BVS.
Srinivasa Reddy K.
Tetrahedron
2003,
59:
5333
19g See also ref. 14a.
20 The reaction conditions employed for the attempted protection of the alcohol were (a) TBDPSCl, 1H -imidazole, CH2 Cl2 ; (b) MOMCl, DIPEA, CH2 Cl2 ; (c) BzCl, py, CH2 Cl2 , and those employed for the attempted ketal deprotection were (a) PTSA (cat.), acetone-H2 O; (b) CSA, acetone-H2 O; (c) PPTS, acetone-H2 O; (d) TMSOTf, CH2 Cl2 .
21 Molecules with a similar core including an epoxide moiety were found to be biologically active, see: Mazitschek R.
Huwe A.
Giannis A.
Org. Biomol. Chem.
2995,
3:
2150
22 1,2-Asymmetric syn reduction was achieved by following a known protocol used for the stereoselective reduction of β-hydroxy ketone, see: Narasaka K.
Pai F.-C.
Tetrahedron
1984,
40:
2233