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Recently, β-amino acids have been actively researched in pharmaceutical chemistry. See the references, a) S. H. Gellman, Acc. Chem. Res. 1998, 31, 173-180;
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Gellman, S.H.1
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19
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0032766821
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We recognized structural similarities between cytosinine 3 and peptide nucleic acid (PNA); this led us to propose a new type of PNA as shown below. Our research efforts into the synthesis and characterization of this new PNA is now in progress. For PNA, see the following reference: P.E. Nielsen, Acc. Chem. Res. 1999, 32, 624-630. (Diagram presented).
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3142691974
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2 in 8) appeared to be very fragile. For example, gradual cleavage of the tert-butylbenzoyl group in 32 occurred even in neutral methanol. For other examples, see: Y. Isido, N. Nakazaki, N. Sakairi, J. Chem. Soc. Perkin Trans. 1 1977, 657-660.
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41
-
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3142656673
-
-
note
-
Although we initially employed 26b as an intermediate, this route was finally abandoned due to the difficulties associated with deprotection of the Cbz group in i, In the case of 26c, separation of the anomeric mixture, as well as deprotection of ii proved to be seriously difficult. (Diagram presented).
-
-
-
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42
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0030462737
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A. B. Smith, G. R. Ott, J. Am. Chem. Soc. 1996, 118, 13095-13096. Attempted removal of the TBS group in 26a in the absence of acetic acid led to the formation of cyclic carbamate i as the major product. (Diagram presented).
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Smith, A.B.1
Ott, G.R.2
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43
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3142708071
-
-
note
-
Oxidative removal of the p-methoxyphenyl group in 29 with ceric ammonium nitrate (CAN) gave the desired product in poor yields. The silver(n) reagent which was finally used successfully can also be used to deprotect PMB ethers as well as PMB amides. Further details will be reported in due course.
-
-
-
-
44
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3142680270
-
-
note
-
Since we observed gradual decomposition of 31 during purification on silica-gel chromatography, we did not attempt to separate the α- and β-isomers. Moreover, this material also slowly decomposed when stored in a refrigerator at -20°C.
-
-
-
-
45
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0028866843
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D. Will, G. Breipohl, D. Langner, J. Knolle, E. Uhlmann, Tetrahedron 1995, 51, 12069-12082.
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Will, D.1
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Knolle, J.4
Uhlmann, E.5
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46
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84982058693
-
-
2, into the reaction mixture that contained the silylated cytosine, we frequently observed the formation of a white precipitate. This appeared to be a α-complex of the silylated base and Lewis acid. For such α-complexes see: a) H. Vorbrüggen, G. Höfle, Chem. Ber. 1981, 114, 1256-1268;
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Vorbrüggen, H.1
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84982068675
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b) H. Vorbrüggen, K. Krolikiewicz, B. Bennua, Chem. Ber. 1981, 114, 1234-1255;
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Vorbrüggen, H.1
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51
-
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3142697806
-
-
note
-
Cytosine N-glycosylation in the current case might involve a delocalized cation such as i, which is also assumed to be an intermediate in the Ferrier reaction. In the Ferrier glycosylation using alcohols and carbon nucleophiles, formation of α-glycosides is usually preferential. Whilst the α- and β-selectivity of O- and C-Ferrier type glycosylations seems to be governed by a transition state that is stabilized by anomeric effects, we feel that the transition state for N-glycosylation in this case is not so strongly stabilized by anomeric effects. Therefore, the moderate selectivity observed in this reaction (7:3) might be the result of steric effects. In particular, the bulky silylated cytosine derivative could approach the probable intermediate i from the relatively less hindered β-face. We discuss the selectivity of the Ferrier N-glycosylation based on kinetic control. However, it should be noted that one of the referees cleverly pointed out an alternative explanation based on thermodynamics in which an exo-anomeric effect is operative in the preferred formation of the equatorial N-glycoside. (Diagram presented).
-
-
-
-
52
-
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3142699290
-
-
note
-
2O, pyridine). The mechanism to form i is unclear. (Diagram presented).
-
-
-
-
53
-
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37049082234
-
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Diester 34 was prepared using a modified procedure reported by Crossley, see Experimental Section and reference: M. J. Crossley, M. L. Fisher, J. J. Potter, P. W. Kuchel, M. J. York, J. Chem. Soc. Perkin Trans. 1 1990, 2363-2369.
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Crossley, M.J.1
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54
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0019406481
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a) M. Ohno, S. Kobayashi, T. Iimori, V. F. Wang, T. Izawa, J. Am. Chem. Soc. 1981, 103, 2405-2406;
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Ohno, M.1
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56
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0030912448
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For representative examples using secondary amides as advantageous carboxylic acid protecting group, see: D.A. Evans, P. H. Carter, C. J. Dinsmore, J. C. Barrow, J. L. Katz, D. Kung, Tetrahedron Lett. 1997, 38, 4535-4538.
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Evans, D.A.1
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57
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a) A. Basha, M. Lipton, S. M. Weinreb, Tetrahedron Lett. 1977, 18, 4171-4174;
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Basha, A.1
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b) M. Lipton, A. Basha, S. M. Weinreb, Org. Synth. Coll. 1988, 6, 492-495.
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T. Fukuyama, C-K. Jow, M. Cheung, Tetrahedron Lett. 1995, 36, 6373-6374.
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Fukuyama, T.1
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Z. X. Guo, A. N. Cammidge, D. Horwell, Synth. Commun. 2000, 30, 2933-2943.
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Guo, Z.X.1
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D. L. Flynm, R. E. Zelle, D.A. Grieco, J. Org. Chem. 1983, 48, 2424-2426.
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Flynm, D.L.1
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63
-
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3142777177
-
-
note
-
An authentic sample of pseudoblastidone (52) was prepared by treatment of blastidic acid dihydrochloride with base (0.5N NaOH, pH 10.0). See ref. [8d].
-
-
-
-
64
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3142741733
-
-
note
-
We would like to thank Prof. T. Kondo, Nagoya University, for his generous gift of blastidic acid dihydrochloride and cytosinine dihydrochloride. These were prepared by hydrolysis of natural 1.
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-
-
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66
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33845280673
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a) P. Knochel, M. C. P. Yeh, S. C. Berk, J. Talbert, J. Org. Chem. 1988, 53, 2390-2392;
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0029160623
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Q. Dong, E. Anderson, M. A. Ciufolini, Tetrahedron Lett. 1995, 36, 5681-5682. The use of freshly prepared Cd/Pb turned out to be essential. Moreover, it should be noted that the yields were time-dependent. Deprotection over an extended period of time led to side reactions to afford highly polar products which were quite difficult to isolate. Most probably, the by-products may arise from hydrolysis of the tert-butylbenzoyl group.
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Dong, Q.1
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B. Castro, J.-R. Dormoy, G. Evin, C. Selve, Tetrahedron Lett. 1975, 16, 1219-1222.
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72
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3142716819
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-
note
-
Blasticidin S purified by this method is considered to be a zwitterion as depicted in i. (Diagram presented).
-
-
-
-
73
-
-
3142718302
-
-
note
-
Since the salt-free blasticidin S gradually decomposes to give cytomycin 55, NMR spectra of our synthetic sample were immediately measured in 1 N DCl after purification, since this provides stable blasticidin S hydrochloride.
-
-
-
-
74
-
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3142675810
-
-
note
-
The overall yield, including the cytosine N-glycosylation step (31→ 32), is calculated to be 44% (63% multiplied by 0.7).
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-
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