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Volumn 10, Issue 13, 2004, Pages 3241-3251

Total synthesis of (+)-blasticidin S

Author keywords

Amino acids; Blasticidin S; Natural products; Rearrangement; Total synthesis

Indexed keywords

AMINO ACIDS; CARBOXYLIC ACIDS; STEREOCHEMISTRY; SYNTHESIS (CHEMICAL);

EID: 3142766959     PISSN: 09476539     EISSN: None     Source Type: Journal    
DOI: 10.1002/chem.200305358     Document Type: Article
Times cited : (36)

References (74)
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  • 2
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    • Blasticidin S and related peptidyl nucleoside antibiotics
    • (Ed.: W. R. Strohl), Marcel Dekker, New York
    • S. J. Gould, Blasticidin S and Related Peptidyl Nucleoside Antibiotics (Ed.: W. R. Strohl), Biotechnology of Antibiotics, Marcel Dekker, New York, 1997, p. 703.
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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;
    • (1998) Acc. Chem. Res. , vol.31 , pp. 173-180
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  • 19
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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).
    • (1999) Acc. Chem. Res. , vol.32 , pp. 624-630
    • Nielsen, P.E.1
  • 28
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    • For representative examples of the allyl cyanate-to-isocyanate rearrangement, see the following references: a) C. Christophersen, A. Holm, Acta Chem. Scand. 1970, 24, 1512-1526;
    • (1970) Acta Chem. Scand. , vol.24 , pp. 1512-1526
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    • d) K. Banert, Angew. Chem. 1992, 104, 865-867; Angew. Chem. Int. Ed. Engl. 1992, 31, 866-868.
    • (1992) Angew. Chem. , vol.104 , pp. 865-867
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    • d) K. Banert, Angew. Chem. 1992, 104, 865-867; Angew. Chem. Int. Ed. Engl. 1992, 31, 866-868.
    • (1992) Angew. Chem. Int. Ed. Engl. , vol.31 , pp. 866-868
  • 35
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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.
    • (1977) J. Chem. Soc. Perkin Trans. 1 , pp. 657-660
    • Isido, Y.1    Nakazaki, N.2    Sakairi, N.3
  • 37
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    • S. Hanessian, P. C. Tyler, Y. Chapleur, Tetrahedron Lett. 1981, 22, 4583-4586. For a useful preparative procedure for the mol-scale synthesis of 14, see Experimental Section.
    • (1981) Tetrahedron Lett. , vol.22 , pp. 4583-4586
    • Hanessian, S.1    Tyler, P.C.2    Chapleur, Y.3
  • 41
    • 3142656673 scopus 로고    scopus 로고
    • 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).
  • 42
    • 0030462737 scopus 로고    scopus 로고
    • 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).
    • (1996) J. Am. Chem. Soc. , vol.118 , pp. 13095-13096
    • Smith, A.B.1    Ott, G.R.2
  • 43
    • 3142708071 scopus 로고    scopus 로고
    • 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
    • 3142680270 scopus 로고    scopus 로고
    • 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.
  • 46
    • 84982058693 scopus 로고
    • 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;
    • (1981) Chem. Ber. , vol.114 , pp. 1256-1268
    • Vorbrüggen, H.1    Höfle, G.2
  • 51
    • 3142697806 scopus 로고    scopus 로고
    • 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
    • 3142699290 scopus 로고    scopus 로고
    • note
    • 2O, pyridine). The mechanism to form i is unclear. (Diagram presented).
  • 63
    • 3142777177 scopus 로고    scopus 로고
    • 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
    • 3142741733 scopus 로고    scopus 로고
    • 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.
  • 68
    • 0029160623 scopus 로고
    • 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.
    • (1995) Tetrahedron Lett. , vol.36 , pp. 5681-5682
    • Dong, Q.1    Anderson, E.2    Ciufolini, M.A.3
  • 72
    • 3142716819 scopus 로고    scopus 로고
    • note
    • Blasticidin S purified by this method is considered to be a zwitterion as depicted in i. (Diagram presented).
  • 73
    • 3142718302 scopus 로고    scopus 로고
    • 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
    • 3142675810 scopus 로고    scopus 로고
    • note
    • The overall yield, including the cytosine N-glycosylation step (31→ 32), is calculated to be 44% (63% multiplied by 0.7).


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.