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Volumn 64, Issue 21, 2008, Pages 4778-4791

The syntheses of rac-inthomycin A, (+)-inthomycin B and (+)-inthomycin C using a unified synthetic approach

Author keywords

[No Author keywords available]

Indexed keywords

ACETAL DERIVATIVE; AMINO ACID DERIVATIVE; INTHOMYCIN A; INTHOMYCIN B; INTHOMYCIN C; NATURAL PRODUCT; OXAZOLE DERIVATIVE; UNCLASSIFIED DRUG;

EID: 42249110694     PISSN: 00404020     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tet.2008.01.116     Document Type: Article
Times cited : (43)

References (64)
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    • Note added in proof: after the submission of this paper a second synthesis of neooxazolomycin was reported ( )
    • Note added in proof: after the submission of this paper a second synthesis of neooxazolomycin was reported (. Onyango E.O., Tsurumoto J., Imai N., Takahashi K., Ishihara J., and Hatakeyama S. Angew. Chem., Int. Ed. 46 (2007) 6703-6705 )
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    • These model studies were based on the following transformation:
    • These model studies were based on the following transformation:
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    • {A figure is presented}The R- and S- enantiomers of I were separated using HPLC with a Daicel Chiralcel OD column, eluting with 9:1 hexane-isopropanol. Variation of solvent, stoichiometry of reagents, times and temperatures gave ee's in the range 53-84% (with yields generally in the 80-90% range). The optimum ee was obtained using the l-valine-derived oxazaborolidinone 25a (84% ee) but the l-phenylalanine-derived oxazaborolidinone 25b was also effective giving I in 82% ee.
    • {A figure is presented}The R- and S- enantiomers of I were separated using HPLC with a Daicel Chiralcel OD column, eluting with 9:1 hexane-isopropanol. Variation of solvent, stoichiometry of reagents, times and temperatures gave ee's in the range 53-84% (with yields generally in the 80-90% range). The optimum ee was obtained using the l-valine-derived oxazaborolidinone 25a (84% ee) but the l-phenylalanine-derived oxazaborolidinone 25b was also effective giving I in 82% ee.
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    • Copper thiophene carboxylate-induced coupling ( ) was investigated to avoid the presence of palladium. However, this procedure gave triene 27 in only 20% yield with complete isomerisation
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    • A range of conditions were investigated for the direct conversion of ester I (R=Me) into the required primary amide II but without success. With acid I (R=H) a number of peptide coupling procedures were explored, the most promising of which utilised HATU in THF (83%), HBTU (69%) and EDCI·HCl/HOBt (29%).{A figure is presented}
    • A range of conditions were investigated for the direct conversion of ester I (R=Me) into the required primary amide II but without success. With acid I (R=H) a number of peptide coupling procedures were explored, the most promising of which utilised HATU in THF (83%), HBTU (69%) and EDCI·HCl/HOBt (29%).{A figure is presented}
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    • The ease with which aldehyde Z,Z-16 undergoes isomerisation meant that this modified approach could not be employed to prepare inthomycin A.
    • The ease with which aldehyde Z,Z-16 undergoes isomerisation meant that this modified approach could not be employed to prepare inthomycin A.


* 이 정보는 Elsevier사의 SCOPUS DB에서 KISTI가 분석하여 추출한 것입니다.