Solid-phase synthesis of bleomycin A5 and three monosaccharide analogues: Exploring the role of the carbohydrate moiety in RNA cleavage

Journal of the American Chemical Society

Volumn 124, Issue 44, 2002, Pages 12926-12927

  Thomas, Craig J ^a   Chizhov, Alexander O ^a   Leitheiser, Christopher J ^a   Rishel, Michael J ^a   Konishi, Kazuhide ^a   Tao, Zhi Fu ^a   Hecht, Sidney M ^a  

^a UNIVERSITY OF VIRGINIA   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

ANTINEOPLASTIC ANTIBIOTIC; BLEOMYCIN A5; MANNOSE; MONOSACCHARIDE; RHAMNOSE;

ARTICLE; DRUG DNA BINDING; DRUG STRUCTURE; RNA CLEAVAGE; SOLID PHASE EXTRACTION; STRUCTURE ANALYSIS;

BASE SEQUENCE; BLEOMYCIN; DNA; MOLECULAR SEQUENCE DATA; MONOSACCHARIDES; NUCLEIC ACID CONFORMATION; RNA; STRUCTURE-ACTIVITY RELATIONSHIP;

EID: 0037032261     PISSN: 00027863     EISSN: None     Source Type: Journal    
DOI: 10.1021/ja0208916     Document Type: Article

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23. 10,12 The resin-bound dipeptide derived from 6 (used for the synthesis of 1) was produced in 43% yield from the initial resin: the resin-bound dipeptide derived from 7 (employed for the syntheses of 3-5) was obtained in yields >75%.
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29. Removal of the NBS group from resin 7 and its coupling products required repeated exposure to the sodium salt of thiophenol. This treatment removed the carbamoyl group from the disaccharide of 1, prompting the use of resin-bound Boc-protected spermidine 6 for the synthesis of 1. Deprotection of both Boc and trityl groups from resin-bound 1 was accomplished by treatment with TFA, isopropylsilane, and dimethyl sulfide. Following deprotection, fully functionalized BLM A5 (1) was removed from the resin using 20% hydrazine in DMF, which also effected disaccharide moiety deacetylation. The monosaccharide derivatives, lacking the carbamoyl group, were prepared using the NBS-protected spermidine resin 7.
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