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1.
Chemistry ; 6(17): 3095-115, 2000 Sep 01.
Article in English | MEDLINE | ID: mdl-11002992

ABSTRACT

In this first of a series of four articles we introduce everninomicin 13,384-1 (1), a powerful antibiotic effective against drug resistant bacteria, as a target for total synthesis and discuss its retrosynthetic analysis. From the three defined fragments required for the synthesis (2: A1B(A)C fragment; 4: DE fragment; 5: FGHA2 fragment), we describe herein two approaches to the A1B(A)C block. The first strategy relied on an olefin metathesis reaction to construct a common intermediate for rings B and C, but was faced with final protecting group problems. The second, and successful approach, involved a 1,2-phenylsulfeno migration and a sulfur directed glycosidation procedure to link rings B and C, as well as an acyl fluoride intermediate to install the sterically hindered aryl ester moiety (ring A1). The final stages of the synthesis of the required 2-phenylseleno glycosyl fluoride 2 required introduction of a phenylseleno group at C-1 of ring C followed by a novel, DAST-promoted 1,2-migration to produce the desired 2-beta-phenylseleno glycosyl fluoride moiety.


Subject(s)
Aminoglycosides , Anti-Bacterial Agents/chemical synthesis , Anti-Bacterial Agents/chemistry , Molecular Structure , Spectrum Analysis
2.
Bioorg Med Chem ; 8(1): 215-22, 2000 Jan.
Article in English | MEDLINE | ID: mdl-10968280

ABSTRACT

The DNA helix destabilizing activity of a series of cyclobisintercaland compounds (CBIs) has been evaluated by measuring their ability to displace a 32P-labelled oligonucleotide primer (17-mer) hybridized to the single stranded DNA of M13. This destabilizing activity appears to be strongly dependent on the cyclic structure (the linear acyclic references are inactive) and the size of the macrocycle; both features being known to determine the preferential binding of the compound to ssDNA. Interestingly, CBIs induced the dissociation of the duplex template in a concentration range (0.5-1 microM) close to that required for the destabilizing activity of single stranded DNA binding proteins (SSBs). Therefore competition experiments between CBIs and an SSB protein (Eco SSB) for binding to a single stranded oligonucleotide target (36-mer) have been performed through gel electrophoresis and nitrocellulose binding assays and strong inhibitory effects on the formation of the SSB:36-mer complex have been observed.


Subject(s)
DNA-Binding Proteins/chemistry , DNA/chemistry , Intercalating Agents/chemistry , Base Sequence , Binding, Competitive , DNA/metabolism , DNA-Binding Proteins/metabolism , Protein Denaturation
4.
Angew Chem Int Ed Engl ; 38(22): 3334-3339, 1999 Nov 15.
Article in English | MEDLINE | ID: mdl-10602188

ABSTRACT

The powerful antibiotic everninomicin 13,384-1 (1, Ziracin) has been prepared for the first time through a total synthesis. The 1-->1'-disaccharide and the two orthoesters of this target molecule were introduced by new methodologies using a tin acetal and 1,2-phenylseleno migrations. The reaction sequence also relies on stereoselective glycosidations and subtle manipulations of protecting groups. In addition to the introduction of new synthetic methodologies, this total synthesis should allow the preparation of combinatorial libraries of semisynthetic analogues of this highly promising antibiotic for biological screening purposes.

5.
Angew Chem Int Ed Engl ; 38(16): 2447-2451, 1999 Aug.
Article in English | MEDLINE | ID: mdl-10458817

ABSTRACT

The immunosuppressive agent sanglifehrin A has been prepared for the first time by total synthesis. The construction of the macrocyclic unit of the target molecule was achieved through a selective intramolecular Stille coupling, and the spirolactam unit by Paterson-aldol reactions. The final steps involve an intermolecular Stille coupling and the opening of the internal acetal unit. This convergent synthesis opens the way for the synthesis of libraries of novel sanglifehrin analogues for biological screening.

6.
La Paz; Chemonics International Inc; diciembre 1998. 35 p. tab, graf.
Monography in Spanish | LIBOCS, LIBOSP | ID: biblio-1335875

ABSTRACT

Mayor cuota de mercado en la micro y pequeña empresa. Servicios no financieroa autosostenibles. Eficiencia y calidad de los servicios. Calidad de Servicios

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