Synthesis and structure-activity relationships of novel 3'-Hty- substituted pneumocandins

Bioorganic and Medicinal Chemistry Letters

Volumn 7, Issue 22, 1997, Pages 2879-2884

  Black, Regina M ^a   Balkovec, James M ^a   Nollstadt, Karl M ^a   Dreikorn, Sarah ^a   Bartizal, Kenneth F ^a   Abruzzo, George K ^a  

^a MERCK RESEARCH LABORATORIES   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

BETA 1,3 GLUCAN; PNEUMOCANDIN DERIVATIVE;

ANTIFUNGAL ACTIVITY; ARTICLE; BINDING SITE; CANDIDA ALBICANS; DRUG SYNTHESIS; FUNGICIDAL ACTIVITY; HYDROGEN BOND; MASS SPECTROMETRY; PROTON NUCLEAR MAGNETIC RESONANCE; STRUCTURE ACTIVITY RELATION;

CANDIDA ALBICANS;

EID: 0030670334     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(97)10107-X     Document Type: Article

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13. 2, 0.24 mL, 0.24 mmol) was added dropwise to the DMF solution. After 30 min, analytical HPLC (Zorbax C8, 50/50 water acetonitrile, 2 mL/min, 210 nm detection) showed no change in the product ratios (1:1:1 1a: mono-iodinated 2a: diiodinated 3a). Neutralization with sodium acetate (1 equiv) followed by purification via preparative HPLC (Zorbax C8, 50/50 water/acetonitrile, 10 mL/min, 230 nm detection) gave 30 mg (11%) of monoiodinated product 2a and 60 mg (19%) of diiodinated product 3a. Nitration: Compound la (2.00 g, 1.88 mmol) was dissolved in 50 mL of glacial acetic acid. An aqueous solution of NaNO2 (1.0 N, 4.0 mL, 4.0 mmol) was added and the mixture was stirred at room temperature for 20 h. The resultant dark yellow solution was concentrated in vacuo to give a dark orange solid. Purification by preparative HPLC (DeltaPak C18, 55/45 to 45/55 water/acetonitrile gradient elution, 230 and 277 nm detection) gave 1.34 g (64%) of 4a as a yellow solid after lyophilization.
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