Antifungal lipopeptides: Structure-activity relationships of 3-hydroxyglutamine-modified pneumocandin B0 derivatives

Robert A. Zambias; Catherine James; Milton L. Hammond; George K. Abruzzo; Kenneth F. Bartizal; Karl H. Nollstadt; Cameron Douglas; Jean Marrinan; James M. Balkovec

doi:10.1016/0960-894X(95)00407-K

Antifungal lipopeptides: Structure-activity relationships of 3-hydroxyglutamine-modified pneumocandin B₀ derivatives

Robert A. Zambias
, Catherine James
, Milton L. Hammond
, George K. Abruzzo
, Kenneth F. Bartizal
, Karl H. Nollstadt
, Cameron Douglas
, Jean Marrinan
, James M. Balkovec

Center for Discovery and Innovation

Merck

Research output: Contribution to journal › Article › peer-review

8 Scopus citations

Abstract

Selective methanolysis or dehydration followed by reduction of the 3-hydroxyglutamine residue of pneumocandin B₀ (1) or its dideoxy analog 5 (L-692,289) gave the methyl 3-hydroxyglutamate and 3-hydroxyornithine analogs 6 and 9, respectively. Further derivatization of these analogs allowed a study of the SAR at this position. In general, carboxylic acid-containing derivatives were poorer antifungal agents than neutral derivatives while amine-bearing analogs displayed the greatest potency.

Original language	English
Pages (from-to)	2357-2362
Number of pages	6
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	5
Issue number	20
DOIs	https://doi.org/10.1016/0960-894X(95)00407-K
State	Published - 19 Oct 1995

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Zambias, R. A., James, C., Hammond, M. L., Abruzzo, G. K., Bartizal, K. F., Nollstadt, K. H., Douglas, C., Marrinan, J., & Balkovec, J. M. (1995). Antifungal lipopeptides: Structure-activity relationships of 3-hydroxyglutamine-modified pneumocandin B₀ derivatives. Bioorganic and Medicinal Chemistry Letters, 5(20), 2357-2362. https://doi.org/10.1016/0960-894X(95)00407-K

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title = "Antifungal lipopeptides: Structure-activity relationships of 3-hydroxyglutamine-modified pneumocandin B0 derivatives",

abstract = "Selective methanolysis or dehydration followed by reduction of the 3-hydroxyglutamine residue of pneumocandin B0 (1) or its dideoxy analog 5 (L-692,289) gave the methyl 3-hydroxyglutamate and 3-hydroxyornithine analogs 6 and 9, respectively. Further derivatization of these analogs allowed a study of the SAR at this position. In general, carboxylic acid-containing derivatives were poorer antifungal agents than neutral derivatives while amine-bearing analogs displayed the greatest potency.",

author = "Zambias, \{Robert A.\} and Catherine James and Hammond, \{Milton L.\} and Abruzzo, \{George K.\} and Bartizal, \{Kenneth F.\} and Nollstadt, \{Karl H.\} and Cameron Douglas and Jean Marrinan and Balkovec, \{James M.\}",

year = "1995",

month = oct,

day = "19",

doi = "10.1016/0960-894X(95)00407-K",

language = "English",

volume = "5",

pages = "2357--2362",

journal = "Bioorganic and Medicinal Chemistry Letters",

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T1 - Antifungal lipopeptides

T2 - Structure-activity relationships of 3-hydroxyglutamine-modified pneumocandin B0 derivatives

AU - Zambias, Robert A.

AU - James, Catherine

AU - Hammond, Milton L.

AU - Abruzzo, George K.

AU - Bartizal, Kenneth F.

AU - Nollstadt, Karl H.

AU - Douglas, Cameron

AU - Marrinan, Jean

AU - Balkovec, James M.

PY - 1995/10/19

Y1 - 1995/10/19

N2 - Selective methanolysis or dehydration followed by reduction of the 3-hydroxyglutamine residue of pneumocandin B0 (1) or its dideoxy analog 5 (L-692,289) gave the methyl 3-hydroxyglutamate and 3-hydroxyornithine analogs 6 and 9, respectively. Further derivatization of these analogs allowed a study of the SAR at this position. In general, carboxylic acid-containing derivatives were poorer antifungal agents than neutral derivatives while amine-bearing analogs displayed the greatest potency.

AB - Selective methanolysis or dehydration followed by reduction of the 3-hydroxyglutamine residue of pneumocandin B0 (1) or its dideoxy analog 5 (L-692,289) gave the methyl 3-hydroxyglutamate and 3-hydroxyornithine analogs 6 and 9, respectively. Further derivatization of these analogs allowed a study of the SAR at this position. In general, carboxylic acid-containing derivatives were poorer antifungal agents than neutral derivatives while amine-bearing analogs displayed the greatest potency.

UR - https://www.scopus.com/pages/publications/0028785615

U2 - 10.1016/0960-894X(95)00407-K

DO - 10.1016/0960-894X(95)00407-K

M3 - Article

AN - SCOPUS:0028785615

SN - 0960-894X

VL - 5

SP - 2357

EP - 2362

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 20

ER -

Antifungal lipopeptides: Structure-activity relationships of 3-hydroxyglutamine-modified pneumocandin B₀ derivatives

Abstract

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