Analogs of N-4909 (1), which had a stimulating activity for apolipoprotein E (apo E) secretion in Human hepatoma Hep G2 cells, were prepared and their activities examined. Cyclic analogs which had different kinds of amino acids or different number of amino acids from N-4909 (1) showed less effect on apo E secretion from Hep G2 cells. The length of acyl chain was found to be an important factor for the activity. Shorter chain reduced the activity. Linear analogs were also prepared. One of their analogs, N-5849 (17), which had six amino acids was found to have strong activity.

1999-01-01·The Journal of Antibiotics4区 · 医学

Solid-Phase Synthesis of Cyclooctadepsipeptide N-4909 Using a Cyclization-Cleavage Method with Oxime Resin.

4区 · 医学

Article

作者: Makoto Yanai ; Toshio Suguro

Cyclooctadepsipeptide N 4909 I (R¹ = OH) was prepared using a cyclization-cleavage method with oxime resin.Tetradecanoic acid derivative II (preparation given) was coupled with the oxime resin using O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate (HATU) and deprotected with TFA/CH₂Cl₂ then coupled with Boc-D-Leu-OH using HATU.This procedure was repeated using other amino acid reactants to give oxime resin bound depsipeptide III (Boc = Me₃CO₂C) which was deprotected and then cleaved along with cyclization using Et₃N and acetic acid to give cyclized depsipeptide I (R¹ = OCH₂Ph) in 43% yield.The benzyl protecting group on aspartic acid was removed to give N 4909 I (R¹ = OH).The authors plan to use this method to develop a combinatorial library of N 4909 analogs.

1999-01-01·The Journal of Antibiotics4区 · 医学

First Total Synthesis of N-4909 and Its Diastereomer; A Stimulant of Apolipoprotein E Secretion in Human Hepatoma Hep G2 Cells.

4区 · 医学

Article

作者: Makoto Yanai ; Shigeru Hiramoto

Both (R)- and (S)-3-hydroxy-13-methyltetradecanoic acids were prepared via a lipase-catalyzed enantioselective acylation. The total synthesis of N-4909 and its diastereomer were achieved by a coupling of either (R)- or (S)-3-hydroxy-13-methyltetradecanoic acid moiety with a hexapeptide moiety and by a cyclization with HATU (O-(7-azabenzotriazol-1-yl)-1,1,3,3-tetramethyluronium hexafluorophosphate) and HOAt (1-hydroxy-7-azabenzotriazole) in a high dilution condition. The R configuration of 3-hydroxy-13-methyltetradecanoic acid was found to be important for stimulating the activity of apolipoprotein E secretion in human hepatoma Hep G2 cells.

100 项与 N-4909 相关的药物交易

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