Compounds for Increasing Lipid Synthesis and Storage

Abstract

This invention relates to methods for increasing lipid accumulation and lipid production in cells. Methods of producing biofuel from cells and preparing nutraceuticals comprising lipids produced according to a method provided herein are also provided.

1 . A method of increasing lipid accumulation in a freshwater algal cell, comprising contacting the cell with an effective amount of a compound of Formula Ia: 
       
         
           
           
               
               
           
         
       
       or a salt thereof, wherein:
 L is selected from the group consisting of, C 1-4  alkylene, and —(C 1-4  alkylene)-NR L -(C 1-4  alkylene); 
 R L  is selected from the group consisting of H and methyl; 
 R 3  is H; 
 R 4  is; 
 Cy 1  is selected from the group consisting of phenyl; 
 R Cy  is selected from the group consisting of halo, C 1-4  alkyl, C 1-4  alkoxy, phenyl, —(C 1-4  alkylene)-(phenyl), C 3-10  cycloalkyl, and —(C 1-4  alkylene)-(C 3-10  cyloalkyl), wherein each phenyl and the phenyl group of —(C 1-4  alkylene)-(phenyl) is optionally substituted by 1 or 2 substituents independently selected from the group consisting of OH, halo, C 1-4  alkyl, and C 1-4  alkoxy; 
 n is 0 or 1; and 
 p is 0, 1, 2, or 3; or 
 a compound of Formula Ila: 
 
       
         
           
           
               
               
           
         
       
       or a salt thereof, wherein:
 L 1  is selected from the group consisting of a bond and C 1-4  alkylene: 
 R 1a  is selected from the group consisting of, C 5-10  cycloalkyl, 8-10 membered heteroaryl, phenyl, and 10-13 membered heteroaryl, wherein the C 5-10  cycloalkyl and phenyl are each optionally substituted by 1, 2, or 3 substituents independently selected from the group consisting of halo, OH, NO 2 , C 1-4  alkyl, and C 1-4  alkoxy, and wherein the 10-13 membered heteroaryl is optionally substituted by one halo group; 
 R 2  is selected from the group consisting of H, halo, OH, NO 2 , C 1-4  alkyl, and C 1-4  alkoxy; 
 R 3  is selected from the group consisting of H, halo, and C 1-4  alkoxy; 
 R 4  is selected from the group consisting of H, OH, and C 1-4  alkoxy; 
 R 5  is selected from the group consisting of H, halo, and C 1-4  alkoxy; and 
 R 6  is; or 
 a compound of Formula IIIa: 
 
       
         
           
           
               
               
           
         
       
       or a salt thereof, wherein:
 L 1  is selected from the group consisting of, NH and N(C 1-4  alkyl); 
 R 1a  is selected from the group consisting of H, C 1-4  alkyl, C 2-4  alkenyl, C 1-4  cyanoalkylene, NH(C 1-4  alkyl), and NH(C 2-4  alkenyl); 
 L 2  is; and 
 R 2a  is selected from the group consisting of H, C 1-4  hydroxyalkyl, —SO 2 (C 1-4  alkyl). 
 
     
     
         2 . The method of  claim 1 , wherein the compound is a compound of Formula Ia. 
     
     
         3 . The method of  claim 1 , wherein the compound is a compound of Formula IIa. 
     
     
         4 . The method of  claim 1 , wherein the compound is a compound of Formula IIIa. 
     
     
         5 .- 6 . (canceled) 
     
     
         7 . The method of  claim 1 , wherein the freshwater algal cell is a  Chlorophyceae  cell. 
     
     
         8 . The method of  claim 1 , wherein the freshwater algal cell is selected from the group consisting of a  Chlamydomonas  cell, a  Chlorella  cell, a  Tetrachlorella  cell, and a  Nannochloropsis  cell. 
     
     
         9 .- 18 . (canceled) 
     
     
         19 . The method of  claim 1 , wherein the contacting the cell with the compound does not reduce the rate of cellular growth compared to a cell that has not been contacted by the compound. 
     
     
         20 .- 21 . (canceled) 
     
     
         22 . The method of  claim 1 , wherein the lipid accumulation is increased without exposing the cell to environmental stress. 
     
     
         23 . The method of  claim 22 , wherein the environmental stress comprises nutrient deprivation. 
     
     
         24 .- 49 . (canceled) 
     
     
         50 . The method of  claim 2 , wherein L is C 1-4  alkylene. 
     
     
         51 . The method of  claim 2 , wherein each R Cy  is an independently selected C 1-4  alkoxy. 
     
     
         52 . The method of  claim 2 , wherein p is 1 or 2. 
     
     
         53 . The method of  claim 3 , wherein L 1  is a bond. 
     
     
         54 . The method of  claim 3 , wherein R 1a  is phenyl substituted by C 1-4  alkoxy. 
     
     
         55 . The method of  claim 3 , wherein R 2  is OH. 
     
     
         56 . The method of  claim 3 , wherein R 3 , R 4 , and R 5  are each H. 
     
     
         57 . The method of  claim 4 , wherein L 1  is NH. 
     
     
         58 . The method of  claim 4 , wherein R 1a  is C 1-4  cyanoalkylene. 
     
     
         59 . The method of  claim 4 , wherein R 2a  is H. 
     
     
         60 . The method of  claim 1 , wherein the compound is selected from the group consisting of: 
       
         
           
           
               
               
           
         
       
       or a salt thereof.