Total synthesis of cyclic tetrapeptide FR235222, a potent immunosuppressant that inhibits mammalian histone deacetylases.
[structure: see text] The total synthesis of FR235222, a potent immunosuppressant with in vivo activities, has been achieved. The key steps include assembling its (2S,9R)-2-amino-9-hydroxy-8-oxodecanoic acid residue via an olefin cross-metathesis of a methyl (R)-lactate-derived homoallyl ketone with protected allyl amino acid and constructing its trans-(2R,4S)-4-methylproline unit from protected (R)-pyroglutamic acid in seven steps.
Xie
Weiqing
W
State Key Laboratory of Bioorganic and Natural Products Chemistry, Shanghai Institute of Organic Chemistry, Chinese Academy of Sciences, 354 Fenglin Lu, Shanghai 200032, China.
Zou
Bin
B
Pei
Duanqing
D
Ma
Dawei
D
D000164:Acremonium / Q000737:chemistry / Q000302:isolation & purification; D000818:Animals; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D056572:Histone Deacetylase Inhibitors; D007166:Immunosuppressive Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D051379:Mice; D015394:Molecular Structure; D010456:Peptides, Cyclic / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011761:Pyrrolidonecarboxylic Acid / Q000737:chemistry; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D004791:Enzyme Inhibitors; C474179:FR 235222; D056572:Histone Deacetylase Inhibitors; D007166:Immunosuppressive Agents; D010456:Peptides, Cyclic; D011761:Pyrrolidonecarboxylic Acid