[医学]天然药物化学第二讲.ppt

Antibiotics Nonribosomal Peptides Antibiotics Nonribosomal Peptides Last resort for against drug-resistant pathogens Nonribosomal Peptides Hybrid NRP-PK Nonribosomal Peptides Hybrid NRP-PK --- C-aminated Nonribosomal Peptides Hybrid NRP-PK --- N-acylated Nonribosomal Peptides Acyl Thioester General Chemistry Aldol and Claisen Condensation Aldol and Claisen Condensation Aldol and Claisen Condensation Malonyl CoA: activated acetyl CoA Malonyl CoA: activated acetyl CoA Overall Biosynthetic Scheme Bacterial Aromatic Polyketides Bacterial Aromatic Polyketides Bacterial Aromatic Polyketides Bacterial Reduced Polyketides A, Acetate; P, Propionate; B, Butyrate; G, Glycerol; S, Starter from branched chain or cyclic units Bacterial Reduced Polyketides Bacterial Reduced Polyketides Fungal Aromatic Polyketides(Non-reduced/Partially Reduced Polyketides) Orsellinic acid Tetrahydroxynaphthalene (THN) 6-Methylsalicylic acid (MSA) Norsolorinic acid Fungal Aromatic Polyketideswith unusual features --- mixed reduced/non-reduced Unusual acetate label Unusual starter Unusual mix Fungal Highly Reduced Polyketides T-toxin Mevacor Statins ?–hydroxy-?-methylglutaryl-CoA (HMG-CoA). Fungal Aromatic Polyketides(Non-reduced/Partially Reduced Polyketides) Orsellinic acid Tetrahydroxynaphthalene (THN) 6-Methylsalicylic acid (MSA) Norsolorinic acid Plant Polyketides(Bacterial polyketides made by the same type of PKS) chalcone in higher plants 1,3,6,8-tetrahydroxynaphthalene (THN) in Streptomyces griseus and S. coelicolor 3,5-dihydroxyphenylacetic acid (DHPA) in Amycolatopsis mediterranei and A. orientalis Plant Polyketides(Starter: Phenylpropanhoid Pathway) chalcone Plant Polyketides(Bacterial polyketides made by the same type of PKS) chalcone in higher plants 1,3,6,8-tetrahydroxynaphthalene (THN) in Streptomyces griseus and S. coelicolor 3,5-dihydroxyphenylacetic acid (DHPA) in Amycolatopsis mediterranei and A. orientalis Nonribosomal Peptides Antibiotics Nonribosomal Peptide