Track topics on Twitter Track topics that are important to you
Paenibacterin is a recently discovered cyclic lipodepsipeptide antibiotic produced by the soil bacterium Paenibacillus thiaminolyticus. It is produced as a mixture of three compounds with isomeric 15-carbon acyl lipids, designated P-A1 (linear lipid), P-A2 (anteiso lipid), and P-A3 (iso lipid). Here, we report the total synthesis of P-A1 and P-A2, as well as two analogues of P-A1 in which the threonine residue in P-A1 was replaced with l-2,3-diaminopropionic acid (P-A1-Dapa) and (2 S,3 R)-2,3-diaminobutyric acid (P-A1-Daba), converting the ring-closing ester bond to an amide bond. Solid phase peptide chemistry was used to prepare branched precursors which were cyclized off-resin to obtain the target peptides in good to excellent overall yields. The use of a pseudoproline dipeptide building block was found to be important for obtaining good yields. The antibacterial activity of the peptides was determined against Escherichia coli K-12 (G) and Bacillus subtilis 1046 (G). The minimum inhibitory concentrations of P-A1 and P-A2 were the same despite the variation in the structure of the acyl tail. Replacing the ring-closing ester bond with an amide bond had little or no effect on activity. The synthetic routes developed here should prove to be useful for creating new antibiotics based on the structure of paenibacterin.
This article was published in the following journal.
Name: The Journal of organic chemistry
Streamlined Total Synthesis of Shishijimicin A and Its Application to the Design, Synthesis, and Biological Evaluation of Analogues thereof and Practical Syntheses of PhthNSSMe and Related Sulfenylating Reagents.
Shishijimicin A is a scarce marine natural product with highly potent cytotoxicities, making it a potential payload or a lead compound for designed antibody-drug conjugates. Herein, we describe an imp...
Comprised of a large collection of structurally diverse molecules, the prostaglandins exhibit a wide range of biological properties. Among them are Δ12-prostaglandin J2 (Δ12-PGJ2) and Δ12-prostagla...
Surfactin has antiviral activity against various enveloped viruses by inhibiting viral membrane fusion. However, the potential utility of surfactin as an antiviral drug is limited by its cytotoxicity....
The first total synthesis of violaceoid A, a cytotoxic agent, and the asymmetric total synthesis of (-)- and (+)-violaceoid B are reported. The precursor was accessed by desymmetrization of a substitu...
The aim of this study is to elucidate whether GLP-1 analogues influence not only appetite but also thirst perception. It is hypothesized that GLP-1 analogues reduce fluid intake in healthy...
The purpose of this study is to examine the correlation between UGT1A1 genotypes and the safety of CPT-11 plus platinum analogues (cisplatin, carboplatin and nedaplatin) regimens for patie...
The purpose of this study is to determine if diabetic retinopathy can be treated with prostaglandin analogues, prostaglandin synthesis inhibitors or carbonic anhydrases inhibitors.
Cholesterol is the precursor of glucocorticoids, mineralocorticoids and sex steroids. Both adrenal and non-adrenal (ovarian + testicular) all steroid hormones are primarily synthesized usi...
This study will evaluate hyperemia and ocular surface tolerability in patients on prostaglandin analogues
A potent, non-nucleoside reverse transcriptase inhibitor used in combination with nucleoside analogues for treatment of HIV infection and AIDS.
Distention of KIDNEY with the presence of PUS and suppurative destruction of the renal parenchyma. It is often associated with renal obstruction and can lead to total or nearly total loss of renal function.
A subtype of von Willebrand disease that results from a total or near total deficiency of VON WILLEBRAND FACTOR.
A procedure in which total right atrial or total caval blood flow is channeled directly into the pulmonary artery or into a small right ventricle that serves only as a conduit. The principal congenital malformations for which this operation is useful are TRICUSPID ATRESIA and single ventricle with pulmonary stenosis.
The total absence of teeth from either the mandible or the maxilla, but not both. Total absence of teeth from both is MOUTH, EDENTULOUS. Partial absence of teeth in either is JAW, EDENTULOUS, PARTIALLY.