Eun Lee

Bio: Eun Lee is an academic researcher from UPRRP College of Natural Sciences. The author has contributed to research in topics: Radical cyclization & Total synthesis. The author has an hindex of 28, co-authored 101 publications receiving 2250 citations. Previous affiliations of Eun Lee include Seoul National University.

Total Synthesis of Oxacyclic Macrodiolide Natural Products

Abstract: 1. Intoduction 4348 2. Oxolane Macrodiolides 4348 2.1. Pamamycin 607 (1) 4348 2.1.1. Thomas Total Synthesis20 4349 2.1.2. Lee Total Synthesis28 4351 2.1.3. Metz Total Synthesis35 4353 2.1.4. Kang Total Synthesis41 4354 2.2. Amphidinolide X (2) 4356 2.2.1. Fürstner Total Synthesis59 4356 3. Oxane/Oxene Macrodiolides 4359 3.1. SCH 351448 (3) 4359 3.1.1. Lee Total Synthesis71 4359 3.2. Swinholide A (4) 4360 3.2.1. Paterson Total Synthesis82 4360 3.2.2. Nicolaou Total Synthesis83 4360 4. Cyclic Acetal Macrodiolides 4362 4.1. Cycloviracin B1 (5) 4362 4.1.1. Fürstner Total Synthesis96 4363 4.2. Glucolipsin A (6) 4366 4.2.1. Fürstner Total Synthesis117 4366 5. Cyclic Hemiketal Macrodiolides 4368 5.1. Boromycin (7) 4368 5.1.1. White Total Synthesis123 4368 5.2. Tartrolon B (8) 4369 5.2.1. Mulzer Total Synthesis130 4370 5.3. Debromoaplysiatoxin (9) and Aplysiatoxin (10) 4373 5.3.1. Kishi Total Synthesis142 4373 6. Conclusions 4375 7. Acknowledgments 4375 8. References 4375

Identification of 4-hydroxyhexanoic acid as a new constituent of biosynthetic polyhydroxyalkanoic acids from bacteria

Abstract: Twenty-four different strains of aerobic Gram-negative bacteria, mainly belonging to the genera Alcaligenes, Paracoccus, Pseudomonas and Methylobacterium, were examined with respect to their ability to utilize 4-hydroxyvaleric acid (4HV), 4-valerolactone (4VL) and 3-hydroxypropionic acid (3HP) as carbon sources for growth and for accumulation of polyhydroxyalkanoic acid (PHA). A gas chromatographic (GC) method for the detection of 3-hydroxyalkanoic acid methyl esters has been extended for the detection of derivatives obtained from the methanolysis of 4-hydroxybutyric acid (4HB) and 4HV. Most of the Alcaligenes species and P. oxalaticus Ox1 accumulated a terpolyester consisting of 3-hydroxybutyric acid (3HB), 3-hydroxyvaleric acid (3HV) and 4HV as constituents from 4HV or 4VL as sole carbon sources in batch, fed-batch or two-stage fed-batch cultures. Poly(3HB-co-3HV-co-4HV) accumulated from 4HV by A. eutrophus strain NCIB 11599 amounted to approximately 50% of the cell dry matter and was composed of 42.0 mol % 3HB, 52.2 mol % 3HV and 5.6 mol % 4HV, respectively. Pseudomonads, which belong to the rRNA homology group I, were not able to incorporate 4HV. With 3HP as carbon source, the GC analysis provided evidence for the presence of 3HP in the PHA of many bacteria. Nuclear magnetic resonance spectroscopic analysis confirmed that, for example, A. eutrophus strain TF93 accumulated poly(3HB-co-3HP) with 98 mol % 3HB and 2 mol % 3HP if the cells were cultivated in the presence of 0.5% (w/v) 3HP.

Biosynthesis of copolyesters consisting of 3-hydroxybutyric acid and medium-chain-length 3-hydroxyalkanoic acids from 1, 3-butanediol or from 3-hydroxybutyrate by Pseudomonas sp. A33.

Abstract: Pseudomonas sp. A33 and other isolates of aerobic bacteria accumulated a complex copolyester containing 3-hydroxybutyric acid (3HB) and various medium-chain-length 3-hydroxyalkanoic acids (3HAMCL) from 3-hydroxybutyric acid or from 1,3-butanediol under nitrogen-limitated culture conditions. 3HB contributed to 15.1 mol/100 mol of the constituents of the polyester depending on the strain and on the cultivation conditions. The accumulated polymer was a copolyester of 3HB and 3HAMCL rather than a blend of poly(3HB) and poly(3HAMCL) on the basis of multiple evidence. 3-Hydroxyhexadecenoic acid and 3-hydroxyhexadecanoic acid were detected as constituents of polyhydroxyalkanoates, which have hitherto not been described, by13C nuclear magnetic resonance or by gas chromatography/mass spectrometric analysis. In total, ten different constituents were detected in the polymer synthesized from 1,3-butanediol by Pseudomonas sp. A33:besides seven saturated (3HB, 3-hydroxyhexanoate, 3-hydroxyoctanoate, 3-hydroxydecanoate, and 3-hydrohexadecanoate) three unsaturated (3-hydroxydodecenoate, 3-hydroxytetradecenoate and 3-hydrohexadecanoate) hydroxyalkanoic acid constituents occured. The polyhydroxyalkanoate synthase of Pseudomonas sp. A33 was cloned, and its substrate specificity was evaluated by heterologous expression in various strains of P. putida, P. oleovorans and Alcaligenes eutrophus.

A carbonyl ylide cycloaddition approach to platensimycin.

Abstract: Platensimycin (1) is a novel broad-spectrum antibiotic (against Gram-positive bacteria) which was isolated from Streptomyces platensis by scientists from Merck: it inhibits bacterial growth by selectively inhibiting the condensing enzyme FabF of the bacterial fatty acid synthesis pathway. Platensimycin (1) shows no cross-resistance to methicillinresistant Staphylococcus aureus, vancomycin-intermediate S. aureus, and vancomycin-resistant enterococci. As a result of its remarkable biological profile and challenging structure, platensimycin (1) has been the focus of intense synthetic activity, and herein we describe the results of our recent efforts towards the synthesis of this intriguing compound. At the outset, a synthesis of the pivotal tetracyclic intermediate 2 from the cagelike ketone A was envisioned (Scheme 1). Rhodium(II)-catalyzed decomposition of a diazoketone D would lead to the formation of A and/or B through [3+2] cycloaddition of the corresponding carbonyl ylide with conformations C and/or C’. This type of cycloaddition in the presence of rhodium(II) acetate is known to favor the formation of B (R = H; A/B/cyclopropanes = 6:41:36), and a reversal of this product distribution seemed necessary to ensure the success of our synthetic approach. In practice, preparation of the quaternary-substituted diazoketone D was problematic. After considerable experimentation, we found that the reaction sequence was successful with R = CN. Thus, diazoketone 6 was prepared from ethyl cyanoacetate (3) in a straightforward manner by sequential alkylation (Scheme 2). In the presence of rhodium(II) acetate, decomposition of diazoketone 6 proceeded smoothly to yield the cagelike ketone 8, accompanied by only a trace amount of the desired product 7, and a small amount of cyclopropane products 9. The use of rhodium(II) trifluoroacetate led to a clean conversion of 6 into 8.

Metabolic Engineering of Poly(3-Hydroxyalkanoates): From DNA to Plastic

Abstract: Poly(3-hydroxyalkanoates) (PHAs) are a class of microbially produced polyesters that have potential applications as conventional plastics, specifically thermoplastic elastomers. A wealth of biological diversity in PHA formation exists, with at least 100 different PHA constituents and at least five different dedicated PHA biosynthetic pathways. This diversity, in combination with classical microbial physiology and modern molecular biology, has now opened up this area for genetic and metabolic engineering to develop optimal PHA-producing organisms. Commercial processes for PHA production were initially developed by W. R. Grace in the 1960s and later developed by Imperial Chemical Industries, Ltd., in the United Kingdom in the 1970s and 1980s. Since the early 1990s, Metabolix Inc. and Monsanto have been the driving forces behind the commercial exploitation of PHA polymers in the United States. The gram-negative bacterium Ralstonia eutropha, formerly known as Alcaligenes eutrophus, has generally been used as the production organism of choice, and intracellular accumulation of PHA of over 90% of the cell dry weight have been reported. The advent of molecular biological techniques and a developing environmental awareness initiated a renewed scientific interest in PHAs, and the biosynthetic machinery for PHA metabolism has been studied in great detail over the last two decades. Because the structure and monomeric composition of PHAs determine the applications for each type of polymer, a variety of polymers have been synthesized by cofeeding of various substrates or by metabolic engineering of the production organism. Classical microbiology and modern molecular bacterial physiology have been brought together to decipher the intricacies of PHA metabolism both for production purposes and for the unraveling of the natural role of PHAs. This review provides an overview of the different PHA biosynthetic systems and their genetic background, followed by a detailed summation of how this natural diversity is being used to develop commercially attractive, recombinant processes for the large-scale production of PHAs.

Diversity of bacterial polyhydroxyalkanoic acids

Abstract: An overview is provided on the diversity of biosynthetic polyhydroxyalkanoic acids, and all hitherto known constituents of these microbial storage compounds are listed. The occurrence of 91 different hydroxyalkanoic acids reflects the low substrate specificity of polyhydroxyalkanoic acid synthases which are the key enzymes of polyhydroxyalkanoic acid biosynthesis. In addition, the importance of bacterial anabolism and catabolism, which provide the coenzyme A thioesters of the respective hydroxyalkanoic acids as substrates to these PHA synthases, is emphasized.