User:Wiki-edits-md/Chlorosulfolipid
Chlorosulfolipids(CSLs) are a class of stereochemically complex chlorinated lipids that contain a sulfate group. These naturally occurring polychlorinated molecules were first reported as unknown sulfated lipids in 1962[1]. They were eventually isolated from the freshwater alga Ochromonas danica in the late 1960s, and are currently proposed to serve a structural role within the membranes of this species[2], however the biological role of CSLs has not been fully established[3]. The high extent of chlorination in these natural products is suspected to be influenced by the concentration of chlorine ion in the surrounding environment. In addition to being proposed integral components of algal membranes, chlorosulfolipids are also known to inhibit protein kinases.
Biological origin
[edit]Chlorosulfolipids were first reported after isolation from Ochromonas danica, a fresh water alga, in the late 1960s[1]. CSLs were found to compose 10-15% of the lipids in the organism, this represents 3% of the dry weight of the cell but more than 50% of the intracellular sulfur content[4]. Over 90% of the total CSLs in the algae were the danicalipin A molecule[3].
A 1979 study by Mercer and Davies analyzed 30 freshwater and marine alga, finding CSLs to be widespread across freshwater alga species, but they were not detected in any marine species. CSLs were detected in notably large quantities in golden alga such as Ochromonas danica and Poterioochromonas malhamensis.[5]
CSLs have also been isolated from toxic mussels associated with diarrhetic shellfish poisoning[6].
Chemical Structure
[edit]
The saturated hydrocarbon backbone of the lipids isolated from Ochromonas danica, contain varying combinations of 1-2 sulfate functional groups as well as 3-6 chlorine atoms. Chlorosulfolipids isolated from the mussel Mytilus galloprovincialis have been shown to contain an alkene group as well as an ester group.
While CSLs were originally isolated from microalga at the end of the 1960s, it took another 40 years to determine their absolute configuration. In 2009 Kawahara and Okino successfully determined the absolute configuration via a synthetic chemistry approach[7], while the Vanderwal group determined the configuration via analytical chemistry. [8]
Synthesis
[edit]Biosynthesis of Danicalipin A
[edit]3'-Phosphoadenosine-5'-phosphosulfate
Initially, docosanoic acid (behenic acid) (2) is constructed via the fatty acid synthesis pathway. Elovson demonstrated that the C-14 secondary hydroxyl group of molecule 3 was incorporated by oxidation of the fatty acid with molecular oxygen, as opposed to alkene hydration with water. The next step involves the enzyme-mediated transfer of the sulfate group from 3’-phosphoadenosine 5’-phosphosulfate (PAPS) to the diol to form molecule 4[9]. Walsh has demonstrated that the halogenation of unactivated methyl groups can be catalyzed by a newly discovered class of α-ketoglutarate-dependent non-heme iron halogenases, suggesting a similar enzyme family could play a role in chlorosulfolipid chlorination. The stepwise chlorination occurs via an order-independent radical mechanism.[10]
Laboratory synthesis of Hexachlorosulfolipid (Mytilipin A)
[edit]In 2009 the Carreira group performed the first laboratory synthesis of a chlorosulfolipid, A Wittig olefination was performed on chlorinated and epoxidated ethyl sorbate to form olefinic epoxide. The allylic epoxide of the olefine was chlorinated nuclophilicly forming a trichloride, and stereoselective conversion then generated the final desired product.[11]
Toxicity
[edit]
Three CSLs have been identified as the causative toxins of diarrhetic shellfish poisoning[6] associated with cytotoxic mussels from the Adriatic sea.[12]
The lipid malhamensilipin A, isolated by the groups of Slate and Gerwick in 1994, displayed both antimicrobial activity as well as an inhibition of the pp60 protein tyrosine kinase[13].
Measurement Techniques
[edit]Detecting and measuring chlorosulfolipids in algal cells requires extracting the compound via centrifugation, freeze drying, and MeOH and EtOAc extractions. This is followed by vacuum drying and fractionation via sequential extractions with hexane, CHCl3, EtOAc, BuOH, and H2O. The fractions are then analyzed via RP-HPLC.
References
[edit]- ^ a b HAINES, THOMAS H.; BLOCK, RICHARD J. (1962-02). "Sulfur Metabolism in Algae. I. Synthesis of Metabolically Inert Chloroform-Soluble Sulfate Esters by Two Chrysomonads andChlorella pyrenoidosa*". The Journal of Protozoology. 9 (1): 33–38. doi:10.1111/j.1550-7408.1962.tb02576.x. ISSN 0022-3921.
{{cite journal}}: Check date values in:|date=(help) - ^ Chen, L L; Pousada, M; Haines, T H (1976-03). "The flagellar membrane of Ochromonas danica. Lipid composition". Journal of Biological Chemistry. 251 (6): 1835–1842. doi:10.1016/s0021-9258(17)33724-9. ISSN 0021-9258.
{{cite journal}}: Check date values in:|date=(help) - ^ a b Kawahara, Teppei; Okino, Tatsufumi (2012-01-01), Atta-ur-Rahman (ed.), "Chapter 7 - Chlorosulfolipids", Studies in Natural Products Chemistry, Bioactive Natural Products, vol. 36, Elsevier, pp. 219–247, doi:10.1016/b978-0-444-53836-9.00024-4, retrieved 2023-05-20
- ^ Elovson, John; Vagelos, P. R. (1969-03). "A NEW CLASS OF LIPIDS: CHLOROSULFOLIPIDS". Proceedings of the National Academy of Sciences. 62 (3): 957–963. doi:10.1073/pnas.62.3.957. ISSN 0027-8424.
{{cite journal}}: Check date values in:|date=(help) - ^ Mercer, E.Jan; Davies, Cledwyn L. (1979-01). "Distribution of chlorosulpholipids in algae". Phytochemistry. 18 (3): 457–462. doi:10.1016/s0031-9422(00)81887-7. ISSN 0031-9422.
{{cite journal}}: Check date values in:|date=(help) - ^ a b Elovson, John; Vagelos, P. R. (1969-03). "A NEW CLASS OF LIPIDS: CHLOROSULFOLIPIDS". Proceedings of the National Academy of Sciences. 62 (3): 957–963. doi:10.1073/pnas.62.3.957. ISSN 0027-8424.
{{cite journal}}: Check date values in:|date=(help) - ^ Kawahara, Teppei; Kumaki, Yasuhiro; Kamada, Takashi; Ishii, Takahiro; Okino, Tatsufumi (2009-08-21). "Absolute Configuration of Chlorosulfolipids from the Chrysophyta Ochromonas danica". The Journal of Organic Chemistry. 74 (16): 6016–6024. doi:10.1021/jo900860e. ISSN 0022-3263.
- ^ Bedke, D. Karl; Shibuya, Grant M.; Pereira, Alban; Gerwick, William H.; Haines, Thomas H.; Vanderwal, Christopher D. (2009-05-15). "Relative Stereochemistry Determination and Synthesis of the Major Chlorosulfolipid from Ochromonas danica". Journal of the American Chemical Society. 131 (22): 7570–7572. doi:10.1021/ja902138w. ISSN 0002-7863.
- ^ Mooney, Carolyn L.; Haines, Thomas H. (1973-10-01). "Chlorination and sulfation reactions in the biosynthesis of chlorosulfolipids in Ochromonas danica, in vivo". Biochemistry. 12 (22): 4469–4472. doi:10.1021/bi00746a026. ISSN 0006-2960.
- ^ Thomas, Graham; Mercer, E.Ian (1974-05). "Biosynthesis of the chlorosulpholipids of Ochromonas danica". Phytochemistry. 13 (5): 797–805. doi:10.1016/s0031-9422(00)91143-9. ISSN 0031-9422.
{{cite journal}}: Check date values in:|date=(help) - ^ Nilewski, Christian; Geisser, Roger W.; Carreira, Erick M. (2009-01). "Total synthesis of a chlorosulpholipid cytotoxin associated with seafood poisoning". Nature. 457 (7229): 573–576. doi:10.1038/nature07734. ISSN 0028-0836.
{{cite journal}}: Check date values in:|date=(help) - ^ Ciminiello, Patrizia; Dell'Aversano, Carmela; Fattorusso, Ernesto; Forino, Martino; Magno, Silvana; Di Meglio, Paola; Ianaro, Angela; Poletti, Roberto (2004-08). "A new cytotoxic polychlorinated sulfolipid from contaminated Adriatic mussels". Tetrahedron. 60 (33): 7093–7098. doi:10.1016/j.tet.2003.12.072. ISSN 0040-4020.
{{cite journal}}: Check date values in:|date=(help) - ^ Chen, Jian Lu; Proteau, Philip J.; Roberts, Mary Ann; Gerwick, William H.; Slate, Doris L.; Lee, Rita H. (1994-04). "Structure of Malhamensilipin A, an Inhibitor of Protein Tyrosine Kinase, from the Cultured Chrysophyte Poterioochromonas malhamensis". Journal of Natural Products. 57 (4): 524–527. doi:10.1021/np50106a015. ISSN 0163-3864. Retrieved 2023-05.
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