Desosamine

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Desosamine
Names
IUPAC name
3,4,6-Trideoxy-3-(dimethylamino)-D-xylo-hexose
Systematic IUPAC name
(2R,3S,5R)-3-(Dimethylamino)-2,5-dihydroxyhexanal
Identifiers
3D model (JSmol)
ChEBI
ChemSpider
UNII
  • InChI=1S/C8H17NO3/c1-6(11)4-7(9(2)3)8(12)5-10/h5-8,11-12H,4H2,1-3H3/t6-,7+,8+/m1/s1 checkY
    Key: VTJCSBJRQLZNHE-CSMHCCOUSA-N checkY
  • InChI=1/C8H17NO3/c1-6(11)4-7(9(2)3)8(12)5-10/h5-8,11-12H,4H2,1-3H3/t6-,7+,8+/m1/s1
    Key: VTJCSBJRQLZNHE-CSMHCCOUBT
  • O=C[C@H](O)[C@@H](N(C)C)C[C@H](O)C
Properties
C8H17NO3
Molar mass 175.23 g/mol
Except where otherwise noted, data are given for materials in their standard state (at 25 °C [77 °F], 100 kPa).
checkY verify (what is checkY☒N ?)

Desosamine is a 3-(dimethylamino)-3,4,6-trideoxyhexose found in certain macrolide antibiotics (contain a high level of microbial resistance) such as the commonly prescribed erythromycin,[1][2] azithromycin, clarithroymcin, methymycin, narbomycin, oleandomycin, picromycin and roxithromycin. As the name suggests, these macrolide antibiotics contain a macrolide or lactone ring and they are attached to the ring Desosamine which is crucial for bactericidal activity.[3] The biological action of the desosamine-based macrolide antibiotics is to inhibit the bacterial ribosomal protein synthesis.[4] These antibiotics which contain Desosamine are widely used to cure bacterial-causing infections in human respiratory system, skin, muscle tissues, and urethra.

Discovery

Although desosamine has been found in many macrolide antibiotics, the complete chemical structure of desosamine was not determined until 1962.[5] Nuclear magnetic resonance spectroscopy data was used to establish the complete configuration of desosamine. The hydrogen atoms at the C1,C2,C3, and C5 positions are all found to be axial.[5]

Biosynthesis

Six enzymes are required for Desosamine biosynthesis from TDP-glucose in Streptomyces venezuelae.[1][6] In addition to the required enzymes, there are eight important open reading frames known as the des regions, they are desI~desVIII, these eight frames are the necessary genes used in Desosamine biosynthesis, among the 8 des regions, the desI gene implements C-4 Deoxygenation by the enzymatic activity of dehydrase. [7]

Degradation

Degradation of several of the aforementioned antibiotics yields the desosamine sugar. It is found in combination with the smaller macrolide rings, always attached at C-3 or C-5 of the aglycone. Alkaline degradation found the sugar to be a D-hexose derivative.[8] Glycosidic cleavage of methomycin produces aglycone methynolide and the basic sugar desosamine, whose structure had been determined by oxidative degradation to crotonaldehyde and by other experiments.[9]

Drug resistance

Macrolide antibiotics that contain Desosamine as an amino sugar in their chemical structures sometimes encounter drug-resistant bacteria. The target-site modification can result in changing chemical structure of the antibiotics, for example, a methylation mutation, which will block the drug from normally functioning.[10]

See also

References

  1. ^ a b Rodríguez E, Peirú S, Carney JR, Gramajo H (March 2006). "In vivo characterization of the dTDP-D-desosamine pathway of the megalomicin gene cluster from Micromonospora megalomicea". Microbiology. 152 (Pt 3): 667–673. doi:10.1099/mic.0.28680-0. PMID 16514147.
  2. ^ Flickinger MC, Perlman D (April 1975). "Microbial degradation of erythromycins A and B". The Journal of Antibiotics. 28 (4): 307–11. doi:10.7164/antibiotics.28.307. PMID 1150530.
  3. ^ Burgie ES, Holden HM (August 2007). "Molecular architecture of DesI: a key enzyme in the biosynthesis of desosamine". Biochemistry. 46 (31): 8999–9006. doi:10.1021/bi700751d. PMC 2528198. PMID 17630700.
  4. ^ Vázquez-Laslop N, Mankin AS (September 2018). "How Macrolide Antibiotics Work". Trends in Biochemical Sciences. 43 (9): 668–684. doi:10.1016/j.tibs.2018.06.011. PMC 6108949. PMID 30054232.
  5. ^ a b Woo PW, Dion HW, Durham L, Mosher HS (January 1962). "The stereochemistry of desosamine, an nmr analysis". Tetrahedron Letters. 3 (17): 735–739. doi:10.1016/S0040-4039(00)70510-7.
  6. ^ Burgie ES, Holden HM (August 2007). "Molecular architecture of DesI: a key enzyme in the biosynthesis of desosamine". Biochemistry. 46 (31): 8999–9006. doi:10.1021/bi700751d. PMC 2528198. PMID 17630700.
  7. ^ Borisova SA, Zhao L, Sherman DH, Liu HW (July 1999). "Biosynthesis of desosamine: construction of a new macrolide carrying a genetically designed sugar moiety". Organic Letters. 1 (1): 133–6. doi:10.1021/ol9906007. PMID 10822548.
  8. ^ Bolton CH, Foster AB, Stacey M, Webber JM (1961). "Carbohydrate components of antibiotics. Part I. Degradation of desosamine by alkali: Its absolute configuration at position 5". Journal of the Chemical Society. 1961 (4): 4831–4836. doi:10.1039/JR9610004831.
  9. ^ Berry M (1963). "The macrolide antibiotics". Quarterly Reviews, Chemical Society. 17 (4): 343–361. doi:10.1039/QR9631700343.
  10. ^ Klugman KP, Lonks JR (June 2005). "Hidden epidemic of macrolide-resistant pneumococci". Emerging Infectious Diseases. 11 (6): 802–7. doi:10.3201/eid1106.050147. PMC 3367596. PMID 15963272.

External links

Retrieved from "https://mdwiki.org/wiki/Desosamine"