Stereochemistry of a methyl-group rearrangement during the biosynthesis of lanosterol
| Autor: | Kenneth H. Clifford, Phillips Gareth Thomas |
|---|---|
| Rok vydání: | 1976 |
| Předmět: |
Stereochemistry
Mycobacterium phlei Malates Molecular Conformation Mevalonic Acid Acetates Tritium Biochemistry law.invention Fumarate Hydratase chemistry.chemical_compound Acetic acid Lanosterol Stereospecificity Biosynthesis law Animals Carbon Radioisotopes Walden inversion biology Stereoisomerism biology.organism_classification Deuterium Rats Cholesterol chemistry Liver Isotope Labeling Methyl group |
| Zdroj: | European journal of biochemistry. 61(1) |
| ISSN: | 0014-2956 |
| Popis: | 1 (3RS,6R)-[6-2H1,6-3H1,6-14C], (3RS,6S)-[6-2H1,6-3H1,6-14C] and (3RS)-[6-3H1,6-14C]mevalonolactones were synthesised from R-[2H1,3H1,2-14C], S-[2H1,3H1,2-14C] and [3H1,2-14C]acetic acids respectively. 2 Each mevalonate was converted into cholesterol by a rat liver preparation. 3 Each cholesterol specimen was converted into androsta-1,4-diene-3,17-dione by incubation with Mycobacterium phlei in the presence of 2,2′-dipyridyl. Each specimen of androsta-1,4-diene-3,17dione was converted into androsta-1,4-dien-3-one-17-ethylene ketal. 4 The samples of androsta-1,4-dien-3-one-17-ethylene ketal were each converted chemically into oestrones in which the methyl group at C-18 is the only carbon atom that originated from C-6 in mevalonolactone. 5 The oestrone from (3RS)-[6-3H1,6-14C]mevalonolactone was oxidised chemically to acetic acid which was converted into p-bromophenacyl acetate and the 3H/14C ratio was measured. 6 There was no overall loss of tritium from the methyl group of acetic acid, as measured by determining the 3H/14C ratios of the p-bromophena-cyl esters, when the synthetic and degradative procedures 1- 5 were tested with [3H1,2-14C]acetic acid. 7 The oestrones derived from the 6R and 6S-mevalonolactones were oxidised. The chiralities of the resulting acetates were determined by an established procedure whereby the acetates were converted into 2S-malates which were examined for loss of tritium an equilibration with fumarate hydratase. 8 The oestrone from (3RS,6R)-[6-2H1,6-3H1,6-14C]mevalonate gave acetic acid which was converted into 2S-malate that retained 68.6 % of its tritium after treatment with fumarate hydratase; the configuration of this acetic acid was R. 9 The oestrone from (3RS,6S)-[6-2H1,6-3H1 6-14C]nlevalonate was oxidised to acetic acid which was converted into 2S-malate that retained 31.9 % of its tritium after treatment with fumarate hydratase; the-configuration of this acetic acid was S. 10 There was no overall change in the configuration of a chiral methyl group between C-6 of mevalonate and C-18 of oestrone. It is concluded that the intramolecular migration of a chiral methyl group from C-15 in 2,3-oxidosqualene to C-13 in lanosterol is stereospecific and occurs with overall retention of configuration. |
| Databáze: | OpenAIRE |
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